Block 7 Brain Sciences 1 - Marcus

Stroke Types

"Burst" (hemorrhagic): blood vessel bursts, bleeds into the brain "Block" (obstructive/ischemic): blood vessel is clogged and blood can't flow to its associated brain regions Treatment: IV tissue plasminogen activator (tPA) within 3 hours (tPA converts plasminogen into plasmin, which cleaves fibrin into FDPs)

Allodynia -Central mechanisms

"Other Pain": it shouldn't hurt, but it does A *non-painful stimulus* is painful (e.g., stroking sunburned skin; moving arthritic joints).

Glymphatic Circulation

"The Brain's Drain" removes metabolic waste and discarded proteins (2-3x as we sleep, leaving us refreshed in the morning).

Tear film layers

((Superficial/exposed to air)) 1. Lipid Layer (from Meibomian glands): reduces evaporation and insures that the optical surface is as smooth as possible 2. Aqueous layer (from tear glands; CN VII): O2 dissolved in this layer is essential for corneal metabolism; flushes away foreign bodies from the cornea 3. Mucin layer (from surface cells): wets the corneal epithelium with goblet cells of the conjunctiva

Cranial Nerve Exits from the Brain

*2,2,4,4 Rule* Above Brainstem: CN I, II Midbrain (pons junction): CN III (ventral), IV (dorsal) Pons: V (pons), VI, VII, VIII (pontomedullary junction) Medulla: IX, X, XI (behind olives), XII (between pyramids and olives) CN VII has two branches that come out. 1. Branchiomotor: wraps around VI and innervates face muscles 2. Visceromotor: salivatory nucleus for salivation/lacrimation (not parotid, IX)

Astereognosis -Inability to perceive the form of solid objects by touch

*A deficit in 3D-perceptual constructs* from skin and position information by the senses, usually in reference to the *inability to perceive the form of solid objects by touch*. A lesion of S1 renders the affected area anesthetic and seriously interferes with all sensory function including stereognosis. Requires primary somatosensory (S1: Brodman 1-3) and posterior parietal cortex (Brodman 5 and 7).

Meniere's Disease

*Acute onset vertigo and hearing loss* in *recurrent* spells lasting 30 mins to hours. Hearing loss is progressive in continued vertigo episodes. Due to intermittent increase in endolymph production, which distorts sound and balance information sent to the brain Treatment: low-salt diet, diuretics (remove fluid)

Brown-Séquard Syndrome (Spinal Hemisection) *Same Side of Lesion: DCML and CST* *Opposite Side of Lesion: AL* 1. *DCML:* fine touch, proprioception, pressure, two-point discrimination 2. *Anterior:* crude touch and firm pressure 3. *Lateral:* pain, temperature, and itch 4. *CST:* paralysis (motor efferents)

*All sensations (but AL pathway) occur ipsilaterally.* Consequence of AL decussating in spinal column (contralateral side of damage affected) and DCML and CST decussating in medulla (ipsilateral side of damage affected). Disassociated sensory loss caused by damage to one half of the spinal cord, resulting in: Below Lesion: 1. *Ipsilateral upper motor neuron (UMN) signs:* paralysis and loss of motor efferents (corticospinal tract) (decussation occurs at the spino-medullary junction in the pyramids which is above the lesion) 2. *Ipsilateral* Dorsal Column (DCML) signs: loss of touch, vibration, and proprioception 3. *Contralateral* Spinothalamic (AL) signs: loss of pain and temperature sensation (spinothalamic (pain/temp/itch/crude touch) tract crosses in the spinal cord (via anterior white commissure) and not in the brainstem (DCML decussates in medulla: fine touch, vibration, proprioception) → contralateral) At the lesion level: 1. *Ipsilateral loss of all sensation* 2. Lower motor neuron (LMN) signs Due to decussation taking place over a few segments for the AL pathway, pain is also lost on the ipsilateral side directly below lesion (zone of complete loss of sensation; see image).

General artery supply regions of the brain. ACA: mesial (midilne): frontomedial and superior cerebrum MCA: traverses the lateral sulcus to supply the lateral cerebrum PCA: inferior surface of temporal; mesial surface of occipital

*Anterior Circulation:* *Anterior Cerebral Artery:* located medially and frontally; supplies frontomedial and superior cerebrum (affects lower extremities and trunk) *Middle Cerebral Artery:* traverses the lateral sulcus (Sylvian fissure) to supply the lateral cerebrum. In the sulcus, the artery passes the insular cerebral lobe (deep to the Sylvian fissure) (affects face and upper extremities) *Posterior Circulation:* *Posterior Cerebral Artery:* located medially; supplies inferior and posterior cerebrum (perfuses the "eloquent"/visual cortex)

Determining the azimuth of a sound requires *head movement*

*Azimuth:* a sound's direction away from the head in a plane through the ears and nose For *higher frequency sounds (>1500 Hz)*, the head casts a *"sound shadow"*. We deduce sound direction by *differences in intensity* between the left and right ears, and we move our head to aid in the process. Sounds sources directly ahead or behind can be ambiguous as to direction. For *lower frequency sounds*, we measure the *time (phase) difference* between sound waves reaching the two ears (sound reaches one ear faster than the other). It takes about 660 microseconds for sound to move from one ear to the other. Although a *unilateral lesion* in the auditory pathway (above the pontomedullary junction) does not produce unilateral deafness, it does *severely impair an individual's ability to localize the source of a sound*.

Benzodiazapines vs Barbituates Hint: ben*z*o ≈ H*z* = frequency

*Barbituate* Mechanism of CNS Depression: *Enhance inhibition* by *increasing the open time of GABAa channels* (allowing more Cl- influx) in the presence of GABA. Note: Barbituates *do not open* GABAa channels themselves, except at very high doses. CNS-Depressant Drugs (reduce neural excitability): 1. Barbituates: *Longer GABA channel open duration* (more Cl- influx) 2. Benzodiazepines: *Higher GABA channel open frequency* (more Cl- influx) Additionally: Gaseous anesthetics (e.g., enflurane) enhance GABAaR currents in a *dose-dependent* manner, resulting in IPSPs and depression of the CNS.

Functional Components of the Cranial Nerves (and Their Nuclei)

*CN I: olfactory* Somatic: Branchio: Viscero: *Sensory:* olfactory (olfactory bulb) *CN II: optic* Somatic: Branchio: Viscero: *Sensory:* vision (lateral geniculate in superior colliculus) *CN III: oculomotor* *Somatic:* extra ocular muscles (4, including levator palpebrae superioris) (oculomotor) Branchio: *Viscero:* parasympathetics for the eye (constriction and accommodation) (Edinger-Westphal) Sensory: *CN IV: trochlear* *Somatic:* superior oblique m. (trochlear) Branchio: Viscero: Sensory: *CN V: trigeminal* Somatic: *Branchio:* muscles of mastication (masseter, temporal, lateral and medial pterygoids) (motor V.) Viscero: *Sensory:* face, head, skin, mucosa, dura (trigeminal; main/spinal) *CN VI: abducens* *Somatic:* lateral rectus m. (abducens) Branchio: Viscero: Sensory: *CN VII: facial* Somatic: *Branchio:* facial muscles; stapedius m. of middle ear (facial) *Viscero:* submandibular and sublingual salivary glands, lacrimal glands (salivatory) *Sensory:* taste (anterior 2/3), skin behind ear (n. solitary tract) *CN VIII: vestibulocochlear* Somatic: Branchio: Viscero: *Sensory:* auditory, vestibular (cochlear and vestibular) *CN IX: glossopharyngeal* Somatic: *Branchio:* stylopharyngeus (swallowing) (ambiguus) *Viscero:* parotid salivary gland (salivatory) *Sensory:* taste (posterior 1/3), carotid sinus (baroreceptors) and body (chemoreceptors), pharynx, skin (ear) (n. solitary tract) *CN X: vagus* Somatic: *Branchio:* larynx (ambiguus) *Viscero:* neck, thorax, abdomen (dorsal motor nucleus of vagus) *Sensory:* visceral, pharynx, soft palate (except tensor veli palatini), larynx, thorax, abdomen (n. solitary tract) *CN XI: spinal accessory* *Somatic:* SCM, trapezius mm. (accessory spinal C1-C5) *Branchio:* larynx for speaking (ambiguus) Viscero: Sensory: *CN XII: hypoglossal* *Somatic:* tongue muscles (hyoglossus, styloglossus, genioglossus) (note: palatoglossus = CN X) (hypoglossal) Branchio: Viscero: Sensory:

Taste signal is transmitted by CNs.... Pathway: 1. CN VII, IX, X 2. Solitary tract nucleus (medulla) 3. VPM 4. Primary gustatory complex (insula)

*CN VII* (anterior tongue), *CN IX* (posterior tongue), and *CN X* (epiglottis) for special sensory. These taste afferents project to gustatory nucleus of the *solitary tract* (medulla), which relays information to the thalamus (*VPM* nucleus) and then the primary gustatory cortex (*insula* of cerebrum). Flavor = gustation + olfaction Taste = gustation + olfaction + somatosensation Other Cranial Nerves Involved: 1. *CN V3* for general sensation: texture, temperature, and general chemosensitivity (sharp, hot, soft, crunchy). Capsaicin activates heat-sensing thermoreceptors (starts depolarization TRPv receptors → Nav1.7 →normal Na+ channels). Menthol activates cold-sensing thermoreceptors by amplifying the cold. 2. *CN I* (olfactory) for smell: odorants released into the oropharynx during mastication rise into the nose via nasopharynx and stimulate olfactory receptors.

Causes of Central Vertigo → NEED IMAGING

*Cerebellar Infarct* -*Vertigo plus gait ataxia, ipsilateral ataxia, diplopia, lethargy, severe headache, etc.* -*PICA infarct* can affect flocculonodular component of cerebellum -EMERGENCY: swelling can cause increased intracranial pressure (Monroe-Kellie Doctrine) (affects the posterior fossa; can cause hydrocephalus)

Glaucoma The filtration angle is a space between the iris and lens.

*Closed-Angle Glaucoma:* the *iris and lens stick together* due to changing rates of formation and removal of aqueous humor. This leads to *increased intra-optic pressure* (aqueous humor cannot reach anterior chamber), pushing the iris against the cornea, *blocking* the trabecular meshwork (*canal of Schlemm*). The optic disc *cups* with this pressure build up, which can lead to glaucoma, an optic nerve neuropathy and a leading cause for blindness. *Open-Angle Glaucoma:* the filtration angle is open, but the drainage system (trabeculae) is obstructed.

Conductive vs. Sensorinural Hearing Loss

*Conductive* hearing ability is mediated by the middle ear composed of the ossicles: incus, malleus, stapes. *Sensorineural* hearing ability is mediated by the inner ear composed of the cochlea with its internal basilar membrane and attached cochlear nerve (CN VIII). *Conductive Loss:* middle and outer ear -Otosclerosis: proliferation of bone around ligamentous attachments of ossicles (especially the stapes) limits movement -Otitis Media: middle ear infection leads to fluid buildup behind the tympanic membrane (acutely) and can lead to scar tissue formation (chronically) -Wax impaction -Ruptured tympanic membrane *Sensorineural Loss:* inner ear -Dysfunction or degenerated *hair cells* or *CN VIII axons* due to injury, infection, genes, loud noises, medications, or tumors.

Cone/Photopic vs. Rod/Scotpic Vision

*Cone/Photopic Vision:* 1. Low light sensitivity 2. Trichromatic 3. Good spatial acuity 4. Fovea most sensitive (cones located at fovea) 5. Most sensitive to *long wavelengths (red)* *Rod/Scotopic Vision:* 1. High light sensitivity 2. Achromatic (light is dim and only affects rods so wavelength discriminations cannot be made) 3. Poor spatial acuity (rods converge in large numbers on second-order neurons) 4. Parafovea most sensitive (rods located outside fovea) 5. Most sensitive to *short wavelengths (blue)*

DCML vs. AL Pathways (SENSORY) DCML = Aα, Aβ, and Aδ: *fine touch, vibration, pressure, two-point discrimination* AL = Aδ and C: 1. Anterior spinothalamic tract carries information about *crude touch and firm pressure* 2. Lateral spinothalamic tract conveys *pain and temperature*

*DCML:* Throughout the spinal cord, *first order fibers* (Aα, Aβ) of the DCML system (axons of dorsal root ganglion cells) are from the *same side of the body (ipsilateral)*. The second-order fibers (axons of neurons in the dorsal column nuclei), *decussate immediately in the medulla* before ascending through the medial lemniscus to terminate in the thalamus. Thus, both the medial lemniscus and the thalamic VPL carry touch and position information from the opposite side of the body (contralateral). *Dorsal Column Nuclei:* -Gracile: mid-thorax and legs (T7 and below) -Cuneate: arms (C2-T6) *DCML Thalamic Nucleus:* -VPL: arms and legs (lateral) → S1 *AL* primary neuron axons (Aδ, C) enter the dorsal horn via Lissauer's tract, ascend a few levels, then synapse in substantia gelatinosa of Rolando, then *decussate in the spinal cord* (via anterior white commissure) and *ascends to thalamic nuclei* (via AL pathway *without synapsing in the medulla*) *Substantia Gelatinosa:* gray matter in the dorsal horn that receives direct input from sensory dorsal nerve roots, especially those fibers from pain and thermoreceptors. AL Thalamic Nuclei: -VPL: arms and legs (lateral) → SI (localized, sharp pain) -Interlaminary: dull, aching, slow pain, and arousal from AL → SII

Dysarthria

*Deficient motor control of the muscles involved in speech proaction* without concomitant weakness in the musculature itself. Difficult or unclear articulation of speech that is otherwise linguistically normal.

*Age-Related Macular Degeneration (AMD)* (Exam) -Most common cause of blindness in Americans over 60 years of age.

*Degeneration of the retinal pigment epithelium and outer retina. Bruch's membrane thickens with age, causing breaks that lead to neovasuclarization.* Hemorrhage of these new, weak vessels causes acute visual loss. Subtypes: 1. *Wet:* *exudative* macular degeneration; breaks in Bruch's membrane allow *choroidal blood vessels* to proliferate under the retina, causing progressive visual loss. 2. *Dry:* degeneration of the retina and underlying retinal pigment epithelium due to *drusen (yellow deposit of lipid) accumulation in Bruch's membrane*; central vision gradually worsens (occurs at macula/fovea)

Anosognosia -No knowledge of pain

*Denial of injury or deficit.* Impairs a person's ability to understand and perceive his or her illness. *The patient will fail to recognize his own limb (as his own) and will deny that the limb is paralyzed* Associated with a posterior parietal lesion (*particularly right side*)(neglect)

Cataract

*Deterioration of lens fibers causing lens to become opaque.* As the lens epithelium cannot repair or replace itself, treatment for cataracts is to replace the affected lens with a plastic lens.

Three Classes of Dichromacy

*Dichromacy:* loss of a pigment (cone class) → X-linked Recessive 1. *Tritanopia:* Loss of *short* wavelengths (blue) → confuse blues and greens 2. *Deuteranopia:* Loss of *middle* wavelengths (green) → confuse greens and reds 3. *Protanopia:* Loss of *long* wavelengths (red) → confuse greens and reds

Basic Types of Pain

*Fast Pain:* Aδ fibers project to somatotopically arranged nuclei (VPL, VPM) to somatosensory cortex -Sharp, well localized, short lasting -No affective component (perceived unpleasantness of a painful event) *Slow Pain:* C fibers project from reticular formation to nonspecific thalamic (laminar) nuclei to post hypothalamus, limbic system, and frontal cortex (anterior cingulate cortex) -Dull, poorly localized, enduring -Positive affective component (emotional)

Wernicke's Aphasia

*Fluent, sensory aphasia.* Patients are unaware of their problem. Lesion: posterior superior temporal gyrus in Wernicke's area. *Comprehension is compromised (difficulty interpreting spoken and written words). Speech is plentiful (logorrhea) with normal melody or prosody, but is empty (no substance). There are a few content words, but mostly gibberish.* Can be mistake for acute schizophrenia with its associated "word salad" speech.

Lesions in the Visual Pathway

*From retina to visual cortex:* 1. Optic nerve (ipsilateral eye axons: N and T) 2. Optic chiasm (nasal retina axons cross) 3. Optic tract (nasal and temporal axons carrying information) *Lesion Results:* 1. Optic nerve (blind in ipsilateral eye; lose binocularity and monocular crescent in ipsilateral eye) 2. Optic chiasm (bitemporal hemianopia: blind in temporal visual field, which is represented in the decussating fibers of the nasal retina; lose binocularity and monocular crescent of both eyes) 3. Optic tract (homonymous hemianopia: nasal field loss ipsi to lesion; temporal field loss contra to lesion)

Gadolinium Contrast

*Gadolinium (Gd)* shortens T1-relaxation of lesions (making them brighter, like fat) with absent or deficient blood brain barriers . This allows for us to look for *brain metastases*.

Dendritic spine shape, number, and biochemistry are affected by:

*Genetics:* -Fragile X babies have a change in spine morphology (more thin and wispy), making it more difficult to make connections with axons from another neuron. -Tay-Sachs patients lack HexA to degrade gangliosides (lipids), resulting in *meganeurites* on cortical pyramidal cells that cause seizures and intellectual disability. *Membranous cytoplasmic bodies* form as lipid molecules accumulate in neuronal cell bodies (see image). *Environment:* -Spine density increases 20-30% during estrogen cycles. -Cortisol (stress) reduces spine density *Age:* spine density decreases with age

Receptor Pharmacology

*Gly-R:* Agonist: glycine Antagonist: strychnine (Indian tree) Sites in CNS: spinal cord, brainstem *GABAaR:* Agonist: GABA, muscimol (mushroom) Antagonist: bicuculline (plant-derived), picrotoxin (East Indian shrub), penicillin Sites in CNS: everywhere *GABAbR:* Agonist: GABA, Baclofen Antagonist: phaclofen Sites in CNS: everywhere

PNS Demyelination

*Guillain-Barré Syndrome:* also known as acute inflammatory demyelinating neuropathy (AIDP) -Demyelinated axons in the PNS -Result of an autoimmune response (which attacks Schwann cells) to a virus (molecular mimicry) -*Rapid onset* (acute) -*Starts peripherally* (fingers/toes) and moves more centrally. This is because longer neurons (most myelin) are most susceptible (distal extremities).

Gyri vs. Sulci vs. Fissures

*Gyri:* folds *Sulci:* valleys *Fissures:* deep furrow/elongated cleft *Folding:* increases the surface area of the superficial cerebrum (cortex) to allow more room for neurons, which allows for more integration (processing power).

Parietal Hemi-Neglect Syndrome

*Hemispatial neglect (inattention to external stimuli contralateral to the posterior parietal lesion).* Patients with astereogenesis often show a striking deficit in self-image of their left side, even denying its existence (throw own leg out of bed). Inability to copy the left-side stimuli is an example of constructional apraxia. Usually a right-side posterior parietal lesion causes the patient to neglect their left world.

Glutamateric Excitotoxicity

*Hypoxia/ischemia and neurodegenerative disorders (e.g., Alzheimer's, Parkinson's, Huntington) lead to excessive release of glutamate.* Excess release of glutamate leads to: 1. *Ca2+ Overload* -Enters through certain subtypes of glutamate receptors (e.g., NMDA) -Increases intracellular Ca2+; binds to calmodulin; leads to activation of Ca2+/calmodulin-dependent protein kinases and other proteins (see image) -This leads to the destabilization of cell membranes (lipid peroxidation products) and ROS synthesis → cell death 2. *Mitochondrial Dysfunction* -Release of free radicals (superoxide and hydrogen peroxide) -Reduced supply of ATP (impaired energy production)

Agnosia -Inability to interpret sensations and hence to recognize things

*Inability to process sensory information.* Often there is a *loss of ability to recognize objects, persons, sounds, shapes, or smells* while the specific sense is not defective nor is there any significant memory loss. Example: Tactile Agnosia (asterognosis): patient can name an object on sight, draw it when asked, and can reach for it if asked. BUT, the patient cannot identify the object by touch (without sight).

GABA (γ-aminobutyric acid)

*Inhibitory in CNS* (decarboxylated glutamate)

Glycine (AA)

*Inhibitory in brainstem and spinal cord* Reminder: AA can only be used as neurotransmitters (and not hormones) because they are obtained through food and must be isolated

Cerebellar Lesions -Disrupt fine coordinated movements, equilibrium, posture, and motor learning (ipsilateral) -Induce ataxia (lack of order): irregular, uncoordinated movements (trunk or limbs)

*Lateral* Lesions: -Affect voluntary movement of extremities (*limbs*) -When injured, propensity to fall toward injured (*ipsilateral*) side. *Medial* Lesions: -Affects *midline* structures (vermal cortex, fastigial nuclei) and/or flocculonodular lobe *truncal ataxia* (wide-based cerebellar gait), nystagmus, head tilting. -Generally result in bilateral motor deficits affecting axial and proximal limb musculature.

The Cornea -Innervated (CN V1): think reflex with VII -Avascular -Dehydrated (H2O removed to not refract or scatter light)

*Layers:* ((Faces air/tear film)) 1. *Epithelium* (Bowman's membrane; multilayered, regenerates well) 2. *Stroma* (collagen fibrils, *mucopolysaccharide matrix*, and corneal cells = keratocytes) 3. *Endothelium* (Descemet's membrane) ((Faces anterior chamber)) *Blood supply:* The cornea is *avascular*, which contributes to the optical clarity of the cornea (no shadow cast). Nutrients are delivered through circulation of fluid between the posterior and anterior chamber from capillary beds. *Innervation:* Free nerve endings of CN V1 *Transparency:* *Water is removed constantly* from the stroma by the epithelium and endothelium by processes involving *active transport of electrolytes* (requires ATP and oxygen provided by aqueous humor). This prevents refraction or scattering of light. Oxygen reaches the cornea from the air and the aqueous humour. Injury to the endothelium or epithelium causes the cornea to imbibe water, swell, and cloud.

