Neuro 19: Cerebral Function

Subdivisions of dementia:

Cortical - prominent disturbances in language, praxis, visual-spatial functions, and other typically cortical functions vs Subcortical - Huntington's disease or progressive supranuclear palsy primary dementia = neurodegenerative conditions for which definitive treatments are usually unavailable vs secondary dementia - often reversible "pseudodementia" caused by depression or other treatable psychiatric disorders. dementia with Lewy bodies typically begins with fluctuating dementia, parkinsonism, visual hallucinations, and REM sleep behavior disorder. Pathologically, there are intraneuronal inclusions called Lewy bodies in the substantia nigra (as in Parkinson's disease) as well as in more widespread cortical and subcortical structures frontotemporal lobar degeneration (FTLD) -> frontotemporal dementia- Onset is often accompanied by behavioral changes suggestive of frontal lobe dysfunction, such as personality changes, abulia, or disinhibition; or temporal lobe dysfunction including impaired understanding of language and visual information, and impaired memory. -> neuronal inclusions contain TDP-43 "Pick Bodies" containing tau, some also contain FUS -> If prominent language dysfunction = primary progressive aphasia -> progressive nonfluent aphasia (L hemipshere peri-Sylvian atrophy) -> Semantic dementia : affects bilat temporal neocrotex (can present as impaired comprehension of words, while bilateral involvement causes visual agnosias for faces and other objects.) -> Logopenic progessive aphasia: left posterior temporal and inferior parietal atrophy producing hesitant speech and impaired repetition similar to conduction aphasia -> limbic predominant age-related TDP-43 encephalopathy (LATE) Corticobasal degneeration; asymmetrical onset of a movement disorder such as dystonia or parkinsonism, accompanied by cortical features most often consisting of a marked apraxia. Posterior cortical atrophy (PCA): degeneration of visual and other posterior corticcal areas - impaired vision or visual processing, with initial sparing of memory Vascular dementia - stepwise; if subcortical = Binswanger's disease -> clinical picture emerges consisting of dementia, pseudobulbar affect, and frontal lobelike features such as shuffling, magnetic gait, and gegenhalten Chronic traumatic encephalopathy (dementia pugilistica) HIV-associated neurocognitive disorder (HAND) - Dementia can also occur as a result of other HIV-associated illnesses, such as PML (progressive multifocal leukoencephalopathy), and other CNS infections Prion diseases, such as Creutzfeldt-Jakob disease, are unfortunately untreatable at present, and they lead to a relatively rapid cognitive decline often associated with an exaggerated startle response, myoclonus, visual distortions or hallucinations, and ataxia Other assoc causes: Electrolyte abnormalities, hepatic/renal/pulmonary failrue, hypo- or hyperthyroidism, vit B12 def (subacute combined degeneration of posterior column), folic acid def, pellagra (3 D's of dementia, dermatitis, and diarrhea) Dialysis dementia has become uncommon since aluminum was removed from dialysate solutions. many many others listed

Other sx of frontal lobe lesions:

Patients may have limited insight into their condition and may confabulate Patients who display utilization behavior/ environmental dependency tend to respond to whatever stimuli are at hand, even when not appropriate. "telephone effect", "next bed over syndrome") -> closing in phenomenon: patients' drawing gradually approaches that of the examiner, possibly exhibiting a form of environmental dependency. Perseveration (i.e. repeatedly answer the same question, even when the examiner is trying to move on.) - Luria sequencing tasks impersistence: can also be seen in right parietal lesions, Huntington's disease, and other conditions that cause inattention frontal release signs/primitive reflexes - i.e. grasp reflex, suck reflex, snout reflex (elicited by tapping lips), root reflex (elicited by stroking cheek) -> Myerson's glabellar sign is associated with movement disorders such as Parkinson's disease Incontinence (esp w/ medial frontal regions) -> pts are characteristically unconcerned about their incontinence) Impaired attention and working memory Deficits on declarative memory testing Stroop test: patients are given a list of color names such as "red, yellow, green" and so on, which are printed in colored ink, but the colors do not match the meanings of the words (e.g., the word "yellow" might be printed in green ink). Patients are then instructed to list the ink colors of the words without reading the words. (evals impulsivity) Impairment in ability to generate lists of related words/drawings (may show subtle decreases in verbal fleuncy in a dominant frontal dysfunction) -> FAS test: the patient is given 60 seconds to produce as many words as possible starting with the letter F, then 60 seconds to produce words starting with the letter A, and so on. Proper nouns, such as names of persons or places, are not allowed. Normal individuals produce 12 or more words for each letter. Similarly, normal individuals can name at least 15 animals in 60 seconds. For detecting nondominant frontal lobe dysfunction, similar tasks based on the generation of simple drawings can be used (referred to as tests of figural fluency). impaired abstract reasoning ability: Two common tools for testing this are proverbs and similarities Impaired judgement Impaired language testing - nonfluent aphasia may suggest L frontal lobe dysfunction L sided neglect (w/ right sided lesion) Skull shape: meningiomas can cause hyperostosis of overlying skull - large palpable bump on the head Olfaction - anosmia can be assoc w/ neurodegenerative dementias, TBIs, and tumors in the orbitofrontal area Saccades - forntla eye field imapirment (impairs saccades away from lesion) (eval via OKN testing) Hemiparesis/UMN findings if precentral gyrus involved lesions of the prefrontal cortex are often associated with other, more elaborate motor findings, reflex abnormalities, or gait abnormalities. Paratonia / gengenhalten = increased tone in which it appears the pt is resisting movements in an almost willful fashion shuffling, unsteady, magnetic gait, in which the patient's feet barely leave the floor

What is the most common cause of acute onset aphasia?What are other causes of aphasia?

cerebral infarct >> chart for other causes of aphasia

Hemineglect syndrome: What are allesthesia and allokinesia? Tactile response test vs crossed response test:

