Week 3/4 Lectures Flashcards
Conductive disorders are principally found in ____.
middle ear –> treatable and reversibl (blockage of sound conducting path from source to cochlea)
Sensorineural hearing loss arises principally in _____.
cochlea –> damage or loss of hair cells + auditory nerve connections, damage to central auditory pathway –> irreversable
T/F Complete deafness can be overcome.
T –>cochlear implant
Natural hearing loss with age is called _____.
Presbycusis
T/F Hearing loss is a predictor of dementia.
T
The amount of condensation in sound translates to a perception of _____.
loudness
The time it takes a sound to go from maximum condensation to the next maximum condensation (or rarefaction) translates to a perception of _____.
pitch
Components of the labyrinth
vestibular (dorsal) and cochlear (ventral segments + outer bony perimeter and membranouse labyrinth soft tissue chamber–> set of channels carved into temporal bone during development
Chambers of the cochlea
upper (Scala vestibuli), meiddle (Scala media), and lower (Scala tympani)
Which cochlear chambers are filled with endolymph?
middle (upper and lower have perilymph)
The vibrational input from the stapes is into the scala ______ and the pressure release of these vibrations is via the round window at the end of scala _____.
vestibuli and tympani
Endolymph is a filtrate of _____ and enters the inner ear via the ________.
CSF and endolymphatic duct
Endolymphatic potential
+80mV in scala media
Two organ of Corti sensory cells
1 row of inner hair cells (afferent to brain) and three rows of outer hair cells (hearing sensitivity)
The tallest row of the sensory hairs on the hair cells are in contact with an acellular overlying membrane, the _________.
tectorial membrane –> Up
and down movements of the organ of Corti during sound stimulation will cause a deflection of the sensory hairs (stereocilia).
What happens when tiplinks are open?
Inner hair cells: Influx of K+ into hair cell –>depolarization –> synaptic release –> glutamate AP /// Outer hair cells –> prestin contraction
What happens when tiplinks are closed
hyperpolarization
High frequency sounds elicit vibrations at the _____ of the basilar membrane.
Base
Low frequency sounds elicit vibrations at the ____ of the basilar membrane
apex
Tonotopic organization
frequency to place translation along hte basilar membrane –> high to low from base to apex
Phasic depolarizations of hair cells occur at high/low frequencies.
low (steady state depolarization with high frequency)
T/F Outer hair cells have efferent feedback from the brain
T
T/F Axons themselves, by virtue of its position of origin, “tells” the CNS the frequency carried in that “wire” independent of any discharge code itself.
T –> labeled line scheme of sensory coding
T/F Mechanical tuning of the basilar membrane and neural tuning of auditory nerve discharges are the same for the same cochlear location.
T –> tuning properties of basilar membrane require sound intensity to achieve displacement at a given frequency; same for nerve –> direct transfer
Prestin
outer hair cells are sensory and motor effectors –> feedbacks energy into the basilar membrane to boost inner hair cell stimulus –> selective attention
T/F Destruction of outer hair cells and the sharpness of type 1 afferent tuning curves from inner hair cells are greatly blunted.
T –> less sharp/exhibit poorer frequency selectivity
T/F There are more unmyelinated auditory nerve axons than myelinated.
F –> more type 1 myelinated afferents per IHC//fewer type ii afferents per OHC
Auditory pathway
hair cell –> cochlear nuclei (3)–> trapezoid body –> superior olivary nuclei –> lateral lemniscus –> inferior colliculus –> medial geniculate- ->auditory cortex
First binaural input in the auditory system
superior olivary nuclei
Interaural time difference
CNS detects sound delay between two ears –> superior olivary nucleus
MSO
measures interaural time differences (medial superior olive) –> if excitatory input from the two ears (contralateral and ipsilateral) arrive at a cell in the MSO at the same time noncoincidentally –> MSO acitvated –>temporal map in the MSO for specific time differences
LSO
measures interaural volume differences
The ipsilateral ear provides ______ input to the LSO cell while the contralateral ear provides _____ input.
excitatory vs inhibitory
T/F detection of sound in the vertical plane requires only one ear.
T –> ear can calculate differences in combined sounds from direct and reflected pathway
The output axons from the MG form the __________ and project to the auditory cortex.
auditory cortical radiations
3 main levels of auditory cortex processing
core (tonotopic + simple sounds), belt and parabelt (no tonotopicness +complex sounds)
3 primary auditory cortices
A1, Rostral, Rostrotemporal
Arcuate fasciculus deficit
can understand speech, can encode speech, but can’t respond appropriately –> connects frontal, parietal, temporal
T/F there are clear frequency gradients in the core auditory cortex [R and A1] and that these gradients become less clear outside of the core.
T
T/F selectivity for certain types of sounds increases between the primary and non-primary auditory cortices
T
What problem do older folks and people with hearing aids have with auditory processing?
cannot distinguish sources of different sounds//disentagle single waveforms to distinct sounds
How the brain distinguishes sounds
detect regularities–> form auditory objects (e.g. location, similarity in timbre/pitch, proximity in space/time, continuity in direction, common fate)
Proximity
a stimulus with similar frequencies tend be heard as a single sound –> frequency proximity; with disparate frequencies –> two sounds
Perceptual categories
forming representations of stimulus-invariant representations of auditory objects
Abstract categories
based on higher order or semantic information;; not based wholly on perceptual similarity
Ventral auditory streams code what features of a sound?
identity
Dorsal auditory streams code what features of a sound?
where a sound is
The primary olfactory sensory neurons (olfactory receptor neurons) are located in the______.
neuroepithelium in the nose
Axons of olfactory receptors are myelinated/unmyelinated
unmyelinated
Second order neurons for smell are where?
olfactory bulb
Smell pathway
olfactory receptors –> olfactory bulb –> olfactory tract –>pyriform cortex (smell perception), amygdala (odor emotions) –> frontal cortex, hippocampus (memory), and hypothalamus (hormone/autonomic response)
T/F humans have a functional vomeronasal organ for pheremone sense.