Left vs. Right Hemisphere

*Left Hemisphere:* verbal, intellectual, rational, analytical: *grammar and lexicon of speech and language* → aphasia *Right Hemisphere:* emotional, spatial, artistic, intuitive, nonverbal: *prosodic features of speech and language (stress, intonation, rhythm)* → neglect In the right hemisphere, the angle of the Sylvian Fissure is larger from a traverse axis

Fiber-Rich Region Terms

*Lemniscus: ascending sensory channel* *Funiculus: white "column" of spinal cord* Fasciculus: slender bundle of axons Commissure: white matter nerve tract that bridges the two hemispheres Decussation: site where tract crosses the midline

Local Anesthetics BLOCK Na+ channels

*Lidocaine:* 1. Crosses lipid membrane 2. Enters Na+ channel from inside the cell, where it can bind to binding sites on the S6 alpha helix of the voltage-gated Na+ channel 3. Extracellular Na+ blocked from entering

MRI of a brain lesion

*MS: white matter demyelination* -FLAIR shows demyelination plaques (white) -Clearer plaques than on T1 images, where they appear black *Brain Tumors:* gliomas appear like additional "water" in the brain T1: appears hypointense (black) T2: appears hyperintense (white)

Main Nucleus vs Spinal nucleus of Trigeminal Nerve (and Pathways) -Both sensory nuclei sit at the dorsal aspect of the brainstem (main @ rostral pons; sensory from mid pons to rostral spinal cord)

*Main Nucleus* (decussation in pons) Location: pons Senses: *fine touch, vibration, pressure, and position (proprioception)* in the face Analogous to: DCML pathway (arms/legs) Pathway: 1. *Aα, Aβ* (large diameter) fibers with cell bodies in trigeminal ganglion enter the pons via middle cerebellar peduncle and synapse in *main sensory nucleus of V* in the pons (analogous to dorsal column nuclei). 2. Second order cells send their axons *contralaterally* into the trigeminal lemniscus (which joins the ML pathway to terminate in the VP nucleus of the thalamus). The trigeminal pathway ends in the VPM (face) nucleus and the ML pathway terminates in the VPL (arms/legs) nucleus. *Spinal Nucleus* (decussates in medulla) Location: throughout lower pons, medulla, and rostral spinal cord (direct extension of the substantia gelatinosa) Senses: *pain, temperature, crude touch, itch* in the face Analogous to: analogous to substantial gelatinosa Pathway: 1. *Aδ, C* (small diameter) fibers with cell bodies in trigeminal ganglion enter the pons and *descend through the spinal tract of V* (midbrain tract analogous to Lissauer's tract of spinal cord gray matter) to synapse in the *spinal nucleus of V* (analogous to substantia gelatinosa). 2. The cells of the spinal nucleus of V send their axons across the midline (decussate) to join the AL system on the other side (so that the information in the AL path in the medulla has information from the contralateral head [spinal tract of V] as well as the body [AL]) 3. Eventually these fibers synapse in their thalamic targets (VPM-sharp, posterior-slow, dull, intralaminar-slow, dull), which project to the same general regions of cortex as those arising from the trunk and limbs).

DCML first synapses at...

*Medulla* at the spino-medullary junction (in *dorsal column nuclei*)

Motor Cranial Nuclei Locations (Medulla)

*Medulla:* medial to lateral 1. Hypoglossal (somatomotor): ventral to 4th ventricle and midline 2. Dorsal motor nucleus of X (visceromotor): ventral to 4th ventricle, but more lateral 3. Ambiguus (branchiomotor): more ventral and lateral Remember to think about basal vs. alar plates for orientation of somato and viscero (medio-dorsal at 4th ventricle) vs. bronchio (ventral and more lateral).

The pons in transverse sections

*Mid/Caudal Pons* 1. Middle cerebellar peduncle (lateral) 2. Superior cerebellar peduncle (dorsal) 3. 4th ventricle (open space at center) 4. Pontine protuberance (ventral) contains descending fibers of the CST *Rostral pons* (pontomesencephalic junction with midbrain) 1. 4th ventricle (dorsal) is now much smaller, collecting to become the cerebral aqueduct 2. Cerebellar peduncles are not present because they are more caudal

Motor Cranial Nuclei Locations (Midbrain)

*Midbrain:* superior to inferior (all nuclei are ventral to periaqueductal gray matter (PAG) 1. EW (visceromotor) 2. Oculomotor (somatomotor): nerve travels through red nucleus and exits midbrain 3. Trochlear (somatomotor): nerve wraps around PAG and exits midbrain dorsally inferior to the inferior colliculi Remember to think about basal vs. alar plates for orientation of somato and viscero (medio-dorsal at 4th ventricle) vs. bronchio (ventral and more lateral).

Miosis (constriction) vs. Mydriasis (dilation)

*Miosis:* iris sphincter muscle wins (CN III para > sympathetics) → constriction via EW nucleus and ciliary ganglion *Mydriasis:* iris dilator muscle wins (sympathetics > CN III para) → dilation (pathway detailed below)

CNS Demyelination

*Multiple Sclerosis* -Plaques of demyelinated axons are visible on staining of brainstem -The central portion of the brainstem (anterior to 4th ventricle and posterolateral to the inferior olivary nuclei) is no longer myelinated (white on myelin stain)

Action Potential Requirements and Channel States

*Na+ and K+ channels are essential for APs. Gating of channels is regulated by voltage and time.* *Na+ Channel States (faster):* -Open -Closed -Inactivated (must be reset by hyperpolarization/reducing Vm/K+ coming into the cell) *K+ Channel States (slower):* -Open -Closed At rest, cells have a high permeability to K+ (leaky). Thus Vm → E(K+) = -90mV ≈ -65 mV (due to open Cl- channels etc.; GHK). Threshold is ≈ -50 to -55mV.

Argyll-Robertson Pupil Accommodation: -Convergence -Rounding of lens -Constriction

*No pupillary light response, but accommodative response is present.* Usually, the pupil constricts during the accommodative response as well as in response to increased illumination of the retina Cause: *lesion in pretectum (due to neurosyphilis)* that interrupts the pathway of the light reflex without blocking access via other pathways to the EW nucleus of signals responsible for accommodation. Mneumonic: ARP (like Argyll-Roberson Pupil) -Accomodation Reflex Present -Pupillary Reflex Absent (to light): pretectal to EW to CN III

Broca's Aphasia

*Non-fluent, motor aphasia.* Patients are aware of their problem. Lesion: near the *posterior end of the inferior frontal gyrus* in Broca's area. Comprehension retained (able to follow commands), but verbal expression is diminished (speech is labored and slow, but what comes out makes sense). Since Broca's area is near the cortical motor representation of the face and right arm, the lesion often causes a right hemiplegia involving the face and arm

Rod and Cone Photoreceptors -Rods (left) have larger outer segments than cones (right) and are more sensitive (used in low light). Cones are less sensitive and need more light energy to activate

*Outer segment:* stacks of membranous discs containing high concentrations of photopigment (right). *Inner segment:* contains high concentrations of mitochondria, allowing photoreceptor cells to maintain their membrane potentials despite the large influx of ions carrying the dark current. Despite the large, depolarizing dark current (Na+ and Ca2+ influx through cGMP-gated channels), photoreceptors continue to function because a very active Na-K pump removes the Na from the cell, maintaining the cation concentration gradients within a functional range so that there is always a membrane potential that can be modulated by light. This uses almost all of the O2 supplied by the choroid. In the dark, rhodopsin is not activated, preventing transducin from activating PDE, maintaining GMP in its cyclic form (cGMP). This keeps cGMP-gated channels open and the cell depolarized.

Cerebellar Blood Supply

*PICA*: branch off of vertebral a. (which travels in front of the midbrain): perfuses inferior cerebellum *AICA*: branch off of (low) basilar a.: perfuses anterior inferior cerebellum *Superior cerebellar a.*: branch off of basilar a. that supplies most of cerebellum (from posterior) The "watershed" is the vascular territory of the posterior cerebellum that may be perfused by more than one major artery.

Pain vs. Nociception

*Pain:* a psychological experience or concept that requires consciousness *Nociception:* the detection of damaging stimuli (something that could cause tissue damage or has caused tissue damage)

*Sensory Processing Pathway* (parietal lobe) 1. First order neurons in PNS to dorsal horn 2. Second order neurons up spinal cord to thalamus 3. Third order neurons from thalamus to primary somatosensory cortex 4. Primary somatosensory cortex (type? from where?) to somatosensory association area (what is it?)

*Pathway:* 1. Receptors sense stimuli and produce APs that move along axons of somatic sensory *first order neurons of the PNS*. 2. Axons of these first order neurons travel through a spinal nerve (into a dorsal root) and synapse in the dorsal horn of the grey matter of the spinal cord. 3. *Second order neurons* relay the somatosensory APs up through the *spinal cord* via a nerve tract to the thalamus. 4. From the *thalamus*, a *third order sensory neuron* relays the AP to the post-central gyrus (primary somatosensory cortex) 5. Neurons in the *post-central gyrus* determine what part of the body the sensation is coming from (location) and what type of sensation it is. 6. Sensation then moves to the *somatosensory association area*, where information is further processed, and, based on prior experience and other incoming sensory information, a determination is made of how that sensory information should be interpreted. Somatic sensation comes to the brain mainly through the skin: -Heat/cold -Pain -Light touch/pressure -Limb position/movement

Conduction Aphasia

*Patient is unable to repeat words spoken to them*. Comprehension is excellent, and speech is fluent, but paraphasic (production of unintended syllables, words, or phrases during the effort to speak). Lesion: *arcuate fasciculus* between Wernicke and Broca's regions (disconnection syndrome); can't produce repeated speech.

________ is located between Heschl's Gyrus and Parietal Lobe at the *superior aspect of the temporal lobe*

*Planum Temporale.* Distinctively larger the left than right hemisphere. Thought to be important in language performance.

Motor Cranial Nuclei Locations (Pons)

*Pons:* superior to inferior (and medial to lateral) (Pons-Midbrain Junction) 1. Motor V (branchiomotor) (Pontomedullary Junction) 2. Abducens (somatomotor): mesial (ventral to 4th ventricle 3. Salivatory (visceromotor): central to VI and VII, but a bit inferior 4. Facial (branchiomotor): lateral and ventral (nerve fiber wraps around abducens nucleus) Remember to think about basal vs. alar plates for orientation of somato and viscero (medio-dorsal at 4th ventricle) vs. bronchio (ventral and more lateral).

Strokes in the cerebellum most likely result from which artery?

*Posterior-inferior cerebellar a. (PICA)*

Quick and Slow Eye Movements

*Quick eye movements (saccades):* move an image across the retina -Pathway: Cerebral cortex → superior colliculus → reticular formation of pons and midbrain → oculomotor neurons *Slow eye movements (smooth pursuit):* prevent an image from moving on the retina (i.e., stabilize the image and stick it to the retina.) -Pathway: Cerebral cortex → vestibular nuclei → cerebellum → oculomotor neuron

The midbrain in transverse sections

*Rostral* 1. Tectum (roof): region dorsal to cerebral aqueduct (includes superior and inferior colliculi) 2. Tegmentum (floor): ventral to the cerebral aqueduct (comprises the cerebral peduncles in the midbrain) → affected in Parinaud's Syndrome 3. Periaqueductal gray (PAG) surrounds the cerebral aqueduct 4. Superior colliculi seen here (not inferior) 5. Red nucleus is more medial and ventral, with the substantial migration between the red nucleus and cerebral peduncles. In Parkinson's patients, neurons in the substantial migration die off (and the region appears less dense in color) 6. Cerebral peduncles (ventral): *carry descending fibers (axons) of the CST* (left and right are separated by the interpeduncular fossa) 7. Medial lemnisci: carry ascending sensory fibers of the DCML *Caudal* 1. Inferior colliculi present (not superior)

What are the scala (fluid-filled spaces) of cochlea filled with?

*Scala Vestibuli:* Perilymph (low K+, high Na+; similar to CSF) ---Reissner's Membrane (can be ignored)--- *Scala Media:* Endolymph (high K+, low Na+; similar to intracellular fluid) ---Basilar Membrane--- *Scala Tympani:* Perilymph (low K+, high Na+; similar to CSF)

Muscle Sensory Receptors (Proprioceptors, Aα)

*Sensory Endings (proprioceptors) in skeletal muscle and joints:* 1. Golgi Tendon Organs (detect *force* of contraction): located at junction of tendon and muscle fibers 2. Muscle Spindles (detect *stretch*): inform the CNS about *muscle length*

Sensory Discriminative vs. Affective-Motivational Features of Pain

*Sensory-Discriminative:* perceived intensity, location, and quality of pain: via VPL → S1, SII, insula *Affective-Motivational:* dimension of pain reflects the perceived unpleasantness of a painful event: via reticular formation → intralaminar nucleus → anterior cingulate gyrus (cortex) AL System: pain, temperature, crude touch 1. Primary neuron (C or Aδ) fibers synapse in spinal cord (substantia gelatinosum) 2. Secondary neurons decussate (via anterior white commissure) and rise through the AL column (contralateral). 3. Secondary neurons synapse in brainstem (reticular formation) or thalamus (VPL). 4. *Discriminative pain travels via 3rd order neurons from the VPL nucleus to S1 cortex.* *Affective* features of pain travel via 3rd order neurons from the *reticular formation to intralaminar nuclei in the thalamus*, where they synapse with 4th order neurons whose axons travel to the *anterior cingulate gyrus (involved with emotional regulation)*.

Cutaneous Mechanoreceptors (Aβ fibers) Mechanism 1. Mechanosensitive channels are cation-selective 2. Pressure (membrane stretching) on a receptor protein coupled to a channel opens the channel 3. Depolarization (Na+ or Ca2+ influx) leads to a receptor potential (Vm changes induced by sensory stimuli) 4. When receptor potential is large enough, it triggers APs

*Shallow Receptors:* small receptive fields 1. Meissner's Corpuscle (*rapid*): light touch on glabrous (hairless) skin 2. Merkels' Disk (slow): positions and static touch (e.g., textures, shape) in hair fibers *Deep Receptors:* large receptive fields 1. Pacinian Corpuscle (*rapid*): vibration, deep pressure, vibration 2. Ruffini's Ending (slow): skin stretch and sustained pressure

Modality Coding

*Shallow Receptors:* small receptive fields 1. Meissner's Corpuscle (rapid): responsible for sensitivity to light touch on hairless skin 2. Merkels' Disk (slow): provide information on mechanical pressure, position, and deep static touch features, such as shapes and edges *Deep Receptors:* large receptive fields 1. Pacinian Corpuscle (rapid): responsible for sensitivity to *vibration* and pressure. 2. Ruffini's Ending (slow): sensitive to skin stretch (and sustained pressure), and contribute to the kinesthetic sense of and control of finger position and movement. *Slow Acting:* pressure and shape *Fast Acting:* flutter and vibration; motion of objects across the skin

Mature Spinal Cord Organization

*Somatic Sensory:* -General: touch, pain, pressure, vibration, temperature, and proprioception in the skin, body wall, and limbs -Special: hearing (VIII), equilibrium (VIII), vision (II) *Visceral Sensory:* -General: stretch, pain, temperature, chemical changes, and irritation in the viscera -Special: taste (VII, IX), smell (I) *Visceral Motor:* -Motor innervation of smooth muscle, cardiac muscle, and glands (autonomic nervous system: sympathetic and parasympathetic) *Somatic Motor:* -Motor innervation of all skeletal muscles

Types and Number of CN Motor Nuclei

*Somatomotor (4):* general somatic efferent (GSE). Most medial column of cranial nerve nuclei in brainstem. 1. CN III: extra-ocular mm. (4) 2. CN IV: superior oblique 3. CN VI: lateral rectus 4. CN XII: tongue mm. (not palatoglossus = CN X) *Visceromotor (3):* general visceral efferent (GVE) 1. Edinger-Westphal (E-W): iris sphincter m. and ciliary m. 2. Salivatory 3. Dorsal motor nucleus of X *Branchiomotor (3):* special visceral efferent (SVE). Most lateral column of cranial nerve nuclei in brainstem. 1. Motor Nucleus of V. (CN V3) 2. CN VII 3. Ambiguus (CN IX-XI)

Pupil Size Regulation

*Sphincter pupillae:* circular muscle of the *iris* intimate to the pupil that contracts to shrink the pupil (CN III, parasympathetic) *Dilator pupillae:* fan of radial muscle cells of the *iris* (around the sphincter pupillae) that contracts to dilate the pupil (sympathetic) *Reminder:* ciliary m. / zonule fibers were for the *lens* *Sympathetic Pathway: dilator muscle* 1. Sympathetic fibers descend from the hypothalamus through the brainstem reticular formation to the thoracic spinal cord where they synapse on preganglionic cells of the intermediolateral cell column (intermediate horn of gray matter). 2. Axons exit the spinal cord via the ventral roots and ascend via the sympathetic chain to the *superior cervical ganglion*, where they synapse 3. Postganglionic fibers enter the skull with the carotid artery and proceed along the ophthalmic artery (of the internal carotid a.) to the orbit. 4. Sympathetic fibers course over the ciliary ganglion but do not synapse. 5. Postganglionic sympathetics enter the globe (via ciliary nerves) and innervate the dilator pupillae.

Neuropathic Pain Manifestations

*Stimulus-Evoked Pain:* described as shooting, stabbing, electrical 1. *Hyperalgesia:* exaggerated pain response produced by normally painful stimuli -Sensitization of primary afferent nociceptors -Neuroma: foci of peripheral nerves that are hyperexcitable 2. *Allodynia:* produced by stimulus that is not usually painful (e.g., cold) -Response to ongoing nociception or overstimulation → central sensitization -Upregulation of receptors, increase in receptive field, loss of inhibitory control (descending from PAG → Raphe nuclei → dorsal horn) *Stimulus-Independent: (Aδ/C fibers):* described as burning, tingling, itching, aching -Persistent (paroxysmal) -Parasthesia (burning, prickling) or dysethesia (discomfort): ectopic impulses due to leaky Na+ channels that excite nerves *Larger Nerve Fibers: (Aα/Aβ fibers):* 1. Hypoesthesia: reduction of normal sensation 2. Anesthesia: (complete) loss of sensation

Inhibitory Synaptic Function: from presynaptic spike to IPSP

*Stops APs and Signal Propagation:* 1. Local anesthetic (prevents Na+ channels from depolarizing cell) 2. Demyelination (reduced saltatory conduction) 3. Ca2+ entry into presynaptic terminal (activates SNARES of inhibitory NT vesicles as secondary messenger → vesicles fuse with the membrane of the presynaptic cell → NT dumped onto postsynaptic dendrite → NT binds to Cl- channels and opens them, allowing Cl- ions to enter the cell) ∴Vm → E(Cl-) = -65mV (anchors Vm below threshold) → prevents depolarization → *IPSP* Note: GABA and glycine are examples of NTs that increase Cl- conductance (opened Cl- channels on post-synaptic dendrite), leading to inhibitory post-synaptic potentials.

Lobes of Cerebrum

*Superficial Lobes* 1. Frontal (somatic motor): cognition, planning, decision making 2. Parietal (somatic sensory): integrating sensory modalities 3. Temporal (audition): houses Wernicke's area (39) 4. Occipital (vision): processing and integration of visual information *Interior Lobes:* 1. Limbic (cingulate gyrus): emotion formation and processing, emotional perception of one's own suffering, learning, and memory 2. Insular: gustation (taste), visceral sensation, consciousness, emotion, homeostasis (wraps above corpus callosum)

Treatments for Peripheral Vertigo

*Suppress vestibular n. and labyrinth function (to depress the CNS):* 1. Meclizine: antihistamine 2. Scopolamine: anticholinergic 3. Diazepam (Valium): anti-depressant Vestibular exercises work to desensitize the body to peripheral vertigo. For BPPV, the Epley Maneuver can be employed to roll otoliths off of the hair cells of the posterior canal (most common)

Vasovagal Syncope

*Syncope:* transient loss of consciousness and postural tone, with spontaneous recovery. Due to *hypoperfusion* to both hemispheres or to brainstem. *Orthostatic hypotension:* BP drops upon standing. Can be caused by: 1. Hypovolemia: *dehydration*, blood loss, etc. 2. Medications: blood pressure, prostate meds *Vasovagal Syncope:* Excessive vasodilation and bradycardia at the same time causes syncope (*autonomic surge; emotional trigger*).

FLAIR Radiology (fluid attenuated inversion recovery)

*T2 image* with black CSF. Suppresses CSF to show plaques, which appear white (e.g., MS). White matter and gray matter are similar to T2-weighted image. Fluid is attenuated (hypo intense) like in T1 images.

How is each taste detected by taste receptors?

*Taste Transduction:* 1. *Bitter, Sweet, and Umami:* *GPCR* pathway (IP3/Ca2+: PIP2 cleaved to IP3 by phospholipase C; IP3 releases intracellular Ca2+ stores, which open Na+ channels and release ATP); *ATP is NT* on gustatory afferent axon 2. *Salty:* sensed by *Na+ permeable channels*; depolarization; Ca2+ channel opening; serotonin is NT on gustatory afferent axon 3. *Sour:* sensed by *Na+ permeable channels sensitive to H+* (which closes K+ channels); depolarization; Ca2+ channel opening; serotonin in NT on gustatory afferent axon *Taste Receptor Proteins (GPCR):* Bitter: T2Rs (>30 receptors) Umami: T1R1 + T1R3 (one receptor) Sweet: T1R2 + T1R3 (one receptor)

Factors Contributing to Seizure Generation Note: *impairment of GABA- or glycine-mediated inhibition* can cause hyper-excitability syndromes (anxiety, epilepsy, etc.)

*Too much excitation by glutamate receptors* -Inward Na+ and Ca2+ depolarize the neuron *Too little inhibition by GABA receptors* -Inward Cl- and outward K+ currents hyper-polarize the neuron

The medulla in transverse sections

*Upper Cervical Spinal Cord* 1. White matter funiculi (lateral and anterior) at periphery carrying caudal extensions of the CST 2. Dorsal column carries ascending fibers of DCML -Fasciculus gracilis (medial): middle thoracic and legs (T7 and below) -Fasciculs cuneatus (lateral): arms (C2-T6) 3. Gray matter in "H" pattern *Spinomedullary Junction* 1. Fibers traveling in the dorsal columns synapse onto the *dorsal column nuclei* (gracilis and cuneatus) at the caudal medulla. From here on up, DCML fibers continue as the medial lemniscus 2. The CST sends a large portion of its fibers across the midline here (pyramidal decussation). After decussating, these fibers continue their descend as part of the spinal cord's *lateral funiculus* (this pushes the central seam between the pyramids off the midline) 3. The 4th ventricle has narrowed down to the central canal, which holds very little CSF through the core of the spinal cord

Midbrain (anatomy) -Contains cerebral aqueduct

*Ventral* 1. *Cerebral peduncles* (basis pedunculi or crus cerebri): a pair of massive fiber bundles on either side of the midline that allow for an extensive outflow of information from the cerebral hemispheres to the brainstem and spinal cord 2. *Interpeduncular fossa:* the little valley on the midline between the cerebral peduncles *Dorsal* 1. Colliculi -*Superior:* vision and oculomotor functions (e.g., generation of rapid eye movement) -*Inferior:* audition 2. CN IV (trochlear) lies just caudal to the inferior colliculus

Medulla (anatomy)

*Ventral* 1. *Olives:* the more lateral pair of "bulges" on the ventral surface of the medulla, apparent in the rostral 2/3 of the medulla, but missing from the caudal 1/3. 2. *Pyramids:* the medial pair of longitudinal "bulges" (visible at *all levels* of the medulla). 3. *Pyramidal decussation:* a midline "smudging" that reflects the presence of an important decussation of the CSTs. This marks a transition from the medulla to the spinal cord (*spino-medullary junction*) *Dorsal* 1. Contains a canoe-shape rostrally to accommodate the *4th ventricle* (which is present in the rostral 1/2 of the medulla). The caudal limit (bottom) of the 4th ventricle is the *obex*.