seen most often with infarcts or other acute lesions of the right parietal or right frontal lobes. Patients with this syndrome often exhibit profound neglect for the contralateral half (the left side) of the external world, as well as for the contralateral half of their own bodies; often unaware of this some patients remain with a permanent deficit in contralateral attention. During the recovery period, patients with hemineglect are more prone to injury and falls, and they may inadvertently bump or injure their contralateral side. Driving should be avoided until patients are able to demonstrate normal attention to both sides. Tests usually evaluate sensory neglect, in which patients ignore visual, tactile, or auditory stimuli in the contralateral hemispace; motor-intentional neglect, in which patients perform fewer movements in the contralateral hemispace; combined sensory and motor neglect; and conceptual neglect, in which the patients' internal representations of their own bodies or of the external world exhibit contralateral hemineglect. Tactile hemineglect is most common, but visual hemineglect is fairly common as well, with auditory hemineglect detected less frequently. visual, tactile, and auditory extinction on double simultaneous stimulation are useful tests of sensory hemineglect Patients with hemineglect commonly exhibit allesthesia, in which they erroneously report the location of a stimulus given to the left side of the body as being on the right. Difficult to differentiate from primary visual field defect - however, patients with a left homonymous hemianopia due to a right occipital lesion usually do not neglect stimuli on the left side if allowed to move their eyes, while patients with a right parietal lesion often neglect the left hemifield even when eye movements are not constrained. Patients should be observed for akinesia or decreased spontaneous movements of unilateral limbs or trunk, or decreased eye movements toward the neglected side. A marked ipsilateral gaze preference (toward the lesion) is common Allokinesia may also be present, in which the patient inappropriately moves the normal limb when asked to move the neglected limb. Tactile response test: Patients are instructed to raise whichever limb is touched, obviating the need for them to attend to and interpret the commands "right," "left," or "both." Once they understand the task, more subtle deficits can be detected during this test if they are asked to close their eyes. Note that the tactile response test is sensitive to both sensory and motor neglect Crossed response test: tests motor neglect in isolation; the patient is asked to move the limb opposite the one touched. spatial akinesia: in which limb movements are impaired when the limbs are located in the neglected hemispace (can demonstrate this deficit by asking patients to cross their arms during testing.) Combined testing: pen and paper testing: -> In the line bisection task, the patient is instructed to cross out a horizontal line by making a mark right in the middle. Patients with hemineglect often bisect the line far to the right of midline -. cancellation tasks are useful in detecting and quantifying more subtle neglect. Such tasks include presenting patients with a page filled with numerous small lines for them to cross out; Patients with neglect tend to miss the targets mainly on the left side of the page, but may also show some evidence of decreased attention to the right side of the page. -Drawing - Construction abilities -Reading/writing: Patients with hemineglect often read only the rightmost few letters or the rightmost few words of headlines. They may also ignore the left half of a picture when asked to describe a visual scene. In addition, while writing, patients with hemineglect tend to crowd their words onto one side of the page.

Broca's aphasia: What is the most common etiology? What is the most damming symptom? What defines this feature? What is the resulting speech? In what 2 scenarios does speech output tend to be better? What aspects of language are usually impaired w/ Broca's aphasia vs preserved? What other symptoms might be present based on the area?

usually caused by lesions affecting Broca's area and adjacent structures in the dominant frontal lobe most common etiology = infarct of L MCA superior division -> can cause associated dysarthria and R hemiparesis Most salient feature = decreased fluency of spontaneous speech -> broca's broken boca Fluency = shorter phrase length (<5 words), # of content words (like nouns) exceeds function words (like prepositions and other syntactic modifiers) Word generation tasks like the FAS test are useful Prosody can also be lacking The resulting speech in Broca's aphasia has an effortful, telegraphic quality, with a lack of grammatical structure and a monotonous sound. * Speech output is often better for certain overlearned, semiautomatic tasks, such as naming the days of the week or singing familiar songs like "Happy Birthday," and performance is often improved by cuing—that is, providing the first sound of a word during naming tests. Paraphasic errors occasionally occur, although these are less common than in Wernicke's aphasia. Features of language that are affected: - marked naming difficulties. (secondary to fluency impairment) -lesions in Broca's area cause a disconnection of this structure from Wernicke's area. Therefore, repetition is impaired as well. Patients tend to have the most difficulty repeating phrases with a high content of function words, such as "No ifs, ands, or buts" or "If I were here, she would be there." -Because the posterior language structures are spared, comprehension is relatively intact (speech and reading) in Broca's aphasia. The one notable exception is impaired comprehension of syntactically dependent structures. For example, when hearing a passive sentence such as "The lion was killed by the tiger," a patient with Broca's aphasia often incorrectly chooses the tiger as the animal that is dead. -Writing and reading aloud in Broca's aphasia have a slow, effortful, agrammatical quality that is similar to the deficits in spoken language. Other common sx = frustration, depression, apraxia may also be present (often affecting the nonparetic left side of the body and oral-buccal-lingual structures.) Other terms used: expressive aphasia, motor aphasia, anterior aphasia, nonfluent aphasia (However, Broca's aphasia is not simply an expressive deficit, since comprehension of syntactically dependent structures is impaired.)

What are the 2 best examples of dominant hemisphere specialization? What caveat is there for left-handers and language?

(1) The most obvious asymmetry in cerebral function is handedness. Approximately 90% of the population is right-handed. although each hemisphere controls simple movements of the contralateral limbs, skilled complex motor tasks for both right and left limbs are programmed mainly by the dominant, usually left, hemisphere. Lesions of the dominant hemisphere therefore are more commonly associated with apraxia, a disorder of formulating skilled movements (2) In most individuals, language function depends predominantly on the left hemisphere. The left hemisphere is dominant for language in over 95% of right-handers, and in over 60% to 70% of left-handers. Thus, lesions of the left hemisphere language areas usually cause language dysfunction, even in left-handed individuals. However, many left-handed individuals have significant bilateral representation of language, especially if there is a family history of left-handedness or ambidexterity. Thus, after a left hemisphere lesion, it is believed that left-handed individuals recover language more quickly than right-handers => dominant (usually left) hemisphere lesions cause impairments of language, detailed analytical abilities, and complex motor planning (praxis)

Aphasia classification scheme: What 3 aspects of the language exam is this classification based on? What kind of infarct/lesion could cause each of the following: Classifications: Broca's aphasia Wernicke's aphasia global aphasia conduction aphasia transcortical motor aphasia transcortical sensory aphasia mixed transcortical aphasia anomic aphasia

**aphasias do not always fit neatly into these categories. Left-handed patients, in particular, have more variable distribution of their language areas between the two hemispheres, and they may have aphasia syndromes that do not fit the classification presented here.** severity consideration: consider a patient with normal fluency who can comprehend and repeat simple phrases but who has difficulty comprehending and repeating more complex phrases and has occasional paraphasic errors. Despite the fact that some comprehension is present, this patient would be considered to have Wernicke's aphasia, but in a relatively mild form. The classification scheme is based on three parts of the language exam: fluency, comprehension, and repetition Brocas aphasia: impaired fluency & repetition, but normal comprehension -> L MCA superior division infarct Wernicke's aphasia: impaired comprehension and repetition, but normal fluency -> L MCA inferior division infarct global aphasia: impaired fluency, comprehension, and repetition -> seen w/ large L MCA infarcts that include both the superior and inferior divisions -> can also be seen in the initial stages of large left MCA superior division infarcts that eventually improve to become Broca's aphasia (big Broca's) and in large subcortical infarcts, hemorrhages, or other lesions. Conduction aphasia: normal fluency & comprehension, but impaired repetition -> infarct or other lesions in the peri-Sylvian area that interrupt the arcuate fasciculus or other pathways in the vicinity of the supramarginal gyrus that connect Wernicke's area to Broca's area -> paraphrasic errors are common and naming is impaired, which can lead to misdiagnosis of Wernicke's despite nl comprehension Transcortical aphasias - resemble Broca's, Wernicke's, or global, but repetition is spared ; classic cause = watershed infarcts ; also, subcortical lesions that involve the BG, or thalamus in the dominant hemisphere; Broca's and Wernicke's areas spared but interconnections w/ frontal or temporoparietal cortices are damaged -> transcortical aphasia is a common pattern seen during recovery from other aphasia syndromes. Transcortical motor aphasia - normal comprehension and repetition, impaired fluency -> ACA-MCA watershed infarct, destroys connections between Broca's and frontal lobe Transcortical sensory aphasia - Normal fluency and repetition, impaired comprehension -> MCA-PCA watershed infarcts , destroys connections between Wernicke's and the parietal and temporal lobes Mixed transcortical aphasia - impaired fluency and comprehension, normal repetition -> combined MCA-ACA and MCA-PCA watershed infarcts ; often seen w/ subcortical lesions as well Anomia/dysnomia - normal fluency, comprehension, and repetition; only symptom = naming difficulty w/ occasional paraphrasias

Alexia + agraphia - what 2 lesions are most common?