F
Smell is ipsilateral/contralateral
ipisilateral
T/F OSN or receptor cells regenerate throughout life
T –> cilitated bipolar neurons, supported by glia-like cells, regnerated by basal stemcell-like cells
Odor g-protein
odor –> Golf –> adneylyl cyclase- ->cAMP –> CNG channels –> Cl- channel –> depolarization (Na/Ca in, Cl out) –> AP
T/F odor quality and intensity are encoded by combinations of receptors/neurons.
T –> population coding at epithelial level
Olfactory glomeruli
axons of sensory neurons synapse with bulb neurons forming neuropils (dense axonal network) –> glomeruli // a few glomeruli receive axons of OSNs with the same receptor
3 cell types in olfactory bulb
mitral/tufted (inputs from OSNs), periglomerular (modulate/temper inputs to mitral/tufted cells), granule (modulate output from tufted cells to cortex)
Piriform Cortical Nuerons
two synapses away from sensory input –> mitral cells project diffusely to the cortex, enabling individual cortical neurons to assemble convergent input from mitral cells from different glomeruli
T/F Odor representation is distributed without apparent spatial preference.
T
Anosmia
absence of smell
Hyposmia/hyperosmia
decreased/increased smell sensation
dysosmia
distortion of smell
phantosmia
dysosmia in the absence of appropriate stimulus
Olfactory agnosia
inability to recognize odor sensation
5 modalities of taste
salty, sour, bitter, sweet, umami (AA)
Taste pathway
taste buds (cirumvallate, foliate, fungiform) –> sensory neurons –>facial, glossopharyngeal, vagus –> solitary tract –> VPM –> ipsilateral, primary gustatory cortex in insula
Gustatory coding
different taste modalities by different taste mechanisms –> salty = ENaC; sour = H+ ions through transient receptor potential channel; sweet = T1R2+T1R3, Umami = T1R1+T1R3, Bitter = T2R
Labeled-line coding
each modality of taste is detected by distinct, non-overlapping receptor cells
Anosmia
absence of smell
Hyposmia/hyperosmia
decreased/increased smell sensation
Hyposmia/hyperosmia
decreased/increased smell sensation
dysosmia
distortion of smell
dysosmia
distortion of smell
phantosmia
dysosmia in the absence of appropriate stimulus
phantosmia
dysosmia in the absence of appropriate stimulus
Olfactory agnosia
inability to recognize odor sensation
Olfactory agnosia
inability to recognize odor sensation
5 modalities of taste
salty, sour, bitter, sweet, umami (AA)
5 modalities of taste
salty, sour, bitter, sweet, umami (AA)
Taste pathway
taste buds (cirumvallate, foliate, fungiform) –> sensory neurons –>facial, glossopharyngeal, vagus –> solitary tract –> VPM –> ipsilateral, primary gustatory cortex in insula
Gustatory coding
different taste modalities by different taste mechanisms –> salty = ENaC; sour = H+ ions through transient receptor potential channel; sweet = T1R2+T1R3, Umami = T1R1+T1R3, Bitter = T2R
Labeled-line coding
each modality of taste is detected by distinct, non-overlapping receptor cells
T/F the sense of flavor results from integration of olfactory, gustatory, and somatosensory inputs.
T –> 70/80% = ofactory, gustatory/somatosensory = everything else
T/F Interocular muscles have no stretch receptors.
T
T/F interocular muscles have a medium twitch time.
F –> fast
T/F While different neural subsystems provide for the various types of eye movements, the final executor of all eye movements are
the motorneurons
T
Which muscle does a given oculomotor nucleus innervate contralaterally?
superior rectus
Pulse and step system
the firing rate must consist of a large, high frequency pulse (burst) followed by a much smaller step (the burst to overcome the inertia/viscous resistance followed by a step to overcome the elastic restoring forces and hold the eye in its new position)
The pulse generator for horizontal eye movements is in the
Paramedian pontine reticular formation
Horizontal saccade pathway
FEF + Superior colliculus –> PPRF –> integrator –> Nucleus of 6 –> lateral rectus
The neural integrator for horizontal eye movements is in the __________
nucleus prepositus hypoglossi –> ensures appropriate step for nuc 6
vertical saccades with the pulse generator in the _________________
rostral interstitial nucleus of the MLF
The superior colliculus mediates ________
“express saccades”, very short latency (~100 msecs) saccadic eye movements in response to the sudden appearance of a visual or auditory stimulus
T/F about half the neurons in the abducens nucleus do not innervate the lateral rectus but instead, they innervate the medial rectus subdivision of the oculomotor complex on the other side
T –> innervation of the medial rectus of one eye and the lateral rectus of the other are always equal. This is the ‘neural yoke’ that provides for the conjugacy of eye movements under normal circumstances
The outputs of semicircular canals, utricles, and sacculus are carried by axons in 8 vestibular whose cell bodies are in ______.
scarpa’s ganglion
In the utricle and saccule, the cilia protrude through a gelatinous layer in which are suspended large numbers of calcium carbonate crystals called _________
otoconia
In the semicircular canals, the kinocillia are embedded in a gelatinous mass called the _____
cupula –> barrier blocking the circulation of endolymphatic fluid. When the head turns in the plane of a canal, the inertia of the fluid distorts the cupula in the direction opposite to the head movement which bends the cilia and produces increased or decreased firing in the 8th nerve terminals at the base of the cupula
T/F linear acceleration of the head produces equal forces on the two sides of the canal and no net signal
T
In angular acceleration, which canal increases its discharge rate
on the side toward which the head is rotating
The afferents from the SSCs carry a signal proportional to head velocity but only
when ______
when head acceleration is not zero
The purpose of the ___ is to provide stability of gaze in spite of head movements
VOR
Nystagmus is named for which phase?
fast –> eg moving head to left produces a left beating nystagmus
The fast phase of nystagmus is directed _____ to the lesioned side.
opposite
COWS
cold water opposite, warm water same, i.e., irrigation of the left horizontal canal with cold water produces a nystagmus with the fast phase towards the right,
______ is defined as the ratio of the output magnitude to the input magnitude of VOR.
gain–> eye movement divided by the head
movement
vestibular pathway
vestibular nuclei –> cross midline –> medial lemniscus –> ascend to vpm –> parietal/vestibular cortex and vestibulospinal tract –> balance and posture
A nearly flat lens has a ____ focal length and will be_____.
long and weak –> power = only a few diopters (diopters = 1/focal length = power | focal length ~ image distance ~ diameter of the eye = 17mm) –> refractive power of the eye is approximately 58D
During accommodation, the ciliary muscle contracts, making the lens _____.
more spherical –> increasing the refractive power of the eye –> near objects
3 layers of retinal cells
ganglion cells, inner nuclear layer (bipolar, horizontal, amacrine) , outer nuclear layer (photoreceptors) + 2 plexiform layers
function of choroid
capture extra light and reduce scatter by reflection –> increase acuity
fovea contains _____
cones
T/F there are multiple rod pigments.
