PHTY 508: Neuro Exam 3

Corona Radiata

Fibers of the IC flare out into the hemisphere as they pass distal to the caudate and putamen - Abrupt divergence forms the corona radiata Contains converging corticofugal fibers and diverging corticopetal fibers

Hypothalamus Role in Controlling the Internal Environment

Four Mechanisms 1. Principle modulator of ANS function 2. Viscerosensory transducer - Contains neurons w/specialized receptors capable of responding to △s in temperature, osmolality of blood, and specific hormonal levels in general circulation 3. Regulates the activity of the anterior pituitary through the production of releasing factors - Hormone-releasing hormones 4. Produces and releases oxytocin and vasopressin (neurohormones) into the general circulation - W/in the posterior pituitary - Endocrine function - △ water intake, etc.

Sensory Functions of PPAC

"Higher order processing" 1. Integration of sensory information - Visual, auditory, tactile, vestibular, somatosensory systems - Formation of perceptions - Interpretation and use of sensory info 2. Attention to the spatial aspects of sensation **Also has motor functions (different card)

Motor Neurons

"LMN" = old term Spinal Cord - Predominantly in LIX we have α and γ motor neurons Brainstem Cranial nerve motor nuclei in... - Abducens - Trochlear - Oculomotor - Hypoglossal - Trigeminal motor - Facial motor - Nucleus ambiguus - Spinal accessory

Mesencephalic Nucleus of V

**Green in picture Proprioception from muscles of mastication - Peripheral process heading out to jaw - Central processes mostly go to principal nucleus, some to motor nucleus, some to cerebellum, some to RF Unique because... - Pseudounipolar neurons within CNS - Pseudounipolar neurons receive synaptic input (other neurons can give input)

Motor Related Interneurons

**One of the reasons why LMN is an inaccurate term Much descending input goes to interneurons - Interneurons often interposed between descending axon and alpha/gamma MN - So it's not a 1-2 relationship (innervating alpha motor neuron directly) like we used to think with UMN and LMN Coordinated function motor units/muscles MN Pools - Distal/proximal - Flexor/extensor

Muscle and Tendon Receptors

- FNE - Ruffini's endings - Pacinian corpuscles - Golgi Tendon Organs (GTO) - Muscle spindles

Merkel Endings (SA-I)

- Unencapsulated - Touch: light pressure - Merkel cell + Aβ nerve terminal - Deep Epidermis - Most in glabrous skin (non-hairy): highest concentration fingertips - Slowly adapting - Small receptive field - Detection of form, texture, points and edges

Function of Reticulospinal Tracts

1. Control & modulate motor activity - Influence MN's of paravertebral mm's and limb extensors - Involved in providing background for primary movements: posture (e.g., stabilize scapula and spine for UE mov't) and balance - Alter γ-MN activity (alter muscle spindle sensitivity); modulate muscle tone and maintain posture 2. Modulation of sensory information, esp. noxious

What needs to occur in order to make voluntary, goal-directed movements?

1. Decision to move 2. Identification and localization of target 3. Knowledge of positions of limbs, body 4. Formation of plan of action 5. Execution of plan of action - Control of both proximal and distal segments **Generally don't do this consciously after the task is learned

Somatic Sensations

1. Haptic Exploration - Using tactile, and proprioceptive/kinesthetic exploration to determine characteristics of an object - keys in pocket - Needed to determine shape, size, texture, etc. - Grasp & Manipulation: grip force; joint angle 2. Environment - i.e. temperature 3. Balance - Cutaneous sensations from foot - Proprioception: joint receptors 4. Tissue Damage 5. General Arousal/ Well Being

PPAC Motor-Related Functions

1. Involved in the initiation of movement knowing what's going on around us 2. Manipulation of objects in space 3. Motor planning - Preparations for movements guided by visual and tactile information - Collect input from sensory systems (visual, auditory, somatosensory cx, vestibular) - Allows us to create 3D map of what's around us - Computation of limb/body trajectory Motor-related efferents: primarily to secondary motor areas

Posterior Horn Neurons

1. Low-Threshold - Non-nociceptive 2. Noxious, high-threshold - Nociceptive specific 3. Wide-dynamic range - Nociceptive and non-nociceptive

Chronic Pain Syndromes

1. Neuropathic Pain 2. Chronic Low Back Pain 3. Fibromyalgia 4. Myofascial Pain Syndrome 5. Trigger points / tender points of muscle 6. Chronic regional pain syndromes - May be sympathetically maintained **Possible role of inflammatory mediators resulting in development of changes in sensory processing in primary afferents or in CNS

What does the ability to localize a stimulus depend on?

1. Receptor Density - Inversely proportional to receptor field size 2. Receptor Field Size 3. Processing in CNS - Homunculus

Input to Motor Related Interneurons and (to Lesser Extent) Motor neurons

1. Sensory - Sensory-related interneurons 2. Descending pathways - Corticospinal - Vestibulospinal - Reticulospinal - Rubrospinal - Tectospinal **Terminate primarily on interneurons 3. Collaterals from motor neurons - To excite/inhibit other MNs - Agonists, antagonists Motor neurons summate - IPSPs or EPSPs

3 Dimensions of Pain

1. Sensory Discriminative Dimension - Refers to the sensation of pain and includes the location, quality (burning, dull, sharp), intensity, and duration 2. Motivational Affective Dimension - Refers to the unpleasantness of pain or how much it bothers one (e.g. nauseating) 3. Cognitive Evaluative Dimension - Examines one's pain in terms of past experiences and expectations - Therefore it can modify both of the above **These dimensions interact and will determine how one responds to the pain

Input to Alpha MNs

1. Sensory receptors 2. Cerebral cortex 3. Brainstem - Vestibular nuclei - Reticular formation - Red nucleus - Tectum (Superior colliculus) 4. Spinal cord interneurons - Including those of Central Pattern Generators

Cortical Interneurons/Local Circuit Neurons

1. Spiny (spiny stellate) cells 2. Aspiny stellate cells (granule cells) 3. Basket cells Major NT of most = GABA - Tends to be inhibitory Axons don't leave the cortex - Form circuits

Corticonuclear Tract Terminations

1. Trigeminal Motor - Muscles of mastication - Bilateral equally 2. Facial Nucleus - Muscles of facial expression - Upper face: bilateral input; so upper face innervated by both hemispheres - Lower face: only contralateral innervation - Upper face has redundancy 3. Nucleus Ambiguus - Larynx, pharynx, upper esophagus (bilateral inn) - Uvula , soft palate (mostly contralaterally inn) 4. Hypoglossal - Tongue: primarily contralateral to genioglossus 5. Spinal accessory - Trapezius, SCM - Primarily ipsilateral inn 6. Oculomotor, Trochlear, Abducens - From frontal and parietal eye fields (not facial motor cortex)

Motor Unit

A motor neuron and all of the muscle fibers it innervates - Fibers it innervates = muscle unit (all contract together)

Nociceptor

A sensory receptor that is capable of transducing and encoding a noxious stimulus High-threshold free nerve endings in glabrous and hairy skin as well as in deep tissues (e.g., joints and mm) - Widely distributed throughout body Several ways of classifying them

M1 vs. SMA

A: Random finger movements = M1 B: Planned and executed in specific order = M1 and SMA C: Movement planned but not executed = SMA

Functions of the Dorsal Thalamus

AKA Thalamus "Functional gateway" Main function: sensory relay - Process, integrate, and relay information related to: 1. Sensory system - VPM ⟶ to somatosensory cortex from trigem. tract - VPL ⟶ to somatosensory cortex from spinothal., DCML tracts - LGN ⟶ primary visual cortex from optic tract - MGN ⟶ primary auditory cortex from inferior brachium 2. Motor system - VA ⟶ to prefrontal cortex from globus pallidum **Supplementary motor area ⟶ supplementary motor area from globus pallidum - VL ⟶ to motor cortex from cerebellum 3. Limbic system **Pools of neurons from subcortical structures that project to the cerebral cortex **Receives and projects via thalamocortical fibers and reciprocally receives connections via corticothalamic fibers

Subthalamus

AKA Ventral Thalamus Subthalamic Nucleus - Rostral and posterior to substantia nigra and inferior to lenticular fasciculus - Receive input from motor areas of cortex - Project to the substantia nigra - Reciprocally connected w/globus pallidus

Hypoalgesia

Absence of p! in response to stimulation that would normally be painful

Thalamic Pain Syndrome

Affects ~8% of stroke pts due to loss of blood supply specifically to thalamus - Tends to be in older patients - Prognosis relates to severity of the lesion Involves... - Contralateral sensory loss - Astereognosis: inability to figure out what something is by feeling it - Progresses to burning, scalding, usually vague symptoms - Allodynia: feel pain from stimuli that don't normally cause pain - Dysaesthesia: spontaneous p! - Frequently only slight hemiplegia and ataxia (bc focused specifically on thalamus; corticospinal only goes through IC) - Delayed, gradual onset of p! symptoms

Visceral Pain

Almost exclusively sympathetic Aδ & C fibers - Carried on sympathetic nerves ⟶ white ramus ⟶ spinal nerves ⟶ DRG of T1 - L2 ⟶ lat div dorsal root ⟶ posterolateral tract of Lissauer Spinal Cord Terminations 1. Posterior horn: lamina I and V OR 2. Intermediate horn: lamina VII (intermediomedial nucleus) and VIII Visceral Reflexes - IMM ⟶ IML (preganglionic sympathetic neurons)