- dominant inferior parietal lobule at the angular gyrus- (recall that it is really important for written language) - dominant posterior middle frontal gyrus (Exner's area) aphasia can be absent or consist only of mild dysnomia and paraphrasias

What is the 6 step bedside examination for language developed by Benson and Geschwind?

1. Spontaneous speech (fluency, prosody, grammar/meaning, paraphasias, articulation) 2. Naming (visual confrontation naming, responsive naming, objects/parts, nouns/verbs/colors) 3. Comprehension (commands, yes/no Q's and multiple choice, pointing to objects, syntax-dependent meaning) 4. Repetition (single words, simple to complex sentences) 5. Reading (aloud, comprehension) 6. Writing (name, copying sentence, spontaneous sentence)

What is the tetrad for Gerstmann's syndrome? Where does Gerstmann syndrome localize to?

1. agraphia 2. acalculia (impaired airthmetic calculating abilities) 3. right-left disorientation (difficulty ID'ing R vs L side of body) 4. Finger agnosia (inability to name or identify individual fingers) Gerstmann's syndrome, when found in isolation, has little specific localizing value and can be seen in a variety of brain disorders. However, when all four components are present in the absence of a global confusional state or other diffuse disorder, this syndrome is strongly localizing to the dominant inferior parietal lobule, in the region of the angular gyrus. Can have other deficits localized to the dominant inferior parietal lobule - contralateral visual field cut, alexia, anomia, aphasia

How is anterior/posterior arrangement in the brain analagous to the spinal cord?

As in the spinal cord, where more posterior regions are sensory and more anterior regions are motor, the posterior parietal and temporal association cortex are more involved in interpreting perceptual data and assigning meaning to sensory information, while the anterior frontal association cortex is more important for planning, control, and execution of actions.

Anatomy of language processing: What are the primary association cortices associated w/ language comprehension and production? What anatomical structure connects these areas to one another? Where do these areas connect to in terms of cortical regions? What specific aspects of language rely predominantly on these cortical connections? How does reading written language work?

Auditory information reaches primary auditory cortex on the superior bank of the Sylvian fissure in the temporal lobe -> Initial language processing that enables particular sequences of sounds to be ID'd and comprehended as meaningful words = adjacent association cortex = Wernicke's area [Brodmann's area 22] - posterior 2/3 of the superior temporal gyrus in the dominant hemisphere -> Articulation of the sounds that constitute speech depends on the face area of the primary motor cortex, located in the inferior portion of the precentral gyrus -> The motor program that activates particular sequences of sounds to produce words and sentences is formulated in the adjacent association cortex= Broca's area [Brodmann's areas 44 and 45.- 44 is double 22 of Wernicke's] - opercular and triangular portion of the inferior frontal gyrus in the dominant hemisphere => the ability to hear a word and then repeat it aloud requires transfer of information across the Sylvian fissure from Wernicke's area to Broca's area. Essentially, neural representations for sounds are converted into words in Wernicke's area, and neural representations for words are converted back into sounds in Broca's area. Wernicke's and Broca's areas communicate with each other via the subcortical white matter pathway arcuate fasciculus -> Broca's and Wernicke's areas have reciprocal connection with a large network of cortical areas engaged in language processing. Broca's area connects with other regions of the frontal lobes, including the prefrontal cortex, premotor cortex, and supplementary motor area. These areas function together with Broca's area, primarily in higher-order motor aspects of speech formulation and planning. -> The correct syntax (grammatrical structure) of both language production and comprehension appears to depend critically on anterior (frontal) structures. -> Wernicke's area has reciprocal connections with the posterior (temporoparietal) language areas like the supramarginal gyrus and angular gyrus of the parietal lobe, as well as with regions of the temporal lobe. In addition, the posterior areas appear to contain the lexicon, which is important in mapping sounds to meaning for both the comprehension and the production of meaningful language. The language areas of the dominant parietal lobe, especially the angular gyrus, are also important for written language. -> When one is reading, visual information first reaches primary visual cortex in the occipital lobes, is processed in visual association cortex, and then travels anteriorly via the angular gyrus to reach the language areas. -> The language network also has important reciprocal connections with subcortical structures such as the thalamus and basal ganglia. Lesions of the thalamus, basal ganglia, or subcortical white matter in the dominant hemisphere can produce aphasia that can sometimes be mistaken for a cortical lesion.

Big Broca's aphasia vs little Broca's aphasia:

Big Brocas = large lesions, like MCA superior division infarct -> often involves much of the dominant frontal lobe + subcortical structures -> likely to be initial global aphasia that improves during recovery to settle into Broca's aphasia Little Brocas = smaller lesions; confined to frontal operculum where Broca's area lies -> initial Broca's aphasia that can settle w/ recovery into mild decreased fluency and some naming difficulties

What function does a naming test serve in terms of ruling out aphasia? Why? What would indicate subtle dysnomia?

Careful testing for subtle dysnomia can be a sensitive indicator of language dysfunction because naming is often the first function to be impaired and the last to recover in language disorders. A careful test of naming is thus an excellent screening test for aphasia. Patients with subtle dysnomia often have particular difficulty naming lower-frequency words or parts of objects asking the patient to identify the parts of a watch (face, band, clasp) or a shirt (collar, pocket, sleeve, cuff) is a useful bedside test. -> sometimes a similar but incorrect word will be used, such as "clock" for watch or "pencil" for pen (semantic paraphrasias) Causes of anomic aphasia are numerous and include subcortical or cortical lesions in the dominant hemisphere and recovery from more severe forms of aphasia.

What role does the nondominant hemisphere play in language processing?

Connections through the corpus callosum allow the nondominant hemisphere to participate in the language-processing network. The nondominant hemisphere appears to be important in both the recognition and the production of the affective elements of speech. Thus, patients with lesions of the nondominant hemisphere usually have no obvious language disturbance. However, they may have receptive or expressive aprosody, meaning they have difficulty judging the intended expression imparted by a particular tone of voice, or they may have difficulty producing emotionally appropriate expression in their own voice. Prosody = the normal melodious intonation of speech that conveys meaning of sentence structure in lesions of the dominant hemisphere, callosal connections may allow the nondominant hemisphere to take over some functions of the damaged areas and to participate in at least partial recovery.

What is mild cognitive impairment?