F –> only one rod pigment –> scotopic/dark vision
T/F rods are key structures in lit environments.
F –> don’t do anything; cones do all color processing
The switching between domination of the ganglion cells by either rods or cones takes place at the level of ____________ in the inner plexiform layer.
amacrine cells
Rhodopsin pathway
photoactivation –> G protein –> cGMP 5’ –> gated Na+ channel kept open by high concentrations of cGMP in dark/opposite in light
In the dark, the outer segment of the rod has _____ permeabilities for Na/K so the photoreceptors are _______
equal; depoloarized and releaseing glutamate
light _______ photorecepotrs to ______ the action of gluatmate on next cells in pathway.
hyperpolarize and decrease
On bipolars, glutamate is _______
inhibitory –> cells are hyperpolarized in the dark and become depolarized as light level increase
Off bipolars, glutame is _______
excitatory –> cells are depolarized in dark and become less depolarized as light increases
_________ carry information about light increments and ______ constitute a channel that carries information about light decrements.
On vs Off bipolars
_________ in the retina generate APs
ganglion cells –> all other cells communicate with graded synaptic release
H cells
lateral pathway in retina –> outer plexiform layer–> collect output of many photoreceptors and presynaptic to bipolar cells –> GABAergic and is opposite to the photoreceptor input –> contrast/receptive field differences
______cells receive from single cone bipolars (small RFs) and convert the input to firing rates
P ganglion
_______ cells receive from many bipolars (large RFs) and are especially responsive to motion.
M ganglion
Which part of the visual field is smallest?
the nasal visual fields
Cortical magnification factor
Want to focus brain on center of vision/macular vision –> 1/3-1/2 of the occipital lobe (posterior of lobe)
Visual field deficit: Lesion of right meyer’s loop
upper left quadrant of each eye’s visual field –>left homonymous quadrantanopsia
Visual field deficit: Lesion of right optic nerve
right eye visual field but normal left eye visual field
Visual field deficit: Lesion of optic chiasm
no temporal vision –> bitemporal hemianopia
Visual field deficit: lesion of right optic tract/radiation
(after chiasm) –> no left side field in either eye –> left homonymous hemianopia
Visual field deficit: lesion of right striate
no left field in either eye
The most common etiology of chiasmal deficit in adults
pituitary tumor
Dorsal visual pathway
M retinal ganglion cells –> magnocell layers of LGN 1 and 2 –> V1 striate cortex (IVB) –> thick CO stripes in V2–> V5 parietal and MT –> Parietal lobe –>where pathway
Ventral visual pathway
P retinal ganglion cells –> Parvocell layers of LGN 3-6 –> V1, II-III –> pale stripes in V2 –> V4 –> Inf. temporal lobe –>what pathway
“What” pathway disorders
alexia without agraphia; visual agnosias and prosopagnosia, cerebral hemi-acrhomatopsia
“Where” pathway disorders
hemi-neglect, balint’s syndrome/simultanagnosia, akinetopsia
Alexia without agraphia
unable to read, able to write + right homonymous hemianopsia –> left occipital lobe + left splenium of corpus callosum
Visual agnosia and prosopagnosia
inability to recognize objects (appercetive and associative); prosopagnosia = unable to recognize faces –> oocipito-temporal (often bilateral –> fusiform face area in medial temporal lobe)
cerebral hemiacromatopsia
lack of color vision in homonymous hemifield, upper quandrantanopsia –> fusiform and lingual gyri in inferior occipital lobe (V4)
Hemi-neglect
ignore or unaware of objects in left hemispace –> right parietal lobe
Balint’s syndrome
simultangosia (can’t put together a scene from parts), ocular apraxia (inability to move eyes under guidance), optic ataxia (inability to reach under guidance) –> bilateral parieto-occipital
akinetopsia
inability to perceive motion –> v5 of lateral occipital parietal temporal lobe
superior colliculus
midbrain structure; orients head and eye movements –> inputs = mostly m cells from retina
pretectal nuclei
receives inputs from RGCs and sends efferents are to the EW nuclei on both sides (via post. commissure) –> preganglionic parasympathetics to ciliary ganglion
accessory optic nuclei
reflex following movements
suprachiasmatic nuclei
optic nerve input synchronizes circadian rhythm to light/dark cycle –> about 1% of “other” RGCs project here
lateral geniculate nucleus
thalamic relay nucleus for primary visual cortex –> input from M and P cells
In the LGN, On/Off cells are separated in ____ layers.
P
Layer organization of LGN
1/2 = magnocellular; 3-6 = parvocellular; 1,4, 6 contralateral; 2,3,5 ipsilateral
T./F the LGN has binocular cells.
F
T/F midget and parasol cells are kept separate in the LGN.
T
T/F djacent points on the retina are represented by adjacent points in the LGN.
T –> produces a map of the contralateral hemifield in each LGN
T/F loss of an eye can cause anterograde transsynaptic degeneration in the LGNs
true
LGN gating
when animal is awake, there are active inputs in the brainstem that keep thalamic cells depolarized, Ca channels are inactivated, gate is open, and RGC activity relayed to cortex vs. at sleep, Ca channels are active, LGN cells are bursty and unpatterned
T/F striate cortex/ V1 is retinotopically organized.