Noxious Stimulus

An actually or potentially tissue-damaging stimulus - Stimulus of sufficient magnitude to potentially damage tissue May be physical, chemical, or thermal If tissue injury occurs ⟶ release and/or activation of chemical mediators from tissue ⟶ attraction of inflammatory cells

Pain

An unpleasant sensory and emotional experience associated with actual or potential tissue damage Highly individual and subjective - There's no "painful stimuli" which invariably elicit the perception of p! in all individuals - Requires sensation and perception (affective component - suffering; not the same in everyone)

Limbic Relay Nuclei

Anterior nuclear group receives limbic projections from mammillary nuclei via mammillothalamic tract and the medial temporal lobe (hippocampus) via the fornix ⟶ cingulate gyrus through the anterior limb of the internal capsule Other Limbic Relay Nuclei: 1. Lateral thalamic nuclei ⟶ lateral dorsal nucleus 2. Medial thalamic nuclei ⟶ dorsomedial nucleus

Cingulate Gyrus and Motor Systems

Anterior region of cingulate gyrus At least in monkeys... - Small contribution to the corticospinal tract - Projections to M1 - Possible role in movements that have a motivational or emotional component

Lesion of Secondary Motor Areas

Apraxia - Difficulty appropriately using the limb during tasks despite ability to move limbs - Automatic vs. purposeful movements - Can't plan movement Decreased ability to coordinate bilateral movements

Facial Pain

Aδ and C fiber nociceptors are found throughout the face, the oral cavity, the dorsum of the head and the ear. - (dull toothache is an example of the C fiber activity) Cranial nerves (ganglia) - Trigeminal ganglion (CN V) - Geniculate ganglion (CN VII) - Superior ganglia of IX & X Central processes descend in spinal trigeminal tract (which extends from the caudal pons to the 2nd or 3rd cervical sc segment) ⟶ spinal trigeminal nucleus - Caudal portion = primarily pain and temperature - Pars interpolaris = pain in & around oral cavity Trigeminothalamic projections - Anterior Trigeminothalamic tract ⟶ contralateral VPM, some VPI

Pain: Aδ Fiber vs C Fibers

Aδ fiber nociceptive FNE - Fast pain - Sharp p! - Fast pricking p! - Localized - Glutamate usually NT C fiber nociceptive FNE - Slow pain - Burning p! - Dull ache - Itch - Substance P (neuropeptide) usually NT **Marked increase in sensitivity of both types partially as a result of liberation of histamine, prostaglandins, bradykinins during inflammation Ex: When you bang your thumb with a hammer, the initial sharp pain is carried by the Aδ fibers. Then the dull aching pain is carried by the SMALL DIAMETER, UNMYELINATED C fibers conducting more slowly at 0.5-2 m/s

Rostral Transmission of Visceral Pain

Bilateral spinothalamic tract ⟶ VPL ⟶ cerebral cortex OR Bilateral spinoreticular tract ⟶ RF ⟶ - Thalamus (intralaminar nuclei) ⟶ cortex - Hypothalamus - Brainstem visceral control centers Cortical terminations: inferolateral post-central gyrus

Primary Visual Area

Brodmann's area 17 of the occipital lobe - Calcarine sulcus and parts of surrounding lingual and cuneate gyri Thalamic afferents from the LGN Lesion Contralateral homonymous hemianopsia

Primary Somatosensory Area (SI)

Brodmann's area 3, 1, 2 - Somatotopically arranged (homunculus) Processes somatosensory info: - Discriminative touch - Position sense - Vibration - Discriminative aspects of p! (i.e., localization) Modality Specific Area 3b and 1 - Primarily cutaneous mechanoreceptors - Temperature - Some p! Area 3a and 2 - Cutaneous and deep receptors, including proprioceptors Major afferents Ascending sensory pathways ⟶ VPL and VPM ⟶ posterior limb of IC ⟶ SI - To a lesser extent other sensory areas and motor areas and other thalamic nuclei Major Intracortical Communications (Efferents) - Contralateral S1 - SII - Motor regions - PPAC

Primary Auditory Area

Brodmann's area 41 + 42 - Transverse temporal gyri (Heschl's gyri) Thalamic afferents from MGB Lesion - Difficulty in interpreting or localizing a sound, but not deafness

Posterior Parietal Association Cortex (PPAC)

Brodmann's area 5 and 7 - Superior parietal lobe Dominant hemisphere has stronger PPAC - Only attends to the opposite side's environment - Non-dominant hemisphere attends to both sides

Inferior Temporal Association Area

Brodmann's areas 20, 21, + 37 Higher order functions including... - Important in learning visual guided tasks and memory of these tasks - Visual memory - Visual discrimination: facial recognition

Inferior Parietal Lobule

Brodmann's areas 39 + 40 of the dominant hemisphere - Supramarginal and angular gyri Functions - Part of wernicke's area - Language processing - Understanding Lesion Cannot read or write - Receptive problem

Broca's Speech Area

Brodmann's areas 44 and 45 of the dominant hemisphere (L) - Inferior frontal gyrus (triangular and opercular regions) Function - Motor control for speech Lesion - Expressive aphasia: difficulty with speech and writing; can't get what they want to say out

Pacinian Corpuscle (FA II)

CT capsule - Concentric rings of cells - Small collagen fibers - Gelatinous material - Aβ nerve fiber Deep dermis and subcutaneous tissue, joints, viscera Rapidly adapting - Large receptive field High freq / rapid changes - Vibration - Pressure - Texture - Perception of distant events through object held in hand

Free Nerve Endings (FNE)

Can be... 1. Nociceptors 2. Thermoreceptors 3. Mechanoreceptors 4. Itch also likely activation of FNE - Chemoreceptors: poison ivy What they sense it based on: - Properties of terminal portion of distal process - What causes channels to open

Lateral (Surround) Inhibition

Capacity of an excited neuron to reduce the activity of its neighbors. Lateral inhibition disables the spreading of action potentials from excited neurons to neighboring neurons in the lateral direction - Enhance signal:noise ratio - Lateral surround inhibition - "Sharpens edges" or contrast

Primary Afferent Pain Pathway

Cell body located in DRG Most of the small afferent fibers (Aδ & C central processes) that carry responses to nociceptive thermal and mechanical stimuli & irritant chemicals enter the SC in the lateral division of the dorsal root Bifurcates and ascends and descends 1-3 segments or so in posterolateral tract of lissauer before terminating in dorsal horn (below) Terminations 1. Lamina I: posteromarginal nucleus - Largest density of terminations - Predominant source of projection fibers in spinothalamic tract (but travel on all tracts of ALS to various places in brain) 2. Lamina II: substantia gelatinosa - Inhibit p! 3. Lamina V 4. Scattered in rest of posterior horn

Ruffini's Endings (SA-II)

Cellular connective tissue capsule - Gelatinous center & collagen fibers - Aβ nerve fiber Deep dermis and subcutaneous tissue especially: - Palms - At joint lines - Under fingernails Slowly adapting Large receptive field Tissue stretch Skin stretch ⟶ - Joint position (fingers and hand) - Detect object motion **Also found in joint tissues, bone

Motor Relay Nuclei

Cerebellum Uses the VL to send information ⟶ M1, premotor area (SMA) Information from ^^ is sent back to cerebellum via pontine nuclei ** Can receive information from spinal cord AND brainstem nuclei ** Can send info back to brainstem nuclei Basal Nuclei (Globus Pallidus and Substantia Nigra) Uses VA to send info ⟶ prefrontal cortex, frontal eye field Uses VL to send info ⟶ SMA, premotor area, and prefrontal area **Doesn't receive info from spinal cord

Transmission of Sensory Information

Cerebrum - Conscious awareness of sensation = perception - Used unconsciously for motor planning & control - Three neuron pathway Cerebellum - "Unconscious proprioception" - Used for motor planning and control - No relay or processing in thalamus - A "2 neuron pathway" from periphery to cerebellum Spinal cord/brain stem - Reflexes - Modulation of motor output - Modulation of sensory input **Modulation can occur at synapses

Interneurons: Central Pattern Generators

Circuits of interneurons Coordinated, multisegmental rhythmic cyclical motor activities (i.e. gait, breathing): basic rhythmic patterns - Stuff done without thinking Receive input from: 1. Supraspinal centers - For modulation to environmental conditions (ex. breathing deeper with higher altitudes) 2. Sensory receptors - Usually not necessary, but give feedback back to spinal cord (not conscious)

Brown-Séquard Syndrome

Complete hemisection damaged - Rare What's interrupted? all of the below 1. Sensory - FG/FC (depending on level of lesion - ALS - AWC - Dorsal Horn - Posterolateral tract of Lissauer 2. Motor - Lateral Corticospinal Tract - Ventral Horn - Spinocerebellar Pathways Symptoms * = Side of the Lesion 1. Lesion 2. Paralysis and loss of vibration, proprioception (position sense), and fine touch - Ipsilateral - Corticospinal tract already crossed - Posterior columns haven't crossed 3. Loss of p! and temperature sensation - Contralateral - ALS from left leg crossed at lower levels (below lesion) - Gap bc info could've gone up in posterior tract of lissauer and then crossed over above the lesion