Dementia should be distinguished from the apparently "normal" mild deterioration of processing speed and memory that occurs with age and does not significantly interfere with daily function. mild cognitive impairment (MCI) is defined as cognitive deterioration beyond statistical norms for age-matched controls. MCI is a prodromal phase at the onset of progressive dementia in some individuals, whereas others with MCI do not progress

Differetnial diagnoses for disorders of sustained attention (4 major categories)

Encephalopathy (diffuse brain dysfunction)- most common -> assoc w/ impaired alertness Focal lesions in the parietal, frontal, or brainstem diencephalic-acitvating systems (thalamus/hypothalamus) ADHD: onset around ~3; disorder of attention, impulsivity, and hyperkinetic behavior -> normal neuroimaging studies and essentially normal neurologic evaluations, except for markedly impaired attention, impulsivity, and perhaps some "soft" findings on exam. -> more likely to cause problems w/ high-level executive functions, organizational skills, and time management vs simpler tasks like digit span -> boys > girls, siblings at increased risk -> tx= CNS stimulants like methylphenidate (Ritalin), amphetamines (Adderrall, Vyvanse), SNRIs like atomoxetine + therapy -> stimulants that enhance dopaminergic and noradrenergic neurotransmission are beneficial in this disorder. Psych disorders: depression, anxiety, bipolar, schizophrenia (pseudodementia)

Detect, pulse, switch, and wave model:

Example: brief visual stimulus shortly after the stimulus (<100 ms), primary cortices are activated, specifically visual cortex in this case. To detect the stimulus, signals interact with higher cortical areas including the frontal eye fields and other frontoparietal regions as well as subcortical areas such as the midbrain tectum. Subcortical arousal systems next provide a dynamic transient pulse that facilitates subsequent massive nonlinear cortical signals necessary for consciousness. The detect and pulse steps overlap bottom-up subcortical and cortical salience networks described for attention. Next, there is a switch off of activity in specific networks to prevent them from interfering with ongoing processing of the conscious stimulus. Such decreases in activity may "chunk" conscious events into discrete moments of time, or serve other functions to selectively control information flow. Finally, a broad wave of hierarchical processing sweeps through lower to higher cortical areas (including the dorsal and ventral visual streams in this case) to fully process the event before it is encoded in medial temporal episodic memory systems

Recovery from aphasias:

Global aphasia seen in big Broca's -> Broca's aphasia -> transcortical motor aphasia -> subtle dysnomia (Other patients have primarily naming and repetition difficulties following recovery, resembling a conduction aphasia.) Dysnomia is the most common long-term deficit

hemispheric specialization: What happens during development to influence hemispheric specialization?

Homologous regions of cerebral cortex on either side of the brain are connected to each other via long association fibers carried by the corpus callosum. For unknown reasons, however, there are marked asymmetries in several brain functions. It has been postulated that these asymmetries allow certain functions to be processed mainly within one hemisphere, eliminating delays caused by long callosal transmission times. -> Handedness and other lateralized aspects of cerebral function are not apparent in humans until they are 3 or 4 years of age, suggesting that developmental processes play a crucial role in hemispheric specialization. -> => When lesions of the dominant hemisphere occur early in life, language and other functions often move to the nondominant hemisphere, resulting in a remarkable preservation of function.

L vs R frontal lesions;

L lesions: depression like sx R lesions: behaivoral disturbances like mania

Anatomy of attention:

The content of consciousness is the substrate upon which consciousness acts and includes sensory, motor, emotional, and mnemonic systems working at multiple levels. The level of consciousness is regulated by brain networks that act on this substrate through the following three distinct but related processes: (1) alertness, (2) attention, and (3) awareness (mnemonic AAA) Attention can be defined as the brain processes that allocate resources to what matters. - attention networks are bilaterally distributed, but asymmetrical: the nondominant (usually right) hemisphere is more important for attention - even at rest brain activity continues to fluctuate. attention includes at least two major functions: (1) selective, or directed, attention, which involves focusing on a particular domain above others -> stimulus in particular location in space, inputs of a specific sensory modality, specific higher-order aspects of a stimulus (color vs shape), a particular object, or an object, emotion, plan, or concept that is not physically present but is either remembered or imagined. -> directed attention activate specific brain regions, following known anatomical principles. For example, attention to a somatosensory stimulus on the body activates the corresponding somatotopic region of somatosensory cortex (2) sustained attention, which includes functions such as vigilance, concentration, and nondistractibility -> can be directed at a specific task, object, or modality, or it can involve a more generalized increased level of vigilance Both involve signal enhancement in stimulus-relevant regions of the brain, as well as noise suppression in stimulus-irrelevant brain regions. Executive or control functions as well as emotional motivational factors may also contribute importantly to attention mechanisms. Task-positive networks are activated during tasks that require attention. Importantly, the same tasks also produce remarkably consistent decreased activity in task-negative networks/default mode networks (decreased activity during tasks but relatively increased activity in the "default" behavioral state of rest with no task) -> The main function of the default mode network in attention appears to be promotion of internal reflection or introspection, which is suppressed during externally oriented behavioral tasks. Default mode networks: precuneus, posterior cingulate, and retrosplenial cortex; ventral medial prefrontal cortex; and posterior inferior parietal lobule (angular gyrus) middle temporal gyrus/inferior temporal sulcus, parahippocampal gyrus, and parts of the cerebellum. Top-down attention network (dorsal attention network, goal-directed network, or endogenous attention network): important for internally motivated allocation of attention -> dorsal regions of the frontoparietal association cortex, especially the frontal eye fields (saccades are voluntary! ) and intraparietal sulcus/superior parietal lobule Bottom-up attention network,( salience network, ventral attention network, stimulus-driven network, or exogenous attention network): responds to important or unexpected external stimuli. -> anterior insula and frontal operculum (extending to the inferior and middle frontal gyri), the anterior inferior parietal lobule (supramarginal gyrus), and the dorsal anterior cingulate (network for amygdala structures)/supplementary motor area + subcortical regions (think need to run quick like attention to an attacking bear) AROUSAL: -> upper brainstem, thalamus, hypothalamus, and basal forebrain may contribute more dynamically through moment-to-moment control of directed and sustained attention The thalamic reticular nucleus plays a role in selectively gating info transfer through the thalamus via inhibitory (GABAergic) projections to the thalamus (and back to the brainstem as well). The lateral parietal association cortex lies at the nexus of auditory, visual, and somatosensory cortices and is thus ideally situated for heteromodal integration in attention The frontal association cortex also plays roles in executive control, directing attention to specific targets, initiating goal-oriented limb movements, reorienting attention to relevant stimuli, sustaining attention, and reducing distractability

Visual association cortex: what are the 2 streams of association cortices that visual input takes after reaching the primary visual cortex? What syndromes happen w/ dysfunction of each:

The dorsal pathways project to dorsolateral parieto-occipital association cortex. These pathways answer the question "Where?" by analyzing motion and spatial relationships between objects, and between the body and visual stimuli. -> Balint's syndrome: bilat lesions - clinical triad of (1) simultanagnosia- impaired ability to perceive parts of a visual scene as a whole; can perceive only one small region of the visual field at a time. deficit in visual-spatial binding.(2) optic ataxia- impaired ability to reach for or point to objects in space under visual guidance, and (3) ocular apraxia - difficulty voluntarily directing one's gaze toward objects in the peripheral vision through saccades. -> associated deficits may include inferior-quadrant visual field cuts (lateral, lower), aphasia, or hemineglect. -> often MCA-PCA watershed infarct The ventral pathways project to inferior occipitotemporal association cortex. These pathways answer the question "What?" by analyzing form, with specific regions identifying colors, faces, letters, and other visual stimuli -> medial portion = color recognition; lateral portion = faces, leterstrings, # recognition -> Complex formed visual hallucinations resulting from seizures of the inferior occipitotemporal visual association cortex -> prosopagnosia; Inability to recognize people/animals by looking at their faces (lesion = bilateral; fusiform gyrus) (perception stripped from meaing - can ID components of a face and ID but not match face to features- "intact generic recognition") (pure associative agnosia vs perceptual appreceptive agnosia) (associated with alexia and with upper-quadrant or bilateral upper visual field defects (medial, upper)) -> Achromatopsia: inability to name or match colors presented visually but can name appropriate colors when described verbally (there is awareness of deficit, vision appears gray); if whole field involved= bilateral; if there is hemiachromatopsia, there is lesion of contralateral cortex (may also see alexia nand upper quadrant visual defects) (in contrast to color anomia described in discussion of alexia w/o aphasia -> lesion in primary visual cortex of dominant hemisphere extending into corpus callosum) -> Micropsia (objects appear small); macropsia (objects appear unusually big); Metamorphopsia (distorted shape/size -> "Alice in Wonderland" syndrome