T –> upper/lower banks with fovea as occipital pole
M pathway
M cell –> magnocellular LGN –> IVCbeta–> IVB –> thickstriped V2 and MT –>PPA
P pathway
P cells –> parvocellular LGN –> IVCbeta –> blobs –> thinstripes and innerstripes of V2 and V4–>ITC
Both M and P cortical pathways send axons into layers V and VI which are the originas of major pathways to ________ anda major feedback to the _____.
pontine nuclei + superior colliculus and LGN
Cells in layer ______ encode the presence of features in the visual scene and their distance from the observer and their motion
IVB
____ are the first neurons in the visual system with binocular RFs
cells in IVB
Lateral connectivity of visual cortex
excitatory, for cells with like orientations, between columns with nonoverlapping RFs
Striate organization
Retinotopically organized; LGN axons terminate in layer IVC with M and P inputs and LE/RE inputs separate; Modular: orientation, ocular dominance, color; Binocular cells (stereopsis)–layer IVb; Diverse outputs: superior colliculus, pontine nuclei, LGN, other cortical areas;M and P largely separate all the way through; Long range connections modify responses elicited from the receptive field
like orientation rule
two cells fire synchronously when their RFs have the same orientation even when their RFs are widely separated in the visual field
Any visual cortex outside of V1 is called _______ and receives input from _________.
extrastriate and V1 and pulvinar
T/F V1 and V2 have similar modular structure.
F. Both are modular. V1 has blobs while V2 has thick, thin, and interstripes
MT (V5) is the homunculus for ____
motion –> direction but not orientation selective
columns of cells in MT respond best to what element of motion?
same direction of motion
Aperture problem
if the RF is smaller than the object moving across the field, can’t tell the direction of the object –> multiple RFs allow you to determine motion of object
V4
no special motion processing, mostly color coded, orientation selective –> lesions produce achromatopsia
Color constancy
correction for spectral properties of the illuminant (kind of like white balance)
Speech is usually lateralized in the _____ hemisphere of right handed adults.
left
The left Sylvian fissure is _________ than right Sylvian fissure in right handers
longer and more horizontal
3 relevant areas for language disorders
Broca’s, Wernicke’s, and Arcuate fasiculus
In right handers, Broca’s and Wernicke’s are larger in _____ hemisphere.
left
Speech is lateralized to ____ hemisphere in left handers.
Both or one or the other but both hemispheres are activated in fMRI
_______ more likely to be aphasic following left or right hemisphere insult.
Lefthanders –> but milder and briefer
T/F speech lateralization is affected by experience.
T
Right handed illiterates and partial illiterates are ____ likely to have strongly lateralized speech.
less
4 clinical features of speech
fluency, comprehension, repetition, naming
Fluency
Non-fluent = effortful, agrammatic, telegraphic; fluent = melodic but with empty content/circumlocution
Broca’s Aphasia
non fluent speech (effortful, telegraphic, agrammatic), intact single-word comprehension, impaired repetition, impaired/mild naming
Wernicke’s Aphasia
fluent speech (empty, circumlocutory), poor single word comprehension, impaired repeittion, poor naming –> involvement of auditory association cortex
Conduction Aphasia
fluent speech with intact comprehension and naming but poor repetition –> interruption of arcuate fasiculus (often by embolus)
Global Aphasia
everything is poor–> often due to carotid occlusion resulting in damage to entire Sylvian area
Right hemisphere language disorders
impaired prosody, poor comprehension of metaphor and humor, limited grasp of extended discourse
Striatal aphasia
non-fluent speech with preserved repetition
Thalamic aphasia
–> lacunar strokes/parkinson
_______ aphasics have difficulty with grammatical expression and grammatical comprehension
Broca’s
Progressive aphasia
neurodegeneration –> language compromised but preserved memory –> frontotemporal dementia (tauopathy)
Semantic dementia
fluent, empty speech with poor single word comprehension and object comprehension –> cortical atrophy in anterior and ventral temporal lobe
Alexias
- peripheral component (letter by letter reading) and 2. central component (pronouncing sight vocabulary and novel words)
Agraphias
- Peripheral (apractic) and 2. Central (spelling sight vocabulary and novel words)
____ hemisphere is responsible for language and praxis.
Left
_____ hemisphere is responsible for prosody, spatial representation, attention
Right
Hetero-modal association cortex
area with multi-modality information –> radar representation of the environment
Praxis
knowledge of manipulation –> hand use, tool use –> 1. premotor cortex for implementation of motor code and 2. inferior parietal lobule for spatial kinesthetic and understanding of physics/tools
Apraxia
deficit in learned or skilled movements in presence of intact strength/sensation (focal lesions, particularly cortico-basilar ganglionic degeneration, and alzheimers)
Damage to premotor cortex will result in ______ apraxia.
contralateral but will be able to understand movements
Numerosity
parietal lobe function b/c of role of 10 digits in hands
Subitizing and estimating are ____ parietal lobe functions
Right –> rapid, confident apprehension of small quantities and estimating ratios
counting and arithmetic have to do with _____ parietal hemisphere.
left
Gerstmann’s syndrome
left parietal lesion/angular gyrus –> agraphia, acalculia, finger agnosia, R/L confusion –> more general body schemadisturbance aka autopagnosia
the ______ parietal lobe is responsible for visual attention
right –> neglect (MCA stroke)
Anosognosia
unilateral unawareness or denial of defects on one side of body –> neglect
Somatophrenia
patient claims contralateral limbs don’t belong to him/her –> neglect
T/F different lesions result in different neglects.
T –> object (ventral) vs space neglect (dorsal/where)
T/F neurons in the parietal lobe reflect all frames of reference (eyes, body, head)
T
T/F Weaker stimuli are easier to neglect.
T
T/F People with neglect are faster to verify words semantically primed by a picture in their neglected field.
