Cortex, cognition and dementia Flashcards
Which layers in the cortex are classically input? Classically output?
input - layer IV output - layer V and VI Primary visual cortex will have a much larger layer IV and small layer V and VI Primary motor cortex will have a much larger layer V and IV and small layer IV
What are the two major categories of cortical neurons? What are their characteristics?
pyramidal cells - principal output cells whose axon leaves the cortex, glutaminergic (excitatory), have spines which receives excitatory input non-pyramidal cells - some are GABAergic interneurons that project locally and do NOT leave the cortex; others are glutaminergic spiny stellate neurons in layer IV that receive input from thalamus
Where do layer VI pyramidal neurons go? Where do layer V pyramidal neurons go? Layer II and III?
VI - thalamus V - striatum, brainstem, spinal cord, corticocortical projections II and III - corticocortical projections
Which layer of pyramidal neurons degenerate in ALS? what part of the cortex degenerates in ALS?
pyramidal neurons in layer V of the primary motor cortex degenerate in ALS
What are the major subtypes of GABAergic interneurons in the cortex? Where do they project?
basket cells - cell body of pyramidal cell chandelier cells - initial segment of the axon of pyramidal cell double bouquet cells - dendritic spines of pyramidal cells
What are the extra thalamic subcortical afferents to the cortex?
monoaminergic projections: 1) dopamine from the ventral segmental area (midbrain) 2) norepinephrine from the locus ceruleus (pons) 3) serotonin from the dorsal raphe (midbrain) 4) acetylcholine from nucleus basalis
Damage to the occipito-temporal region of the brain will result in what syndromes?
damage to the “what” cortex prosopagnosia - inability to recognize faces or learn news faces visual object agnosia - inability to recognize the generic class of an object
Damage to the occipito-parietal region of the brain will result in what syndrome?
Damage to the “where” cortex (visual-spacial cortex) Balint’s syndrome - impairment of pointing to a target, inability to shift gaze to new visual stimuli, can’t see more than one thing at a time
Where in the brain is the “no-go” signal/”the brakes” initiated?
orbital prefrontal cortex
Where in the brain is the “go” signal initiated?
medial frontal lobe (anterior cingulate cortex)
What is the function of Wernicke’s area? Of the transcortical sensory area? Of Broca’s area? Of the transcortical motor area? Of the arcuate fasciculus?
Wernicke’s area - detects auditory stimuli and identifies these stimuli as having linguistic value; location of our “dictionary”
Transcortical sensory area - determines what the auditory stimuli actually means
Transcortical motor area - assembles language in the correct structure and syntax
Broca’s area - final motor output for language
arcuate fasciculus - connects Wernicke’s area and Broca’s area; important for language repetition
What are the characteristics of Broca’s aphasia?
non-fluent speech; effortful or frustrated speech
missing relational words (articles and conjuntions) so the speech becomes “telegraphic” or “text speech.”
What are the characteristics of transcortical motor aphasia?
impaired fluency
preserved comprehension
preserved repetition
What are the characteristics of Wernicke’s aphasia?
impaired comprehension
syntactically correct language but the words don’t mean anything
What are the characteristics of a transcortical sensory aphasia?
preserved repetition and fluency
Impaired comprehension
What are the characteristics of a conduction aphasia (damage to the arcuate fasciculus)?
impaired repetition
preserved fluency and comprehension
What do the areas in the non-dominant hemisphere that correspond to Wernicke’s and Broca’s area do?
Non-dominant Wernicke’s area - detects prosody (patterns of stress in language)
Non-dominant Broca’s area - imbuing prosody into speech
What is alexia without agraphia?
A disconnection syndrome due to infarct of the splenium of the corpus callosuma and left visual cortex (PCA infarct)
The patient can write but cannot read because the left visual cortex has been damaged and thus, cannot send information to the language areas. The right visual cortex is functional but is unable to send this information to the language areas (Broca’s area, Wernicke’s area, etc.) in the left brain because of the damage to the splenium of the corpus callosum
What part of the brain is reponsible for attention? For registration? Evaluation for relevance? For encoding? For storage/consolidation?
attention - anterior cingulate gyrus and parietal lobe
registration - primary sensory cortex and prefrontal cortex
evaluation for relevance - limbic, anterior cingulate gyrus, dorsolateral prefrontal cortex
encoding - hippocampus
storage - diffuse, distributed circuitry (older memories are more distributed and newer memories are more localized and thus more fragile)
What is Capgras syndrome?
Head trauma causes patients to have delusions that the people around him/her are imposters of people he knows
Disconnect between visual information and emotional information (amygdala)
The dominant parietal lobe pays attention to what area of space? The non-dominant parietal lobe pays attention to what area of space? What would happen to your attention if you knocked out the dominant parietal lobe? The non-dominant parietal lobe?
Dominant parietal lobe pays attention to the contralateral visual field
The non-dominant parietal lobe pays attention to both visual fields (ipsilateral and contralateral)
If you knocked out the dominant parietal lobe, you would still be able to pay attention to everything in your visual fields
If you knocked out the non-dominant parietal lobe, you would neglect half of the world (usually the left half because the left hemisphere is usually dominant)
What is an agnosia?
Intact perception of a stimulus but dysfunction of associational sensory processing which leads to impaired recognition (The Man Who Mistook His Wife for a Hat)
What is anosagnosia? What is an example of anosagnosia?
an inability to recognize one’s own deficit
Anton’s syndrome is when a patient is blind due to damage to the visual cortex but is unaware that they are blind
What is dyspraxia?