Mental status exam:

The patient's level of alertness, attention, and cooperation will influence virtually every other part of the exam. Therefore, the exam usually begins with an evaluation of these functions, which tend to depend on more widely distributed networks. (ex. global confusion state due to toxic or metabolic disorder) localized brain regions: dominant (usually left) hemisphere (language and related functions), right hemisphere (neglect and constructions), and frontal lobes (sequencing tasks and frontal release signs). more global functions (logic and abstractions), psychiatric disorders

Binding problem::

The question of how unified percepts are formed in the brain our experience of someone speaking to us is not fragmented into a perception of sounds, verbal comprehension, facial recognition, facial color, location of the face in space, and emotional impact of the words spoken, even though these functions each occur in a different cortical area (A second area of research is visual mental imagery—that is, our ability to imagine a scene even when it is not present.) (blindspot = individuals with lesions of the primary visual cortex are able to perform tasks such as inserting an envelope correctly in a slot, despite having no conscious visual perception of the slot. Blindsight apparently depends on information transmitted to association cortex by extrageniculate visual pathways.)

Auditory hallucinations:

Tinnitus: peripheral auditory disorders affecting the tympanic membrane, middle ear ossicles, cochlea, or eighth cranial nerve self-audible bruits: pulsatile "whooshing" sounds elderly patients with sensorineural deafness can develop elaborate auditory hallucinations (music, voices, etc.), which may be a release phenomenon analogous to Bonnet syndrome (visual hallucinations caused by visual loss). Lesions or ischemia of the pontine tegmentum involving the trapezoid body, superior olivary nucleus, and other auditory circuits can, rarely, cause auditory hallucinations, such as rain on a roof, buzzing, or musical tones like an orchestra tuning up, which are analogous to the visual phenomena of peduncular hallucinosis Paracussis - sound heard once is then heard repeatedly (analagous to palinopsia) Psychotic disorders are a relatively common cause of either simple or elaborate auditory hallucinations seizures in primary auditory cortex can cause simple auditory phenomena but also cause transiently decreased hearing. Involvement of the auditory association cortex gives rise to more elaborate auditory phenomena such as voices or music. Musical hallucinations are more often caused by seizures in the nondominant hemisphere

Wernickes aphasia: What is the most common etiology? What is the most damming feature? What is the resulting speech like? What are the 2 kinds of paraphrasias that the pt may exhibit? What aspects of language are usually impaired w/ Wernicke's aphasia vs preserved? What other symptoms might be present based on the area? What feature sharply contrasts to Broca's aphasia?

Wernicke's aphasia is usually caused by a lesion of Wernicke's area and adjacent structures in the dominant temporoparietal lobes The most common etiology is infarct in the left MCA inferior division territory most salient feature = impaired comprehension -> do not respond appropriately to questions and follow virtually no commands. -> Interestingly, a few commands relating to axial muscles, especially "close your eyes" and sometimes "stick out your tongue," may elicit a correct response despite severe Wernicke's aphasia -> Spontaneous speech has normal fluency, prosody, and grammatical structure, but is empty, meaningless, and full of nonsensical paraphrasic errors -> reading and writing follow similar patterns Paraphrasic errors = either inappropriate substitutions of a word for one of similar meaning (verbal or semantic paraphrasias) or of part of a word for a one w/ a similar sound (literal or phonemic paraphrasias) -> examples: "ink" instead of "pen" or "bus" instead of "taxi." // "pish" instead of "fish" or "rot" instead of "rock." - occasional neologisms (nonwords) are used. - Naming is impaired - Due to disconnection from Broca's area, repetition is impaired Other associated features : - contralateral visual field cut (esp RUQ due to involvement of lower (temporal) portion of optic radiation) - Apraxia -Angry or paranoid behavior may occur - Dysarthria and R hemiparesis is typically absent in marked contrast to Broca's aphasia, patients often appear unaware of their deficit (anosognosia), behaving as if carrying on a normal conversation despite their markedly abnormal speech -> When examining the patient with Broca's aphasia, the patient often feels frustrated, while when examining the patient with Wernicke's aphasia, the examiner may feel frustrated. Other terms used: receptive aphasia, sensory aphasia, posterior aphasia, fluent aphasia

What does repetition rely on?

an intact connection between Broca's and Wernickes via the arcuate fasciculus Damage to either Broca's or Wernicke's areas or the connection between them thus causes impaired repetition

Conceptual neglect w/ hemineglect syndrome:

anosognosia: lack of awareness of illness; (anosognosia is also seen in patients with Wernicke's aphasia, frontal lobe disorders, amnesia with confabulation such as that seen in Wernicke-Korsakoff syndrome, and cortical blindness, as well as psych illnesses) Anosodiaphoria: pts are aware of their deficits yet show no emotional concern or distress about it hemiasomognosia: pts deny that the left half of their body belongs to them; A patient may become distressed because "someone left an arm in my bed."

Prefrontal cortex:

bidirectional connections role in higher order processing that requires intergation of multimodal sensory, motor, and limbic information Cortical connections are mainly with the association cortex of the parietal, occipital, and temporal lobes, including unimodal sensory association cortex and heteromodal association cortex + motor assoc cortex in fontal lobes Important connections of the prefrontal cortex with limbic cortex: anterior cingulate gyrus + posteromedial orbitofrontal cortex Subcortical connections; amygdala is connected with the orbital and medial portions of the frontal lobes by the uncinate fasciculus The frontal lobes are connected to anteromedial temporal cortex by the uncinate fasciculus and to the hippocampal formation via the cingulate gyrus and parahippocampal gyrus The prefrontal cortex projects to the basal ganglia mainly via the head of the caudate nucleus The most important thalamic nucleus that relays information to and receives projections back from the prefrontal cortex is the mediodorsal nucleus