T
Balint’s syndrome
bilateral parietal (advanced tauopathy, prion, PML) –> optic ataxia (can’t reach for targets), ocular apraxia (gaze), simultagnosia (can see one object at a time) –>disorder of reaching and looking
Episodic memory
memory for prior experiences and events –> mental time travel/self related/time/place related–> hippocampal
Anterograde vs. retrogade amnesi
inability to acquire new info vs loss of old info
Item vs associative memory
pictures vs pictures with context
Medial temporal lobe
hippocampus (subiculum, dentate, subfields) and extrahippocampal medial temporal structors (entorhinal, parahippocampal, perirhinal)
_____ receive inputs from both unimodal and multimodal association cortices and provide the major input into the entorhinal cortex
Perirhinal and parahippocampal cortices
the ______ serves as the convergence zone for multipmodal information and is critical for associative memory formation.
hippocampus
Perirhinal cortex
represents elements of an event –> what pathway at an item level –>familiarity
Parahippocampus
serves spatial contextual memory (dorsal visual pathway)
Capras disease
“delusional misidentification syndrome” in which an individual thinks that someone they know well has been replaced by an identical imposter. As the person recollects the details of the visual appearance and other characteristics of the person, this is thought to represent an example of recollection without familiarity.
Fregoli syndrome
involves thinking people that you don’t know are embodied by someone that you do (familiarity without recollection). Probably the best example of hyperfamiliarity is that of the aura of déjà vu experienced by patients with temporal lobe epilepsy (TLE). Imaging has revealed that these patients have specific involvement of anterior MTL (including perirhinal cortex).
Papez circuit
fornix, mamillary bodies, anterior thalamic nucleus, posterior cingulate/retrosplenial cortex –> lesions = amnesia similar to isolated hippocampal lesion
Wernicke Korsakoff syndrome
petchial hemorrhage of the mamillary bodies due to alcohol –> amnesia
Ribot’s law
distant memories are safer than recent memories in retrograde amnesia as in MTL injury –: standard consolidation modelßß:as memories are formed, teh MTL-hippocampus binds neocortically represented features of an event ßß: over time, neocortical representations form their own associations and isolate from the MTL
Impact of MTL lesions on semantic memory
episodic system is important for formation of new semantic memories
patients with frontal lobe damage frequently exhibit _______ impairment
episodic memory–> patients tend to have false memories, difficulty with event order, immediate recall, free recall. However, performance is often normal on tests of cued recall or item memory or familiarity vs. MTL lesions.
Important bit of frontal cortex for memory
ventrolateral frontal cortex
Parietal lobe on episodic memory
patients appear to retrieve contextual details of a prior episodes to a similar extent as controls, they seem to have greater difficulty doing so spontaneously and their memories may be associated with less confidence or vividness. midline and lateral parietal activations associated with successful retrieval of memories
______ is the most common form of dementia and most common condition associated with acquired amnesia.
alzheimers
Biggest risk factor for alzheimers
age
pathologic features of alzheimers
amyloid plaques- extracellular accumulation of aß protein, neurofibrillary tangles-intracellular, helical structures composed of hyperphosphorylated tau
T/F 95% of Alzheimer’s cases are sporadic.
T
The major genetic risk factor for Alzheimer’s is ____
apolipoprotein E4
amyloid processing mutations
trisomy 21, presenelin 1 on chromosome 1, presenilin 2 on chromosome 1
Alzheimers
syndrome involving insidiously progressive episodic memory deficits accompanied by progressive impairment in several other cognitive domains, including executive functioning, language, visuospatial function and praxis.
Difference between Alzheimer’s and memory loss from aging
age-associated memory loss is marked by a greater impairment on tasks requiring the retrieval of associative information or the need to spontaneously instantiate appropriate encoding or retrieval strategies. Performance on tasks that provide environmental support or do not require associative details to be retrieved (e.g. item recognition memory) are generally spared. In contrast, patients with AD do not demonstrate significant sparing on the latter types of tasks.
Cholinergic input effect on Alzheimer’s
pathology of the basal forebrain, greatly diminishing cholinergic input to the neocortex and hippocampus. While the specific role of acetylcholine in learning and memory still remains incomplete, it has been known for years that cholinergic blockers reduce memory performance in healthy subjects. Further, lesions of the basal forebrain, often associated with Anterior Cerebral Artery aneurysms, are frequently associated with memory loss. As seen above, patients with AD are particularly vulnerable to the effects of cholinergic blocking drugs, such as scopolamine. It is, in fact, the relationship of cholinergic dysfunction to AD and memory loss that was the logic behind the development of cholinesterase inhibitors as the major current therapy for AD
Temporal nature of memory
Short term (attention) –> Long-term (rehearsal) –> Remote memory (consolidation)
Phonological working memory deficits tend to localize to the left/right.
left
Visuospatial working memory deficits tend to localize to the right/left
right parieto occipital cortex
the _______ is implicated in almost all working memory tasks.
dorsolateral prefrontal cortex
Symptoms and causes of working memory deficits
multitasking, forgetting rules, inefficient learning, reduced contextual memory, impaired verbal fluency –> infarcts, tumors, ms, alzheimers, parkinsons, huntingtons, lew bodies, schizo, depression, adhd
_____ involves gradual transfer of informaiton from hippocampal circuits to neocortical ones.
consolidation
_________ memory involves conscious recall of events or information
declarative/explicit –>encompass information that can be consciously recalled, and includes episodic and semantic memory.
__________are unconscious memories that affect current behavior
non declarative –> nonassociative learning, classical, operant, and emotional conditioning, procedural memory, and priming (non hippocampal/MTL)
nonassociative learning
habituation - decrease in response to benighn stimulus that is presented repeatedly; sensitization- enhanced response to stimuli after presentation with noxious/painful stimulus
Where does habituation and sensitization take place in mammals?
spinal reflexes –> preattentive/do not require conscious awareness
________learning a relationship between an organism’s behavior and the consequences of that behavior
operant conditioning
______involves the learned association between a stimulus and an emotional response
emotional conditioning
What portion of the brain is implicated in classical conditioning?
vermis or nucleus interpositus of cerebellum –> Thus when climbing fiber and mossy fiber stimulation are paired, mossy fiber stimulation comes to evoke an eyeblink, in the same way that a behavioral CS would eventually elicit a conditioned response.