Globus Pallidus

Component of the basal ganglia that connects to the thalamus which relays information to the motor areas and the prefrontal cortex - Doesn't get much, if any, information from the spinal cord (like the cerebellum does) so it's very important in planning automatic movement - Receives information from all over the cortex Separated from thalamus by posterior limb of IC

Medial Thalamic Nuclei

Comprises the dorsomedial nucleus Linked to the frontal and temporal lobes for motor planning

Meissner's Corpuscle (FA-I)

Connective tissue capsule - Epithelioid cells - Aβ fibers Dermal papillae of glabrous skin - Most numerous in fingertips Rapidly adapting Small receptive field Changes in pressure/sudden forces on skin - Form - Vibration - Motion detection (object slip): grip control

Internal Capsule

Contains axons passing between thalamus and the cerebral cortex - Thalamocortical (afferent) fibers - Corticothalamic fibers (efferent) Also contains cortical efferent fibers that project to the brainstem (corticorubral, corticoreticular, corticonuclear-corticobulbar) or spinal cord (corticospinal)

Lesion of S1

Contralateral hemianesthesia (for specific body region) 1. Loss/decreased discriminative sensation - Two-point discrimination - Texture discrimination - Astereognosis 2. Loss/decreased position and vibratory sense 3. Inability to localize painful stimuli

Symptoms of Loss of Blood Flow to the Thalamus and Internal Capsule

Contralateral hemiparesis combined with hemianesthesia (discriminative touch and p!) - Corticospinal tract going through posterior limb hasn't crossed yet - Damage to thalamocortical fibers in posterior limb If branches of the PCA, specifically the thalamogeniculate a (supply to thalamus), are disrupted ⟶ thalamic p! syndrome, total or dissociated sensory loss, or "pusher syndrome"

Reticular Formation

Control and modulate motor activities Modulate sensory information Motor related input from... - Cerebellum - Corticoreticular: motor regions of cerebral cortex - Collaterals sensory paths (vestibular, visual, auditory, somatic) - Spinoreticular tract (of ALS)

Central Processing of Sensory Information

Convergence - Decreased resolution - Increases receptive field size while decreasing resolution - So it doesn't overwhelm the system Divergence - Amplification of signal - Multiple CNS targets Inhibition and Facilitation - Next card lol

Descending Fiber Paths From Motor Areas

Cortico - spinal nuclear (bulbar) striate rubral reticular pontine Many of these pathways also have fibers originating in non-motor regions of the cortex

Cranial "Parasympathetic" GVA

Cranial Nerves that Carry Parasympathetic Info 1. Glossopharyngeal (CN IX) - Inferior ganglion 2. Vagus (CN X) - Inferior ganglion 3. Facial (CN VII) - Geniculate ganglion Central Processes - Head into Solitary Tract and terminate at Solitary Nuc. (intermediate & caudal) Solitary nucleus ⟶ activate dorsal vagal nucleus, nucleus ambiguus, anterolateral medulla, or RF Anterolateral medulla ⟶ reflex visceral responses RF ⟶ up to cerebral cortex and hypothalamus in widespread projection

Nociceptors Found Throughout Body

Cutaneous - Glabrous and hairy skin - Mechanical, heat, cold, polymodal Joints (Capsules, Ligs, Tendons) - P!: movement in excess of range, inflamed joints - Pressure directly over capsule Muscles - Pressure and ischemia Periosteum - Covering bone and medullary cavity - Not bone itself Visceral Organs - Polymodal - Disease or trauma - Hollow viscera: distention - Gradual onset and poor localization - May be referred to other location (e.g., skin)

Stretch Reflex

Deep tendon reflex Phasic (dynamic) component Stretch muscle ⟶ Ia afferent ⟶ alpha MN ⟶ contraction of homonymous and synergistic muscle Muscle Spindle Reflex Connections Type Ia Afferents 1. Monosynaptic EPSP - Homonymous muscle α MN - Synergistic muscle α MN 2. Multisynaptic IPSP (through interneurons) - α MN of antagonists Type II Afferents 1. Multisynaptic EPSP - Homonymous and synergist muscle α MN GTO Segmental α MN Connections/Reflexes Multisynaptic - EPSP to antagonist MN to prevent damaging amounts of tension developing in the muscle - IPSP to homonymous and syngergist MNs Clinically - Absent or weak: problem at segmental level - Hyperactive/Excessive: something going on with descending influence

Lateral Thalamic Nuclei

Divided into: Dorsal Tier: 1. Lateral dorsal nuclei ⟶ cingulate gyrus 2. Lateral posterior nuclei ⟶ parietal lobe 3. Pulvinar nucleus - Anterior, medial, and lateral divisions: project to areas of the temporal, parietal, and frontal lobes concerned with visual function and eye movements - Inferior division: receives input from the superior colliculus and projects to the visual association cortex Ventral Tier: 1. Ventral anterior (VA) and ventral lateral (VL) nuclei - Motor relay nuclei; planning movement - Contralateral cerebellar nuclei ⟶ VL ⟶ primary motor (M1), SMA, and premotor area: control, anticipate, and modify movement (specific) - Globus pallidus ⟶ VL ⟶ SMA, premotor area: planning automatic movement - Globus pallidus ⟶ VA ⟶ prefrontal cortex and frontal eye field: planning automatic movement 2. Ventral posterior nuclei (VPL, VPM, VPI) - Arranged somatotopically and by function: proprioceptive neurons are most anterior; tactile neurons are in mid-region; nociceptive neurons are most posterior **MGN and LGN considered parts of the lateral thalamic nuclear group

Dominant vs. Non-Dominant Hemisphere

Dominant hemisphere - Understanding and producing language - Mathematical and computational skills Non-dominant hemisphere - Aspects of attention to spatial details - Non-verbal aspects of language

Primary Afferent Neurons

Dorsal root ganglion - Pseudounipolar neurons - First order cell body Dorsal root entry zone - Lateral: small fibers; nociceptors, temp ⟶ synapse in dorsal horn ⟶ ALS - Medial: large fibers; touch, proprioception ⟶ FG/FC Some cranial nerves - Somatic: e.g. CN V in trigeminal ganglion - Visceral: e.g. X - Special: e.g. I Receptors translate stimulus to neural code 1. Opening of channels in response to stim 2. Graded receptor potential 3. Summation at trigger zone 4. If threshold ⟶ AP

Function of Primary Motor Area

Execution of specific well-defined motor responses Stimulation of individual cells or small groups of cells: - Simple and stereotypical movements - Discrete movement of individual muscles - Especially distal muscles; fine motor Populations of neurons code for force of contraction and movement direction Pyramidal cells in layer V - Source of projection fibers - Corticospinal tract

Posterior Limb of the Internal Capsule

Extends caudolateral from the genu and separates the (dorsal) thalamus from the globus pallidus Contains 1. Corticospinal Fibers - Motor cortex ⟶ contralateral spinal cord - Somatotopically arranged in the caudal 1/2 - UE ⟶ T ⟶ LE sup to inferior 2. Central Thalamic Radiations (thalamocortical-corticothalamic fibers) - Thalamic nuclei to cortex - VPL ⟶ premotor, somatosensory, and motor areas (trunk and limbs) - VPM ⟶ premotor, somatosensory, and somatomotor, and motor areas (head)

Anterior Limb of Internal Capsule

Extends rostrolateral from genu and is situated between the caudate and lenticular nuclei Contains: 1. Frontopontine fibers - Especially those from prefrontal areas - Descending fibers 2. Anterior thalamic radiations (thalamocortical + corticothalamic fibers) - Interconnect the dorsomedial and anterior thalamic nuclei ⟶ prefrontal cortex and cingulate gyrus

Tonsillar Herniation

Extrusion of the cerebellar tonsil through the foramen magnum Compresses medulla and upper cervical spinal cord Results in cardiac and respiratory dysfunction - Because the reticular formation is getting compressed - May have difficulty breathing, HR dysfunction - No CN to impinge

Posterior Column/Medial Lemniscus System

From Periphery to CNS: 1st order neurons - FC & FG 2nd order neurons - NC & NG Info into fasciculus G/S ⟶ medulla ⟶ synapse at nucleus G/S; some to lateral cuneate for proprioception ⟶ cross via internal arcuate fibers ⟶ medial lemniscus (contralateral) ⟶ ascend to thalamus ⟶ synapse in VPL ⟶ S1 somatosensory cortex (postcentral gyrus) predominantly

Proprioceptive Information to the Cerebellum

From the LE and Lower Trunk - Posterior spinocerebellar tract - Anterior spinocerebellar tract From the UE and Upper Trunk - Cuneocerebellar tract - Rostral spinocerebellar tract

Trigeminocerebellar Connections

From the mesencephalic nucleus of V via SCP ⟶ ipsilateral cerebellum From the trigeminal nucleus via ICP ⟶ ipsilateral cerebellum

Eye Fields

Frontal; Supplemental; parietal areas deal w eye movements Coordination of eye movements - Visual tracking Voluntary override of visual reflexes **aren't controlled by normal motor areas on previous cards