Pons (anatomy)

*Ventral* 1. *Pontine protuberance:* a characteristic swelling on the ventral surface of the pons 2. *Middle cerebellar peduncle:* the peduncle (fiber tract) anchored in the pons carrying information to the cerebellum from the brainstem. *Dorsal* (peduncles) 1. Superior: from cerebellum to midbrain and thalamus 2. Middle: from pons to cerebellum 3. Inferior: from medulla to cerebellum

*Visual Pathway Deficits* (Exam)

*Vision loss in 1 eye:* problem in front of chiasm (prior to nasal fiber crossover) *Vision loss in both eyes:* problem at chiasm or below (nerve tract and on)

Arterial Blood Supply for Spinal Cord

1. *Anterior Spinal Artery (offshoot of the vertebral arteries)* supplies the *ventral* (anterior) portion of the spinal cord. This single, ventral, midline artery supplies the ventral 2/3 of the spinal cord (motor areas). 2. The paired *Posterior Spinal Arteries (branches from PICA)* supply the *dorsal* (posterior) portion of the spinal cord. These arteries supply the dorsal 1/3 of the spinal cord (sensory areas). The anterior spinal artery and the two posterior spinal arteries form an anastomosis at the spinal arterial plexus. Blockage of these arteries can lead to regional syndromes of the spinal cord. Since the middle of the cord is farthest from the heart, it tends to suffer more than the periphery → central cord syndrome. Radicular (aka radiculomedullary) arteries arise from the thoracic and abdominal aorta. These arteries are affected by atherosclerosis and dissecting aneurism (dilation of the vessel wall, vessel intima tears, allowing blood to form a new channel between layers of the vessel wall) of the aorta. The Great Radiculomedullary Artery (of Adamkiewicz) is the major source of blood for the lower thoracic and lumbar cord. *Occlusion of the anterior spinal artery:* would affect the pain and temperature sensations from the spinothalamic tract (anterolateral pathway)(ventral 2/3), but would not affect fine touch (DC-ML pathway)(dorsal 1/3).

Telencephalon Components 1. Cerebral cortex 2. Cerebral lobes 3. Commissures 4. Specialized cortical centers (Brodmann) 5. Limbic system 6. Basal ganglia

1. *Cerebral cortex* -Gray (neuron cell body) and white (myelinated axons) matter -Central (Rolandic: frontal/parietal) and lateral (Sylvian: frontal/temporal) fissures -Precentral (motor) and postcentral (somatosensory) gyri 2. *Lobes of the Cerebrum* -Outer: frontal (motor), temporal (audition), parietal (sensory), and occipital (vision) -Inner: insula (beneath lateral sulcus: taste, visceral sensation, social and emotional functions) and limbic (cingulate gyrus above corpus callosum: attention, drive, emotional perception of one's own pain = "suffering") 3. *Commissures*: white matter tracts that connect the hemispheres. 4. *Specialized Cortical Centers* -Primary Cortex: auditory (41/42), visual (17), motor (4), and somatosensory (1/2/3) -Language Centers: Broca's area (45; left temporal lobe; production of speech; expressive aphasia: can't articulate what they want, but know what they want to say) and Wernicke's area (39; left temporal lobe; comprehension of speech; fluent aphasia: speaks non-sensically, but fluently) 5. *Limbic System*: hippocampus, amygdala, limbic cortex, fornix, mammillary body (5 Fs: feeding, feeling, fighting, fleeing, and fornication) 6. *Basal ganglia*: modulates voluntary motor control, procedural learning, eye movement, and cognition

Regions of Cerebellum and Roles

1. *Cerebrocerebellum (Lateral):* -Regulates highly-skilled *voluntary movements* with the cerebral cortex (especially those involving complex spatial/temporal sequences and the *distal extremities*) -Dentate nucleus (*motor planning* to pre-frontal cortex) 2. *Spinocerebellum (Medial/Intermediate):* includes vermis -Uses proprioceptive information (i.e., where the body is in space) from the spinal cord to coordinate the *trunk and limbs* (e.g., *posture, gait, balance*) -Interposed nuclei: emboliform and globose (*motor execution* to lateral descending systems) -Fastigial nucleus: (in vermis) and *motor execution* to medial descending systems 3. *Vestibulocerebellum:* nodulus and flocculus -Interacts with the vestibular system to regulate *balance (axial muscles) and eye movement (extra-ocular muscles)*

Types of Hydrocephalus

1. *Communicating (no blockage):* impaired CSF resorption by arachnoid granulations due to damage following infection, inflammation, or hemorrhagic events 2. *Non-Communicating (blockage):* CSF outflow obstruction treated with a probe that can create a new hole to bypass obstructions in the ventricular sinuses Reminder: 80% of CSF is produced in the brain parenchyma; only 20% is produced in the choroid plexus (contrary to dogma). CSF consists of water, metabolites, peptides, waste products, etc. in the head.

The two major spinal tracts of the brain that allow for communication between the brain and the spinal cord in order to integrate sensory information (DCML) and direct motor output (CST) are...

1. *Corticospinal Tract (CST):* descending voluntary motor information to contralateral limbs 2. *Dorsal Column, Medial Lemniscus (DCML):* ascending sensory tract: pressure, vibration, touch, and proprioception

Types of Dizziness

1. *Lightheadedness:* feeling like you might pass out (e.g., standing up too quickly) (brain hypofusion (too little O2 to the brain)) 2. *Disequilibrium:* feeling unsteady, like walking on a boat or a dock, "dizzy from the neck down" 3. *Vertigo:* sensation of spinning, or movement due to a disturbance in the vestibular system

Local Anesthetics Preferential Action (on small axons)

1. *Local anesthetics block small axons better than large axons* (differential nerve block due to the number of nodes affected by the drug). -Pain and temperature sensation (C fibers) is blocked more easily than fine touch discrimination and motor axons (Aβ, Aα fibers) -*Local anesthetics only spread a given distance.* Since smaller axons have more nodes per given distance, APs can be blocked more easily. In larger axons, there are fewer nodes in a given distance, and if 3 or more are not "blocked", signal propagation can continue and the AP is only slowed down in the region of anesthetic, but not stopped. -Hypoxia works in the opposite direction (large axons have greater requirements for diffusion of oxygen) 2. *Local anesthetics more effectively block rapidly firing axons* (e.g., pain-carrying) than slowly firing or resting axons (e.g., autonomic). -In the presence of local anesthetic, *Na+ channels cannot open as frequently* (blocked from inside the cell); spikes cannot fire as often (fewer APs); painful signals are reduced and less pain is perceived.

Staining of the Nervous System

1. *Myelin:* dark stain for fatty myelin sheath (showing white matter); neuronal cell bodies (gray matter) do not pick up stain and appear white 2. *Nissl:* stains neuronal cell bodies (gray matter) black

*Separation of retina causes problems because...*

1. *No O2 for inner segment mitochondria* of photoreceptors to use to create ATP that power Na/K pumps (to remove Na+ coming in via dark current). *Vm depolarizes* (rising Na+ levels) and can no longer be modulated by light (no graded potentials). 2. *Prevents pigment regeneration in choroid.* Activated (all trans) retinal separates from opsin, is carried via transport molecules to the pigment epithelium and converted to the 11-cis form. Other transporter molecules take it back to the outer segment where it is spontaneously incorporated into the opsin. A separation between the retina and the pigment epithelium prevents this recycling of photopigment. 3. *Prevents disk renewal.* Disks are formed continuously at the junction of the inner and outer segments of rods and migrate toward the distal end of the outer segment (where older disks are shed into the pigment epithelium and phagocytose by pigment epithelial cells). *Retinal detachment disrupts this process of disk renewal and the outer segments atrophy.*

Types of Pain *Nociceptive:* activation of pathways in response to potentially-damaging stimuli *Neuropathic:* caused by a primary lesion or dysfunction in the nervous system

1. *Nociceptive Pain:* (damaging stimuli): from direct activation of nociceptors in response to mechanical, inflammatory, or thermal tissue injury (e.g., contusions, sprains, inflammation, tumor) -Nociceptive circuits are located in the most dorsal laminae of the dorsal horns (pain travels through Lissauer's Tract, synapses in substantia gelatinosa, travels through anterior white commissure, travels up AL pathway to brain) 2. *Neuropathic Pain:* from direct injury to nerves in the PNS or CNS (e.g., postherpetic neuralgia [shingles], phantom limb pain following amputation). Common qualities include burning or coldness, "pins and needles" sensations, numbness, and itching. 3. *Psychogenic Pain* (in the brain, no physical damage): not well defined; psychological state can influence degree of perceived pain, but it can also be used to categorize pain with unidentified source

Intensity of stimulation (strength of stimulus) reflected by...

1. *Number of axons stimulated (receptors activated) in a particular location* 2. *Frequency of action potential firing in single receptors:* more frequent APs are fired with increasing intensity Longer stimuli (with larger amplitudes of stimulus/receptor potential) trigger more frequent APs (above threshold) over a longer duration, leading to increased neurotransmitter release (output signal).

Neural Pathway for Visual Perception (Vision)

1. *Retinal ganglion cells* send their axons through the optic nerve, chiasm, and tract to synapse in the *lateral geniculate nucelus (LGN)* of the thalamus. 2. Axons from the LGN travel in the optic radiation through the temporal, parietal, and occipital lobes to reach the primary visual cortex (V1) (aka calcarine cortex or striate cortex). *Axons from the LGN also travel to the pretectal nucleus of the midbrain and then to the EW nucleus for the pupillary reflex.*

Why does the brainstem matter?

1. *Spinal reflex circuits* establish basic motor patters (e..g, walking) 2. Descending inputs can modulate context and coordinate with other circuits for *complex behavior* 3. The brainstem is a conduit and a way station for ascending information (e.g., somatic sensation). A major synapse (gracile or cuneate nucleus in medulla) occurs at brainstem levels in the DCML ascending pathway for discriminative/fine touch. 4. The brainstem is a "spinal cord for the head," because it: -Contains lower motor neurons (source of motor output for CN) -Receives its own primary sensory input -Has its own sensorimotor reflex arcs linking sensory input to motor output (e.g., blinking in response to irritation of the cornea (V and VII); gagging (IX and X)) -*Cranial nerves (sensory and motor) are the brainstem equivalent of spinal nerves*

How is sounds frequency represented in the nervous system?

1. *Tonotopy:* CN VIII units are most sensitive at a particular frequency, but they also respond at adjacent frequencies if the stimulus intensity is high enough. This relates to the fact that *a given locus on the basilar membrane is maximally displaced by one frequency so afferent fibers terminating there would be excited at the lowest stimulus intensities*. Hair cells at the apex (wide) and base (narrow) of the basilar membrane prefer low and high frequencies, respectively, and send axons to different portions of the cochlear nucleus (low frequency anterior, high frequency posterior). The brain knows that if anterior cells of the cochlear nucleus are activated, then it must have been from low frequency sound. 2. *Timing:* auditory nerve fibers fire action potentials in synchrony with sound waves (only at lower frequencies). Higher frequencies are very quick and require a different brain coding.

Pain Cases and Treatment

1. 60yo: chronic hip pain; arthritis; pain at hip (local); rest helps relieve the pain Pain: nociceptive Treatment: 1. NSAIDs 2. Physical therapy 2. 63yo: diabetes; burning pain in feet; worse at night Pain: peripheral neuropathy (stocking/glove) secondary to diabetes Treatment: 1. Reduce A1C levels 2. Comfortable footwear 3 Pregabalin or gabapentin (Anticonvulsants) 4. Tricyclic antidepressant (TCA: amytriptiline); SSRI (duloxetine) 3. 83yo; severe burning and stabbing pain across left shoulder blade and under left breast; has occurred since shingles 4 months ago Pain: radicular pain secondary to herpes zoster infection Treatment: 1. Lidocaine patches (local anesthetic) 2. Capsaicin cream (depletes substance P, an excitatory NT involved in the transmission of pain information into the CNS) 3. Intercostal nerve block 4. Pregabalin or gabapentin (anticonvulsants used for neuropathic pain) 4. 32 yo; chronic hip pain; L5/S1 fusion for disc herniation; new pain in lower right extremity; mottling (swelling) is occurring in right foot Pain: Complex Regional Pain Syndrome (CRPS) Treatment: 1. Sympathetic nerve blocks 2. Physical therapy 3. Gabapentin 4. TCA (amytriptiline)

Audition Pathway

1. A pressure wave propagates into the external auditory meatus. 2. The tympanic membrane vibrates, setting in motion the ossicular chain. 3. This couples the pressure wave into the fluid filled cochlea, producing *motion of the basilar membrane* and *activation of the Organ of Corti*.

*Branchiomotor Nuclei (3)* -Muscles of mastication -Facial muscles -Stapedius (of middle ear) -Sylopharyngeus (swallowing) -Away (ventral and lateral) from the ventricular system

1. Ambiguus (IX - XI) 2. Facial (VII) 3. Motor Nucleus of Trigeminal (V3) AFM = America's 9-11 Funniest 7 Movies, Version 3

Symptoms of *Chronic Hydrocephalus*

1. Concentration and reaction time problems 2. Slow thought process 3. Forgetfulness 4. Headaches 5. Changes in personality 6. *Often misdiagnosed as senile depression* On CT, there are generally no signs of edema around the ventricles. In the past, ICP monitoring was done using the Lundeberg A and B waves O/N. *Treatment:* ventricular shunts (with adjustable valves and tubing) that bring CSF to the abdominal cavity (ventriculoperitoneal), lungs (ventriculopleural), or heart (ventriculoatrial).

Ocular problems leading to impaired vision

1. Corneal scarring (wrecks the major refracting surface of the eye) 2. Cataract (opacification of the lens) 3. Glaucoma (high intraocular pressure predisposes to optic neuropathy) 4. Papilledema (high intracranial pressure damages the optic nerve and retina -- bulges out) 5. Refractive errors (result in fuzzy images) 6. Presbyopia (increased lens density with age results in loss of accommodative power)

3 Planes of Section

1. Coronal: vertical plane perpendicular to midline 2. Sagittal: vertical plane parallel to the midline of the body. 3. Horizontal (axial): a plane perpendicular to the coronal and sagittal planes; parallel to the floor for a standing person

Roles of CSF

1. Cushions the CNS from contact with the skull 2. Lavages (rinses) the CNS, bringing waste material back out to the blood, which helps maintain homeostasis (glymphatic system) 3. Lends buoyancy to the brain (the brain's effective weight is only 2% of its actual weight), allowing it to maintain high density without weighing itself down (or cutting off it's blood supply from its weight in the skull)

*Visceromotor Nuclei (3)* -Parasympathetic -Near the ventricular system but a bit off midline

1. Dorsal Motor Nucleus of the Vagus (X) 2. Salivatory (VII-submandibular and sublingual, IX-parotid) 3. Edinger-Westphal (III) DSE = Do Seals Eat?

Cranial Nerve Motor Nuclei General Rules

1. Each nucleus belongs to one class (somatic, visceral, or branchial) 2. Each nerve gets fibers from *at most 1 nucleus of each class* 3. *Each motor nerve has either a somatomotor or a branchiomotor component, but not both* (spinal accessory nerve = exception) 4. One nucleus may supply more than 1 nerve

*Somatomotor Nuclei (4)* -Near the ventricular system and very close to midline -The associated nerve exists nearer to the midline than other cranial nerves

1. Hypoglossal (XII) 2. Abducens (VI) 3. Trochlear (IV) 4. Oculomotor (III) HATO = Has Aaron Tried Oranges?

Symptoms of *Acute Hydrocephalus* -More noticeable and threatening -People can die within the hour -Emergency exit routes (optic nerve/spinal nerves) can't accommodate

1. Increased ICP (intracranial pressure) 2. Headaches 3. Lethargy 4. Double Vision 5. Nausea 6. Vomiting *On CT, there are signs of edema around the ventricles.* No sulci/gyri are seen because CSF has pushed on the brain, making it a gray homogenous mass. *Treatment:* place a drain into the ventricles

Two point resolution can be increased by...

1. Increasing receptor density (*overlapping fields*; larger amount of cortex dedicated to a certain area; better spatial resolution) 2. *Decreasing receptive field size*

Two ways to increase current velocity

1. Larger diameter axons (decrease internal resistance) 2. Increase myelination (allows for spacing nodes of Ranvier further apart) Explained: -Inward Na+ current at nodes is relatively *slow* (ions diffusion facilitated by channels) -Conduction of current down an axon between nodes is relatively *fast* (ions bump into neighboring ions inside axon) -Fewer nodes of Ranvier between points A and B = faster conduction velocity because you have to "wait" at fewer nodes. -Larger diameter of axon and thicker myelin allow for greater spacing between nodes

Pathway of CSF from Lateral Ventricles to Jugular Vein

1. Lateral Ventricles 2. Interventricular Foramen of Monro 3. 3rd ventricle 4. Cerebral Aqeuduct (Sylvius) 5. 4th ventricle 6a. (lateral) Foramina of Luschka → subarachnoid space 6b. (medial) Foramen of Magendie → subarachnoid space 7a. Arachnoid Granulations 7b. Down the spinal cord into the lumbar cistern at the end of the cord around the caudal equina 8. Superior Sagittal Sinus (via arachnoid granulations) 9. Transverse Sinus 10. Sigmoid Sinus 11. Internal Jugular Vein

Damage to the right side of the body. Where might there be a problem in the CST?

1. Left side of CST before caudal medulla decussation (contralateral) 2. Right side of CST after caudal medulla decussation (ipsilateral) This is due to a decussation at the caudal medulla (pyramid), where axons (90%) cross the midline. Look at Brainstem lecture for images of transverse sections (1/5/18).

Treatment for *Neuropathic* Pain (Exam)

1. Local anesthetics: *Lidocaine* (patch or cream); capsaicin cream (deplete substance P) 2. Antidepressants: tricyclics (TCA: *Amitriptiline* treats pain and sleep) and SSRIs (*Duloxetine*: serotonin repute inhibitor) 3. Anticonvulsants: *Gabapentin* and *Pregabalin* (Ca channels), *Carbamazepine* (for *trigeminal neuralgia*; Na channel blocker) 4. GABA-B agonist (inhibition): *Baclofen*

Causes of Neuropathic Pain

1. Lowered threshold for activation to noxious and non-noxious stimuli 2. Larger receptive fields 3. Upregulation of and altered expression of receptors 4. Neuroma formation 5. Disinhibition (of descending PAG pathway) 6. Hyperexcitability of peripheral nerve terminals 7. Increased release of inflammatory mediators

Optic Lesion Specifics (*on right side*)

1. Macular degeneration (on right) → central scotoma in right eye 2. Optic nerve → right anopsia 3. Optic chiasm → bitemporal hemianopsia 4. Optic tract → left homonymous hemianopsia 5. Meyer's loop (located in temporal lobe) → left upper quadrantic anopsia 6. Dorsal optic radiation (located in parietal lobe) → left lower quadrantic anopsia 7. Posterior cerebral lesion → left hemianopsia with macular sparing

Temperature Receptors Menthol: amplifies cold signal (CMR1/TRPM8) Capsaicin: agonist for TRPv1 receptor (starts depolarization before Na v1.7 kicks in)

1. Menthol amplifies "cold" signals (increases current into thermoreceptors *CMR1 and TRPM8*); the same temperature change is perceived as more cold with menthol as compared to not. *CMR = cold and menthol sensitive. TRP = transient receptor potential.* 2. Capsaicin is an agonist for TRPv1 receptor and starts depolarization (mediates chemical spicy and thermal painful heat stimuli) Warm and cold receptors are most sensitive to temperature changes, with their firing rates adapting to steady temperatures. When skin temperature changes (more cold), more cold receptor APs fire. When temperature remains constant (even if it's just as cold), APs slow down. When skin temperature changes (more hot), more warm receptor APs fire. When temperature remains constant, APs slow down (even if it's just as hot).

Foveal Vision is Acute because...

1. No blood vessels 2. Higher concentration of cones than rods (thin, closely packed together) 3. Cones have "private" ganglion cell pathways to brain. *Midget ganglion cells each receive input from a single cone via a single midget bipolar cell. Bipolar cells do not emit APs, but Vm is modulated in response to glutamate released by photoreceptors.* Outside the fovea, ganglion cells receive convergent signals from many photoreceptors. The fovea lies in the center of the macula, appearing as a pit in the retina because *inner retinal cells are displaced to the side here (to reduce scattered light by elements overlying photoreceptors that normally degrade retinal images)*. Retinal vessels do not reach this area, so foveal receptors are fed by choroidal circulation behind them.

Neurons of Retina (from outside, in)(back of retina to front)

1. Photoreceptor cell (rod/cone) 2. Bipolar cell 3. Ganglion cell: send axons (CN II) to optic disc and brain Also, horizontal cells (outer plexiform) and amacrine cells (inner plexiform) mediate lateral interactions that enhance the patio-temporal coding features in the retinal image. Interplexiform cells connect the two plexiform layers.