What portion of the brain is implicated in emotional conditioning?
amygdala –> lesion = kluver bucy –> blunted emotionality, lack of fear, altered sexual behavior, hyperorality, visual agnosia
Operant conditioning
formation of predictive relationships between actions and consequences –>decision making and planning via the law of effect
Operant conditioning pathway
ventral tegmental area of midbrain –> dopamine –> nucleus accumbens –> dorsomedial frontal cortex implicated in reward related behavior
Procedural learning
unconscious acquisition of perceptual, motor, or cognitive behaviors –>distinct from the episodic and semantic memory systems –>
The ______ demonstrates learning is separate from awareness in procedural learning
serial reaction time task
Areas of the brain implicated in procedural learning
supplementary motor area, basal ganglia, cerebellum–> parkinson’s, movement disorders, tumors, strokes, depression
Priming
improvement in the ability to detect or identify words or objects after recent experience with them –> unconcious –> have to do with cortex related to the stimulus/modality specific (eg. visual - visual cortex)
In Aplysia sensitization, _____ modulates the synapse and ______ is the NT at the synapse.
serotonin –> Gs –> cAMP –>PKA –> close K channels –> and glutamate
mammals the equivalent of short term synaptic plasticity is ____ while the equivalent of long term plasticity is _____
E ltp and L ltp
4 key properties of ltps
rapid onset, long lasting, pathway specificity, associativity
The ____ receptor mediates LTP.
NMDA glutamate –>NMDA receptors have a special property in which both glutamate and depolarization are required for the permeation of ions through the channel; During high-frequency synaptic activation, or when synaptic activity occurs concomitantly in many synapses onto the postsynaptic neuron, the cell depolarizes and NMDA receptors can open.
T/F after induction, the maintenance of LTP does not require NMDA receptor activity
T
NMDA receptor antagonist
AP5
Calcium influx during NMDA receptor activation induces activity of ____
Calmodulin kinase II –> inserts more AMPA receptors into the membrane + other effects
Long-lasting LTP requires translation and transcription, and is mediated, at least in part through the action of _____.
CREB
Low frequency transmission and activation of NMDA receptors results in _______
long term depression via phosphatase activity that degrades AMPA receptors
3 most common Non-alzheimer’s dementias
lewy body, vascular, frontotemporal
Frontal lobe hypothesis of aging
problems attributable to a deficit in executive control mediated by prefrontal cortex –> slowed information processing, multitasking, reduction in working memory, attention, switching attention, forgetfullness, contextual/source memory but not semantic memory
______ is an intermediate stage between cognitive decline in normal againg and more pronounced dementia impairments
MCI –> normal daily living but subjective and objective impairment in cognitive function not caused by other causes like b12 deficiency
Amnestic MCI
memory impairment dominates –> single domain, multiple domain
Non-amnestic MCI
deficits in executive, language, or visuospatial domains with relative preservation of memory function
Pathological changes seen in most patients with MCI
atrophy, lewy bodies, plaque, vascular changes
Amnesic MCI tends to result in _____
Alzheimers
Non-amnestic MCI tends to result in______
non-AD dementia
Frontotemporal dementia
onset typically between 45-65; relative sparing of memory; focal degeneration of the frontal and temporal lobes corresponding to cognitive and behavioral disturbances
The _______ cortex is connected to limbic centers and contributes critically to emotional valence and to the ability to control behavior (including the ability to inhibit inappropriate behaviors).
orbitofrontal
The ______ prefrontal cortex plays an especially important role in the ability to organization thoughts and actions (organization, executive function).
dorsolateral
______ cortex is critical for language production in most individuals.
left frontal lobe
_____ are theorized to play an important role in semantic knowledge.
anterior and inferior temporal lobes
The behavioral variant of FTD (bv-FTD) preferentially affects the prefrontal cortex, with a right/left-sided predominance
right
Progressive nonfluent aphasia
includes broca’s area; reduced words/minute, effortful, nonfluent speech, insight into impairment, sound-related errors, agrammatism, speech apraxia
Semantic dementia
difficulty with contextual memory –> problems with word finding, anomia, poor comprehension, poor object recognition, surface dyslexia
right/left temporal semantic dementias are associated with deficits in knowledge about emotions and the ability to recognize emotions in others
right
Pathology of FTD
either tauopathy (usually pnfa) or TDP43 proteinopathy (usually semantic dementia)
Dementia with Lewy Bodies
overlap with parkinson’s but second most common after AD; progressive dementia with deficits in attention and executive function –> recurrent complex hallucinations, fluctuation cognition with attention and alertness, Parkinsonisms; (occasionally sensitivity to neuroleptic and anitemetics) –> levodopa, ache inhibitor
Lewy body
ubiquitin and alpha synuclein –> cortex + brainstem + substantia nigra (vs. parkisons with just substantia nigra)
Vascular dementia
usually a gradual decline but in CVD more stepwise
3 main types of vascular dementia
multi-infarct (large vessel stroke) vs small infarcts in white/grey matter structures –> subcortical, strategic infarct
Multi-infarct dementia
ACA, MCA, PCA –> stepwise decline
____ cerebral artery strokes are associated with aphasia on left and and neglect on right.
MCA
____ cerebral artery strokes are associated with apathy, abulia, akinetic mutism.
ACA
____ cerebral artery strokes are associated with amnesia, agnosia, anomia.
PCA
Subcortical Vascular dementia
small vessel lesions of white matter –> psychomotor slowing, impaired concentration, forgetfulness, apathy and depression (absence of focal cortical deficits like aphasia and agnosia)
Strategic infarct dementia
a single strategically placed infarct (e.g. in the anterior or dorsomedial thalamus or the genu of the internal capsule) lead to cognitive impairment by interrupting critical frontal-subcortical connections –> e.g. lesion of dorsomedial nucleus of thalamus with stroke of paramedian PCA or thiamine deficiency; lesion of anterior thalamus causing amnesia with apathy and reduced emotional expression via infarct of PCOM
T/F The treatment of vascular dementia (VaD) is aimed at preventing or minimizing cerebrovascular disease
T
3 types of primary headache
cluster, migraine, tension
Migraine
constellation of symptoms: headache + pulsing, severity, movement aggravated + nausea or photo/phonophobia + 20% get an aura of visual, sensory, speech disturbances
Tension headache
No associated features of migraines
Why can migraine be felt in the back of the head?