Muscle Spindle

Function - Sense static muscle length - Sense changing muscle length (dynamic) - Determine limb position (together with information from other receptors) CNS can adjust gain/sensitivity of spindle - Via intrafusal fibers In parallel with muscle Not just a receptor like GTO that just sits there that has an afferent nerve interweaved within capsule of organ...they have to be more complex cause it senses stretch and shortening...have to have a mechanism to change the length of the spindle or else it would become useless when you contract muscle - Gamma MNs inn tiny little muscle fibers (intrafusal) on ends of muscle spindle fibers themselves so when m contracts, they're activated Contractile Ends - Innervated by γ - motoneurons - Contract/relax to adapt to length extrafusal fibers and maintain/alter gain (sensitivity) Non-Contractile Center - Contain nuclei - Innervated by afferent endings - Respond to stretch

Temporal Lobe: Anteromedial Area

Functions with - Orbitofrontal region of frontal lobe - Limbic system Includes the Parahippocampal gyrus and Uncus Functions related to - Olfaction - Emotions & drives (motivation) - Memory

Non-Discriminative Aspects of Touch

Hair Follicle Receptors - Unencapsulated - Aβ nerve terminals surround hair follicle - Both rapidly and slowly adapting varieties - Sensitive to displacement of hair Cutaneous Mechanoreceptors - FNE - Light touch - Non-nociceptive - Aδ and C fibers

Insula

Hidden by: - Frontal, parietal, and temporal opercula - Long and short gyri Multimodal convergence & processing - Visceral motor & sensory - Somatic motor - Somatic and special sensory - Language Involved in processing info that allows attention, determines emotions, processes taste, vision, sound, smell, tactile sensory data Lesion may play a role in some anxiety and mood disorders

Why do we each feel pain differently?

How we react to pain is determined by many factors, past experiences, and emotional context 1. Actual stimulus - Type - Intensity - Location 2. Sensitization of receptor 3. Modulation - Sensitization - Suppression 4. Cognitive and emotional states 5. Memory

Spinomesencephalic Tract

In ALS Projects to contralateral midbrain periaqueductal gray - Reciprocal connections with limbic system through the hypothalamus Limbic system: appreciate "suffering" and emotional modulation of p! input

Blood Supply to Spinothalamic Tract

In spinal cord - Supplied by anterior spinal a and vasocorona - Patchy loss if only one is occluded In ventrolateral medulla - PICA In ventrolateral pontine tegmentum - Branches of basilar and superior cerebellar aa. In lateral midbrain tegmentum - Branches of posterior cerebral and superior cerebellar aa.

Autonomic Reflexes Example

Increased BP sensed by baroreceptors ⟶ information passes through CN IX and X ⟶ solitary nucleus ⟶ dorsal vagal nucleus and nucleus ambiguus ⟶ vagus nerve (pregang. parasymp.) ⟶ postgang. parasymp. ⟶ vasodepressor response (dec HR and BP) ⟶ anterolateral medulla ⟶ pregang. symp. ⟶ postgang. symp. ⟶ INHIBIT vasopressor response (inc HR and BP

Peripheral Sensitization

Increased responsiveness and reduced threshold of nociceptors to the stimulation of their receptive fields

Sensitization of Free Nerve Endings

Increased responsiveness of neurons to their normal input or recruitment of a response to normally subthreshold inputs - Lower threshold to feel pain/AP generation - Increased spontaneous activity/AP generation of neuron - Decrease in threshold of response to noxious stimuli - Increase in responsiveness to the same noxious stimuli - Increased magnitude of receptor potential - And/or an increase in receptor field size **patient may experience hyperalgesia

Central Sensitization

Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input

Hyperalgesia

Increased sensitivity to noxious stimulus

Gate Control Theory

Inhibition of p! transmission by non-noxious sensory input - Modulation at the SC - Ex: hitting your knee and rubbing it to make it stop hurting Projection neurons of the ALS receive... - EPSPs from Aδ and C fibers & some interneurons - IPSPs from inhibitory interneurons that are activated by Aα and Aβ fibers ⟶ inhibits activation of projection neuron Thus, the inhibitory interneuron controls the gate

General Afferents (Input) to Motor Areas of Cortex

Intracortical communication of motor areas - Within and between hemispheres Motor areas receive somatosensory info from... - Sensory & Association cortical areas - Ascending sensory pathways via thalamic nuclei (i.e. VPL & VPM) Cerebellum - Motor planning - Smoothing ongoing movements and making it efficient - Motor learning - Posture, balance, equilibrium Basal Nuclei - Motor planning & execution - Scaling amplitude & velocity

Reflexes

Involuntary stereotyped responses to specific sensory stimuli. - The locus of stimulus determines the muscles that will contract - The strength of the stimulus will determine the strength of the response Spinal reflexes: all circuitry for the reflex is located in the SC Descending influences modulate the reflex response

Processing of Nociception: Pain Matrix

Large distributed cortical network Sensory/Discriminative Aspects of Pain: VPL ⟶ - Primary sensory - Some secondary sensory - SI and SII involved in perception of sensory features (location, duration, intensity, quality) Perception of Unpleasant Sensation/Affective Aspects of Pain: VPI ⟶ - Insular cortex - Anterior cingulate gyrus - Prefrontal cortex

Putamen

Large subcortical structure, part of the basal ganglia

Ventral Posterolateral Nucleus (VPL)

Larger and more laterally located than VPM The medial lemniscus and spinothalamic fibers terminate somatotopically (cervical = medial, sacral = lateral) here - Receives contralateral somatosensory input from trunk and limbs Projects to the somatosensory cortex of the parietal lobe - SI and SII sensory areas and some motor areas

Descending Motor Control Pathways

Lateral Motor System - Primary effect on motor neurons of more distal muscles - Lateral corticospinal tract - Rubrospinal tract Medial Motor System - Primary effect on MNs of more proximal and axial muscles (often bilaterally; ex. postural mm) - Anterior corticospinal tract - Vestibulospinal tracts - Reticulospinal tracts - Tectospinal tract - Control/modulation of balance, proximal stability, head position, etc.

Hypothalamic Zones

Lateral Zone - Separated from medial zone by line drawn thru fornix to the mammillary bodies in sagittal plane - Involved in CV function and water intake - Blue Medial Zone - Regulate hormone release - It is divided into three regions: the supraoptic region (green), the tuberal region (pink), and the mammillary region (black) Periventricular Zone - Includes neurons that border ependymal surfaces of the third ventricle

Prefrontal Area

Lateral and medial surfaces and orbitofrontal region Functions - Higher order thought processes (i.e., abstract processing, problem solving, strategic planning) - Self control - Initiation, motivation - Judgment, foresight, responsibility Lesion - Phineas Gage

Secondary Visual Areas

Lateral surface occipital lobe Brodmann's areas 18, 19

Lateral Vestibulospinal Tract

Lateral vestibular nucleus ⟶ ipsilateral intermediate and anterior SC gray area ⟶ EPSP on MNs (generally), especially for axial and LE extensors Postural adjustment: trunk and LE in response to vestibular apparatus input Maintain balance

Granular Heterotypical Cortex

Layer IV is well developed and layer V is indistinct Terminations of sensory specific thalamic nuclei - i.e., primary visual, auditory, somatosensory areas

Agranular Heterotypical Cortex

Layer V is well developed and layer IV is indistinct Predominance of pyramidal cells - Origin of many long projection fibers Mostly motor related functions - i.e., primary motor cortex

Lesion of Posterior Limb or Genu of IC

Lenticulostriate Arteries (br of middle cerebral a.) Corticospinal 1. Contralateral hemiplegia 2. Spastic - Hyperreflexia - Increased resistance to passive movements - Babinski sign Corticonuclear problems (bc genu) Thalamocortical fibers come up through here - Sensory loss - Contralateral hemianesthesia If retrolenticular & sublenticular fibers also involved - Visual deficits - Auditory deficits

Decerebration

Lesion between inferior and superior colliculi - Remove influence of cortex on brainstem-SC systems - Whatever is left is controlled by brainstem-SC systems Severed - Descending cortical projections - Rubrospinal tract Retained - Reticulospinal tract - Vestibulospinal tract Unopposed hyperactivity in extensor mm's in all four extremities

Lesion of Subthalamic Nucleus

Lesion involving posteromedial branches of PCA or posterior communicating artery Can result in hemiballismus - Involuntary movement disorder - Rapid and forceful flailing movements of the contralateral extremity

Decortication

Lesion rostral to superior colliculus - Removal of cortical influence on brainstem motor nuclei Severed - Cortical projections including corticorubral fibers Retained - Cerebellar input to red nucleus - Rubrospinal Tract: UE flexion rigidity - Reticulospinal Tract: LE extension

Somatosensory Thalamic Nuclei

Primarily VPM and VPL - Pass most of the info to the cortex for conscious appreciation VP, VM, and posterior complex as well

Proprioception + Kinesthetic Awareness

Limb position sense Limb movement Provided by proprioceptors and exteroceptors - Other sensory input from vestibular, visual, and auditory systems Information is Used by the CNS for... 1. Sensory awareness - Cerebral Cortex - Conscious knowledge of limb/body position - Shape awareness (stereognosis) 2. Motor control & planning - Cerebral cortex and Cerebellum - Alterations of SC interneuron circuits (e.g., central pattern generator activity) 3. Reflex responses - Spinal cord and Brainstem