Pain Therapies in Development

1. Sodium Channel Inhibitors (non specific; more systemic) -Na v1.7: CNS and PNS (side effects widespread); inhibit low threshold pain receptors -Na v1.8: block PNS → CNS 2. Anti-NGF Abs: Neuronal Growth Factor (NGF) promotes painful stimulation and transmission (increases histamine, bradykinin, prostaglandin release from mast cells) 3. TrkA Receptor (which bind NGF) Antagonists

Patterns of Pain

1. Stocking/glove (feet and hands affected first): peripheral neuropathy 2. Single dermatome: radiculopathy/herpes 3. Spinal cord level: myelopathy (any neurologic deficit related to the spinal cord)

Pupillary Light Reflex Pathway 1. CN II to both pretectal nuclei 2. Bilateral projection to EW 3. EW to ciliary ganglia 4. Ciliary ganglia to sphincter pupillae

1. The afferent limb starts in the eye, proceeds bilaterally via both optic tracts, and terminates in specific *pretectal nuclei* on both sides. 2. The pretectal nuclei project bilaterally to the *Edinger-Westphal nuclei* 3. EW nuclei send preganglionic *parasympathetic* innervation to the *ciliary ganglia* 4. Ciliary ganglia send parasympathetics to the *sphincter pupillae* of each eye, causing constriction. The redundancy and bilateral configuration of this pathway explains why light shone in one eye causes both pupils to constrict. *Pupillary constriction of the illuminated eye is called the direct response, that of the non-illuminated eye, the consensual response.* *The pathway's redundancy also makes it very difficult to interrupt this response by lesions posterior to the optic chasm* (i.e., interruption of the visual pathway at or posterior to the chiasm does not eliminate the direct or consensual pupillary light reflex in either eye). As such, to have an effect, the pathway is usually interrupted in the parasympathetic postganglionic efferents (CN III from ciliary ganglia) or in the optic nerve (CN II) before the optic chiasm (see image). *Damaged right optic nerve:* Shine light on left: both eyes constrict Shine light on right: no response *Damaged right oculomotor nerve (CN III):* Shine light on left: left eye constricts; right eye does not Shine light on right: left eye constricts; right eye does not

How does hearing work?

1. When the tympanic membrane displaces into middle ear, the stapes footplate pushes into perilymph of the cochlea at the oval window near the scala vestibuli, causing the round window, at the end of the scala tympani, to bulge out into the middle ear. 2. When the round window returns to its original position, it sends a pressure wave down the basilar membrane with the given frequency of the sound. 3. Stiffness of basilar membrane is highest at the oval window causing it to be more responsive to high frequencies. Stiffness decreases over the course of the cochlea (towards the apex). Travelling waves due to different acoustic frequencies produce their maximal displacements of the basilar membrane at different distances from the basal (stapedial) end. 4. As such, stimulus frequency is coded along the length of the basilar membrane in the sense that one place on the membrane is displaced maximally by a particular frequency and not by others (place coding of frequency on the basilar membrane). 5. As the basilar membrane rises and falls (due to traveling waves), there is a relative lateral shift of the reticular lamina under the tectorial membrane, which produces a *shearing force on the cilia* and bends them. *This bending of hair cells is the critical event in converting mechanical displacement to nerve impulses.* 6. The inside of the hair cell is 140 mV negative to the endolymph bathing the cilia (large potential difference). Bending the cilia opens mechanosensitive K+ channels in the tips of the ciliary membrane, allowing a K+ current (high concentration in the endolymph) to flow into the hair cell because of the large potential drop across its membrane. (These *apical K+ channels are blocked by amnioglycoside antibiotics*, e.g., streptomycin and gentamicin.) 7. Hair cells depolarize, Ca2+ influx, release of excitatory transmitter onto CN VIII nerve fibers of the spiral ganglion. Very slight bending of hairs causes large membrane voltage changes.

The internal carotid a. branches into which three arteries to provide anterior circulation to the brain?

1. anterior cerebral a. (ACA): medial aspect of cerebral hemisphere; results in lower extremity and trunk neurologic deficits if occluded 2. middle cerebral a. (MCA): lateral aspect of the cerebral hemisphere; results in face and upper extremities deficits if occluded 3. posterior communicating a. (PCA): rise laterally to the mammillary bodies of the hypothalamus to meet the ICA of the anterior circulation. The left and right ACA are joined by the anterior communicating aa.

The vertebral aa. rise through the transverse processes of the cervical vertebrae to the skull where they give off which three aa.? Note: the vertebral arteries fuse into the basilar a. at the pons, and give off the AICA. The PICA is off of each vertebral a. inferior to that junction.

1. anterior inferior cerebellar aa. (AICA): just below pons, wraps around cerebellum 2. posterior inferior cerebellar aa. (PICA): wraps around and under cerebellum at medulla 3. superior cerebellar a. The 2 vertebral aa. fuse at the level of the brainstem to form a single, midline *basilar a.*.

Cerebellar Histology

3 Layers of Cerebellar Cortex (gray matter): 1.* Molecular:* cell poor; mostly axons and dendrites 2. *Purkinje:* monolayer of pyramidal efferent neurons 3. *Granular:* densely packed granule neurons with synaptic globules Folia = ridges of cerebellar cortex matter (similar to gyri of the cerebral cortex)

Retinotopic Organization of the Visual Cortex

50% of V1 represents the central 10 degrees of the visual field.

Hyperalgesia -Central and Peripheral (Substance P) Mechanisms

A *painful stimulus* is even *more painful* than it should be.

Optic Neuritis -Optic nerve defect

A demyelinating inflammation of the optic nerve also known as optic papillitis (inflammation of the optic nerve head often due to viral causes). Retrobulbar optic neuritis is often associated with *multiple sclerosis (MS)*. May lead to complete or partial loss of vision in one or both eyes. This can also present with a *Marcus-Gunn pupillary sign* (relative afferent pupillary defect).

Dermatomes

A dermatome is an area of skin that is mainly supplied by a single spinal nerve. -Dermatomes from adjacent dorsal roots overlap -Individual peripheral nerves contribute axons to several adjacent dorsal roots -Damage to one dorsal root yields small sensory deficits (3 adjacent roots must be cut to lose sensation in the whole dermatome), whereas cutting a distal cutaneous nerve may leave a large area without sensation. Reminder: sensory information from the anterior face is conveyed via CN V (trigeminal nerve).

Aphasia

A global disturbance of language affecting every form in which it is expressed (speech, writing, reading, etc.).

*(Chronic) Open-Angle Glaucoma* (Exam) -90% glaucoma

A group of diseases with a characteristic optic neuropathy characterized by *slow, progressive loss of peripheral vision* (central vision not affected until late and patients are often unaware of early vision loss). This is usually due to *slowed exit of aqueous humor through the trabecular meshwork (Schlemm's canal)*. The optic disc is the anatomical location of the eye's "blind spot", the area where the optic nerve and blood vessels enter the retina. The optic disc can be flat or it can have a certain amount of normal cupping (30-40% of the diameter of the disc). But *glaucoma, which is associated with an increase in intraocular pressure, often produces additional pathological cupping of the optic disc*. The pink rim of disc contains nerve fibers. The white cup is a pit with no nerve fibers. As glaucoma advances, the cup enlarges until it occupies most of the disc area.

Apraxia -Inability to carry out skilled actions that the patient could do previously

A motor disorder caused by damage to the brain (specifically the posterior parietal cortex), in which the individual has *difficulty with the motor planning* to perform tasks or movements when asked, provided that the request or command is understood and he/she is willing to perform the task. An *acquired inability (due to brain injury) to carry out skilled actions that the patient could do previously*, despite the absence of paralysis. Apraxias are signs of loss of 'higher functions'

Reticular Formation

A network of fibers and nuclei that run throughout the core of the brainstem. Appearance: diffuse (a mixture of gray and white matter); defined nuclei are visible The rostral (*midbrain and rostral pons*) reticular formation helps maintain a *conscious state*. The caudal (*lower pons and medulla*) reticular formation helps with *motor, reflex, and autonomic nervous system functions*.

Central Auditory Pathways

A partial decussation of the auditory pathway immediately above the cochlear nuclei (to both superior olives) provides bilateral representation of both ears. *Cells at levels above the medulla tend to be activated from either ear.* *Lesions of cochlear part of CN VIII or cochlear nuclei at pontomedullary junction cause profound unilateral sensory hearing loss.* All other lesions to the auditory pathway above the cochlear nuclei cause bilateral suppression of hearing and decreased ability to localize a sound source. Cells with adjacent best frequencies are located next to one another in the central pathways. Thus, there is a tonotopic mapping of the organ of Corti to the CNS which preserves the intrinsic geometry of the place coding principle up to cortical levels. Mnemonic: SLIM Fibers from the cochlear nuclei and the *superior olive* travel up the *lateral lemniscus* to the *inferior colliculus*, and then to the *medial geniculate nucleus*.

Hyphema

A pooling or collection of *blood inside the anterior chamber of the eye* (the space between the cornea and the iris). The blood may cover most or all of the iris and the pupil, preventing light from reaching the retina and *blocking vision partially or completely*.

Marcus-Gunn Pupil

A relative *afferent pupillary defect* often seen in optic neuritis (demyelinating inflammation). When the optic nerve or retina is involved in disease, the *flow of afferent information can be reduced* with the result that illuminating the affected eye elicits a reduced pupillary constriction in both eyes. When light is shown in the normal eye, both pupils constrict normally. *When the light is shifted to the diseased eye, restricted neural traffic in the affected optic nerve reduces input to the efferent limbs of the reflex and both pupils dilate.* Thus, there is a paradoxical dilatation of the pupils when the affected eye is illuminated.

*AL Pathway (Spinothalamic System for VPL)* Aδ and C fibers 1. *Anterior:* crude touch and firm pressure 2. *Lateral:* pain and temperature Pathway: 1. Primary axons enter dorsal horn via Lissauer's tract, synapse in substantia gelatinosa 2. Decussates in the spinal cord (via anterior white commissure) and ascends to thalamic nuclei (without synapsing in the medulla)

A sensory pathway from the skin to the thalamus. From the VP nucleus in the thalamus, sensory information is relayed upward to the somatosensory cortex of the postcentral gyrus. In the spinal cord, the spinothalamic tract has somatotopic organization. This is the segmental organization of its cervical, thoracic, lumbar, and sacral components, which is arranged from most medial to most lateral respectively. *The pathway decussates at the level of the spinal cord, rather than in the brainstem like the DCML pathway and lateral corticospinal tract.*

Neural Tube Differentiation

A single layer of cells post-neurulation derived from ectoderm collectively referred to as the neuroepithelium (ventricular layer/germ cells for the entire CNS). Eventually, the outer neuroepithelial cells will differentiate into *neuroblasts*, which mature into neurons. *Neuroblasts organize into "plates" that become horns*, setting up the basic organization of the spinal cord. 3 Zones/Layers of the Developing CNS: 1. *Ventricular layer* (ependymal zone): lines the central canal (deepest layer); eventually ependymal cells produce CSF 2. *Mantle Zone:* gray matter, neuron cell bodies -*Alar plate: dorsal horn*; cell bodies of interneurons receive input from sensory neurons -*Basal plate: ventral horn*; cell bodies of somatic motor neurons. At T1-L2, pre-ganglionic sympathetic neurons will also form (lateral horn). 3. *Marginal Zone:* white matter, axons (outer-most layer)

Neuroretinitis

A star-pattern of exudate in the macula that can be caused by syphilis and Lyme disease.

Symptoms of *Normal Pressure Hydrocephalus*

A type of brain malfunction caused by *expansion of the lateral cerebral ventricles* in absence of sulcal enlargement (no ICP). Generally affects aging people (>65 years old). *Hakim's Triad:* 1. Gait Disturbances (wide; slow, shuffled steps) 2. Cognitive Symptoms (dementia; problems with short term memory and depression) 3. Incontinence (increases urinary frequency)

Lateral Rectus Movement

Abduction

Medications to Control Seizures

Actions: 1. Enhance GABA (increase IPSPs / inhibition) 2. Block Na+ channels (only when AP frequency is high; localized anesthetic blocks rapidly firing axons (e.g., pain-carrying) more so than slowly firing axons (e.g., autonomic); spikes cannot fire as often (fewer APs); painful signals are reduced and less pain is perceived.) 3. Block Ca2+ channels (t-type); less cellular depolarization 4. Block glutamate receptors (stop excitation)

*(Acute) Closed-Angle Glaucoma* (Exam) -10% glaucoma

Acute obstruction of aqueous outflow (aqueous humour cannot leave via Schelmm's canal) that raises *intraocular pressure* and compresses the optic nerve (the lens attaches to the iris, preventing aqueous exchange to the anterior chamber). Findings: 1. *Sudden* onset of pain 2. Midsized, nonreactive pupil 3. Injected conjunctiva (red eye) 4. Visual loss from retinal artery occlusion 5. Corneal edema from reversal of pressure gradient Treatment (immediate): *Laser-made hole in the iris to drain the fluid to lower the high intraocular pressure* (usually IOP >30mm Hg).

Wada Test

Add barbiturate (sodium amytal) into one internal carotid artery, which will travel through the MCA to anesthetize one hemisphere of the brain (lateral aspect). *This test is used for determining language dominance in advanced of ablative cortical neurosurgery.* If left-hemisphere anesthetized patient can talk, then they are right dominant. This is quite rare. *Most patients have language lateralized to the left.* This is evidence of language asymmetry.

Medial Rectus Movement

Adduction

Alar Plate vs Basal plate

Alar = Sensory Basal = Motor The sulcus limitans separates motor and sensory cranial root nuclei Reminder for the image: Somatomotor: general somatic efferent (GSE) - midline near the ventricular system Visceromotor: general visceral efferent (GVE) - near the ventricular system but off midline (closer to sulcus limitans) Branchiomotor: special visceral efferent (SVE) - *ventral and lateral* from ventricular system

Causes of Peripheral Vertigo

All vertigo is *worse with movement*, but vertigo brought on *solely by movement → peripheral!* Causes: 1a. *Labyrinthitis (hearing loss):* Ramsay-Hunt Syndrome: reactivation of herpes in the spiral and vestibular ganglion; presents with deep, burning ear pain, and ear rash 1b. *Vestibular Neuronitis (no hearing loss)*: usually following viral infection 2. *Meniere's Disease:* excessive stimulation of nerve from excess fluid (faulty vestibular and audition information sent to the brain) 3. *Benign Paroxysmal Positional Vertigo (BPPV):* excessive stimulation of nerve (hairs) from loose otoliths (stones) → diagnosed by Dix-Hallpike → treated with Epley Maneuver 4. Injury to nerve, labyrinth or hair cell by: -*Acoustic Neuroma* -*Aminoglycoside Antibiotics* (streptomycin and gentamicin) can permanently damage hair cells → bilateral peripheral vestibular dysfunction

Loudness

Amplitude of pressure waves. Above 120 dB is "high risk"

Angular motions (and rotary acceleration) of the head detected by ...

Ampulla of Semicircular Canals

Draw and Label Circle of Willis

An anastomosis that joins the anterior and posterior circulations in the brain. Depending on the pressure within arterial circulation, blood flow can change direction and somewhat compensate for insufficient perfusion of a region of brain tissue.

Nociceptor

An axon or receptor that fires when tissue is damaged or nearly damaged (high threshold). Activity in nociceptors doesn't necessarily lead to a perception of pain (e.g., battlefield vs. on couch).

Air Pressure to dB Relationship

An increase in 20dB = 10x change in air pressure (perceived loudness roughly doubles)

Primary vs. Secondary Hyperalgesia 1. *Primary:* mechanical and thermal hyperalgesia in local region due to *peripheral and central* mechanisms; 2. *Secondary:* mechanical hyperalgesia throughout due to peripheral and central mechanism.

An injury to the skin is followed by the classic tetrad of inflammation: pain, swelling, and vasodilatation over several millimeters, which tends to warm the area and cause local reddening (flare). *In the injured region, the threshold for pain is lowered in the center (primary hyperalgesia)* and accompanied by allodynia (non-painful stimulus feels painful). If the nerve innervating the damaged region is cut, the flare component of the response disappears, suggesting that *the flare is caused by an axon reflex in which impulses from the injured zone, in addition to travelling centrally in the 'normal' (orthodromic) direction, send impulses backwards (antidromically) down the other branches of the activated sensory fibers to neighboring skin regions (site of secondary hyperalgesia)*. These antidromic APs release substances (e.g., bradykinin and Substance P) from the sensory terminal which cause vasodilatation. Potassium is also released from injured cells, depolarizing the local nociceptor terminals, increasing transmission to the CNS. The continuous flow of nociceptive input from the injured zone modifies circuits across the CNS so that *Group II input from the zone of secondary hyperalgesia is switched into the central pain pathways*.

Vertebral Venous Plexus

Anterior and posterior spinal veins drain blood from the spinal cord into plexuses located in the epidural space (outside the dura). Vertebral venous plexus anatomoses with brachiocephalic, (hemi)azygos and renal veins, and the IVC). *Internal venous plexus (of Batson):* -Valveless longitudinal channels in epidural space from clivus to sacrum -Drains vertebral bodies through basivertebral veins *External vertebral venous plexus* encircles the vertebral column *Intervertebral veins* within neural foramina connect internal to external vertebral venous plexuses.

*Junctional Scotoma* (Exam)

Anterior chiasmal lesions may cause unilateral visual loss and contralateral superior temporal visual field defects.

Blood Circulation in the Brain

Anterior circulation comes from the *internal carotid a. (ICA)*, a branch of the carotid a. (bifurcates at C3). Left CCA from aorta; Right CCA from brachiocephalic trunk. Posterior circulation comes from the *vertebral a.*, a branch of the subclavian artery that travels through the transverse foramina of the cervical vertebrae (C2-C6) and then the foramen magnum.

Action Potentials

Approximately 100mV, 1 mS "spikes" of membrane potential change that occur at the *initial segment* (axon hillock: high density of Na+ channels) when synaptic potentials (EPSPs) are summed up. Membrane depolarization causes Na+ channels to open up and carry inward current that further depolarizes the membrane. Na+ channels are present at the initial segment and nodes of Ranvier. After a spike starts at the initial segment, it triggers Na+ channels to open up at the next segment of axon not covered in myelin (*regeneration* of AP at node of Ranvier), and so on...

Venous Drainage of the Brain

Arterial circulation drains into capillaries and then into the venous circulation. The dural venous sinuses form within the dura (thick, fibrous covering of the brain; pachymeninges)

Vestibulo-Ocular Reflex (CN VIII → VI → MLF → III) -CN VIII and III are on the same side -CN VI is on the opposite side

As head moves and is detected by vestibular system, eyes reflexively move in opposite direction to correct for movement. Works even in absence of consciousness and light.

Diabetic Retinopathy

Associated with high blood glucose. Subtypes: 1. *Nonproliferative Diabetic Retinopathy * • Microaneurysms • Ischemia • Macular edema 2. *Proliferative Diabetic Retinopathy* • *Neovascularization (growth of abnormal vessels)* • Hemorrhage • Tractional retinal detachment

Retinitis Pigmentosa

Associated with point mutations in the rod opsin or cGMP phosophodiesterase (PDE) genes. This prevents the phototransduction cascade, which prevents hyperpolarization of photoreceptors required for reducing NT and uninhibiting bipolar cells to send signals to ganglion cells, and thus CN II. *Retinal pigment epithelium clumps into bone spicules, causing a waxy pallor of the disk.*

Trigeminal V3 *BRANCHIOMOTOR* Component

Associated with the muscle receptors of the *muscles of mastication* (to give the jaw position sense). Group I axons have cell bodies *inside the CNS* (not in a peripheral ganglion). These cell bodies lie scattered at the border of the central gray in the mesencephalon (midbrain) and constitute the *mesencephalic nucleus of V*.

T1 vs T2 weighted radiology

At t=T1 after RF pulse, 63% of longitudinal (z-plane) magnetization has recovered. At t=T2 after RF pulse, 63% of transverse (x-y plane) magnetization has been lost. *T1 Relaxation:* longitudinal (z-plane) White: (quickest to recover) fat > white matter > gray matter (slowest) (gray and white matter colors match "gray and white") Black: CSF *T2 Relaxation:* transverse (x-y plane)(good for looking at fluid) White: CSF (loses x-y polarization slowly) Black: white matter > gray matter (opposite of "reality") Remember: CSF color: Issues are "black and white" (black 1, white 2). Also, CSF most closely resembles gray matter.

Other *Sensory* Lobes (not parietal) 1. Temporal lobe (auditory) 2. Occipital lobe (visual)

Audition: 1. Stimulation of cochlear receptors produce APs in the first order sensory neurons that are relayed to second and third order sensory neurons before reaching the primary auditory cortex of the *temporal* lobe. 2. Integration of AP inputs begins in the primary auditory cortex (below Sylvian fissure), where the fundamental nature of sounds is interpreted. 3. Signals are then sent to the *auditory association area* (inferior), where prior experience and other current sensory information plays into your interpretation of what the sound is. Vision: 1. Stimulation of rods and cones of the retina produce APs that enter the primary visual cortex of the *occipital lobe*, where initial integration begins (colors/shapes). 2. Impulses then travel to the *visual association areas*, where further integration occurs and specific objects are recognized (e.g., faces of people you know)

Abduction

Away from nose

Inversion of Retinal Images

Axons carrying information about the right superior visual quadrant are located inferiorly in the visual pathway and pass through the left temporal lobe in a region called Meyer's Loop. In the primary visual cortex the *upper visual field is represented below the calcarine sulcus and the lower visual field above the sulcus*.

DCML Pathway Fibers and Types of Sensation

Aα, Aβ, Aδ Fine Touch, Vibration, Pressure, Proprioception

Aδ (fast) vs. C (slow) Pain Fibers

Aδ fibers are responsible for "first" pain (fast, more intense). C fibers are responsible for "second" pain (slow, dull).

AL Pathway Fibers and Types of Sensation

Aδ, C A: Crude Touch, Pressure L: Pain, Temperature, Itch

Extraocular Muscle Innervation

Because the cranial nerve axons have their longest course on the same side as the muscles they innervate, *weakness or paralysis of an extraocular muscle almost always indicates an ipsilateral lesion*, i.e., on the same side as the affected muscle.

*Alterations in GABA Receptor Function*

Blocking GABAaR can cause seizures by preventing IPSPs from depressing the nervous system (large amplitude; uncontrolled EEG waves; neural excitability not repressed). *Anti-convulsant drugs act by enhancing GABA function (benzodiazapines (higher GABAaR open frequency) and barbituates (GABAaR open longer)) or by blocking GABA breakdown (vigabatrin).* Epilepsy can be caused in various ways by affecting GABA function (reducing its ultimate action on GABAaR): 1. Altered GABA synthesis, reuptake, degradation, and storage 2. Reduced GABA release from synaptic terminals (changes in presynaptic proteins or K+ channel genes) 3. Reduced GABA effects (changes in GABA receptor genes)

Opiates work on the...

Brainstem (midbrain, pons, medulla) and spinal cord. These drugs are *NOT helpful in neuropathic pain*.

Bruch's Membrane

Bruch's membrane is the innermost layer of the choroid, the vascular layer of the eye, containing connective tissues (between the retina and the sclera).

Compensation for CN IV Lesion -Affected eye extorts -Tilt head to unaffected side -Normal eye intorts to match -Patient generally leans away from lesion

CN IV is responsible for us looking down and in (superior oblique). To test for a problem with CN IV, have the patient look down and at their nose. *Tilting head toward shoulder of unaffected eye* activates VOR, causing intorsion of unaffected eye to match extorsion of affected eye.