Consciousness;

carried froward from conversation regarding attention The content of consciousness is the substrate upon which consciousness acts and includes sensory, motor, emotional, and mnemonic systems working at multiple levels. The level of consciousness is regulated by brain networks that act on this substrate through the following three distinct but related processes: (1) alertness, (2) attention, and (3) awareness (mnemonic AAA) The consciousness system networks that control these functions include the upper brainstem, thalamic, hypothalamic, and basal forebrain arousal systems, along with the medial and lateral higher-order association cortex Conscious states are situations where a particular level of consciousness lasts for a relatively long period of time. Different conscious states include sleep, wake, drowsiness, heightened vigilance, or disorders of consciousness such as coma, minimally conscious state, or epileptic seizures. conscious events there is briefer conscious awareness, usually of a specific sensation, action, thought, or combination of these to form an experience. Two other important properties of consciousness are nonlinearity and the involvement of large-scale neural networks -> Nonlinear transitions between conscious states are common, as we all experience when abruptly returning to a more alert state while drowsing -> although neural responses at lower levels tend to be graded more linearly in response to stimulus strength (e.g., signals in primary visual cortex), subsequent higher-order neural responses are highly nonlinear. Conscious events can be described as occurring on a timeline of consciousness -> Important precursors or prerequisites of consciousness may contribute to whether or not an event reaches conscious awareness. These precursors of consciousness include level of alertness and arousal, attentional vigilance or anticipation, previous experiences related to an upcoming event, motivational state, and the phase of brain oscillations such as the alpha rhythm -> consequences of consciousness: post-perceptual processing, encoding of information into memory systems, and preparation for subsequent report or description of the experience at a later time. -> For a conscious event to be available for later report as an episodic declarative memory or experience it must reach the medial temporal memory circuits. Thus, memory systems must be engaged during or toward the end of the conscious event. The green box or conscious event is thus at the nexus or temporal transition between attention and memory systems—or, in short, consciousness is where attention meets memory. However, consciousness is not the same as memory encoding, but rather may represent the stage just prior to memory encoding, where a potential memory reaches the gateway to memory systems in regions such as the medial temporal lobe.

Alexia without agraphia: What is the common lesion? What other sx might be present?

caused by lesion in the dominant occipital cortex extending to the posterior corpus callosum (often a PCA infarct) The lesion in the dominant (usually left) occipital cortex prevents the processing of visual information from the right hemifield, including written material. A right hemianopia is therefore usually present; Meanwhile, information about the left hemifield that has reached the right occipital cortex is prevented from crossing to the language areas by the lesion in the posterior corpus callosum (disconnection syndrome) normal writing, but cannot read even their own writing ; however, they can name words that are spelled out loud to them Color anomia may be present, but aphasia is not usually present. May also have right hemianopia

Disconnection syndrome: What examples have we already discussed? (3) How does a L MCA superior division infarct cause L hand apraxia?

cognitive dysfunction is caused by damage to pathways that connect one cortical area to another Examples include conduction aphasia/impaired repetition in Broca's and Wernicke's areas (normal fluency & comprehension, but impaired repetition), alexia w/o agraphia (posterior corpus calloseum; dominant occipital cortex), and pure word deafness (dominant auditory cortical extending to subcortical, cutting off contralateral hemisphere) L MCA superior division infarct: Can cause Broca's aphasia + apraxia of the L (nonweak) hand due to disconnect between language area and premotor cortex of dominant L hemisphere from R hemisphere premotor cortex lesions of the corpus callosum lead to several disconnection syndromes - seen in MS, gliomas, metastases, lymphoma, lipoma, ACA/PCA infarcts

Cortical blindness (Anton's syndrome):

complete visual loss caused by bilateral lesions of the primary visual cortex + anosognia + loss of blink to threat, loss of eye closure in response to bright lights, and loss of optokinetic nystagmus (OKN) (may be seen in instances of combined occipital and frontal lesions (resulting in confabulation) or combined occipital and right parietal lesions (resulting in neglect).)

Aphasia/dysphasia: How do you distinguish it from dysarthria or aphemia? What about peripheral or central auditory disorders? What other conditions may be confused for aphasia?

defect in language processing caused by dysfunction of the dominant cerebral hemisphere Because aphasia is a disorder of language and not a simple sensory or motor deficit, both spoken language and written language are affected Aphasia is not caused by impaired audition or articulation, although deficits in these modalities may coexist with aphasia. In dysarthria (motor disorder) or aphemia (verbal apraxia), speech may be difficult to comprehend; however, it has normal content and grammar, and written language would likely be normal In peripheral or central auditory disorders, perception of spoken language is impaired, but reading and other aspects of language are normal Disorders of arousal and attention from a variety of causes, including toxic or metabolic disorders, post-ictal state, brainstem ischemia, and sleep disorders, are occasionally mistaken for aphasia because of the impaired comprehension and incoherent speech seen in these conditions. Finally, psychiatric disorders are sometimes confused with aphasia. In particular, schizophrenic patients may have very disordered, nonsensical, clanging speech, full of neologisms, which may resemble aphasia.

Aphemia:- where is the lesion commonly?

described as a "verbal apraxia" = effortful, poorly articulated speech, "foreign accent syndrome" -> if severe, can cause muteness -> can also be developmental in children seen in pts who have severe apraxia of the speech articulatory apparatus w/o a language diturbacne usually caused by a small lesion of the dominant frontal operculum restricted to Broca's area ("Little Broca's") normal written language (in contrast to Broca's aphasia)

Evaluating for sustained attention disorders: how can you evaluate vigilance?

digit span - a random series of numbers is recited to the patient, and the patient is asked to repeat them back immediately to the examiner. Normal digit span is five to seven or more digits. (can also request backwards version- normal would be 4 or more) recite the months of the year forward and then backward asking the patient to spell "world" backward or to count backward by threes from 30, or by sevens from 100. Motor impersistence: indicates impaired attention (often seen w/ frontal lesions) -> The patient is asked to stick out their tongue, or hold up their arms for 20 seconds, without subsequent prompting. Vigilance = "A" random letter test - the examiner recites a random sequence of letters at a rate of about one per second, and the patient is instructed to tap the desk each time they hear the letter A.

Dorsolateral convexity lesions vs Ventromedial orbitofrontal lesions:

dorsolateral lesions: produce apathetic, lifeless, abulic states (abulia = passive, apathetic, little spontaneous activity; markedly delayed responses, and a tendency to speak briefly or softly. In the extreme, abulic patients may be totally immobile, akinetic, and mute) ventromedial lesions: produce impulsive disinhibited behavior and poor judgement - can take the form of silly behavior, crass jokes, and aggressive outbursts -> inappropriate jocularity, or witzelsucht, seeming unconcerned about potentially serious matters. -> go-no-go test (similar to Simon say's): pt unable to suppress inappropriate responses

Functions of the frontal lobe:

functions important for (1) restraint (inhibition of inappropriate behaviors), (2) initiative (motivation to pursue positive or productive activities), and (3) order (the capacity to correctly perform sequencing tasks and a variety of other cognitive operations) -> RIO Working memory is the ability to hold a limited amount of information in an immediately available store while a variety of cognitive operations are performed. the dorsolateral prefrontal cortex may function together with the medial temporal lobes in learning new material - Activation of the dorsolateral frontal cortices has also been shown during tasks that require shifting cognitive set the frontal lobes are also activated during tasks that require selective attention role of the frontal lobes in integrating information from limbic (e.g., medial orbital frontal and anterior cingulate) and heteromodal association cortex in decision making.