Limbic System

Limbic lobe, mammillary bodies, anterior thalamic nucleus Functions 1. Olfaction 2. Memory (& Learning) - Short term memory consolidated into long term memory 3. Emotions & Drives (Motivation, fear, pleasure) 4. Homeostasis

Genu of the Internal Capsule

Located immediately lateral to anterior thalamic nucleus, at about the level of the interventricular foramen Contains: 1. Corticonuclear Fibers - Primary motor cortex ⟶ motor nuclei of cranial nerves 2. Information from VA/VL relay system

Primary Motor Cortex (M1)

Located in precentral gyrus Brodmann's area 4 Somatotopic arrangement - homunculus Subcortical afferents: cerebellum ⟶ VL + VPL ⟶ M1 (other motor areas to a lesser degree) Connections to areas of thalamus related to motor and sensory info

Secondary Somatosensory Area (SII)

Located in the dorsal wall lateral sulcus in line with primary sensory area (insular cortex) - Has homunculus Less discriminative aspects of sensation - Process pain information - Memory and recall of somatosensory information Afferents primarily from S1 Thalamic nuclei related to somatosensory pain - VPL or VPM - Ventral posteroinferior - Ventromedian (pars oralis) - Posterior complex

Ventral Posterior Intermediate/Inferior Nucleus (VPI)

Located ventrally between VPL and VPM Process vestibular input and project to lateral areas of the postcentral gyrus - SI and parieto-insular vestibular cortex

Long vs. Short Association Fasciculi

Long - Cingulum - Superior longitudinal fasciculus - Uncinate fasciculus - Inf. Fronto-occipital fasciculus - Arcuate fasciculus Short association fibers - Arcuate fibers

Hypothalamus

Mainly involved in visceromotor, viscerosensory, endocrine activities - Receives sensory input regarding internal environment ⟶ regulate the motor systems that modify internal env (four mechanisms) Landmarks: hypothalamic sulcus and lamina terminalis - Tuber cinereum: btw mammillary bodies and optic chiasm - Infundibulum: proximal part of posterior pituitary

Traditional Functional Classification of Nociceptors

Mechanical Nociceptors - Aδ & C fibers - Most effectively activated by sharp objects (pinprick, pinch) - Also activated by high intensity mechanical stimuli (like heavy pressure) Thermal Nociceptors - Extreme heat: Aδ (> 45°C) - Extreme cold: Aδ and C (< 5°C) - High frequency firing Chemical Nociceptors - C fibers - Chemical mediators - e.g., prostaglandins and bradykinins during acute inflammation Polymodal - C fibers - Respond to all Silent Nociceptors - FNE - Don't respond to anything - Becomes more responsive when chemical mediators are present - Doesn't normally happen

Discriminative Aspects of Tactile Sensation

Mechanoreceptors 1. Slow Adapting type I (SA I): Merkel receptors 2. Slow Adapting type II (SA II): Ruffini endings 3. Fast Adapting type I (FA I): Meissner endings (corpuscles) 4. Fast Adapting type II (FA II): Pacinian corpuscles All are terminal endings of Aβ afferent nerve fibers Receptor and/or peripheral terminal endings may be... 1. Encapsulated - Surrounded by a non-neural (cellular or connective tissue) capsule 2. Unencapsulated - Not surrounded by non-neural capsule - e.g. Free Nerve Endings

Proprioceptors

Mechanoreceptors located in... - Joint capsules - Ligaments - Menisci, etc. - Tendon - Muscle - Skin and subQ tissue **Joint structures and mm also contain nociceptors

Medial Vestibulospinal Tract

Medial Vestibular Nucleus ⟶ descends bilaterally via the medial longitudinal fasciculus ⟶ Cervical & Upper Thoracic SC only; bilateral LVII & VIII - Influences neck musculature for reflexes Reflex adjustments: head position in response to activity in vestibular apparatus

ALS vs. PC/ML System: Modalities, Resolution, Separation of Modalities, Somatotopic Organization

Modalities ALS: p!, temperature, crude touch PC/ML: discriminative touch, stereognosis, proprioception, kinesthesia, vibration Resolution ALS: - Higher levels of convergence - Little lateral inhibition - Less resolution PC/ML: - Limited convergence - More lateral (surround) inhibition; sharpens edges Separation of Modalities ALS: yes PC/ML: yes Somatotopic Organization ALS: less precise somatotopy than PC/ML PC/ML: somatotopic and sub-modality specific organization maintained

Sensory Receptors

Modified axon terminals of sensory neurons - May be associated with non-neural structures - Pseudounipolar neurons Each receptor is responsive to a specific type of stimulus energy - Mechanoreceptor: mechanical pressure or distortions - Chemoreceptor: taste, smell - Thermoreceptor: hot and cold - Nociceptor: high intensity stimulus or some chemicals Location 1. Somatic - Exteroceptors (cutaneous) - Proprioceptors (muscle/joint) 2. Interoceptors - Visceral 3. Special receptors - Auditory, visual, olfactory, vestibular, and tase **Natural Stimuli activate multiple receptors of more than one type!!! **Receptors have a lower threshold to certain stimuli, but can often respond to many.

Sacral "Parasympathetic" GVA

Monitor fullness, distension, etc. of pelvic and abdominal visceral Done through sacral nn ⟶ S2-S4 ⟶ DRG ⟶ terminate in posterior horn and intermediate region of SC ⟶ projections from second order cell bodies to ⟶ preganglionic neurons (sacral autonomic and thoracic/sympathetic-IML cell column) Projects to cerebral cortex via ALS and reticular formation - ALS is direct - Indirect to cerebral cortex (alternate pathway): ALS (spinoreticular tract ⟶ RF) ⟶ thalamus ⟶ insular and parietal opercular (SII) cortex - Widespread regions (from RAS) - Hypothalamus: control center for ANS

Spinothalamic Tract

Most prominent of ALS tracts Originate in LI and V primarily AWC ⟶ anterolateral funiculus ⟶ VPL of thalamus mostly (also to VPI, VM, and intralaminar with collaterals to RF on way to thalamus)

Lesion of PPAC

Most significant if in non-dominant hemisphere: non-dominant side attends to both sides of body; dominant only focuses on the opposite side Leads to deficits in... - Spatial perception - Visuomotor integration - Directed attention Neglect syndrome: agnosias; contralateral body parts not recognized - Mostly on the L side of world cause there's a redundancy on the R side Astereognosis: can't ID objects via sensory stimulation Apraxia: not able to plan movements - Challenges initiating movements of contralateral limb - Difficulty with visually and tactilely guided movements

GTO vs. Muscle Spindle

Muscle Spindle Primary endings (Ia) - Changing muscle length - Speed of movement Secondary endings (II) - Muscle length - Joint position - Static position GTO (Ib) Muscle tension - Force of muscle contraction - Tension on tendon - Passive stretch

Sensory Nerve Fiber Size Classification

Myelinated 1. Aα - Ia & Ib - Proprioception from muscle and tendon 2. Aβ - II - Discriminative touch, 2-pt discrimination, vibration 3. Aδ - III - Temp, faster pain Unmyelinated 1. C (p!) - IV - Slow pain, temperature 2. C (tactile) - IV - Light stroking, gentle touch 3. C (autonomic) - IV - Autonomic, sweat glands, vasculature **I - IV typically used for joint / muscle afferents **A - C typically used for cutaneous & visceral afferents

Neurochemistry of Primary Nociceptor Afferents

NTs/modulators for termination: glutamate, substance P, calcitonin gene related protein (CGRP) Terminal endings of central processes have receptors for: ATP, GABA, serotonin, opioids - Areas for presynaptic inhibition and facilitation and target sites for therapies Posterior horn cells that receive nociceptive input (post-synaptic neuron to primary afferents) have surface receptors for: glutamate, substance P, GABA, serotonin, opioids - Acted on by SC interneurons and descending pathways to inhibit or facilitate pain transmission

Cortical Histology

Neocortex (Isocortex) - 6 layers evident at some stage of development - Seen in most of the cortex Paleocortex - 3-5 layers - In parts of the olfactory cortex (parahippocampal gyrus and uncus) Archicortex - Max of 3 cell layers - In parts of the limbic cortex (hippocampal formation and dentate gyrus)

Thermoreceptor FNE

Non-noxious Cold (5 - 40 deg C) Heat (29 - 45 /50 deg C) Increased response with temp change

Adaptation of Neural Receptors

Not all receptors/afferent neurons have AP as long as stimulus is present. Some AP only generated at start and end of stimulus Slowly adapting: continue to respond to continuous stim; slight decrease in freq of AP or might actually have increased AP with continued stimulus = (peripheral) sensitization

ALS Somatotopic Organization

Not as precise as PC/ML system Differences in loss depending on where tumor presses (intra/extramedullary tumor)

Chronic Pain

Not protective with no biological purpose Considered Chronic if.. 1. It outlasts normal tissue healing time 2. Impairment is greater than would be expected from the physical findings or injury AND 3. P! occurs in the absence of identifiable tissue damage Or may... - Be associated with a chronic pathologic process - Recur at intervals for months or years without renewed injury - Be a pathology (or group of pathologies) unique to any initiating injuries or disease Costly health care problem !!!! - Usually imposes severe emotional, physical, economic stress on pt. and family **Some define as p! lasting > 3-6 mos after an injury - But....this could happen if non adequate tx, athlete that constantly reinjures not waiting to recover, etc.