Corticospinal Tract (CST): anterior and lateral -Anterior CST (10%): axial muscles; decussate at spinal cord via anterior white commissure to ventral horn cells -Lateral CST (90%): distal limb muscles; decussate at caudal medulla (pyramids)

CST Pathway (starting in left brain hemisphere): 1. Origin: Pre-central (motor) gyrus of cerebral cortex (left) 2. Axons pass through internal capsule (white matter) of diencephalon 3. Axons continue through cerebral peduncle of midbrain (left) 4. Axons continue through pontine tuberance (left) 5a. At the *spino-medullary junction* (pyramid of rostral medulla; ventral to inferior olivary nucleus), 90% of motor neurons *decussate to the lateral CST* (right lateral funiculus). 5b. 10% of motor neurons remain ipsilateral and travel in the *anterior funiculus* until they *decussate and synapse at the ventral horn* with lower motor neurons. Motor neurons at the *ventral horn*: -Ventral: axial muscles (anterior CST) -Dorsal: distal limb muscles (lateral CST)

Caloric Testing (changes endolymph temperature) 1.Make sure lateral ventricles are vertical 2. *Nystagmus:* COWS -Cold = opposite -Warm = same

Caloric testing evaluates cranial nerves III, VI and VIII, as well as their brainstem connections. It can be applied even in a comatose patient and it gives a crude measure of depth of coma. Since the quick and slow phases are generated by different mechanisms, they become dissociated in certain situations. *As coma deepens the quick phase disappears. Since there is no reset action, the eyes execute one slow phase and stop. This is called tonic deviation.* *Test:* First, tilt the head to that the *lateral canals are vertical*. While standing, tilt head back 60° to orient lateral canals vertically. While laying down, tilt head forward 30° to orient lateral canals vertically. Then apply water: 1. *Warm water* slow phase *away* from ear, quick phase towards ear. 2. *Cold water* slow phase *towards* ear, quick phase away from ear. Responses to Assess Level of Coma: 1. *Light:* good nystagmus with calorics 2. *Moderate:* quick phase drops out (tonic deviation with no reset) 3. *No response:* ominous (brainstem damage); patient unlikely to recover unless due to hyperthermia or drug overdoses Remember: *Slow Phase:* Brave the cold (slow toward cold); escape the heat (slow away from hot). *Quick Phase (Nystagmus):* COWS: cold opposite, warm same Rationale: hot water enters ear, warms endolymph, which rises, moving the ampulla towards the utricle (stimulating the canal).

Bilateral Peripheral Vestibular Dysfunction

Can be caused by *antibiotics* (aminoglycosides: streptomycin/gentamicin) that affect the vestibular system. -Damage hair cells → vestibular dysfunction -*Gait ataxia or disequilibrium* is more common than vertigo

*Alexia without Agraphia* Alexia: *Cannot read* a written language No Agraphia: *Can write* in a language

Can write (graphia) but cannot read (alexia) what they have written. Lesion: *lesion (PCA infarct) restricted to left primary visual cortex (splenium of corpus callosum) in the occipital lobe* Associated with *right homonymous hemianopia* Thus, written material is "seen" only by the right hemisphere and the callosal lesion has interrupted the projection to the left hemisphere language areas. Only the right eye can see words, but since connection through corpus callosum is impaired the right eye cannot convey information to Wernicke's area.

Lateral Medullary Syndrome (Wallenberg's Syndrome, PICA Syndrome) -Everything is ipsilateral, but pain/temp from body (contra) -Includes vertigo, hoarseness, dysphagia, and Horner's Syndrome

Cause: Usually *vertebral a. (or just PICA) thrombosis that causes a pontomedullary infarct*, impacting spinothalamic tract (contralateral), trigeminothalamic tract (ipsilateral), inferior cerebellar peduncle (ipsilateral), vestibular nucleus, and nucleus ambiguus. Symptoms: 1. *Contralateral* loss of pain and temperature senses on the body (anterolateral tract) 2. *Ipsilateral* loss of pain and temperature senses of the face (spinal nucleus of V) 3. *Ipsilateral* ataxia (inferior cerebellar peduncle) 4. Vertigo, Nystagmus, and Nausea (vestibular nucleus) Other Signs: 1. Hoarseness (branchiomotor): nucleus ambiguus (lateral medulla) 2. Dysphagia (branchiomotor): nucleus ambiguus (lateral medulla) 3. *Ipsilateral* Horner's Syndrome (descending sympathetics of the face) Horner's Mnemonic: RAMP 1. *Rubor* (flushing) 2. *Anhydrosis* (loss of sympathetic innervation to sweat glands of the face) 3. *Miosis* (paralysis of dilator pupillae; extreme constriction of the pupil) 4. *Ptosis* (Müller muscle paralysis)

Somatotopic Maps (in pre- and post-central gyri)

Certain regions of the pre- and post-central gyri contain upper motor and sensory neurons, respectively, for different parts of the body. Notice that *legs are more medial, and the hands and face are more lateral*. Each hemisphere represents the half of the body on the opposite side. The amount of cortex devoted to a certain region of the obeyed corresponds to how fine the motor control to, and sensation from, that part of the body is.

Transverse Foramina typify what type of vertebrae?

Cervical (C2-C6). This hole allows the vertebral a. (off of subclavian a.) and v. to travel up to and down from the brain.

Central Retinal Artery Occlusion (CRAO)

Characteristics: 1. Sudden painless loss of vision 2. Common cause: embolus from ulcerated plaque in carotid a. (e.g., *Hollenhorst plaque* (intraretinal embolus) may be visible (plaque lodged in ophthalmic a.)) 3. May involve only a branch of the retinal a. 4. Retinal edema, attenuated vessels, and cherry red spot (*The cherry red spot is seen because the macula receives its blood supply from the choroid, supplied by the posterior ciliary arteries, while the surrounding retina is pale due to retinal artery infarction.*)

Cochlear Implants

Cochlear Implants treat *sensorineural* hearing loss (usually *damage to hair cells*, not nerves). *One must have intact CN VIII nerves.* The implants work by bypassing the hair cells by *transforming sound into appropriate stimulation patterns delivered directly to axons*. This is done with 22 electrodes arrayed within the scala tympani.

Funiculi

Columns of spinal white matter (a bundle of nerve fascicles, myelinated axons) that carry motor and sensory information up and down the spinal cord. *Dorsal funiculus/column:* carries ascending sensory information from somatic mechanoreceptors. *Lateral funiculus (lateral corticospinal tract):* descending motor signals from the brain down the spinal cord and to the target muscle or organ *Ventral funiculus:* ascending (pain and temp); descending (posture modulation)

Central Retinal Vein Occlusion (CRVO)

Commonly associated with hypertension, diabetes, glaucoma. There is decent arterial supply, but blood backs up due to its inability to leave (increased resistance). This causes areas of isolated infarcts of the retina. Disease State: 1. *Non-ischemic* form presents with *good visual acuity* and few retinal hemorrhages but may progress to ischemic form 2. *Ischemic* form presents with *poor vision*, macular ischemia, and can lead to neovascularization

Brainstem

Components: 1. Mesencephalon → midbrain 2. Metencephalon → pons and cerebellum 3. Myelencephalon → medulla

Conjugate Horizontal Eye Movement (Oculomotor) Pathway

Conjugate movement of the eyes to the left requires that the lateral rectus of the left eye and the medial rectus of the right contract together, meaning that the left abducens (VI) nucleus and the medial rectus component of the right oculomotor (III) nucleus must be activated simultaneously. This synergism is accomplished through a pathway that begins with internuclear neurons in the *nucleus of VI*. These send their axons *across the midline into the contralateral MLF*. The axons ascend to the *nucleus of III* and excite the motor neurons innervating the medial rectus. Thus, activation of the left VIth nucleus produces contraction of the left lateral rectus and, indirectly, the right medial rectus, resulting in a conjugate deviation to the left. *All conjugate horizontal eye movements employ this circuitry.*

Arcuate Fasciculus

Connection between Wernicke and Broca areas.

Blur Circle and Pupil Size

Constriction of the pupil increases the crispness of retinal images by reducing blur circle diameter. The object is not in perfect focus, but it is much more like a point when the pupil is small. Because of this effect, narrowing the pupil brings objects at varying distances from the eye into better focus on the retina, increasing the depth of field. *Squinting at an out-of-focus object is an attempt to decrease blur circle size by using the edges of the lid to keep peripheral light rays from entering the eye.*

Superior Orbital Fissure

Contains CN III, IV, V1 (ophthalmic nerve), and VI

Pons (bridge) Origin: Metencephalon -Repiration

Contains a respiratory nucleus that works with the respiratory nuclei of the medulla. Mainly composed of nerve tracts (peduncles) that connect the cerebrum to the cerebellum (comparator function of the cerebellum, fine motor control, and motor learning).

Midbrain Origin: Mesencephalon -Subconscious control of voluntary motor functions

Contains nuclei that function in *subconscious control of voluntary motor functions*. -Colliculi: auditory and visual reflexes -Red nucleus -Substantia Nigra: produces dopamine that inhibits postural muscles (not functional in Parkinson's)

Optic Foramen

Contains optic nerve (CN II) and ophthalmic artery

X-Rays

Contrast: the relative absorption of x-rays (based on atomic number / electron and physical density of the tissue) *Radio-opaque* Metal (white) Bone (white) Calcification (white) Muscle (gray) Fat (black) Air (black) *Radio-lucent*

Astigmatism and correction

Corneal surface is not spherical (but has a steeper curvature long one axis than at other axes). Because of this an object is not imaged in the plane of the retina. Some points on the object are imaged in front of the retina and others behind, creating a blur zone between focal points. *Corrected with a cylindrical lens* that has refractive power along one dimension and can *compensate for the corneal asymmetry.* The cylindrical lens may be combined with a spherical lens needed to correct for myopia (diverging) or hypermetropia (converging).

Anomia

Deficiency in the recalling the *names* of familiar objects which are clearly recognized. Difficulty "finding the words."

Dendrite Purpose and Characteristics

Dendrite Roles: 1. Act as the site of neuronal inputs (synapses) that occur on dendrite spines. 2. Generate excitatory and inhibitory post-synaptic potentials (EPSPs and IPSPs). 3. Conduct synaptic events (PSPs) to the soma (cell body) and axon (for summation). Dendrite Characteristics: 1. Lengths of dendrites vary 2. Some dendrites span multiple layers of cortex to collect various synaptic inputs 3. Some dendrites are short to limit synaptic input 4. *In the cerebral cortex, dendrites come off of pyramidal cells (the principal neurons that run through the cerebral cortex)*. Reminders: 1. Synapses closer to the soma have a greater effect than do those farther away (due to leakage of current down the dendrite). 2. Nissl staining is useful to localize the cell body, and it can be seen in the soma and dendrites of neurons, though not in the axon or axon hillock 3. *Dendritic spines* (microfilaments protruding from dendrites that provide shape and a post-synaptic density) are the *input sites for synapses*, compartmentalizing synaptic molecular machinery to keep it separate from that of adjacent synapses.

Inferior Rectus Movement

Depression

Superior Oblique Movement

Depression Abduction Intorsion When you tilt your head to the right Left eye: extorts (to pull to left)(inferior oblique) Right eye: intorts (to pull to left)(superior oblique) i.e., superior oblique of ipsilateral eye intorts

CT Scans *Indications:* -Traumatic injury of head or spine (acute *hemorrhage*, fracture) -Acute stroke (hemorrhagic or ischemic?) -Headache (headache, tumor, acute hydrocephalus?) -Temporal bone -Paranasal sinuses

Detector cells receive x-ray attenuation data from a fan-beam of x-rays generated by opposing point sources in overlapping helical rotations. X-Ray Attenuation Values (Hounsfield): -1000 (air)(radio-lucent)(lower attenuation) +1000 (bone)(radio-dense)(higher attenuation)

Aβ axon fibers (Group II)

Diameter (um): 2nd largest (6-12) Speed (m/s): 2nd fastest (25-75) Sensory Receptors: *Mechanoreceptors of skin (touch and pressure)*

Aδ axon fibers (Group III)

Diameter (um): 3rd largest (1-5) Speed (m/s): 3rd fastest (5-30) Sensory Receptors: *Fast Pain, Cold Temperature*

Aα axon fibers (Group I) -*Most myelin* -Most responsive to anoxia (low O2); least responsive to local anesthetic

Diameter (um): Largest (13-20) Speed (m/s): Fastest (80-120) Sensory Receptors: *Proprioception of skeletal muscle* Ia: Muscle Spindle (stretch) Ib: Golgi Tendon (force)

C axon fibers (Group IV) -*No myelin* -Least responsive to anoxia (low O2); most responsive to local anesthetic

Diameter (um): Smallest (0.2-1.5) Speed (m/s): Slowest (0.5-2) Sensory Receptors: *Slow Pain, Warm Temperature, Itch*

Nuclei Gracilis vs Nuclei Cuneatus

Dorsal Column Funiculi Nuclei Gracilis: legs (medial) (T7 and below) Nuclei Cuneate: arms (lateral) (C2-T6)

Diplopia

Double Vision -- can be caused by CN IV palsy (which causes *ex*torsion of the ipsilateral eye).

How do we measure gross cortical activity non-invasively?

EEGs (electroencephalogram) measure voltage fluctuations resulting from ionic current within the neurons of the brain.

Superior Rectus Movement

Elevation

Inferior Oblique Movement

Elevation Abduction Extorsion When you tilt your head to the right Left eye: extorts (to pull to left)(inferior oblique) Right eye: intorts (to pull to left)(superior oblique)

Dendritic structure is affected by:

Environment. *Chronic Placental Insufficiency* (decreased uterine blood supply) causes intrauterine growth restriction (IUGR), and stunted hippocampal neurons, which are smaller than normal.

Channels involved in nociception 1. *TRPvR:* transient receptor potential vanilloid receptor initially depolarized in response to capsaicin 2. *Na v1.7 channels (SCN9A):* low threshold allows for amplification of initial depolarization by capsaicin

Excitatory current running through TRPv channels is amplified by Na v1.7 channels, bringing the nociceptor to threshold. TRPv channels sensitive to capsaicin (a vanilloid) cause depolarization (not above threshold yet). Na v1.7 channels depolarize (low threshold), amplifying this signal, and bringing the nociceptor to threshold. Standard, everyday voltage-gated Na channels then fire and propagate APs down the axon into the CNS. *SCN9A Gene:* Na v1.7 channel differentially expressed in *nociceptive sensory ganglion neurons:* -Overactive (low threshold Na v1.7 channels open more easily and stays open longer) → *lower threshold for pain* -SCN9A channelopathy → *Congenital Insensitivity* to pain and erythromelalgia (lower density of Na v1.7 channels → higher threshold for pain)

Cranial Nerve Injury Observations

Eyes straight? CN III, IV, VI (somatic) Head straight? CN XI (somatic) Tongue Midline? CN XII (somatic) Jaw Straight? (mastication mm.) CN V (branchio) Face symmetric? CN VII (branchio) Uvula midline? CN IX, X (branchio)

Oculomotor Pathway

Eyes want to move to the left. Pathway: 1. The horizontal gaze center (*paramedian pontine reticular formation*) gives input to the abducens nucleus to direct gaze to the ipsilateral side (left). This pathway *starts in the vestibular nucleus from the contralateral side*. 2. From there, one set of neurons projects directly to the ipsilateral lateral rectus (CN VI). 3. *Another subset of neurons in the abducens nucleus crosses the midline and travels in the MLF (medial longitudinal fasciculus) to the contralateral oculomotor nucleus.* (Note: The MLF connects the abducens nucleus (CN VI) in the pons to the contralateral oculomotor nucleus (CN III) in the midbrain). 4. The contralateral oculomotor neurons innervate the ipsilateral medial rectus, and the eye moves to the contralateral side. 5. Both eyes move, in this case, to the left. Note: the MLF is the main central connection for CN III, IV, and VI.

In pons and midbrain, legs vs arms vs face in medial lemniscus

Face most medial, arms more lateral, legs most lateral. Pons: FAL is inferolateral Midbrain: FAL is posterolateral

Presbyopia

Failure of lens in eye to be able to change shape (relatively fixed refractive power in the eye). This often occurs in the elderly because lens fibers grow stiffer and less able to change shape. *Light converges after the retina, leading to farsightedness.* Corrected by a converging lens (as done in hypermetropia).

Deep Cerebellar Nuclei (DCN) Mnemonic: *lateral to medial* Don't: dentate (in cerebrocerebellum; lateral) Eat: emboliform (interposed) (in spinocerebellum) Greasy: globose (interposed) (in spinocerebellum) Food: fastigial (in vermis; medial)

Found in the white matter of the cerebellum, which lies beneath the cerebellar cortex. These nuclei receive massive input from the Purkinje cells of the cortex and blend this with signals from other brain areas to coordinate accurate and well-timed movements. DCN are the source of virtually all cerebellar output to other brain areas (brainstem and thalamus). Dentate: (motor planning) to motor and premotor cortices Interposed: (motor execution) to lateral descending systems Fastigial: (motor execution) to medial descending systems

Human Auditory thresholds are lowest for ...

Frequencies 3000-5000 Hz. Normal (young) human hearing is between 20-20,000 Hz. With hearing loss, the curves shift up (first, at higher frequencies), indicating that louder volumes (dB) are required to hear the same frequency. This is an elevation of threshold due to damage of hairs in the cochlea.

Tone

Frequency of pressure waves. Number of waves per unit time

PNS Sensory Axons Large: touch and position (encapsulated) Small: pain and temperature (free nerve endings)

From most myelinated to least (fast to slow): 1. *Aα:* proprioceptors of skeletal muscle (fast) (DCML) 2. *Aβ:* mechanoreceptors of skin (cutaneous): fine touch, pressure, vibration, proprioception (DCML) 3. *Aδ:* sharp pain, cold temperature, crude touch (AL spinothalamic) 4. *C:* slow dull pain, warm temperature, itch, referred pain (AL spinothalamic) Note: Aδ and C fibers terminate peripherally as free (not encapsulated) nerve endings. Aα and Aβ fibers terminate in encapsulated nerve endings.

Corticospinal axon trajectory

From primary motor cortex through the internal capsule (white matter of cerebrum) to the spinal cord (where axons meet up with lower motor neurons at ventral horn of gray matter). Decussation occurs at the spino-medullary junction (pyramids).

Full Facial Palsy vs Lower Facial Palsy (CN VII Lesion)

Full Palsy: Peripheral lesion of lower motor neuron Lower Facial Palsy: Central lesion of upper motor neuron (in cerebrum). The forehead is spared in UMN lesions because it is innervated by both cerebral hemispheres.

Glutamate Receptors

Glutamate receptors can be *ionotropic (ion channels)*: 1. NMDA: Na+ and Ca2+ permeable (*fast* excitatory) 2. Non-NMDA: Only Na+ permeable (*fast* excitatory) Glutamate receptors can be *metabotropic (GPCRs)*: -e.g., mGluR1 to mGluR8 -*Slower* excitatory and inhibitory (variety of responses)

Digital Subtraction Angiography (DSA)

Good for vascular imaging (detecting vasculopathy, aneurysms, or AV malformations). Method: 1. Femoral artery puncture (large, accessible) 2. Thin, hollow, flexible catheter advanced over guide-wire (iodine-based contrast instilled to opacify vessel of interest) 3. Serial digital radiographic images Note: neurologic complications can arise due to dislodgment of atherosclerotic plaques.

The end (apex) of the cochlear spiral is the...

Helicotrema. The scala vestibuli and scala tympani communicate here.

Primary auditory receiving area in cortex

Heschl's Gyrus (A1), located on the superior aspect of the temporal lobe and buried in the fissure of Sylvius.

Choroid Plexus

Highly vasucular tissue inside the lateral, 3rd, and 4th ventricles that produce 500cc CSF per day. The total volume of CSF in the ventricular system is 150cc, and water and solutes (ions and proteins) from the blood enter the choroid plexus via *fenestrated capillaries*. Blood-CSF barrier is between choroid capillary endothelium and choroid epithelium. O2 and CO2 can diffuse across epithelium, but most substances must be actively transported across the choroid epithelium to enter ventricular CSF.

Vestibulo-Ocular Reflex (VOR)

If we are intent on looking steadily at something as we move about, the eye must move to compensate for the movements of the head, which would otherwise redirect gaze away from the target. Thus, when the head turns to the right, the eyes must move to the left by about the same amount to keep the image of a target fixed on the fovea. This automatic adjustment of the eye's position in the head depends on *powerful projections to the oculomotor system primarily from the semicircular canals and is called the vestibulo-ocular reflex or VOR*. VOR involves CN III, VI, and VIII (and the MLF) and works even in the dark. Unlike the attached image, imagine the activated vestibular system CN VI nucleus on the same opposite side of the vestibular apparatus and CN III on the same side. Pathway: CN VIII (vestibular apparatus) → vestibular nucleus (ipsilateral) → abducens nucleus (contralateral) → oculomotor nucleus (ipsilateral) Head moves to the left: Eyes track to the right to maintain gaze (slow component); nystagmus moves left (direction of head motion). 1. Left eye: CN VI inhibits medial rectus, CN III excites lateral rectus to move eye right 2. Right eye: CN VI excites medial rectus, CN III inhibits lateral rectus to move eye right

Diabetic Neuropathy

Impairment of mechano-responsive receptors (e.g., nociceptors) that result in not feeling pain.

Where do olfactory receptor cells synapse?

In glomeruli of similar receptors in olfactory bulb

Language Proficiency

In learning a second language, after the age of 7, the ability to develop grammatical proficiency declines. From ages 17-29, proficiency obtained is quite low.

Ventricular System 1. *Lateral:* C-shaped spaces within cerebral hemispheres 2. *Foramen of Monro:* paired narrow channels connecting each lateral ventricle to the third ventricle 3. *Third Ventricle:* single midline chamber separating the diencephalon on the left from that on the right 4. *Cerebral aqueduct:" single midline narrow tube at the level of the midbrain that connects 3rd and 4th ventricle 5. *Fourth Ventricle:* midline, has choroid plexus (also found in 3rd ventricle and lateral ventricles)

In the brain, the central canal (hollow portion of nerve tube) grows and changes shape to become the ventricular system, which produces and contains CSF. In particular, ependymal cells form gland-like structures (choroid plexuses) in the lining of the ventricles that produce CSF. CSF flows through the ventricles via cilia moving it along. Organization: 1. Lateral ventricles (I and II) form deep to the cerebrum (telencephalon). 2. Interventricular foraminae (Foraminae of Monro) connect the 1st and 2nd ventricles to the 3rd ventricle. 3. The 3rd ventricle forms between the thalamic lobes / hypothalamus (diencephalon) 4. The cerebral aqueduct (Aqueduct of Sylvius) connects the 3rd and 4th ventricles, passing through the midbrain (mesencephalon). 5. The 4th ventricle forms between the pons and the cerebellum (metencephalon) 6. Central canal of the spinal cord CSF exits the 4th ventricle into the subarachnoid space in 3 places: 1. Median Aperature (Magendie) (single) 2. Lateral Aperatures (Luschka) (paired) -This CSF eventually drains into the venous system (through arachnoid granulations into the superior sagittal sinus) and is returned to the blood. At arachnoid granulations, arachnoid villous cells transport CSF through giant vacuoles into the venous sinus. -Since there is *no monitoring of total CSF pressure or volume*, if more CSF is produced than is drained back into the venous system, pressure will build up in the ventricles → *hydrocephalus*

Brain Development

In the cerebrum and cerebellum, neuroepithelial cells produce an additional population of daughter cells that migrate out through the white matter and form a second, outer layer of grey matter, the cerebral and cerebellar cortex. In addition to the neurons of the CNS, the *neuroepithelial cells also give rise to the neuroglia (support)* cells of the CNS, with the exception of the microglial cells (macrophages), which develop in the bone marrow.