Inability to preform a previously learned motor task
Where are learned motor tasks (praxicon) stored?
dominant parietal lobe
What parts of the prefrontal cortex are involved in executive functions?
dorsolateral prefrontal cortex - how to go
anterior cingulate gyrus - initiation/”go”
orbital frontal cortex - “no-go”/the brakes
What are the reversible causes of dementia?
Hypothyroidism
normal pressure hydrocephalus
dietary deficiencies (Vit B12 deficiency)
Infection (neurosyphillis)
depression
tumor
What are the histological hallmarks of Alzheimer’s disease?
hyperphosphorylated tau proteins that form intracellular neurofibrillary tangles
extracellular deposits of beta-amyloid plaques
cerebral cortical atrophy with dilatation of lateral ventricles
hippocampal atrophy with dilation of temporal horn of the lateral ventricles
Loss of cholinergic neurons in cortico-cortical projections
What genetic mutations are associated with early-onset Alzheimer’s dementia?
Chromosome 21: amyloid precursor protein (patients with down syndrome have an increased risk of Alzheimers)
chromosome 14: presenilin 1
chromosome 1: presenilin 2
Chromosome 19: ApoE (apoE4 allele increases risk of Alzheimers)
How is amyloid precursor protein normally processed? How is APP processed in Alzheimer’s disease?
Upregulation of beta-secretase in Alzheimer’s
What are the pharmacological treatments of alzheimer’s disease? What are the experimental treatements?
acetylcholinesterase inhibitors - rivastigmine, donepezil, galantamine
NMDA receptor antagonist - memantine (AD is thought to result from an imbalance between glutaminergic and cholinergic synapses. Since the cholinergic synapses are dying, knocking out the glutaminergic signals might restore that balance)
Experimental: antibodies against A-beta protein; plaque busters; beta and gamma secretase modulators; A-beta clearance enhancers
What is the function of the ascending reticular activating system? What neurotransmitter does it use?
ARAS functions in arousal
Utilized acetylcholine
What breathing pattern is associated with diffuse forebrain dysfunction?
Cheyne-Stokes respiration
What breathing pattern is associated with midbrain injury?
hyperventilation
What pattern of breathing is associated with an injury to the rostral pons?
apneusis (deep, gasping inspiration with a pause at full inspiration followed by a brief, insufficient release)
What pattern of breathing is associated with an injury to the caudal pons?
ataxic breathing (completely irregular breathing with increasing periods of apnea)
What pattern of breathing is associated with injury to the medulla?
respiratory arrest
What characteristics of pupillary size and reactivity are associated with damage to the thalamus? Damage to the pretectum? Damage to the midbrain? damage to the pons? Herniation of uncus?
Thalamic pupil - small and reactive
pretectal pupil - dilated and fixed
midbrain pupil - normal size and fixed
pons pupil - pinpoint and fixed
uncal herniation pupil - one fixed, very dilated pupil, the other pupil is normal
The hypothalamus gives rise to the sympathetic nerves. Lesions above the hypothalamus (i.e. thalamic lesions) will spare the sympathetic pathway and allow for normal dilation and constriction. Lesions below the hypothalamus (pretectal, midbrain, pons) will knock out the sympathetic pathway, leading to a fixed pupil
If a patient is in decorticate positioning, where is his lesion? How is he positioned?
Lesion in upper midbrain - decorticate positioning
bent arms, clenched fists and legs out straight
If a patient is in decerebrate positioning, where is his lesion? How is he positioned?
lesion in the upper pons = decerebrate posturing
arms and legs held straight out, toes pointed downward, head and neck arched backwards
What are the reversible causes of dementia? What are their clinical manifestations?
- Normal pressure hydrocephalus - wet, wobbly and wacky
- Vitamin B12 deficiency - peripheral neuropathy, pernicious anemia, ataxia
- hypothyroidism - cold hands, dry skin, weight gain
- HIV associated neurocognitive disorder (HAND) - long standing low CD4 counts
- neurosyphillis - tabes dorsalis, argyll-robertson pupil
- Wilson’s disease - Parkinsonism symptoms, Kaiser-flescher rings, liver failure
What are the irreversible causes of dementia?
- Alzheimer’s disease
- Huntington’s disease
- Lewy Body disease
- Frontal-temporal dementia
- Vascular dementia
- CJD
What areas of the brain is usually effected in Alzheimer’s disease? In Lewy Body disease? In Huntington’s disease?
- Alzheimer’s disease - hippocampus and cortex
- Lewy Body disease - substantia nigra and cortex
- Huntington’s disease - caudate nucleus atrophies
What are the findings on pathology of the irreversible causes of dementia?
- AD - hyperphosphorylated Tau tangles and beta amyloid plaques
- vascular dementia - red neurons and gliosis/glial scar
- Lewy body dementia - alpha-synuclein and ubiquitin in cells
- Fronto-temporal dementia - Tau inclusions
- Huntington’s disease - none
- CJD - spongiform appearance
What are the genetic mutations associated with Alzheimer’s disease?
APP on chromosome 21 (explains why people with Down’s syndrome get early AD)
PSEN1 and PSEN2
ApoE gene allele epsilon4
What is the difference between memory loss in normal aging and Alzheimer’s disease?
Alzheimer’s is thought to be caused by neuronal death but normal aging is thought to be caused by a loss of plasticity in dendritic spines
What are the two types of dendritic spines? What is their function?
Large Mushroom spines - stable, AMPA receptors, functions in storing expertise
Thin spines - can expand or retract, NMDA receptors, functions in learning
What drugs are used to treat Alzheimer’s disease?
Anticholinergics (acetylcholinesterases) - donepazil, rivastigmine, galantamine
Memantine - NMDA receptor antagonist which blocks glutamate excitotoxicity