Acute Pain

Occurs as a direct result of tissue damage or potential tissue damage - It is a symptom - Has a time of onset with clear pathology Serves to protect tissue from damage - If damage has occurred, it serves to allow time for healing Usually requires a tx - e.g., motrin and ice Typically resolves in 3 mos Examples of deficit in this function: diabetes, leprosy

Caudate Nucleus

One of the basal ganglia; it has a long extension or tail. Separated from the putamen by the anterior limb of the IC Anterior horn of lateral ventricles border head of caudate

Corticonuclear Pathways

Origin - Similar to CSpTr (parallel) - Cortical neurons that influence movement of muscles innervated by motor nuclei of cranial nerves (V, VII, XII, Nucleus Ambiguus (IX and X), and accessory nucleus) Course M1 ⟶ layer V of facial motor cortex ⟶ genu of IC ⟶ crus cerebri in midbrain just medial to CspTr ⟶ fibers project bilaterally in pons and medulla

Corticospinal Tract

Origin of Axons in Tract - Pyramidal cells - ~ 30% from M1 - ~ 30% from secondary motor areas - ~ 40% from parietal regions (SI, PPAC, SII; cingulate gyrus) Course Lateral CSp Tr: motor cortices ⟶ posterior limb of IC ⟶ crus cerebri ⟶ basilar pons ⟶ pyramidal decussation ⟶ anterior horn of SC (LVII, VIII, IX) ⟶ synapse on interneurons (EPSPs) ⟶ EPSP or IPSP on MNs of distal muscles - Some synapse directly on MNs (not as many) - More fine motor Anterior CSp Tr: fibers from lateral tract that don't decussate at pyramidal decussation ⟶ anterior horn of SC (LVII, VIII, IX) ⟶ synapse bilaterally on interneurons ⟶ MNs for proximal muscles Somatotopic organization - Go to appropriate pools in SC Motor Functions 1. Controlled, integrated, coordinated movements - esp. distal mm's in extremities (Lateral Corticospinal Tract) 2. Initiation / modulation of central pattern generators Sensory Functions From Sensory cortices ⟶ - Some fibers from SI and SII travel in Corticospinal Tract to the Spinal Cord posterior horn & intermediate region - Influence/ Modulates sensory transmission

Neurogenic Pain

P! arising as a direct consequence of a lesion of disease affecting the somatosensory system

Neuropathic Pain

P! initiated or caused by a primary lesion or dysfunction in the NS Peripheral: secondary to peripheral nerve injury or pathology 1. Deafferentation pain (post peripheral nerve injury) - Phantom limb pain: not stump pain; cramping, shooting, burning pain; usually normal for about 1 year 2. Painful neuropathies - Trauma, entrapment, ischemia, metabolic alterations of PN 3. Post herpatic pain: - Chicken pox virus resides in DRG; recurs - pain persists after shingles outbreak Central: CNS alterations following PNS injury - Abnormal afferent function in sympathetic NS causing sustained release of nor-epi in SC Central: secondary to CNS injury or pathology - Post CVA, SCI - Thalamic Syndrome: CVA in VP thalamus results in exaggerated response to painful stimuli

Anterolateral System

Pain (nociception), temp, non-discriminative touch Info from FNE receptors ⟶Aδ or c fibers ⟶ lateral division of dorsal root ⟶ bifurcate in posterolateral tract (of Lissauer) ⟶ ascend and descend ⟶ synapse in dorsal horn (L I, II, or V) ⟶ decussate in AWC ⟶ ALS (spinothalamic tract) ⟶ thalamus (VPL) ⟶ cortex

Referred Pain

Pain perceived at site other than site of tissue damage - e.g.: noxious stimulation of deep tissue (muscle or visceral) perceived as superficial Spinal innervation patterns (picture) - Diaphragm ⟶ pain in neck & shoulder - Heart ⟶ T1 distribution (angina) - Appendix ⟶ T10 - Kidneys ⟶ T10-L1 - Prostate or uterus ⟶ T10-12 More deeply situated structures tend to refer to more distant sites Visceral pain poorly localized 1) Low receptor density 2) Large receptive fields 3) Large convergence in pathway to ctx

Allodynia

Painful response to a non-nociceptive stimulus

Lesion of CST + Other Descending Tracts

Paralysis or Paresis Initially: - Flaccid muscle Often develop: 1. Spasticity/hypertonicity: - Increased resistance to passive stretch - Velocity dependant - Clasped knife effect 2. Hyperreflexia and possible clonus 3. Babinski sign - Upward mov't of big toe - Should normally flex 4. Synergistic mov't patterns of groups of muscles •Also seen with lesion to motor regions of cortex

M1 Isolated Lesion

Paresis of voluntary movements - Nothing is wrong with AMN...it's the descending control that has been interfered with - Contralateral side - Usually starts as flaccid limbs (no resistance to passive movement) - May become spastic overtime (resistance to passive movement) Often regain some movement of proximal limb segments - Movements are not smooth - Distal muscles may remain paralyzed Synergistic contractions - Lack independent control Some return of myotactic reflexes - It is this return and resultant hyperreflexia that results in changing from flaccidity to spasticity - The reflex return is not to the extent as in lesions of the projection fibers (corticospinal fibers) or when the lesion affects larger regions of the cortex

Spinoreticulothalamic Pathway

Part of ALS - Diffuse multisynaptic pathway Older system phylogenetically - Visceral states - Role in behavior awareness, modification of motor and sensory activities Spinoreticular tract - Projects to medulla and pontine RF - RF is one means by which p! signals from lower body reach cortex. It's also one origin of analgesic pathway. Nerve fibers in these pathways act in the spinal cord to block the transmission of some p! signals to brain (modulation) Reticulothalamic pathway - Increases alertness - Dull, poorly localized, persistent p!

Reticulospinal Tracts

Pontine (medial) reticulospinal Tr. - Predominantly excitatory effect on MNs Medullary (lateral) reticulospinal Tr. - Predominantly inhibitory effect on MNs Both terminate on Intermediate & anterior SC (LVII & VIII) - Influence neurons supplying paravertebral and limb extensor mm's - Entire length of spinal cord - Bilateral - Ipsilateral > contralateral

Blood Supply of Diencephalon

Posteromedial branches of the PCA and the posterior communicating a. including thalamogeniculate and the thalamoperforating aa - Supplies regions of the hypothalamus, subthalamus, anterior and medial portions of the thalamus, caudal thalamus, and geniculate nuclei - Perforates at the posterior perforated space (in floor of interpeduncular fossa) Anterior Choroidal Artery supplies posterior limb of IC Lenticulostriate artery supplies most of basal ganglia and IC

Function of Secondary Motor Areas

PreMC and SMA - Subtle differences btw the two Function 1. Planning of movement A. Especially more complex motor responses - Goal oriented movements (guided by visual or tactile sensory input) - Movements planned based on memories (learned movements) - Movements requiring interlimb coordination B. Control of proximal and axial muscles C. Initial phases of movement (i.e., orienting body and limb to target) 2. Possible role in motor learning

Neocortex Lamellar Organization

Predominance of different cells/layers in different areas of the cortex - Homotypical: all 6 layers are clearly definable (all same size) - Heterotypical: some layers aren't well defined; related to the function of that area of the cortex Molecular Layer (Plexiform; 1) - Most superficial; right under pia mater - Few neuron cell bodies - Meshwork of axons running parallel to surface and apical dendrites coming into it External Granular Layer (Small Pyramidal; II) - Small cells - Form cortical circuits; send axons to molecular layer - Afferent and efferent corticocortical fibers External Pyramidal Layer (Medium Pyramidal; III) - Medium cells - Form cortical circuits; send axons to molecular layer - Afferent and efferent corticocortical fibers Internal Granular Layer (Granular; IV) - "Primary receptive layer"; most info going into cortex goes here - Spiny and aspiny cells - Afferents: primarily thalamocortical; outer line of Baillarger - Sends efferents to nearby cortex Internal Pyramidal Layer (Large Pyramidal; V) - Medium and large pyramidal cells - "Principal efferent layer": primarily to subcortical regions (brainstem, SC, striatum); fewer to thalamus - Corticospinal, corticobulbar, corticostriate Multiform Layer (Polymorphic VI) - Primarily pyramidal cells - Primarily corticothalamic projections

UE Information to Cerebellum

Primary afferents at levels C2-T4 1. Central processes travel rostrally via FC ⟶ synapse on lateral (accessory) cuneate nucleus ⟶ Cuneocerebellar Tract ⟶ ICP ⟶ ipsilateral cerebellum - UE equivalent to PSCT OR 1. Synapse on LVII of C4-C8 ⟶ Rostral Spinocerebellar Tract ⟶ ascend uncrossed ⟶ ICP ⟶ ipsilateral cerebellum - Not as important - UE equivalent to ASCT

LE Information to Cerebellum

Primary afferents from LE and lower trunk ⟶ travels up a little in FG ⟶ L2 ⟶ 1. Synapse in posterior thoracic nucleus/Dorsal Nucleus of Clarke (LVII; in T1-L2) ⟶ Posterior Spinocerebellar Tract (only located above L2) ⟶ inferior cerebellar peduncle ⟶ ipsilateral cerebellum (aka restiform body) OR 2. Synapse in LV-VII of L2-5 ⟶ Anterior Spinocerebellar Tract ⟶ decussate at AWC ⟶ ascend in contralateral SC ⟶ most decussate again in superior cerebellar peduncle ⟶ ipsilateral cerebellum (most)