C2 innervates occipital area and communicates with trigeminal ganglion which can also use V1 to get pain in the forehead/eyes
the _________, is involved in the parasympathetic system, and it plays a role in blood vessel dilatation as well as autonomic symptoms that can accompany headache.
superior salivatory nucleus
the _____ makes ascending connections with the hypothalamus, which explains why there are changes in appetite and sleep during the headache.
spinal nucleus of v
the ______ projects to the posterior nucleus of the thalamus, which in turn projects to multiple association areas of the cortex. These contribute to disturbances in neurological functions involved in vision, hearing, memory, motor, and cognitive performance during the headache.
spinal nucleus of v
Mutations in familial hemiplegic migraines results in ion channel changes that cause increased release or decreased uptake of the nt ______.
glutamate
migraine pathway
hyperexcitability –> cortical spreading depression –>activation of trigememinovascular system (CSD is accompanied by large increase in the concentration of extracellular potassium ions and protons as well as neuropeptides –> vasodilation and inflammatory soup –> hypersentization of meningeal nociceptors –> normal pulsation of blood vessels are perceived as painful)
T/F Central sensitization causes allodynia
T –> pain from non-painful touch in migraines
Working definition of coma
no response to external stimuli other than reflexes, eyes closed without sleep wake cycles, prolonged
2 systems required for consciousness maintenance
cerebral cortices and ascending reticular activating system/thalami
ARAS
diffuse network of neurons that lies in the paramedian portion of the posterior (dorsal) pons and midbrain; extends from superior pons through midbrain to posterior portion of hypothalamus
T/F Unilateral hemispheric lesions should not produce abnormal consciousness unless they are large enough to compress the
brainstem or raise ICP
T
4 coma mimics
- locked in syndrome (ventral pons), 2. severe neuromuscular disease (e.g. Guillaine Barre), 3. Psychiatric disease (e.g. catatonia), 4. Akinetic mutism (injury to medial frontal lobes)
If the coma exam localizes to the ______, think
structural lesion
brainstem
If the coma exam localizes to the _______,
think systemic abnormality
hemispheres
4 elements of classical neurologcal coma exam
pupillary response, eye movements, position/movement of limbs, breathing patterns
T/F the nuclei of 3 and 4 and MLF are amid neurons of the ARAS
T
Parasympathetic fibers in 3 are the ______ limb of the pupillary light reflex
efferent
Abnormalities of the pupillary light reflex generally imply structural injury to the
__________.
midbrain or oculomotor nerve
Small pupils in comatose patients are typically with injury to the _________ due to loss of descending _________
innervation
pontine tegmentum due to loss of descending sympathetics
Sympathetic eye pathway
1st order neurons synapse in intermediolateral column –> 2nd order exit at C8, T1, T2 –> arch over apex of lung and synapse in superior cervical ganglion –> sweat fibers travel with external carotid, remaining fibers ascend with internal carotid –> enter cavernous sinus –> follow abducens nerve –> switch to V1 –> join nasociliary branch of trigeminal –> ciliary ganglion –> eye
With ______ injury, pupils are large and non-reactive due to ______.
bilateral midbrain due to to bilateral oculomotor nerve injury
With left midbrain dysfunction the _____ pupil is _______ due to unilateral nerve dysfunction. The difference between pupils is accentuated in the light/dark.
left midbrain dysfunction, dilated and non-reactive; enhanced in light
With L pons dysfunction, the left pupil is ________ due to interruption of _____ fibers. The difference is accentuated in light/dark.
small and non-reactive due to interruption of sympathetic; in dark
With ___________ both pupils are small and minimally response b/c of interruption of _____ fibers.
diffuse pontine injury due to interruption of sympathetic fibers
T/F Comatose patients make voluntar eye movements as well as reflex eye movements.
F only reflex eye movements
If an eye field is damaged on one side, the eyes will look toward which side due to unopposed activity of the contralateral eye fields?
the side of the damage
Each eye field connects to the contra/ipsilateral PPRF.
contralateral PPRF (voluntary = FEF, involuntary = parietal eye fieldsl/7)
Conjugate horizontal gaze
PPRF innervates ipsilateral abducens and via hte MLF, the contralateral oculuomotor nucleus
Roving eye movments
normally, eye fields exert tonic inhibition on the brainstem to prevent roving eye movements; if cortex is damaged but brainstem intact, eyes move side to side slowly/rove
Doll’s head, oculocephalic reflex
turn head –> ipsilateral horizontal semicircular canal sends impulse to ipsilateral vestibular nucleus –> synapses on contralateral abducens and via MLF to ipsilateral oculomotor –> conjugate eye deviation in opposite direction of head turn
Oculovestibular reflexes
instillation of cold water into the external auditory canal decreases firing rate of the ipsilateral vestibular nucles and is analogous to a head turn toward the opposite side (eyes turn towards cold ear)
COWS in coma
normal pt: eyes deviate slowly toward cold water and then have fast phase away back to midline; coma pt: absence of slow phase = brainstem, absence of fast phase = cortical dysfunction
T/F the presence of spontaneous venous pulsations implies normal cranial pressure.
T
T/F The presence of purposeful behavior implies some degree of higher cortical function.
T
Decerebrate posturing implies injury below the level of _____
red nucleus –> extensor posturing
Decorticate posturing implies injury above level of ______
red nucleus –> flexor posturing
Cheyne Stokes respiration
may follow diffuse cortical injury but more often reflects bilateral thalamic injury
Central neurogenic hyperventilation
reflects pontomesencephalic injury
Apneustic respirations
implies lateral tegmentum of lower half of pons
Ataxic/biot respirations
suggest lower dorsomedial medulla
herniation of one hemisphere into the other across midline
subfalcine herniation
herniation of central brain down onto interpeduncular space
central/diencephalic herniation
Subfalcine herniation
herniation of cingulate cortex under falx; compression of contralateral ACA and ischemia of contralateral medial frontal lobe; ipsilateral lower extremity weakness –> usually no coma
Uncal herniation
Midbrain compression, ipisilateral 3 palsy, contralateral hemiparesis, (sometimes also ipsilateral hemiparesis due to compression of peduncle against tentorial notch) –> usually coma
Diencephalic hernation
early: small pupils, somnolence, Cheyne Stokes, decorticate ; intermediate: midsize pupils non reactive, breathing hyperventilation and then apneustic decerebrate posturing; late: oculovestibular and oculocephalic rostrocaudal progression of edema down brainstem –> reflexes absent, ataxic breathing –> arrest
Tonsillar herniation
sudden respiratory arrest
What is the most important recovery mechanism for peripheral nerve injury
sprouting of axons from adjacent motor pools
What genes do denervated Schwann cells turn on to promote axonal generation?