Biomarkers for Hydrocephalus

Increase in *neurofilament protein in CSF*. This protein is released from skeletal neurons upon death, a sign of breakdown.

(Downward) Cerebellar Tonsillar Herniation

Increased pressure in the posterior cranial fossa (where the cerebellum sits with the brainstem) can lead to herniation of the tonsil through the foramen magnum. The cerebellar tonsils can compress the brainstem and cause the medullary respiratory centers to cease to function, leading to apnea or abnormal breathing (respiratory arrest).

Ventricular System (image)

Individual horns and atria of the ventricular system are outlined in the image.

Cochlear Amplifier

Inner hair cells are mainly responsible for triggering auditory nerve (CN VIII). Outer hair cells are highly sensitive to frequencies that maximally displace the basilar membrane where they are located. (Basilar membrane movements would only be 1% as large without this amplification.) Depolarization of the outer hair cells *increases the displacement* of the basilar membrane where they are located (a voltage sensitive motor molecule called *prestin* shortens the outer hair cell) and *augments the response of the inner hair cells* located near them, boosting the strength of the signal sent to the brain.

Tensor Tympani

Innervated by CN V3. *Increases the tautness of tympanic membrane (eardrum)* when contracted to lower efficiency of the system to transfer mechanical energy into electrical energy. Ear muscles reduce sound vibrations in the ossicles.

Stapedius Muscle

Innervated by CN VII. *Pulls the stapes out from the oval window,* tightening the fibrous band attaching it to the temporal bone. Ear muscles reduce sound vibrations in the ossicles.

Ventricular System Blockages

Internal (*non-communicating/obstructive*) hydrocephalus: -*CSF outflow obstruction* -Cerebral/Sylvian aqueduct External (*communicating/non-obstructive*) hydrocephalus: -*Impaired CSF resorption by arachnoid granulations* due to damage following infection (e.g., meningitis), inflammation, or hemorrhagic events (e.g., rupture of cerebral aneurysm causing subarachnoid hemorrhage)

Horner's Syndrome

Interruption of *sympathetic innervation* to the eye (can occur between hypothalamus and the eye itself) causes *ipsilateral*: Mnemonic: RAMP 1. *Rubor* (flushing) 2. *Anhydrosis* (loss of sympathetic innervation to sweat glands of the face) 3. *Miosis* (paralysis of dilator pupillae; extreme constriction of the pupil) 4. *Ptosis* (Müller (superior tarsal) muscle paralysis) Ptosis can result from CN III palsy (superior tarsal m.) or Horner's Syndrome (LPS m.). However, the *pupil* of the eye ipsilateral to the ptosis will be *dilated (mydriasis) in CN III palsy and constricted (miosis) in Horner's Syndrome*. This is due to what autonomic system is affected: Horner's (sympathetic), CN III palsy (parasympathetic).

MLF Syndrome

Interruption of the oculomotor circuitry (see above) causes a disorder of conjugate horizontal eye movements called *Internuclear Ophthalmoplegia* (in between nuclei VI and III). The MLF is heavily myelinated to quickly conduct signals from abducens (VI) nucleus to oculomotor (III) nucleus. MS can demyelinate the MLF, causing lack of communication such that when CN VI nucleus activates ipsilateral lateral rectus, *contralateral CN III nucleus does not stimulate medial rectus to contract.* *Signs:* gaze to the left (lesion on the side that cannot move = right) 1. *Inability to adduct* right eye voluntarily during horizontal gaze to the left (contralateral eye cannot move) 2. *Nystagmus* of left eye (CN VI overfires to stimulate CN III). 3. *Preservation of convergence* (which is controlled from the rostral midbrain and does not require the circuitry of the internuclear neurons and MLF)

Cerebellar hemispheres control _________ side of the body

Ipsilateral. Therefore, lesions affect the ipsilateral side of the body.

Where does the spinal cord end (at which vertebral segment)?

L2 (called the conus medullaris). Caudal to this, the hollow of the vertebral column contains only spinal *roots* coursing to lower vertebral levels. These roots comprise the *cauda equina* (horses tail) and are bathed in CSF of the lumbar cistern.

Language Areas

Language is localized to one "dominant" hemisphere (usually left). Perfused by the MCA (lateral). *Left hemisphere lesion:* aphasia *Right hemisphere lesion:* neglect (can't see left side, ignore it) *Language Centers:* 1. *Broca's area* (45): frontal lobe (production of speech) -Expressive aphasia: can't articulate what they want, but know what they want to say) 2. *Wernicke's area* (39): posterior, superior temporal lobe (comprehension of speech) -Fluent aphasia: speaks non-sensically, but fluently)

CSF Cisterns

Larger, focal spaces within the CSF circulation pathway. 1. Perimesencephalic Cisterns -Interpenduncular: anterior to midbrain, above pons -Ambient: around midbrain -Quadrigeminal Plate : superior to cerebellum, posterior to midbrain (after cisterna magnum CSF makes it around cerebellum) 2. Prepontine: in front of pons 3. Cisterna Magna: at the junction of the medulla and inferior cerebellum (median aperture empties here) 4. Lumbar: space around cauda equina where CSF is obtained during a lumbar puncture (spinal tap at L3/L4)

Production of language is usually localized to the ______ hemisphere

Left. 96% of right handers; 70% of left handers. Left handers seem to recover more from left hemisphere strokes. Women also recover better than men (from left hemispheric lesions).

In Medulla, legs vs arms position in Medial Lemniscus

Legs anterior, arms posterior

Neural Circuitry of the Retina

Light entering the eye travels across most of the retina before reaching the photoreceptors. The neural signals then travel out to the ganglion cells and thence to the brain.

Hypermetropia (*"Far sightedness"*) and Correction

Light focuses after retina (because the retina of the eyeball is too short. *Corrected with converging (plus) lens.* Notice that incoming light rays converge and enter the eye at a different angle.

Myopia (*"Near Sightedness"*) and Correction

Light focuses before retina (eyeball is abnormally long -- axial myopia). *Corrected with diverging (minus) lens.* Notice that incoming light rays diverge and enter the eye at a different angle.

Nuclear Imaging

Look at the biodistribution of radiotracer + pharmaceutical: decay of radiotracer produces γ rays that a gamma camera can determine the concentration (intensity) and biodistribution (location). *SPECT (single photo emission CT):* -*99mTc-HMPAO* investigates brain perfusion in dementia or seizure (white matter is less perfused) -*Alzheimers: reduced blood flow to temporal and parietal association areas* *PET Scan (positron emission tomography):* -Positron-emitting isotopes of organic elements react with electrons in a mutual annihilation event -*18F-deoxyglucose (FDG)* can detect tumors as they use glucose quickly -*Amyloid-b PET estimates density of neuritic plaques in patients with suspected Alzheimer Disease*

Anosmia

Loss of smell. Can be caused by nasal congestion, obstruction of nasal passages, aging, trauma (ethmoid bone fracture), lack of Zn, neurodegenerative diseases.

Alexia

Loss of the ability to *read* a written language

Agraphia

Loss of the ability to *write* in a language

Anterior Ischemic Optic Neuropathy (AION) -Optic nerve defect

Loss of vision caused by *damage to the optic nerve as a result of insufficient blood supply (ischemia)*. The optic nerve is swollen. Subtypes: 1. *Arteritic:* loss of vision due to arterial inflammation (more common in females; contralateral eye risk ~95%; tx: steroids) 2.*Non-arteritic:* painless loss of vision due to non-inflammatory disease of small blood vessels (e.g., due to hardening of the arteries).

How to differentiate the 4 spinal cord levels

Lumbar and lower cervical spine cross sections have lateral enlargements of the ventral horn (due to the need for more processing for the upper and lower limbs as compared to the neck or torso). Thoracic levels don't have lateral enlargements of the ventral horn (gray matter is "skinny" and looks like an H), but they do have an *intermediolateral cell column (levels T1-L2) that look like little spikes on the lateral sides of gray matter (comprised of sympathetic neurons). Cervical: big ventral horn, lots of white matter Thoracic: small ventral horn, plenty of white matter Lumbar: big ventral horn, less white matter Sacral: gray matter > white matter

Where do lumbar punctures take place?

Lumbar puncture needles are inserted at the level of vertebrae L3/L4 (around iliac crest level) into the lumbar cistern to avoid damaging the spinal cord. The roots will move around the needle as they are suspended in CSF.

Retinal Detachment -Separates the photoreceptors from their choroidal blood supply

Lying *between the layers that become the retina and the pigment epithelium* is a space that is initially continuous with the cerebral ventricles. This *subretinal space* closes as the eye matures, but can reappear due to trauma or other pathological processes that cause *accumulation of fluid in the space*. The retina then detaches from the pigment epithelium and ceases to function. Two Main Causes: 1. Vitreous humour escapes into the sub retinal space through a retinal hole 2. Collapse of vitreous pulls the retina away from the pigment epithelium

Which artery? Stroke affecting face and hands (think about homunculus on cerebral hemisphere)

MCA Stroke. Lateral portion of brain. Weakness and sensory problems: affects the pre-central gyrus (primary motor cortex) and the post-central gyrus (primary somatosensory cortex).

Magnetic Resonance Imaging (MRI) *Indications:* -Ischemic infarction (stroke) -Mass in brain or spinal cord -White matter disease (can look for plaques) -Seizure -Cranial neuropathy -Meningeal disease

MRI Overview: good for functional imaging of the brain or spinal cord (soft tissue) 1. *Highest image contrast for soft tissues* (easiest to differentiate white and gray matter) 2. MRI is versatile (anatomy and physiology) 3. Relatively safe (non-ionizing radiation) (radio frequency waves have 10^12 less energy than x-rays) Image Constrast: -Complex interactions of protons in water and fat -Requires strong external magnetic field (1.5-3 Teslas) -The signal intensity of protons in tissues indicates the number of protons, biochemical environment, and relaxation times (which describe return to equilibrium after radio frequency pulse)

Linear accelerations of the head detected by ...

Macula of Otolith Organs. 1. Utricle (horizontal orientation when the head is straight up) 2. Saccule (vertical orientation when the head is straight up)

Trigeminal sensory information (via trigeminal ganglion thick axons Aα, Aβ) synapses at...

Main sensory nucleus V (trigeminal) in Pons

Serotonin modifies pain in the ...

Medulla (where the Raphe Nucleus is located).

Cephalic Flexure

Midbrain-diencephalon junction (~80° bend between brainstem-forebrain axes)

Brainstem 1. Midbrain 2. Pons 3. Medulla oblongata

Most of the brainstem is composed of ascending and descending nerve tracts that are either *bringing sensory information to the brain* for processing (ascending) or *transmitting action potentials from the brain* that will cause muscles to contract (descending).

Cranial Nerve Nuclei Organization

Motor nuclei: medial (somatic most medial, branchio most lateral) Sensory nuclei: dorsal and lateral Nuclei are not continuous cell columns like the spinal dorsal (sensory) and ventral (motor) horns.

Optokinetic Nystagmus

Movement of an image across the retina causes eyes to follow target. Slow (optokinetic) phase stabilizes image on the retina, fast phase resets eyes to allow for a new slow phase follow of a new moving object. Displacements of the entire visual scene evoke slow, optokinetic eye movements that tend to oppose the resulting motion of the retinal image. The moving visual scene essentially 'drags' the eyes along with it. Optokinetic eye movements made in response to motion of the retinal image can also take the eye nearly to the limits of its movement range, with the result that a quick phase is added in the opposite direction.

Does AL synapse at medulla, pons, or midbrain?

NO, it synapses in the substantia gelatinosa of the *spinal cord* gray matter. It does send some branches (via the spinoreticular tract = spinothalmic, but ends at reticular formation) to reticular formation (medulla, pons) and peri-aqueductal gray matter (midbrain).

Are taste receptors neurons?

NO. Taste receptor cells are *modified epithelial cells* that interact with the nervous system. Their apical end detects chemicals (e.g., NaCl, sucrose, etc.). Main basic taste qualities: salty, sour, bitter, sweet, umami (glutamate)

First line of treatment for *Nociceptive* Pain (Exam)

NSAIDS: Aspirin, Ibuprofen, Naproxen, Indomethacin, Diclofenac

Opioids (for *Nociceptive* Pain)

Natural: *Morphine, Codeine* Semisynthetic: *Heroin, Oxycodone, Hydrocodone* Synthetic: Methodone Endogenous: Endorphins Order of weakest to most potent: Codeine < *Morphine < Hydrocodone < Oxycodone* Side effects: nausea, vomiting, constipation, itching, and respiratory depression (at higher doses, this causes death)

White Matter Commissures

Nerve tracts that connect the left and right sides of the brain. a. *Anterior:* connects the two *temporal lobes* of the cerebral hemispheres across the midline b. *Posterior:* interconnects the *pretectal nuclei*, mediating the consensual pupillary light reflex c. Corpus callosum: connects cerebral hemispheres

Effective Treatment for Chronic Pain

No cure. A 30% reduction on pain scales is clinically important and equivalent to "moderate relief."

*Pituitary Adenoma* (Exam)

Non-secreting tumors (just below the optic chiasm) may present with bitemporal visual field loss (due to compression of the chiasm injuring crossing nasal fibers from each eye). Anterior chiasmal lesions may cause unilateral visual loss and contralateral superior temporal visual field defects (junctional scotoma).

Emmetropia

Normal focusing of light in the eye on the retina

Accommodative (Near) Response (*CN III*)

Occurs when the distance from the eye to the fixated object decreases: 1. Eyes converge (simultaneous activation of medial rectus muscles via CN III) 2. Lens Rounds (*reduced torsion on zone fibers* by ciliary muscles allows the intrinsic elastic properties of the lens to make it *rounder and more curved*, increasing the optical power of the lens and *shortening its focal length*) 3. Pupils constrict (parasympathetic visceromotor innervation of the sphincter pupillae m.)

Olfactory Pathway

Odorants bind to receptor proteins on cilia and trigger a depolarizing receptor potential. If the local receptor potential is large enough, it can trigger one or more APs. The APs propagate along the olfactory axons to the olfactory bulb (glomeruli). Olfactory receptor genes are the largest gene family, allowing for a wide array of unique olfactory sensations. Each olfactory receptor neuron expresses only one, however. Each olfactory neuron responds to many odorants, but to different degrees. Similar to taste, olfactory information is encoded by the activity of populations of neurons (a population "code"). All of the olfactory neurons that express a particular receptor gene project to the same glomerulus in the olfactory bulb. As such, 25,000 primary receptor neurons converge onto just 100 second-order neurons in each glomerulus.

Receptor Divergence -Conductance = # of ion channels open -GABA and glycine are both *inhibitory*

One NT can activate multiple receptors and effectors. Examples of IPSP generation: 1. *GABA* binds GABAaR, GABAbR, and GABAcR: a. *(aR) ligand-gated Cl- channel*: increases Cl- conductance (opens Cl- channels) b. *(bR) GPCR:* increases K+ conductance (opens K+ channels); decreases Ca2+ conductance (closes Ca2+ channels) c. *(cR) ligand-gated Cl- channel:* increases Cl- conductance (opens Cl- channels) 2. *Glycine* binds Gly-R → increases Cl- conductance (opens Cl- channels) Note: GABAaR/GABAcR are *ionotropic*; GABAbR is *metabotropic*

Dorsal Column-Medial Lemniscus System (DCML) -Ascending sensory tract -Conveys *fine touch, pressure, vibration, and proprioception* (one's sense of body position in space) -Decussates in medulla

One of the two major ascending somatosensory tracts bringing information up to primary somatosensory cortex S1 (post-central gyrus). Pathway: 1. Dendrites of afferent primary sensory neurons reach dorsal root ganglion (cell body) and travel up dorsal root column (gracile=lower limbs or cuneate=upper limbs fasciculus) 2. This primary sensory neuron synapses at the gracile or cuneate nucleus in the medulla 3. Decussation to contralateral side (in brainstem). *∴Spinal lesions cause ipsilateral loss; cortical lesions cause contralateral loss.* 4. Axons then travel up the brainstem (medulla, pons, and midbrain) in the *medial lemniscus (ML)* to the ventral posterolateral (VPL) nucleus of the thalamus. 5. From the VPL nucleus, axons travel to the post-central (somatosensory) gyrus of the cerebral cortex. Fasciculi Locations: 1. *Cuneatus (lateral): upper body, arms (C2-T6)* 2. *Gracilis (medial): lower body, legs (T7 and below)* The ML appears differently on its rise: -Mid-medulla: oblong triangle at medial center -Pons: between the 4th ventricle and the CST located in the pontine protuberance (ventral to the reticular formation) -Midbrain: a boomerang-like shape lateral to the red nuclei and dorsal to the substantia nigra. Reminder: 1. Sensory *facial* information travels via primary afferents to the main sensory or spinal nucleus of V. before traveling to the *VPM*. 2. *Main sensory nucleus of V. (Aα/Aβ): fine touch, vibration, pressure, proprioception; analogous to DCML*; joins ML pathway 3. *Spinal nucleus of V. (Aδ/C): pain, temp, crude touch, itch*; joins AL pathway 4. Tertiary afferents then travel to the somatosensory cortex (lateral side of brain; think homunculus)

Two kinds of hair cells in inner ear

One row of *inner hair cells (sensory)* near modiolus. Fewer in number, but have more connections to the brain via the auditory nerve (90% of spiral cell ganglion cells innervate the inner hair cells). Three rows of *outer hair cells (amplifiers)* lie closer to outer cochlear wall. Larger in number, but have fewer connections to the brain via the auditory nerve (10% of spiral cell ganglion cells innervate the outer hair cells).

Optokinetic (Slow Phase) vs. VOR

Optokinetic movements can occur when the head is still, but the eyes must be open. The VOR can occur with the eyes closed when the head moves. *Optokinetic movements (slow pursuit) move the eyes in the same direction as the visual motion* (imagine train tracks to the left). Rotation of the head to the right with the eyes open causes the stationary background to appear to move to the left. The *VOR causes the eyes to move in the same direction as the apparent motion of the background*. With head motion and open eyes, both mechanisms work together to stabilize the retinal image.

What is the sensory organ of audition, and where is it located?

Organ of Corti in Scala Media. Endolymph is located here (generated by the stria vascularis). The Organ of Corti sends signals via CN VIII to the ventral cochlear nucleus in the brainstem, which sends signals to the superior olivary complex (SOC), which sends signals via CN VII to the stapedius m.

How do semicircular canals work?

Oriented 90 degrees with respect to each other (anterior/superior, posterior, and lateral canals). Cilia of hair cells in the ampullae are imbedded in a gelatinous cupula which is deflected by movement of endolymph. Movement one direction is excitatory and movement in opposite direction is inhibitory. Relative motion of fluid is opposite movement of head (i.e., move head to the right; endolymph flows to the left). For lateral canals (tilted up 30 degrees with respect to a plane through the eyes and auditory meati): Imagine nose turning for directionality. From lateral to medial, each canal is AUS (ampulla, utricle, saccule). To Remember(?): Aussie Aussie Aussie Oi Oi Oi (3 canals, 3 structures that matter) Example: *Moving the head to the right (right canal output > left canal output)* 1. Left side: Fluid movement *away* from utricle is *inhibitory* (utricofugal). The ampulla moves away from the utricle as the head moves in the opposite direction. 2. Right side: Fluid movement *toward* the utricle is *excitatory* (utricopetal). The ampulla moves toward from the utricle as the head moves in the opposite direction. Since utriculopetal flow is excitatory in the lateral canals, afferent impulse frequency from the right canal would increase while that from the left canal would decrease.

How to utricle and saccule work?

Oriented 90 degrees with respect to each other. Contain otoliths (ear stones) on top of gelatinous cap on top of hair cells (more dense than surrounding endolymph). Hair cells have stereocilia and kinocilium (which defines the sensitivity of the cell by creating receptor potentials). When the stereocilia are bent toward the kinocilium, the cell is depolarized and impulse traffic in the afferent fibers increases. Bending in the opposite direction decreases firing rates. *Hair cells of the vestibular organs, like those of the cochlea, do not fire action potentials. They release neurotransmitter at a rate related to their membrane potentials.*

Otoacoustic Emissions

Otoacoustic emissions (spontaneous or evoked) are sounds generated by the ear. *Spontaneous otoacoustic emissions* are common and can be audible to others. Dysfunction of outer hair cells can cause spontaneous movement of the basilar membrane, causing the tympanic membrane to vibrate and actually EMIT sound. *Evoked otoacoustic emissions* may be produced by short, loud clicks and one can test for cochlear damage in newborn infants by analyzing the frequency content of the emitted sound.

Pitch

Our perception of the tone of sound waves

Spinal Cord Modulation of Pain -"Gate Control Theory" (aka, why do we rub our shin after we bump it?)

Pain impulses reaching the spinal cord must pass through a control point in the substantia gelatinosa of the dorsal horn (gate-keeper interneuron). 1. When nociceptive AL afferents are stimulated (pain), they inhibit the gatekeeper and activate the projection secondary neuron to send pain signals up the AL system, with pain resulting. 2. Rubbing the leg activates Aβ fibers in the DCML pathway, which excites the gatekeeper interneuron to inhibit the projection secondary neuron, This reduces its firing rate and the level of pain felt (counter-irritation effect). 3. DCML stimulation prevents the nociceptive signals of Aδ and C axons (nociceptive signals from AL pathway) from ascending to the cerebrum by overriding the inhibitory signals they usually send to the inhibitory gate-keeper interneuron. A prediction of this model is that electrical stimulation of the dorsal columns should also reduce pain by antidromically activating the non-nociceptive afferent axon (Aβ, touch) and its synapse with gate-keeper cells (inhibiting pain relay cells).