Altered mental status:

impaired cognitive abilities, often nonlocalizing- consisting of prominent inattention, confusion, and memory deficits, together with variable degrees of impaired alertness and attention = encephalopathic (exhibit diffuse brain dysfunction) -> Patients often have marked difficulty with writing, calculations, and constructional abilities, any of which could be misconstrued as focal deficits if the underlying deficit in attention is not recognized. Acute confusional states tend to wax and wane in severity over the course of hours, and they are often exacerbated in the evening (a phenomenon referred to as "sundowning") Acute encephalopathy is most often toxic or metabolic in origin and is often reversible; chronic encephalopathy has a poorer prognosis for recovery, and in elderly patients it most often represents dementia of the Alzheimer's type impaired attention is usually prominent in acute mental status changes, while it may be minimal in chronic encephalopathies, especially early on Delirium = commonly used to describe acute confusional state in which agitation and hallucinations are prominent -> develop over hours to weeks w/ prominent attentional disturbances, tend to wax and wane over the course of hours, often have marked slowing on the EEG, and are most often caused by toxic or metabolic disorders, alcohol withdrawal, head trauma, infection, and seizures The most common causes of acute confusional states are toxic or metabolic disorders, followed by infection, head trauma, and seizures-> The patient's medications should be reviewed for those with known central nervous system side effects (e.g., anticholinergic, sedative-hypnotic, narcotic) In elderly patients or patients with previous neurologic disorders, acute confusional states are often provoked by seemingly minor causes, such as a urinary tract infection, or even by a change from home to the hospital setting. Patients in intensive care units are prone to acute confusional states from the combination of sedative use, immobilization, sleep deprivation, and sensory deprivation ========= Chronic mental status changes = Alzheimers (progressive), anoxic brain damage (static) -> early in their course tend to have less prominent disturbances in attention and a relatively normal EEG. -> other causes of chronic mental status changes = static encephalopathy 2/2 head injury, anoxia, cogential abnoramlities ->Intellectual disability= impaired general intellectual ability and adaptive function originating during development that is approximately two or more standard deviations below average an important goal is often to distinguish delirium versus dementia.

Alexia and agraphia - what do these terms mean? Does aphasia have to be present? Are either of these sx always present w/ aphasia?

impairments in reading and writing ability, respectively (think dyslexia) can occur together or in isolation caused by deficits in central language processing and not simply sensory or motor deficits ; Lesions that cause aphasia are the most common cause of alexia and agraphia, but aphasia does not have to be present for these sx to exist. In patients with aphasia, agraphia is invariably present. -> normal writing requires intact functioning of the entire language apparatus. When alexia or agraphia occurs as part of an aphasic disorder, the reading and writing abnormalities tend to parallel those of the aphasic syndrome for spoken language. -> Writing in Broca's aphasia is usually performed with the ipsilateral (usually left) nonparetic hand and is labored, agrammatical, and sparse. Writing in Wernicke's aphasia is paraphasic and largely incomprehensible.

Apraxia:

inability to carry out an action in response to verbal command, , in the absence of any comprehension deficit, motor weakness, or incoordination. -> caused by an inability to formulate the correct movement sequence In mild apraxia, patients may exhibit body part substitution (or "body part as tool")—for example, using their index finger like a toothbrush instead of holding an imaginary toothbrush between their fingers in the normal fashion not a well localized disorder, however, there is an association between aphasia and apraxia of the oral and buccal muscles is particularly common in Broca's aphasia, and in neurodegenerative disorders causing progressive aphasia

Frontal lobe anatomy:

largest region of the brain (1/3 of cerebral cortex) separated from parietal lobes via central sulcus and from temporal lobes via Sylvian fissure see images medial = supplemental motor area, frontal eye fields, micturition inhibitory center Lateral= limbic, Broca's area

Pathophysiology of Alzheimers: What markers are useful in the diagnosis of Alzheimers?

major pathologic changes are cerebral atrophy, neuronal loss, amyloid plaques, and neurofibrillary tangles. occur initially and are most severe in the following locations, in decreasing order: (1) medial temporal lobes, including the amygdala, hippocampal formation (especially CA1), and entorhinal cortex; (2) basal temporal cortex extending over the lateral posterior temporal cortex, parieto-occipital cortex, and posterior cingulate gyrus (including the default mode network); and (3) frontal lobes the primary motor, somatosensory, visual, and auditory cortices are relatively spared Cell loss and neurofibrillary tangles are also prominent in the nucleus basalis, septal nuclei, and nucleus of the diagonal band, where cholinergic projections arise, and to a lesser extent in the locus ceruleus (norepinephrine), and raphe nuclei (serotonin). Amyloid plaques are composed of an insoluble protein core containing β-amyloid, along with apolipoprotein E, surrounded by a rim of abnormal axons and dendrites called dystrophic neurites. -> β-amyloid is a specific protein associated with Alzheimer's disease, derived from proteolytic cleavage of a transmembrane protein of unknown function called amyloid precursor protein (APP). Sequential cleavage of APP by β-secretase and γ-secretase is thought to promote the formation of toxic soluble β-amyloid oligomers -> the ε4 allele of apolipoprotein E (ApoE4) carries a 3-fold increased risk of developing late-onset Alzheimer's disease in heterozygotes and a 15-fold increase in homozygotes.(Aside from age, the strongest risk factor is presence of the ApoE4 allele) Neurofibrillary tangles are intracellular accumulations of hyperphosphorylated microtubule-associated proteins or paired helical filaments known as tau proteins. Alzheimer's disease can rarely be inherited as an autosomal dominant disorder in some families with early onset - mutations= (1) the APP gene located on chromosome 21, (2) the presenilin 1 gene on chromosome 14, and (3) the presenilin 2 gene on chromosome 1. -> Patients with Down's syndrome develop early pathologic and clinical features of Alzheimer's disease after the age of 30 years. FDG-PET to detect regional hypometabolism, amyloid PET to detect brain amyloid-β deposition, or lumbar puncture for CSF Alzheimer's biomarkers such as Aβ42 and tau can be diagnostically helpful. initial sx= memory loss; patients often develop word-finding difficulty, or an anomic aphasia and later may develop other features of posterior temporoparieto-occipital dysfunction, including apraxia and visual-spatial deficits Typically, behavioral abnormalities occur later in this illness than in frontotemporal dementia Treatment: The NMDA glutamate receptor antagonist memantine and several cholinesterase inhibitors, including donepezil, rivastigmine, and galantamine

Corpus callostomy:

performed in cases of medically refractory, poorly localized epilepsy, in which falls are a major problem. The goal in these cases is to prevent propagation to bilateral motor activity -> the right hemisphere is unable to access language functions in the left hemisphere. Therefore, there may be agraphia of the left hand, inability to name objects placed in the left hand with the eyes closed, and inability to read in the left hemifield (usually detectable only with special testing apparatus). Some patients may have difficulty with tasks that require bimanual coordination, and in extreme cases the two hands may even work against each other. -> classic example is a patient who buttons their shirt with one hand while the other hand follows, unbuttoning, right behind.