N-cadherin, L1, NCAM, neurotrophins, cytokines
Cajal’s neurotropic theory
regenerating axons are drawn to denervated Schwann cells at the distal nerve stump
T/F severing a nerve makes regeneration more difficult
T –> scarring interrupts regeneration process and large gaps are difficult to cross –> basal lamina are discontinuous so axons may grow into the wrong targets
T/F Central neurons tend to die when their axons are severed
T
___________ appears to be an important inhibitory component of the glial scar; removing it with chondroitinase promotes axonal regeneration
Chondroitin sulfate proteoglycan
NOGO, MAG, Split, and OMGP receptors activate _____, a key signaling component, inhibiting axonal growth.
Rho
The modification of what intrinsic element promotes CNS regeneration of axons?
Local application of cAMP enhances axonal regeneration, but keeping injured cells alive does not help
The modification of what extrinsic element promotes CNS regeneration of axons?
adding chondroitinase and trophic factors lochttp://www.cu2000.med.upenn.edu/home/bnb/2013/Week4/Lectures/Slides/bb_030613_kasner_vascular_neurology_2_stroke.pdfally
T/F sensory neurons in olfactory epithelium are continually renewed.
T
Pulse labeling reveals that cells in a few specialized regions, especially the __________, of the adult mammalian brain give rise to neurons, astrocytes, and especially oligodendrocytes
subventricular zone
Most of the neuroblasts from the _____ of the adult mammalian brain migrate to the olfactory bulb, where they form interneurons. In the hippocampus, stem cells also give give to ___________cells.
subventricular zone and pyramidal
T/F enriched environments can increase neuronal generation in mice.
T
T/F stress can reduce the number of new neurons in mice.
T
T/F Implantation of fetal nigral cells can lead to parkinson improvements
T –> some benefit but immunosuppression needed and inflammation marked
T/F Exogenous stem cells can remylinate the CNS
to a degree–> ex. Pelizaeus-Merzbacher
stroke
sudden focal neurological deficit due to vascular cause (ischemia = 80, hemorrhage = 20%)
TIA
sudden focal neurological deficit due to ischemia of less than 24 hours in duration without permanent damage
7 P’s of ischemic stroke
pumps, pipes, perfusion, platelets, pressure, penumbra, prevention
________ is most commonly associated with atrial fibrillation, mural thrombus, post-MI akinetic ventricular segment, dilated cardiomyopathy, and valvular disease.
cardioembolic stroke –> thrombus breaks off from heart and blocks cerebral vessel –> cortical and wedge-shaped
Most “hemorrhagic conversion of an ischemic stroke” occurs in patients with __________ infarctions.
cardioembolic
__________ is usually a result of carotid artery stenosis (narrowing).
Large vessel atherothromboembolism –> at bifurcations like carotid
The classic syndrome of bilateral watersheds in the _________territory causes weakness of both arms, sometimes referred to as “man in a barrel syndrome.”
ACA-MCA
Small vessel occlusive disease is often synonymous with__________
“lacunar infarction” –> lipohyalinosis –>small infarct in deep hemispheric white matter, basal ganglia, or pons–> e.g. internal capsule: pure motor hemiparesis, pure sensory stroke, clumsy hand-dysarthria syndrome, and ataxic hemiparesis. –> absence of visual effect and cortical signs
Cryptogenic (idiopathic) stroke is diagnosed when:
all other studies fail to identify any likely stroke mechanism
What is the target of acute stroke therapy—
to save the penumbra –> brain tissue that can be saved –> on border of infarct –>t-PA
The three major medical causes of death in stroke patients are _______________ all of which may be preventable with close observation and good medical care
infections (aspiration pneumonia and urinary tract infection), deep vein thrombosis and pulmonary embolus, and myocardial infarction
The higher the ABCD2 score, the lower/greater the risk of subsequent stroke.
greater
In the brain, heparin is a good treatment for:
cerebral vein thrombosis (but not arterial)
_______ events involve the very early formation of neuronal connections, for example axons finding their initial targets and the formation of dendrites and synapses in those targets.
prenatal
______ events involve the proliferation of axonal projections and a dramatic formation of synapses
perinatal
_____ period is when the brain is highly plastic and sensitive to external stimuli (known as ‘critical periods’). This stage, thus, is dependent upon evoked activity—or experience
postnatal
In layer ____ of the visual cortex, the units will be driven by either one eye or the other, and they will cluster into alternating ipsi- and contra-lateral columns.
IV
T/F Outside layer IV, some units will be dominated by one eye, others by the other eye, and some will receive equal inputs.
T
ocular dominance plasticity
visual cortex was incredibly plastic shortly after the eyes open. This was only true for a period of about a month; after this ‘critical period’ , the system was no longer as plastic.
The critical period for the formation of ocular dominance columns are about _______ in humans, consistent with the relatively leisurely pace of our maturation.
3-5 years
T/F If MD occurs within the critical period, the effect on ODs is permanent and largely irreversible.
T
T/F If MD occurs within the most sensitive part of the critical period (e.g., first 6 wks in monkeys), just a few days of MD results in a complete loss of vision in the sutured eye.
T
Critical Period
Postnatal period during which nerve connections are shaped by activity (experience) and are sensitive to perturbation.
Hebb’s Postulate for Learning
cells that fire together wire together (LTP) and neurons out of synch lose their link (LTD)
T/F That is, there has to be a certain level of GABAergic (inhibitory) tone in the cortex to ‘open’ the critical period.
T –> without inhibitory circuits, critical period plasticity does not occur