Referred Pain

Painful sensations arising from one organ may be felt in another (due to crossing of wires). There is a *convergence of primary afferent nociceptive (e.g., from skin) and visceral (e.g., from GI) fibers onto the same dorsal horn neuron* before traveling to the brain on a single ascending tract (single secondary neuron in AL pathway). Since pain signals from the skin are more common than from visceral organs, the brain associates activation of the pathway with pain in the skin.

Dural Venous Sinuses

Parenchymal veins drain into dural venous sinuses. Dural sinuses drain mainly into the internal jugular v., which drains into the SVC. Pathway: 1a. Superior Sagittal Sinus (runs in midline from front to back of brain) 1b. Inferior Sagittal Sinus → straight sinus 2. Confluence of Sinuses (Torcular Herophili) 3. Transverse/Lateral Sinus 4. Sigmoid Snus 5. Internal jugular vein (leaves through the jugular foramen)

Parinaud's Syndrome (Upward Gaze Palsy/Paralysis)

Parinaud's Syndrome is a *paralysis of vertical gaze*, which requires CN III and IV (whose *nuclei lie in the midbrain tegmentum*). *Causes:* 1. *Lesions of the midbrain tegmentum* (ventral to 4th ventricle) 2. *Pineal tumors* compress midbrain tegmentum (ventral to 4th ventricle) To *distinguish this from a bilateral paralysis of the superior rectus muscles*, it is helpful to hold the patient's eyes open and ask him to close them. The eyes will usually move up (*Bell's Phenomenon*), indicating superior rectus contraction (not paralyzed) and confirming Parinaud's.

Why does AL pathway also synapse in reticular formation?

Part of affective-motivational pathway of pain → emotion

Olfactory Pathway (Exam)

Pathway: 1. Odorants bind to olfactory receptor cells 2. Olfactory receptor cells are activated and send electrical signals to glomeruli containing other neurons with the same receptor gene. 3. Signals are relayed in the glomerulus to higher regions of the brain. 4. *Signals can go directly to the olfactory cortex (bypassing the thalamus)* or can synapse in the olfactory tubercle then medial dorsal nucleus before traveling to the orbitofrontal cortex.

Pathway of Aqueous Humor

Pathway: 1. Produced by *ciliary processes* (aqueous humor contains numerous nutrients as well as *dissolved oxygen*, nourishing the lens and cornea) 2. Flows around anterior lens and iris into anterior chamber 3. 90% drains through canal of Schlemm (trabecular mesh) located at the filtration angle. 10% passes through the tissues of the ciliary muscle and sclera (uveoscleral outflow).

Nyctalopia (night blindness)

Patients with *vitamin A deficiency* may experience night blindness because *11-cis retinal is an aldehyde of vitamin A*. Rods are much more sensitive to light than cones, so vision at low light levels is rod-dependent.

How do you identify a pediatric brain from an adult brain?

Pediatric has larger occipital horns than ventral (white matter hasn't yet fully developed to push the occipital horns of gray matter in).

Peripheral vs. Central Vertigo

Peripheral: vestibular apparatus or CN VIII Central: vestibular cortex, thalamus, cerebellum, brainstem *HINTS Exam:* (1) head impulse, (2) nystagmus, (3) test of skew *Central:* abnormal TS 1. Accompanying findings: brainstem (double vision or trouble swallowing) 2. Not as severe 3. Vertical component to nystagmus (upgaze) 4. Thermally-induced nystagmus (caloric testing) *preserved* 5. *Normal head impulse test* 6. *Impaired skew test* (when eye is uncovered, it moves up and medially) *Peripheral:* abnormal HIN 1. Vertigo in isolation (or with hearing loss/tinnitus) 2. Severe with vomiting 3. Unidirectional nystagmus; suppressible with visual fixation. 4. Thermally-induced nystagmus (caloric testing) *absent or impaired* 5. *Abnormal head impulse test*! 6. Normal skew test 7. *Vertigo brought on solely by movement* (potentially vestibular apparatus)

Analogous Trichromacy

Persons with the normal complement of three pigments are called trichromats. When the spectral sensitivity of one pigment is shifted away from the normal due to slight *variation in opsin amino acid composition*, the individual is called an anomalous trichromat.

Phototransduction Cascade

Phototransduction: 1. Light isomerizes 11-cis retinal to the *all trans* configuration, activating rhodopsin (GPCR-photopigment) 2. Activated rhodopsin is catalytic and activates *Transducin* (G-protein) 3. Transducin activates *phosphodiesterase* (PDE) 4. PDE converts cGMP → GMP 5. cGMP-gated Na+ channels close, hyper-polarizing the cell, stopping NT release. Normally, *NTs inhibit bipolar cells in the dark (dark current), but in the light, reduced NTs allow bipolar cells to transmit the signal to the optic nerve.*

Retina is attached to...

Pigment epithelium (where retinal detachment occurs). The opening of the subretinal space in retinal detachment deprives the photoreceptors of their blood supply.

Major cause of bitemporal visual field loss

Pituitary adenoma pressing on optic chiasm

Trigeminal sensory information decussates at...

Pons into Medial Lemniscus (before ascending) At pons level, medial lemniscus is arranged Face, Arm, Leg (medial to lateral of midline).

One and One Half Syndrome

Pons lesion that interrupts both CN VI nucleus and MLF pathway to ipsilateral CN III nucleus from contralateral CN VI nucleus. The eye opposite the lesion can abduct only. *Symptoms:* 1. Horizontal paralysis of ipsilateral (to lesion) eye (in both directions) 2. Paralysis of contralateral eye in moving towards the lesion. The lateral rectus is still functional, so the eye can abduct.

Subacute to Chronic Extrapyramidal Disequilibrium

Postural instability in Parkinson's Disease. "Pull" test (patient can usually take a few steps back and catch themselves).

Where does pupillary light reflex first synapse?

Pretectum in superior colliculus (midbrain) via optic nerve tracts (CN II)

Area around the central sulcus

Primary Somatosensory Cortex -Post-central gyrus -S1 -Broaman areas 1-3 -"Sensory strip" In the primary somatosensory cortex, the DC-ML system is more medial to the central sulcus, whereas the anterolateral (AL) system (for S1 sharp pain) is more posterior. The AL system for SII (slow, dull pain and arousal) is located more posteriorly in the posterior parietal cortex on the ceiling of the lateral sulcus (Sylvian fissure). Primary Motor Cortex -Pre-central gyrus -M1 -Broaman area 4 -"Motor strip"

Brain Vesicles Mneumonic: *Tell Di, Mes Met Myel* Divisions of the CNS: 1. Telencephalon: cerebral cortex and basal ganglia 2. Diencephalon: thalamus and hypothalamus 3. Brainstem -Mesencephalon: midbrain -Metencephalon: pons -Myencephalon: medulla 4. Cerebellum (metencephalon) 5. Spinal Cord (neural tube/neuroepithelium)

Primary and Secondary (lettered) Vesicles: 1. *Prosencephalon (forebrain)* 1a. Telencephalon → cerebral hemispheres (cerebral cortex, subcortical white matter, basal ganglia, basal forebrain nuclei) 1b. Diencephalon → thalamic nuclei (thalamus, hypothalamus, epithalamus) 2. *Mesencephalon (midbrain)* → midbrain 3. *Rhombencephalon (hindbrain)* 3a. Metencephalon → pons and cerebellum 3b. Myelencephalon → medulla

Calcarine (Striate) Cortex (Brodmann 17)

Primary visual interpretation area of brain in occipital lobe. Macula is most posterior and outer field (more peripheral vision) is most anterior.

Acoustic Reflex

Protective against damagingly loud, low-frequency sound. Active during vocalization. Loud, low frequency sounds induce a reflex arc that causes the stapedius to contract (restricts stapes), leading to protection of middle and inner ear by adjusting "gain" for low frequency sounds in response to sound input. Pathway: CN VIII (inner ear) acts on ventral cochlear nucleus in the brainstem, which sends signals to the SOC (superior olivary complex), which sends CN VII to the stapedius m. for contraction (middle ear). *Hyperacusis:* damage to CN VII: sounds seem louder than usual (no dampening of sound by stapedius m.)

Saccade

Quick eye movements for following *without a target*

Wernicke-Geschwind Model

Reading then speaking (pathway). Not super accurate, and not on exam.

Acoustic Neuroma

Really a *Schwannoma along CN VIII or cerebellopontine angle*. Causes disequilibrium or vertigo. Starts as hearing loss → disequilibrium or vertigo (NF Type II can cause bilateral CP angle tumors) Treatment: resection or radiosurgery

Posterior Parietal Cortex

Receives input from somatosensory, visual, auditory cortex, and hippocampus (Brodmann areas 5 and 7).

Receptive Fields

Receptive fields of cutaneous receptors overlap. If one neuron is damaged, one won't lose coverage to that receptive field due to such overlap.

Binocular Visual Field

Retinal axons from the nasal retina decussate in the optic chiasm to join the temporal axons from the other eye. Thus, the axons carrying signals from one side of the binocular field are gathered together in the contralateral optic tract. *Because of this partial decussation, objects to the left of the fixation point are "seen" by the right hemisphere and objects to the right of the fixation point are "seen" by the left hemisphere.* This arrangement is perfectly analogous to the somatic sensory and motor systems where one side of the body is represented in the contralateral hemisphere. *Because the optic chiasm, optic tract, and optic radiation contain fibers from both eyes, lesions at and posterior to the chiasm usually produce visual field defects in both eyes.* Monocular segments of our visual field are imaged on the edges of the nasal retina (the most anterior portion closest to the tip of the nose).

Rod Photopigment

Rhodopsin, composed of 11-cis retinal (chromophore) and opsin (GPCR). When the eye is dark adapted, the spectral sensitivity of vision is identical to the absorption spectrum of rhodopsin. Rods and their pigment are thus responsible for the dark adapted or scotopic sensitivity of the eye. *Rods and cones both employ 11-cis retinal as their chromophore but have different opsins, which determine their spectral sensitivities.*

Dark Current

Rods and cones are relatively depolarized in the dark by a *"dark"* cationic (Na+) current entering the outer segments (cGMP-gated ion channels). *Neurotransmitters are released and inhibit bipolar cells.* *Light* exposure decreases the number of open cation channels in the outer segment (due to PDE conversion of cGMP → GMP), resulting in relative hyperpolarization of the receptor and a *decrease in neurotransmitter release* (bipolar cells can transmit signal to the optic nerve). Photoreceptors work "backwards": ↑light intensity, ↓Vm (hyperpolarization), ↓neurotransmitter released (bipolar cells are able to transmit signal to CN II) *Although photoreceptors are true neurons, they do not generate action potentials. The release of transmitter at their synaptic terminals is modulated continuously by light (via graded potentials).*

Dark and Light Adaptation in the Retina

Rods are much more sensitive than cones and switch back and forth with them depending on light levels. *Dark (Scotopic) Conditions:* sensitivity of the eye is set by the low threshold rods. Cones do function in the dark, but require more light than rods to respond. *Light (Photopic) Conditions:* Less sensitive cones dominate vision and the eye is said to be light-adapted. At these levels, the rods are essentially switched off by intrinsic cellular mechanisms. Thus the human eye is said to have a duplex retina, one for nighttime and one for daytime.

Cerebellum -Acts indirectly on the spinal cord by modulating cortex and long descending motor tracts -Coordinates and regulates somatic motor activity

Roles: 1. Coordinates and regulates somatic motor activity initiated in the frontal lobe. -*Frontal lobe:* thought, planning, and execution of somatic motor activity -*Cerebellum:* monitors motor activity and modulates it so that movements are as close to possible as the movements we intend to make (e.g., learning to shoot a basketball) 2. Receives information from: a. Motor: upper motor neurons (pre-central gyrus) (what you want to do) b. Sensory: from the body and sensory organs (what you're actually doing) 3. Fine-tunes movement (precision, coordination, and timing of voluntary movements) -*The cerebellum compares what you want to do with what you're actually doing (comparator function)*, and sends information to the frontal lobe to adjust motor output so that what you're actually doing more closely matches what you're trying to do (e.g., makes your basketball shot closer).

Brain Directionality

Rostral: anterior (nose) Caudal: posterior (tail) Dorsal: superior Ventral: inferior Contralateral: opposite side of body Ipsilateral: same side of body

Difference between SI and SII parts of cortex?

S1 cortex receives localized, sharp, fast pain axons. SII cortex receives dull, slow pain, and arousal signals from interlaminar nuclei (crescent moon above VPM) or posterior nucleus. These signals travelled via the AL pathway.

After synapsing in thalamus, where do dull aching pain and arousal AL pathways travel?

SII cortex

Treatment of Intractable Seizures (those that are not controlled with treatment)

Sectioning of the corpus callosum and anterior commissure. The surgery prevents the propagation of the seizure from one hemisphere to the other and usually reduces the frequency and severity of seizures. *Visual information from the right occipital lobe (left visual field) normally gets to left Broca's via the corpus callosum.* Without the splenium (posterior end of the corpus callosum), patients are: 1. Unable to name objects placed in their left hands, though they can identify them in other ways indicating recognition. 2. Unable to read words flashed into the left visual field. 3. Unable to carry out movements of the left hand on verbal command but may carry these out spontaneously (this is a form of apraxia, the inability to perform a previously learned act on command). There is some evidence that the two hemispheres can function relatively independently, as illustrated in the following anecdotes: 1. One patient's left hand would unbutton his shirt as his right "voluntarily" buttoned it. 2. Another patient's left hand attempted to strangle his wife as the right hand struggled to control it

Somatotropy in S1

See right side of image for sensory somatotropy. Visualize a skiier doing a flip with his head down and feet in the air. After the discontinuity, the face is upright and goes down to the intra-abdominal region. Multiple Maps: each area of primary somatosensory cortex (3a,3b,1,2) has a separate somatotropin map; each also specializes in certain sub modalities (cutaneous, deep receptors) Somatotropy is plastic: mapping of body onto cortex can be altered by sensory experience or periphery damage (e.g., phantom hand sensations on face following amputation)

Sensitizstion of Pain

Sensitization can occur when stimuli are repeated. *Repeated stimuli increases activity (AP signals) dramatically as the receptor is sensitized.* This is unique for pain and unlike most other sensory systems, which are habituated, reducing in responsiveness over time to repeated signal.

Central fissure

Separates the frontal lobe (somatic motor) from the parietal lobe (somatic sensory). Other names: -Central sulcus -Rolandic fissure

Lateral fissure

Separates the temporal lobe (audition) from the frontal (somatic motor) and parietal (somatic sensory) lobes. Other names: -Lateral sulcus -Sylvian fissure

Purkinje Shift (at night)

Shift from cone to rod light sensitivity (light to dark) causes shift from sensitivity to *red light to* sensitivity to *blue light*. *In dim light, shorter wavelength light (blue) appears brighter than long wavelength light (red).*

Shingles (radiculopathy)

Shingles is a viral disease characterized by a painful skin rash with blisters in a localized area (typically a single, wide stripe either on the left or right of the body or face). Shingles is due to a reactivation of varicella zoster virus (VZV) within a person's body. The disease chickenpox is caused by the initial infection with VZV. Once chickenpox has resolved, the virus may remain inactive in nerve cells. *When it reactivates, it travels from the nerve body to the endings in the skin, producing blisters (affects particular dermatomes).*

Demyelination (Axonal Pathology)

Slows and then blocks conduction (if more than 3 nodes lack myelin sheaths between them). In axons lacking myelin, there can be failure of an AP to reach the synaptic terminal as the signal is diminished in time and space. Demyelination also causes cross-talk between demyelinated axons (as they are no longer isolated); this can cause ectopic APs. Adjacent axons can also conduct APs in both directions from the demyelination site.

GABAaR function can be reduced by...

Small AA changes (even just 1) can leave a GABA-gated Cl- channel insensitive to particular drugs, preventing IPSPs. This shows great specificity in GABAaR binding of drugs and GABA itself (with mutations in GABAaR eliminating dose-dependent drug responses). Mutant receptors can be drug-insensitive.

Sound

Small, periodic audible fluctuations in air pressure (compressed air vs. rarefied air).

Smooth Pursuit

Smooth eye movements for *following moving target*

*Alexia with Agraphia* Alexia: *Cannot read* a written language Agraphia: *Cannot write* in a language

Speech is intact, but deficit is in translating written visual material into spoken language (alexia) or language into writing (agraphia). Usually lesion in *angular gyrus*.

AL Decussates at....

Spinal Cord through anterior white commissure to AL System

AL First synapses at...

Spinal cord in Substantia Gelatinosa (after this synapse, axons decussate through the anterior white commissure before reaching the AL system to ascend).

DCML decussates at...

Spino-Medullary Junction (after synapse in dorsal column, internal arcuate fibers travel to decussation site before traveling up medial lemniscus) Medial Lemniscus (shaped like a triangle in medulla during decussation located ventral to CSF). Dorsal: Arm; Ventral: Leg.

*Acute Cerebellar* Disequilibrium

Stroke, hemorrhage, or *mass* causing: -Gait ataxia -Truncal ataxia

Subacute to Chronic *Proprioceptive Disequilibrium*

Subacute myelopathy due to *B12 deficiency causes chronic trouble with proprioception*. A *Romberg Test* can check for proprioception (2/3: vision, DCML, cerebellum).

Basal Ganglia -A complex circuit that aids in communication between the cortex, thalamus, and basal ganglia

Subcortical nuclei centers that play a role in *movement and coordination* (modulate voluntary motor control). Also involved in learning, eye movement, and cognition. Telencephalic Components: 1. Caudate: cognition 2. Putamen: motor control 3. Globus pallidus Di/Mes-encephalic Components: 1. Subthalamus (di) 2. Substantia nigra (mes)

Where does AL pathway synapse in spinal cord?

Substantia gelatinosa (of spinal column gray matter)

Fast eye movements controlled by ...

Superior colliculus Reticular formation (PPRF) The superior colliculus of the midbrain is involved in reflex orientation to novel stimuli. Electrical stimulation elicits saccades. The superior colliculus projects to the paramedian pontine reticular formation (PPRF) to control horizontal movements and to the rostral midbrain for vertical movements.

Great Radiculomedullary Artery (Adamkiewicz)

Supplies: T8-conus medullaris (L2) Location: radiculomedullary artery of T9-T12 Most strokes occur here because this artery supplies ALL of the lower thoracic and lumbar region (lower cord). There is not much collateral supply for this aortic corollary artery. Strokes can be caused by AAA, dissection, or surgical repair.

Olivocochlear System

System of efferent fibers to the cochlea (from the superior olivary cortex), which terminate principally on *outer hair cells and inhibit them* through a cholinergic mechanism. This serves to *block low-intensity masking sounds and unmask sounds of higher intensity*. This adjusts the sensitivity of the cochlea to filter out sounds of our own voice and chewing.

Taste Receptor Cells

Taste receptor cells are in taste buds (in circumvallate, foliate, and fungiform papillae). There are 2000-5000 taste buds per human tongue (50-150 taste cells per taste bud + basal cells that provide support and are the source of new taste receptors).

Rinne's Test

Tests for unilateral conductive hearing loss by comparing a *tuning fork held in the air vs. against the mastoid bone (sensorineural)*. Normally the air conduction pathway is more sensitive than the bone conduction pathway (due to the high gain tympanic membrane-ossicle chain acoustic amplifier). However, if it's louder from bone conduction, then there's a conductive hearing problem on that side (e.g., wax impaction, ruptured eardrum, etc.)

Limbic System

The "old brain" network crucial for emotion, motivation, and memory. Telencephalic Components: 1. Amygdala (walnut): emotions (fear/anxiety) 2. Hippocampus (seahorse): memory 3. Fornix (arch) 4. Hypothalamus: HAM BEETSS 5. Thalamus (posterior parts) 6. Cingulate gyrus

Diencephalon (thalamic nuclei)

The "tween" brain that bridges the brainstem and cerebrum. Components: 1. *Thalamus:* gateway to cortex -Filters and relays sensory input (*except olfaction*) moving toward the cerebrum -Modulates consciousness and awareness -Lateral geniculate nucleus (LGN): vision (input from the retina to the optic cortex; L=Looking) -Medial geniculate nucleus (MGN): audition (sends input from inferior colliculus to primary auditory cortex; M=Music) -Ventral posterior (VP) nucleus: somatic sensation (can be medial or lateral) 2. *Hypothalamus:* neuroendocrine and autonomic control -Mnemonic: *HAM BEETSS*: Hunger, ANS, Memory, Behavior, Endocrine, Emotion, Temperature, Sleep-Wake Cycle, Sexual Urges 3. *Posterior pituitary:* derived from neuroectoderm, extensions from the hypothalamus -Secretes ADH (water retention) and oxytocin (lactation and uterine contraction) formed in hypothalamus -Can be reached via a *transphenoidal* approach through the nasal cavity and sphenoid sinus to *remove a pituitary tumor* 4. *Epithalamus:* dorsal diencephalon -Pineal gland (secretes melatonin at night to regulate circadian rhythms) -Habenular nucleus (modulates visceral/emotional responses to odors; involved in sleep and reward processing) 5. *Subthalamus* (subthalmic nuclei of basal ganglia)

Cerebellar Sectors

The 2 cerebellar hemispheres are joined at the *vermis* (midline ridge). 3 Cerebellar Lobes: 1. Anterior Lobe (superior) 2. Posterior Lobe (inferior) 3. Flocculo-Nodular Lobe (under vermis, adjacent to the 4th ventricle and brainstem): responsible for balance and eye movement

Eustachean Tube

The Eustachean tube connects the middle ear to the outside via the nasopharynx, and serves to *equalize air pressure on both sides of the tympanum* (via salpingopharyngeus m.), permitting it to vibrate normally. The connection to the pharynx also permits fluids generated in the middle ear to drain away, but provides an avenue for infections to reach the middle ear.

How does lens change shape?

The circular muscle fibers within the ciliary body form a sphincter around the lens and are connected to it by zonule fibers. When ciliary muscles contract, the diameter of the ring of attachment of the zone fibers decreases, and the tension on the fibers is relieved. *The causes the lens to become more round and reduce focal length.* Innervation: Parasympathetic (cholinergic innervation); signal from E-W Nucleus via CN III with a synapse in the ciliary ganglion

Vitreous Hemorrhage

The extravasation (leakage) of blood into the areas in and around the vitreous humor of the eye. The vitreous humor is the clear gel that fills the space between the lens and the retina of the eye. *Diabetic Retinopathy:* Abnormal blood vessels can form in the back of the eye of a person with diabetes (neovascularization). These new blood vessels are weaker and prone to breakage, causing hemorrhage. Deposits of lipids from leaky vessels can also be seen.