Wada test:

predicts severe deficits that can happen following callosotomy : could show that a patient is left hemisphere dominant for language but has significant memory function only in the right hemisphere. In this case, callosotomy would disconnect language (left hemisphere) from memory functions (right hemisphere) and could produce a severe verbal memory deficit. Similarly, a patient who writes with the left hand could be found on Wada testing to be left hemisphere dominant for language. In this case, callosotomy would disconnect left hand motor control (right hemisphere) from language (left hemisphere) and could produce agraphia

Deafness and language: cortical deafness vs pure word deafness vs nonverbal auditory agnosia (where is the lesion?)

pts w/ cortical deafness have bilateral lesions of the primary auditory cortex in Heschl's gyrus -> These patients are often aware that a sound has occurred but are unable to interpret verbal stimuli and cannot identify nonverbal stimuli such as a telephone ringing or a dog barking -> completely deaf Pure word deafness (verbal auditory agnosia) = ability to ID nonverbal sounds but cannot understand any spoken words -> unlike in Wernicke's, these pts can speak, read and write normally ; however, they cannot understand speech, even their own -> usually caused by an infarct in the auditory area of the dominant hemisphere that extends to the subcortical white matter, cutting off auditory input from the contralateral hemisphere (disconnection syndrome) nonverbal auditory agnosia: pts understand speech but cannot ID nonverbal sounds (lesion = nondominant hemisphere)

Agraphia without aphasia- 3 instances where this can occur:

seen in lesions of the inferior parietal lobe of the language-dominant hemisphere -> may or may not be a part of Gerstmann syndrome Writing requires focused attention and is therefore usually severely abnormal in patients with global confusional disorders agraphia in the hand ipsilateral to the language-dominant hemisphere can occasionally be seen in lesions of the corpus callosum because of disconnection of language (usually left hemisphere) from motor function (right hemisphere for left hand)

Nondominant hemisphere specialization: How do lesions in either hemisphere affect attention?

specialized for certain nonverbal functions - visuospatial skills, imparting emotional significance to events and language, and for music perception Although the right and left hemispheres are each involved in attention to the contralateral environment, only the right hemisphere is significantly involved in attending to both sides ) [spatial attention]. Lesions of the right hemisphere attention areas usually cause marked inattention to the contralateral (left) side, even in individuals who are right hemisphere dominant for language. Right hemisphere specialization for spatial attention may therefore be even more highly conserved than left hemisphere dominance for language. => nondominant (usually right) hemisphere lesions cause impairments of spatial attention and complex visual-spatial abilities, especially those involving spatial orientation and perception of the overall integrated visual-spatial gestalt, or big picture -> the parietal association cortex at the junction of the parietal, temporal, and occipital lobes is especially important for spatial analysis (R side) -> visual information is analyzed by two streams of higher-order information processing: a "What?" stream in the ventral occipital, temporal, and prefrontal cortex, and a "Where?" stream in the dorsal occipital, parietal, and prefrontal cortex; -> The parietal association cortex lies directly in the dorsal stream, analyzing location and movement of visual objects in space. The posterior parietal cortex is also ideally situated to integrate other sources of spatial information from adjacent cortical areas. -> Spatial analysis thus encompasses both the surrounding environment and the relative position of the individual's body in space, using visual, proprioceptive, vestibular, auditory, and other information from adjacent cortical areas -> ATTENTION: -attention (like alertness and awareness) depends on the medial and intralaminar thalamic nuclei and its many projections -lesions of the right hemisphere often lead to prominent and long-lasting deficits in attention to the contralateral side -The hemispheric asymmetry of attentional mechanisms, and the effects of lesions, are shown schematically with "attention rays"; Under normal conditions, the right hemisphere attends strongly to the left side and less strongly to the right side, while the left hemisphere attends mainly to the right side. The result is a very slight net attentional bias toward the left in most individuals, which may explain why many languages are written from left to right. SEE CHART TO UNDERSTAND NONDOMINANT LESIOSN Pts w/ lesions in the right hemisphere who do not have severe hemineglect syndrome can still present w/ difficulty in visual-spatial analysis or constructional abilities (esp when it is the right parietal lobe lesion) -> tend to make errors in the overall organization of the picture or block design, often rotating elements inappropriately in space. In contrast, patients with dominant-hemisphere lesions tend to understand the overall concept yet omit certain important details. -> Patients with nondominant-hemisphere lesions often have relatively severe personality and emotional changes. They may appear bland or apathetic and, in addition to hemineglect, they often display an overall decrease in the level of alertness and attention, especially if they have acute lesions. On the other hand, irritability is common. Patients with acute right parietal infarcts sometimes exhibit bilateral ptosis, lying in bed with both eyes forcibly closed, and become quite irascible when one attempts to examine them. Some patients are overtly psychotic and have delusions and hallucinations. Patients with nondominant hemisphere lesions also often have difficulty comprehending the emotional content of others' speech (receptive aprosody) and conveying appropriate emotional expression in their own speech (expressive aprosody). Other right hemisphere lesion presentations: - right temporal seizures or lesions: déjà vu and other mystical or religious phenomena. - Capgras syndrome, in which patients insist that their friends or family members have all been replaced by identical-looking imposters; - Fregoli syndrome, in which patients believe that different people are actually the same person who is in disguise; - reduplicative paramnesia, in which patients believe that a person, place, or object exists as two identical copies. **assoc w/ Lewy body dementia as well (according to psych- Capgras and reduplicative paramnesia are synonymous)

Brain lesion localization - what caution must be taken to avoid false localization?

the brain is both a collection of specialized areas and a cluster of network connections involving multiple areas -> Localized regions of the brain do carry out specific functions, but they do so through network interactions with many other regions Hence, focal brain lesions can cause specific deficits, however, false localization can occur because of the network connection mediation. For example, so-called frontal lobe functions involve networks that encompass diverse regions including the frontal, parietal, and limbic cortices; thalamus; basal ganglia; cerebellum; and brainstem. Therefore, lesions in these other structures, or in their white matter connections, can sometimes produce deficits that mimic frontal lobe lesions.

Unimodal vs heteromodal association cortices:

unimodal = modality specific -> somatosensory, visual, auditory, motor (premotor and supplementary motor) -> Unimodal sensory association cortex receives its predominant input from primary sensory cortex of a specific sensory modality and performs higher-order sensory processing for that modality. Unimodal motor association cortex projects predominantly to primary motor cortex, and it is important in formulating the motor program for complex actions involving multiple joints. heteromodal = higher order mental functions that require integration of abstract sensory and motor information from unimodal association cortex, together w/ emotional and motivational influences from the limbic cortex -> bidirectional connections w/ both motor and sensory association cortex of all modalities and w/ limbic cortex -> Heteromodal association cortex is found in the frontal lobes (prefrontal cortex) and at the parieto-occipitotemporal junctions (parietal and temporal heteromodal association cortex)

Other lesions that can cause visual disturbances:

visual reorientation: environment appears tilted or inverted to the pt (associated with vestibular or lateral medullary dysfunction) palinopsia: lesions of the visual association cortex cause a previously seen object to reappear periodically -> ex. patient looked at a plant, and then a few minutes later the plant reappeared and seemed to be growing out of her omelet. -> can occasionally be caused by medications, including trazodone, topiramate, risperidone cerebral diplopia/polyplopia: pt seems more than 1 image; monocular or binocular double vision, triple vision, and so on can also occasionally be seen with occipital lesions, corneal lesions, or cataracts erythropsia: which is characterized by gold, red, purple, or other unnatural coloring of the visual field Digitalis toxicity: objects appear to have yellowish halo

Disconnection syndromes:

white matter lesions based on the result of network properties of brain function For example, when a lesion in the white matter disconnects the network connections between visual cortex and the language processing areas, a patient may lose the ability to read. Many functions are carried out through combinations of different specialized skills of L and R hemispheres and are mediated by distributed networks involving frontoparietal connections, connections w/ limbic memory structures, and reciprocal connections w/ subcortical nuclei ; Lesions that disconnect these networks, either within one hemisphere or between hemispheres at the corpus callosum, can cause specific disconnection syndromes