Pyramidal Cells

Primary efferent neuron of the cortex - Very big cells Have long axons with extensive collaterals and an apical dendritic tree that comes up into other layers of the cortex Primarily use glutamate and aspartate NTs (excitatory) Axons leave the cortex

Areas of Cerebral Cortex that Control Motor Activities

Primary motor area (M1) Secondary areas - Just in front of M1 - Supplementary motor area (learning) - Premotor cortex Post. parietal assoc. area/cortex - AKA Post. Parietal motor area - Modulates motor areas (packaging) Cingulate gyrus

Epithalamus

Principal Components: 1. Pineal Gland - Alters melatonin production into general circulation 2. Habenular Nuclei - Sends input to the midbrain RF to influence emotional responses to odors 3. Stria Medullaris Thalami - Fiber bundle containing afferent fibers from the septal nuclei, lateral preoptico-hypothalamic region, and anterior thalamic nuclei - Projects to the habenular nuclei - Septal nuclei receive input from olfactory system + hippocampus (via fornix)

Medial System of Transmission of Pain Sensation from Thalamus to Cortex

Projects from DM and intralaminar nuclei ⟶ limbic system association cortices (anterior cingulate cortex) - Affective-motivational component - Emotional component (suffering)

Lateral System of Transmission of Pain Sensation from Thalamus to Cortex

Projects from VPL and VPM in the thalamus ⟶ primary somatosensory cortex - Rapid and precise localization and discrimination of nociceptive stimuli

Anterior Thalamic Nuclei

Receive limbic-related projections (input) from: 1. The mammillary nuclei/bodies via the mammillothalamic tract 2. The medial temporal lobe (hippocampus) via the fornix Output through the anterior limb of the internal capsule to the cingulate gyrus Function: emotion + memory acquisition

Medial Geniculate Nucleus/Body (MGN)

Receives ascending auditory input via the brachium of the inferior colliculus (from the lateral lemniscus) and projects to the primary auditory cortex in the temporal lobe - Heschl's gyrus in the superior temporal lobe

Lateral Geniculate Nucleus/Body (LGN)

Receives visual input from the retina via the optic tract and projects to the primary visual cortex on the medial surface of the occipital lobe - Lingual gyrus and cuneus (around calcarine sulcus)

Peripheral Mechanisms Related to Pain

Receptor - Free nerve endings (nociceptor) - Functional classification on next card ⟶ Fiber Classification - How info gets from receptors to CNS - Aδ fibers: thinly myelinated - C fibers: unmyelinated

Rubrospinal Tract

Red nucleus receives input from: - Ipsilateral motor areas of Cerebral cortex (4, 6 and some from 5 and 7) - Cerebellum Red Nucleus ⟶ interneurons contralateral cervical spinal cord - Primarily flexors Function - Primarily influence on contralateral UE flexor MN's - Supplement the corticospinal system in UE's

Vestibular System and Motor Responses

Reflex Adjustments - Axial and LE muscles in response to changes in head position relative to gravity Inputs to Vestibular Nuclei - Vestibular apparatus (CN VIII) - Cerebellum

Classification of Dorsal Thalamic Nuclei Based on Their Connections

Relay nuclei (specific nuclei) - Receives input from a single subcortical source - Information is processed and projected to a localized region of sensory, motor, or limbic cortex - Include MGN, LGN, VPL, VPM, VL, VA, anterior thalamic nuclei Association nuclei (specific nuclei) - Receives input from a number of different structures/cortical regions and sends its information to more than one of the association areas (cingulate, limbic, prefrontal, visual, parietal) - Reciprocal connection (sending and receiving) ^^ - Include dorsomedial, lateral dorsal, lateral posterior, pulvinar nuclei Non-specific nuclei - Produces widespread activity in the cortex of both hemispheres - Play role in modulating excitability of large, nonspecific regions of the cortex, specifically in consciousness, alertness, attention (similar to reticular formation) - Includes intralaminar nuclear group, midline/thalamic reticular group, and a portion of VA - Continuation of brainstem RF ***All thalamic nuclei except the reticular nucleus have reciprocal connections with the cerebral cortex. - Reticular nuclei are just within the thalamus - In the external medullary lamina

Possible Mechanisms for Sensitization of Primary Afferents

Released inflammatory mediators & pro-inflammatory cytokines (bradykinin, prostaglandins) cause: - Altered receptor / channel sensitivity on FNE - Altered receptor or channel protein production on FNE Peripheral release of: - Excitatory amino acids (e.g. glutamate) - Neuromodulators (e.g. substance P) Sympathetically released transmitters (noradrenaline/ norepinephrine): - Pain ⟶ increased activity of sympathetic NS - Nociceptor terminals appear to sensitize to nor-epi - Other uninjured nociceptors develop sensitivity to nor-epi - "sympathetically maintained pain"

Occlusion of Anterior Choroidal Artery

Results in contralateral visual and motor deficits reflecting damage to optic tract and posterior limb of IC

Collaterals of Corticospinal Tract

Reticular Formation - Pons - Medulla Inferior Olivary Nucleus - Cerebellar inputs Posterior Column Nuclei

Pineal Gland

Retinal cells ⟶ hypothalamus (suprachiasmatic nucleus) ⟶ intermediolateral cell column of spinal cord (IML; sympathetic preganglionic cells) ⟶ superior cervical nucleus (postganglionic sympathetic) ⟶ pineal gland ⟶ altered melatonin production as circadian rhythm Increased production at night

Myotomes

Review!!

Examples of Motor Pathways (from PPT)

SMA and PMC both get information from prefrontal lobe: example decision PMC - more important for learning, planning, control of movements requiring visual or other sensory input SMA - more important for initiation, planning and control of movements based on learned patterns - Activity of SMA decreases as movement patterns become more automatic All pathways get back to M1 MI - fire off populations of cells control force of contraction, direction of movement. Most drive multiple motoneurons at the spinal cord level - Input from all the other areas PMC and SMA communicate during the learning process

Afferent (Sensory) Innervation to Muscle Spindles

Sensory fibers terminate on central region of IFF (intrafusal fibers) Stretch whole muscle ⟶ stretch of IFF ⟶ stretch of central region ⟶ depolarization of afferent endings (AP if reaches threshold) ⟶ SC Primary Endings Ia/Aα fibers - Terminate on all types of IFF - Greatest response to stretch of dynamic nuclear bag fibers - Changing length of m Secondary Endings II/Aβ fibers - Terminate on nuclear chain and static nuclear bag fibers (predominantly chains) - Static (absolute) length

Sublenticular Limb of Internal Capsule

Sits inferior to the lenticular nucleus, but not typically seen in axial sections Contains 1. Auditory Radiations (geniculotemporal) - Auditory information from MGN ⟶ transverse temporal gyri 2. Some geniculo-occipital radiations - Meyer's loop

Intrafusal Muscle Fibers

Small muscle fibers on ends of muscle spindle 2 Types: 1. Nuclear Chain + Static Nuclear Bag Fibers - Bag 2 - Innervated by static γ-MNs - Sensitive to changes in length only (not dynamic) 2. Dynamic Nuclear Bag - Bag 1 - Innervated by dynamic γ-MNs - Sensitive to rate of change in length mainly Differ in... - Contractile properties - Passive mechanical properties Intrafusal and extrafusal fibers generally contract simultaneously - CNS activates both α- and γ- motoneurons - CNS adjusts length of muscle spindle to length of surrounding muscle - α-γ co-activation

Ventral Posteromedial Nucleus (VPM)

Smaller and more medially located than VPL Trigeminothalamic fibers from the spinal trigeminal nucleus and the principal trigeminal sensory nucleus terminate here - Receives contralateral somatosensory input from head Projects to the somatosensory cortex of the parietal lobe - SI and SII sensory areas and some motor areas **Gustatory (from superior solitary nucleus; taste) ⟶ VPM ⟶ near SI and insula

Descending Modulation of Pain

Spinothalamic Tract Descending pathways important in localizing p! and modulating/inhibiting it Spinoreticular and Spinomesencephalic Tracts Descending pathways important in modulating pain perception based on motivational/emotional states Primarily inhibitory from higher centers Endogenous Opioids - Endorphin, enkephalin, dynorphin - Similarities to morphine-induced analgesia - Opiate containing neurons: PAG, substantia gelatinosa, hypothalamus - Opiate receptors: PAG, nucleus raphe magnus, SC (posterior horn), hypothalamus, other Periaqueductal Gray - E-stim produces morphine-like effect

Flexor Withdrawal and Crossed Extension Reflexes

Step on glass ⟶ interneurons ⟶ inhibit quads, excite hams to get off glass On opposite side, excite quads and inhibit hams so you can stand on one leg

How does the afferent response change with IFF contraction?