Uvea

The fibrovascular pigmented layer of the eye, lying beneath the sclera and cornea, and comprising the iris, choroid, and ciliary body.

Long-Lasting Analgesia

The gate control mechanism can also be activated from supraspinal structures. *Electronic stimulation of PAG (midbrain), PVG (pons), or Raphe Nucleus (medulla) inhibits nociceptive neurons in the lumbosacral cord.* Naloxone (an opioid antagonist) blocks the effects of such electrical stimulation of PVG, PAG. *Pain Inhibition Pathway:* 1. Stimulate periaquductual gray (PAG, midbrain) and periventricular gray (PVG, pons) electrically. 2. Neuronal projections synapse in and activate raphé nuclei (serotonin) of the medulla. 3. Descending fibers from the raphé nuclei travel via the DC fasciculi to the dorsal horn of the spinal cord, where they activate inhibitory gate-keeping interneurons, reducing pain. This "inhibitory" pathway uses *serotonin* (located in Raphe nucleus of the brainstem) and *GABA* (found in the nucleus accumbens).

The Lens

The lens begins as a vesicle of surface ectoderm. Anterior vesicle: lens epithelium Posterior vesicle: transparent lens fibers (aculeate) *Avascular:* receives nutrients from aqueous humor The lens is surrounded by a transparent capsule that attach to *zonule fibers that suspend the lens from the ciliary processes*, centering it on the pupillary aperture where it focuses light rays on the retina. Transparency of the lens depends on water soluble proteins called *crystallins,* which at high concentrations cancel laterally scattered light (similar to collagen/mucins in the cornea that remain dry via active transport of ions). Any deterioration of the lens fibers (e.g., by injury, infection, radiation, or metabolic diseases such as diabetes) can cause *opacifications called cataracts*. Treatment: replacement of the lens with a plastic lens.

Arterial Supply of the Visual Pathways

The main blood supply of the eye is from the *ophthalmic artery*, the first intracranial branch of the internal carotid. The optic chiasm, optic tract and lateral geniculate nucleus (thalamus) rarely infarct because they are supplied by branches of both the anterior (carotid) and posterior (vertebro-basilar) circulations. The *optic radiation passes in succession through the perfusion zones of the middle cerebral artery and the posterior cerebral artery and is a frequent site of infarction due to arterial occlusion. Because the fibers of the radiation are spread out in a relatively large fan, infarcts are often associated with defects restricted to a quadrant.* Most of the striate cortex is supplied by the posterior cerebral artery, but anastomoses with middle cerebral branches at the occipital pole may account for some cases of macular sparing.

Medulla Oblongata Origin: Myelencephalon -Survival functions!

The medulla contains nuclei that control *cardiac, respiratory, and vasomotor function, and reflex centers* that control coughing, sneezing, swallowing, gagging, and vomiting. Within the medulla the baroreceptor reflex is integrated, keeping our blood pressure relatively constant. *Injury of the medulla is typically fatal, because of the important survival functions it performs.*

*Motor Processing Pathway:* (frontal lobe) 1. Pre-frontal cortex 2. Frontal association area (motor programming) 3. Pre-central gyrus (upper motor neurons) 4. Descending motor control

The most anterior region of the frontal lobe (pre-frontal cortex) is involved in: -Personality -Motivation -Forethought -Judgment After decisions are made there, that information is sent to the *frontal association area*, where movements are *planned and refined* (motor programming). Information from the frontal association area then passes to the most posterior region of the frontal lobe, the primary motor cortex (*pre-central gyrus*). Upper motor neurons form descending nerve tracts that travel down the spinal cord and synapse with lower motor neurons in the *ventral horn of the grey matter* of the spinal cord (motor). The axons of these lower motor neurons travel out of the spinal cord (through the ventral root), and join with sensory neurons of the dorsal root to form spinal nerves.

Benign Paroxysmal Positional Vertigo (BPPV)

The most common cause of vertigo in adults. Episodic vertigo *acutely triggered by movement* then windup and then improvement. Patients *feel worse lying on affected side*, better when still. Test: *Dix-Hallpike* Maneuver (lay patient down, move ears to each side and look to see if nystagmus occurs when the offending ear is down) Cause: *Otolithic debris in semicircular canals* stimulates hair cells (especially in the posterior canal) (can occur more frequently in elders as utricle degenerates) Treatment: *Epley Maneuver*: roll the otoliths off of hair cells

Compressive Optic Neuropathy

The optic nerve can be compressed by a mass or enlarged extra-ocular muscle (EOM). Enlarged EOM can result from thyroid eye disease.

Stereognosis

The parietal cortex posterior to S1 integrates the several types of somatic sensory information available to the cortex and constructs 3D percepts from skin and joint-position information

Visual Field

The part of space that is imaged on the retina. Because of the inversion of the retinal image by the eye's optics, the nasal field is imaged on the temporal retina and the temporal field on the nasal retina. Similarly, the superior visual field (above the fixation point) is imaged on the inferior part of the retina and the inferior field on the superior part. The *optic disc* (where the retinal axons enter the optic nerve) lies in the nasal retina and, because the retina is discontinuous here, it *causes a blind spot* in the temporal visual field. At the extreme periphery of the visual field there is a zone seen only by the eye on that side (monocular vision), i.e. by the nasal retina of the ipsilateral eye. O.D. (oculus dexter = right eye) O.S. (oculus sinister = left eye)

Retina Anatomy

The photoreceptors are in intimate contact with the pigment epithelium and are dependent on the choroidal circulation for oxygen and nutrients, whereas the cells of the inner retinal layers are fed by the branches of the central retinal artery.

Slow eye movements controlled by...

The pontine nuclei (*vestibular*) play a major role in smooth pursuit, receiving input from cortical areas and projecting to the *cerebellum*. Following cerebellectomy, there is a total loss of smooth pursuit. The cerebellar region most clearly involved is the flocculus, where electrical stimulation elicits smooth conjugate movements (responsible for balance and eye movement).

Purpose of the Tympanic Membrane and Ossicles

The principal function of the tympanic membrane and ossicular chain is to couple the acoustic energy from the air to the endolymph in the cochlear duct. *Impedance Matching:* large amplitude, low energy sound waves in *air* are transformed into smaller amplitude, higher energy waves in the *fluid* of the inner ear by: 1. Tympanic membrane area is 30x larger than stapes footplate (at the oval window entrance to cochlea) 2. Leverage action between the malleus and incus, reducing stapes movement (mechanical advantage) 3. Movements are minuscule (ossicles move only a few nm at threshold). This allows air energy to affect endolymph (fluid within the cochlea).

Direction of nystagmus is named for...

The quick phase because it is the most visible. *Quick phase is towards the direction of movement of the head.* When moving the head to the right, your eyes look left to maintain gaze. If you keep moving to the right, your eyes will eventually jump to the right (quick phase reset) and then maintain gaze again (slow phase).

Receptive Field

The region of stimulus space (e.g., on skin) within which stimulation can activate a single axon or neuron. Areas that need to discriminate fine touch (finger tips) have Merkel's disks/Meisner's corpuscles (small receptive fields; shallow). Deep receptors (like Pacinian corpuscles) cover larger receptive fields. Receptor fields can overlap and primary sensory neurons can also activate the same secondary neuron (sometimes two might be needed to activate the next neuron in the sensory pathway).

Retina Embryology

The retina and pigment epithelium develop from the optic vesicle, an out-pouching of the neural tube in the region of the diencephalon. The layer of the optic vesicle next to the surface ectoderm moves inward to form the inner layer of the optic cup and eventually the retina itself. Thus, the retina is a bit of brain, banished to the periphery, that also gives rise to the sphincter pupillae, the dilator pupillae, and the epithelia of the iris and ciliary body. Axons of the optic nerve (CN II) are thus part of the CNS.

Different vestibular CNS connections have different functions and dysfunctions

The sensory receptors in the otolith organs and semicircular canals are innervated by distal processes of cells located in Scarpa's ganglion (ganglion of CN VIII) that send axons into the vestibular nucleus. 1. *Posture and Locomotion* *Purpose:* Allows for adjustment of the somatic motor system to linear and angular accelerations of the body and head. *Projections:* vestibular nucleus to lateral vestibulospinal tract, reticulospinal system (via reticular formation), cerebellum *Dysfunctions:* disequilibrium, falling (motor neurons and *cerebellum* affected) 2. *Gaze Stabilization* *Purpose:* Stabilization of the direction of gaze during head movements is accomplished by projections from the vestibular nuclei and the oculomotor system that produce a rotation of the eyes that is equal and opposite to that of the head (the Vestibulo-Ocular Reflex = VOR). *Projections:* Medial Longitudinal Fasciculus (connects to oculomotor nuclei III, IV, VI) *Dysfunctions:* nystagmus (eyes make repetitive, uncontrolled movements) 3. *Position Sense* *Purpose:* These cortical projections are involved in our conscious sense of orientation in space. *Projections:* vestibular nucleus to thalamus to cortex: parietal lobe (relationship of the body to extracorporeal space), temporal lobe (auditory), S1 (area 3a) *Dysfunctions:* Vertigo (dizziness)

Somatotrophy

The somatic periphery is mapped onto the CNS (pre- and post-central gyrus) via homunculus. In practice: two points on the back must be sufficiently far apart to activate a different region of the cortex (which has little space dedicated to sensation from the back).

Stroke

The sudden onset of local neurologic deficit (e.g., weakness, inability to speak or to understand language) from a vascular cause such as a vessel occlusion (80%) or hemorrhage (20%). Stroke is the 3rd leading caused of death in the US.

Monroe Kellie Doctrine x-axis: change in volume y-axis: change in pressure

The total volume of the intracranial contents must remain constant because the cranial vault is a rigid, fixed space. An increase in one volume leads to a compensatory decrease in another. The brain can accommodate 30% additional volume → any more leads to death. When ventricles and blood vessels are already collapsed, smaller increases in volume increase ICP more exponentially .

Neurointerventional Radiology

Therapeutic intervention via microcatheter. Treatment of Acute Stroke: -Mechanical thrombectomy (stenth-retriever) -Mechanical thrombolysis (tPA) -Angioplasty Treatment of Cerebral Aneurysm: -Endovascular coils placed in aneurysm (thin wall outpouch) prevent blood from entering (BP could rupture aneurysm) and induces thrombus formation

Headache

There are no pain receptors (nociceptors) in the brain parenchyma itself. Headache is caused by *innervation of blood vessels, meninges (dura), scalp, and skull*. CN V1 innervates supratentorial dura (most of the cranial cavity). CN X (also CN IX and C1,2,3) innervate the more posterior dura. *Migraine (vascular headache)*: dilation of the cranial vessels triggered by various processes. Treatment: serotonin receptor agonist (serotonin helps stop pain signaling)

*DCML Pathway* Aα, Aβ, and Aδ fibers Sensory pathway of the CNS that conveys: -Fine Touch -Pressure -Vibration -Proprioception (position sense) -2 point discrimination Pathway: 1. Sensory afferent axons enter the spinal cord via dorsal roots. 2. Sensory afferents then branch, send some collaterals to several segments above and below entry level for reflex arcs (in dorsal horns) and most axons into the dorsal columns 3. Decussation takes place in the medulla after first synapse in gracile (middle thoracic and legs) and cuneate (arms) fasciculi -Synapses again in thalamus before synapsing in cerebral cortex (post-central gyrus)

There are three neurons involved in the pathway: first-order neurons, second-order neurons, and third-order neurons. 1. First-order neurons: reside in dorsal root ganglia and send their axons through the gracile fasciculus and cuneate fasciculus. 2. The first-order axons make contact with second order neurons at the gracile and cuneate nuclei in the lower medulla. 3. The second-order neurons decussate and send their axons to the thalamus. The third order neurons arise from thalamus and send fibers to the postcentral gyrus. The posterior column is composed of gracile fasciculus and cuneate fasciculus. The gracile fasciculus carries input from the lower half of the body (T7 and below) and the cuneate fasciculus carries input from the upper half of the body (C2-T6). The gracile fasciculus arise from the fibers more medial than the cuneate fasciculus. When the axons of second-order neurons of the DCML *decussate in the medulla*, they are called *internal arcuate fibers*. The crossings of the internal arcuate fibers form the medial lemniscus.

Romberg's Test (proprioception) -Tests for sensory ataxia (people require vision for balance)

This is a clinical test probing the integrity of the DC-ML system (which monitors conscious position sense, proprioception). To maintain balance, we need 2/3 of the following: 1. Visual confirmation of position 2. Non-visual confirmation of position (DC-ML proprioception and vestibular system) 3. Normally functioning cerebellum A person with disease affecting the DC-ML system has great difficulty telling the location of the affected limbs. They rely on their vision when walking and, if blindfolded or in the dark, their walking is uncoordinated and unsteady. This is called *sensory ataxia*. The loss of position sense upon closing the eyes is called a positive Romberg sign; it is a sign of the loss of conscious proprioception resulting from dorsal column dysfunction. Ordinarily, loss of proprioception can be overcome by vision; when this is blocked, the deficit is revealed. If the patient keeps their balance when their eyes are open, there is most likely a cerebellar problem.

Corticocortical axon trajectories

Through the corpus callosum and subcortical white matter (to the same or opposite hemisphere of the cerebral cortex)

Myelin Advantages: 1. *Speed*: conduction velocity of a 10um diameter axon with myelin ≈ 500um axon without myelin) 2. *Space*: the space occupied by one 500um axon is about equal to that of 2500 axons of 10um diameter 3. *Economy*: metabolic cost of axons is greatly reduced

Tightly wrapped spirals of *glial membrane* around the axon that ensure current travels down an axon by increasing distance between intra- and extra-cellular fluid, speeding up conduction velocity. CNS: produced by oligodendrycytes (which myelinate multiple axons) PNS: produced by Schwann cells (which myelinate a single axon) In unmyelinated axons, APs are continuous. In myelinated axons, APs are saltatory.

Blink/Corneal Reflex

Touching one cornea normally causes both eyes to close reflexively. The afferent limb of the reflex is the trigeminal nerve whose sensory axons terminate in the *main sensory and spinal nuclei of V*. These nuclei send a projection to the motor neurons of the *facial nuclei (CN VII) on both sides* (via reticular formation), which innervate the *orbicularis oculi m.*, which *closes the eye*. This reflex can be used clinically to test intactness of cranial nerves V (pain) and VII (close eye) as well as the brainstem circuits connecting the central nuclei of the two nerves.

Adduction

Towards nose

Lesion in cortex (*not midbrain*) will usually cause eyes to move ...

Towards side of lesion (*tonic deviation*). Remember: *Look at the lesion.*

Cerebellar Peduncles

Trio of white matter tracts that allows the *cerebellum to communicate with other parts of the brain (brainstem)*. 1. *Superior:* outputs signals *from* the cerebellum to the midbrain and thalamus 2. *Middle:* inputs signals *to* the cerebellum from the pons 3. *Inferior:* inputs signals *to* cerebellum from medulla and spinal cord

T/F: Auditory information in conveyed to both hemispheres

True

Weber's Test

Tuning fork on forehead to test for unilateral deafness. Normal patients hear equal loudness in both ears. 1. In an affected patient, if the defective ear hears the tuning fork louder, the finding indicates a conductive hearing loss in the defective ear (e.g., stuffed up ear). 2. In an affected patient, if the normal ear hears the tuning fork sound better, there is sensorineural hearing loss on the other (defective) ear.

Light does what to rods...

Turns 11-cis retinal into all-trans retinal (activating rhodopsin).

Thermal, Mechanical, and Polymodal nociceptors use which kinds of fibers?

Types of Nociceptors: Aδ and C fibers 1. *Thermal:* activated by extreme temperature (>45C; <5C) (Aδ fibers) 2. *Mechanical:* activated by intense pressure or tissue damage (Aδ fibers) 3. *Polymodal:* high-intensity mechanical, chemical (e.g., capsaicin), or thermal (C fibers) Other: 4. *Itch:* selectively sensitive to histamine (C fibers) *Discrimination of Painful Sensations:* the *touch and pressure receptors (Aα and Aβ) contribute to the specificity of pain sensations*. If these axons are blocked, then a pin prick, pinch, and ice are indistinguishable and produce burning pain sensation.

Cerebellar Infarct or Hemorrhage

Typically presents with acute (central) vertigo, along with other symptoms like *gait ataxia and ipsilateral ataxia* (fall *towards* the lesion). If not fixed by surgical intervention, hydrocephalus could lead to death.

Homonymous Hemianopia with Macular Sparing (near the fixation point)

Usually associated with a lesion of the optic pathway near the visual cortex (V1 of occipital lobe). Note: *when the visual field defects are on the same side (e.g., left or right in both eyes), the lesion is behind the chiasm*. The sparing of the macula area has been attributed to: 1. Poor mapping technique 2. Unstable fixation 3. Dual representation of the macula in the orbital cortex 4. *Survival of part of the expanded representation of the macula in the cortical map (the fovea has a large area of cortex devoted to it, so part could be spared by a tumor)* 5. *Dual blood supply* of the macular representation at the occipital pole (the extreme tips of the occipital poles, where the fovea is represented, may receive some *anastomotic arterial support* from the *middle cerebral artery/deep optic branch*) 6. A combination of these factors

Type of Lesion: Jaw Deviates Toward Lesion

V3 motor lesion (mastication: unopposed opposite pterygoid m.)

Type of Lesion: Droop of face on side of lesion

VII Lesion 1. Upper motor neuron (damage from eye down) 2. Lower motor neuron (entire side of face)

What do ototoxic antibiotics do?

Various ototoxic antibiotics can destroy the outer hair cells (at high enough concentrations), reducing the sensitivity of the organ of Corti and resulting in partial deafness. At lower concentrations, the antibiotics block K+ channels, especially for outer hair cells

Where do *arms and legs* DCML and AL pathways synapse in Thalamus then travel?

Ventral Posterolateral Nucleus (VPL) then S1 cortex. This lies more lateral to the VPM.

Where do *face* DCML and AL pathways synapse in Thalamus?

Ventral Posteromedial Nucleus (VPM) then S1 Cortex. This lies more medial to the VPL.

Sensory Nuclei

Vestibular (VIII) Cochlear (VIII) Trigeminal (V) Nucleus of Solitary Tract (VII, IX, X) VCTN

**Weakness vs. Numbness**

Weakness (CST = no motor) Numbness (DC-ML = no vibration or touch)

GABAaR -Structurally similar to nicotinic ACh receptor -5 subunits to form a channel (2α, 2β, 1γ)

When GABA binds to GABAaR, it changes the conformation of the GABA-gated Cl- channel (allowing Cl- influx). Cl- ions think they they are hydrated and are transported across the membrane through an aqueous pore. This Cl- influx maintains a negative polarization (inhibitory) of the post-synaptic neuron (IPSP).

Nernst Potential E(Na+) = +61 mV Meaning: 1. Restates the equilibrium potential in electrical terms 2. Concentration at which there is no net movement of Na+ (equilibrium) 3. Where Vm is drawn toward when Na+ ions are open

When the membrane is in thermodynamic equilibrium (i.e., no net flux of ions), the membrane potential (Vm) must be equal to the Nernst potential. However, in physiology, due to active ion pumps, the inside and outside of a cell are not in equilibrium. In this case, the resting potential can be determined from the GHK equation (which takes into account more than one ion). *The potential across the cell membrane that exactly opposes net diffusion of a particular ion through the membrane is called the Nernst potential for that ion.* The magnitude of the Nernst potential is determined by the ratio of the concentrations of that specific ion on the two sides of the membrane. The greater this ratio, the greater the tendency for the ion to diffuse in one direction, and therefore the greater the Nernst potential required to prevent the diffusion.

Motor Cranial Nuclei Locations (Overview)

When thinking about these nuclei, track the path the efferent neurons (CN) take (thinking about their brainstem exits). *Midbrain* Visceromotor: EW Somatomotor: III (superior colliculus), IV (inferior colliculus) *Pons (caudal)* Branchiomotor: motor V *Pontomedullary Junction* Somatomotor: VI Visceromotor: salivatory (CN VII, IX) Branchiomotor: VII *Medulla* Somatomotor: XII Visceromotor: dorsal motor nucleus of X Branchiomotor: ambiguus (CN IX-XI)

Type of Lesion: Uvula deviates away from side of lesion (due to intact palatal muscle pull)

X Lesion

Type of Lesion: Weakness turning head to contralateral side of lesion (SCM) and Shoulder droop on ipsilateral side of lesion (trapezius)

XI Lesion

Type of Lesion: Tongue deviates toward side of lesion

XII Lesion (lick your wound) -Due to weakened tongue muscles on the affected side

Are olfactory receptor cells true neurons?

YES. The *olfactory epithelium contains receptor neurons*, other important cells (supporting cells, basal cells), and a layer of mucus that includes immunoglobulins and catabolic enzymes that dissolve olfactants to act on the receptor cilia of olfactory receptor cells (primary neurons that send signals to the olfactory bulb). *Cilia help by greatly increasing the surface area available for detecting odorant molecules.*

Parietal Lobe Defect

• *Superior fibers* predominate in the parietal lobe • Defects cause *homonymous hemianopia denser inferiorly* • Most common etiology is stroke (or parietal lobe tumor)

Occipital Lobe Defect

• Macular fibers project to primary visual cortex (V1) and occipital tip • *Stroke involving the posterior cerebral artery (PCA) spares the occipital tip and macular field* • Hypoperfusion affects tip and results in homonymous paracentral scotoma (abnormal blindness)

Temporal Lobe Defect

• Meyer's Loop is a bowing of *inferior fibers* into the temporal lobe (superior visual field) • *Temporal lobe lesions cause homonymous superior quadrant visual field defects (pie in the sky)* • Associated with temporal lobe seizures • Most common etiology is tumor

Which artery? Stroke affecting lower limbs (think about homunculus on cerebral hemisphere)

ACA Stroke. Medial portion of brain.

Glutamate (AA)

*Excitatory in CNS* -More permeable in infants (blood-brain barrier) -Involved in cognition functions (learning and memory) in the hippocampus

CNS vs. PNS

CNS: 1. Brain 2. Brainstem 3. Spinal Cord PNS: 1. Cranial nerves (nerves that exit through the skull) 2. Spinal nerves (nerves that exit through the spine)

Mechanism: Glutamate → GABA

Decarboxylation of glutamic acid by glutamic acid decarboxylase (GAD). Glutamate: *excitatory* neurotransmitter in the brain GABA: *inhibitory* neurotransmitter in the brain

Nuclei

Neuronal cell bodies located in grey matter regions deep in the brain

Strokes in the pons most likely result from which artery?

Perforating branches of the *basilar a.*