Stimulation of static γ-mn ⟶ contraction of nuc chain and static nuc bag fibers ⟶ increase in the steady state AP frequency along Ia & II afferents Stimulation of dynamic γ-mn: ⟶ contraction of dynamic nuc bag fibers ⟶ increase sensitivity of primary (Ia) endings ⟶ increased AP frequency Ia during dynamic (& static) phases of stretch

Golgi Tendon Organ

Stimulus = muscle tension Located at muscle-tendon junction in series with muscle fibers - Thin nerve fibers intertwined with muscle fibers Force ⟶ stretches GTO ⟶ Ib fiber (afferent nerve; heavily myelinated) ⟶ (+; EPSP) interneurons⟶ (-; IPSP) MN's of same muscle

Stimulus Characteristics are Coded to the CNS

Stimulus Intensity (including depth of indentation) can lead to AP trains Increase intensity by... - Number of receptors activated: population coding - AP frequency: frequency coding Stimulus Location Receptor location ⟶ tract ⟶ thalamus ⟶ region of cortex stimulated - Somatotopic organization Stimulus Type Leads to specific type of Receptor(s) activated: - Modality specific organization (Tracts and Cerebral cortex) - Each receptor makes specific contacts within the CNS Resolution 1. Discrimination between closely placed stimuli - Receptor density & Receptor Field Size - High resolution = Discriminative touch - Poor resolution = Crude, non-discriminative touch 2. Central processing - Convergence - Divergence - Inhibition (e.g., lateral inhibition)

Limbic Lobe

Subcallosal area - Septal Nuclei Cingulate gyrus - Isthmus of cingulate gyrus Parahippocampal gyrus - Hippocampal formation Uncus - Amygdala

Tectospinal Tract

Superior colliculus: where neurons of this tract are located - Integration of visual, somatosensory, and auditory input Superior colliculus ⟶ cross over to contralateral ventral cervical spinal cord Involved w reflex movements of head and neck in response to visual, auditory, and painful stimuli

Secondary Motor Areas

Supplementary motor area (SMA) and Premotor area (preMA) Brodmann's area 6 - Motor planning networks Few thalamic connections; some from motor areas Subcortical afferents: globus pallidus and substantia nigra ⟶ VA/VL of thalamus ⟶ SMA (and to a lesser degree other motor areas) Send major efferents to M1, RF, and SC

Gamma Motor Neuron Activation

The degree of γ-mn activation is task specific - γ-mn activation (and therefore intrafusal muscle shortening) is greater with tasks that require more precise movements Control Centers of γ-mn - Near red nucleus - Reticular formation - Vestibular nuclei - Substantia nigra pars compacta

Nociception

The neural process of encoding and processing noxious stimuli

The "Gamma Loop"

Theoretically CNS can activate: γ-motoneurons alone ⟶ Intrafusal fiber contraction ⟶ AP along Ia afferent endings ⟶ enhance excitation of α-motoneurons ⟶ increase extrafusal muscle contraction

Convergence-Projection Theory

Theory for referred pain Visceral nociceptors & somatic afferents converge on same SC pain-projection neurons - The brain is unable to differentiate - Result: Heart pain perceived as chest & arm pain

Sensory (GSA) From the Head

Trigeminal system (sensory for face) V1, 2, and 3 ⟶ trigeminal ganglion (cell bodies of neurons) in skull; lateral of sella turcica ⟶ central processes go into brainstem and synapse in one of the nuclei ⟶ cross over ⟶ contralateral ventral/anterior trigeminothalamic tract (joining p! tract) ⟶ synapse VPM, VPI, VM, Po ⟶ Cortex **Some don't cross and go up ipsilateral posterior (dorsal) trigeminothalamic tract ⟶ esp oral cavity Chief (principal) Sensory Nucleus = adjacent to ganglion ⟶ discriminative touch Spinal Nucleus of V= continuous w dorsal horn of SC - Rostral: crude touch - Pars interpolaris: p! in oral cavity - Caudal: p! and temperature Mesencephalic Nucleus of V= proprioception - Unique - Pseudounipolar (primary) cell bodies within midbrain (normally these are located in ganglia)

GVA Receptors

Two Types 1. Nociceptors - FNE 2. Physiological Receptors - Continuous monitoring A. Rapidly adapting mechanoreceptors - Dynamic events; cough, change B. Slowly adapting mechanoreceptors - Stretch or tension, sense of fullness C. Specialized receptors in visceral organs - Chemoreceptors - Baroreceptors - Information sent to hypothalamus which has its own receptors D. Hypothalamus - Chemo-, osmo-, thermo- receptors 90% of GVA fibers are unmyelinated or small myelinated Most GVA are associated with the parasympathetic system - Craniosacral - Continuous monitoring & adjustments of visceral functions (visceral/autonomic reflexes; help us stay in steady state) - Some conscious awareness

Telencephalon

Two large hemispheres separated by the longitudinal fissure Outer surface: cerebral cortex - Layers of cells - Gyri and sulci Inner surface - Subcortical white matter - Gray matter, basal nuclei, amygdala

Joint Receptos

Type I - Ruffini ending - Slow adapting - Activated at extremes of motion; stretch of capsule Type II - Lamellated corpuscle/pacinian corpuscle - Rapid adapting - Activated by changes in direction and speed (start/stop) Type III - Golgi Tendon Organ-like - Slow adapting - Activated by extreme stretch - Ligament or horns of menisci Type IV - FNE (C and Aδ) - Slow adapting - Mechanoreceptors and nociceptors - Mechanical and chemical **Information of movement is mediated by these different types of receptors located in the joints - Respond to specific arc of motion - Receptor density varies with location - Some exteroceptors (skin for example) provide information used for joint sense

Medullary Center

Types of Fiber Pathways: ACP 1. Association 2. Commissural - Corpus callosum - Anterior commissure 3. Projection - Corona radiata - Internal capsule

Lesion to Motor Neurons

Typical signs - Weakness - Flaccidity - Atrophy - Fibrillation potentials - Fasciculation - Decreased or absent reflexes (hyporeflexia, areflexia)

Pusher Syndrome

Uncommon condition caused by infarction centered on the posterolateral thalamus, possibly extending into the internal capsule Involves the pt "pusing" to their hemiplegic side that they can't support, thinking that they are upright - Push away from side of lesion

Wernicke's Area

Understanding language Brodmann's areas 21 and 22 - Temporal lobe of the dominant hemisphere - Mostly auditory Supramarginal (40) and angular gyri (39) of parietal lobe - Mostly written Lesion: if dominant hemisphere - Deficit in understanding speech and written language - Auditory discrimination - Recognition of sound patterns - Perceptual deficit in understanding language - Hearing is fine

Hierarchal vs. Parallel Distributed processing in Motor System

Used to be thought of as hierarchical, but now considered a parallel descending system (i.e., cortical and brainstem descending pathways) Numerous regions of the central nervous system are required to plan and execute motor skills - Series of parallel systems linking various motor areas of cortex more directly with spinal motor circuits - Many fibers in corticospinal tract not from M1 - Each descending cortical pathway contributes to the movement control - For many movements, commands aren't for specific muscle action but rather to pattern generator cells in spinal cord (or brainstem) Cerebellum and basal nuclei have separate input to to descending motor pathways Parallel systems

Vascular Supply to Corticospinal Tract

Vascular Supply 1. Internal capsule - lenticulostriate off middle cerebral a. 2. Midbrain - post. cerebral a. 3. Medulla - anterior spinal a. 4. Spinal cord - arterial vasocorona

Using Sensory (and Motor Testing) to ID a Lesion Location

Want to determine central vs. peripheral lesion and CNS vs. PNS Clinically 1. Sensory Testing - Patterns of sensory deficit (anatomical region) - Sensory modalities affected - Dermatome vs. peripheral nerve patterns 2. Voluntary Motor - Patterns of paresis or paralysis (m testing) - Ataxia 3. Altered deep tendon reflexes Root Lesions 1. Ventral root (A) - Myotomal loss 2. Posterior root (B) - Dermatomal and peripheral nerve patterns Spinal Nerve Lesion (C) - At IV foramen - Affects both roots Spinal Cord Lesion - Ex. Brown Sequard Syndrome

Retrolenticular Limb of Internal Capsule

White matter located immediately caudal to lenticular nucleus Contains: 1. Optic Radiations (geniculocalcarine radiations/geniculo-occipital) - Visual input from the LGN ⟶ occipital cortex

Internal Medullary Lamina of Thalamus

Y shaped sheet of white matter (myelinated fibers) that divides dorsal thalamus into principal cell groups (nuclei): 1. Anterior 2. Medial 3. Lateral 4. Intralaminar - Located in the portion of the internal medullary lamina that separates the lateral and medial nuclear groups **Book: In addition, there are midline thalamic nuclei located just superior to the hypothalamic sulcus. Finally, attached to the caudolateral portion of the thalamus are the medial and lateral geniculate bodies. Although considered here as components of the lateral nuclear group, the geniculate nuclei are sometimes considered as a separate part of the thalamus, the metathalamus

What happens when there's degeneration of spinocerebellar tracts and/or posterior columns?

⟶ symptoms of cerebellar ataxia Ataxia - Inability to coordinate voluntary motor activities - Uncoordinated movements, unsteady gait - Wide based gait Tabes Dorsalis - Secondary to untreated syphilis - Degeneration of post columns - Don't know where limbs are - ex. Foot slap Friedreich's Ataxia - Genetic - Degeneration of post columns, spinocerebellar tracts, corticospinal tracts within the spinal cord itself (not in cerebellum)