Part 1 Learning Objectives Flashcards
Bone, blood, brain, CSF on CT scan
Bone is white, blood is white, brain is grey, CSF is black
Gray matter, white matter, CSF on T1 MRI
T1 is “fairthful to neuroanatomy”: white matter is white, gray matter is gray, CSF is black
Gray matter, white matter, CSF on T2 MRI
White matter is black, gray matter is gray, fluid/CSF/edema is white (good for seeing problems)
Axial, coronal, sagittal cuts on imaging
Axial = horizontal, coronal = parallel to face, sagittal = vertical
Right/Left on neuroimages
reversed. “through the feet”
Epidural hematoma
On top of dura; tends to be arterial; limited by sutures; fills up faster; appears as bulge on imaging.
Subdural hematoma
Below dura; tends to be venous; not limited by sutures; fills up more slowly; appears as crescent on imaging
Anterior-posterior patterning of neural tube
Early, wnt = posterior; later, combinatorial code of hox genes specifies segments (rombomeres)
Dorsal-ventral patterning of neural tube
Notochord secretes Shh, inducing more Shh from ventral portion. Ectoderm secretes BMPs, patterning dorsal portion
How do neurons assume specific identities?
Extrinsic patterning: multipotent cells differentiate in response to extrinsic signals which induce combinatorial code of TFs
Cell migration in developing CNS
Excitator cells only: radial migration. New neurons move past older neurons to form new layers (lamination or “inside-out maturation”). Inhibitory: transverse migration. Neurons born in different regions of telencephalon and migrate (requires MTs)
How do axons find their targets?
Growth cone guided by long range (chemoattractive and chemorepulsive) and short-range (contact repulsion or adhesion) cues. Navigation of cue gradients depends on axon receptor profile
How does neuron survival depend on target finding?
Neurons that find targets get neurotrophins: factors secreted by post-synaptic cells (different neurons need different trophins). Local (growth cone/synapse) and nuclear (anti-apoptotic) action.
Resting membrane potential
-65mV (usually)
Types/locations of synaptic potentials
EPSPs: usually axo-dendritic; IPSPs usually axo-somatic
Principles of synaptic transmission
AP-> Calcium influx -> vesicle fusion -> NT release. (Amount of NT depends on amount of Ca2+)
Consequences of axon injury in PNS
Wallerian degeneration/chromatolysis-> MPhages remove debris -> Schwann cells support re-growth of axon.
consequences of axon injury in CNS
Wallerian degeneration (much slower than PNS)/chromatolysis-> microglia remove debris -> Damage spreads
Basic spinal organization (Dorsal columns, gray matter)
Dorsal columns are sensory tracts. Dorsal horns are interneurons receiving sensory input. Intermediate zone is interneurons and preganglionic ANS neurons. Ventral horns are motor neuron soma/dendrites
Muscle spindles
sense muscle stretch. innerated by single Ia, single II, two gamma neurons
Golgi tendon organs
sense tension. Innervated by single Ib neuron
Myotactic (stretch) reflex organization
Ia axon ipsilaterally excites motor neuron innervating same muscle, ipsilaterally inhibits antagonist muscle via an interneuron
Golgi tendon organ reflex
Ib axon ipsilaterally inhibits MN innervating same muscle (via interneuron) and ipsilaterally excites antagonist MN (via interneuron)
properties of spinal reflexes
unconcious, rapid, graded. SUBJECT TO DESCENDING CONTROL
withdrawal reflex
A-delta afferents –> ipsilateral flexion/contralateral extension (via interneurons). proportional to stimulus intensity
Criteria for identifying transverse spinal sections
Large ventral horn –> Limb (C5-T1 or L2-S2); Both dorsal columns present –> above T5; Lateral horn present –> T1-L2 (and Clarke’s present); thick central gray matter –> Sacral
Organization of spinal cord
31 segments: 8C, 12T, 5L, 5S, 1C. chord ends around L2.
Dorsal root organization
Sensory. Cell bodies in DRG. lateral division: pain and temp. medial division: touch, pressure, vibration
Sensory neuropathy general features
often length-dependent. Sensory response diminished on EMG
Radiculopathy general features
Often result from compression. Sensory responses look normal on EMG but nothing will be felt. Numbness/weakness
Motor neuropathy general features
collateral sprouting, atrophy/hypertrophy
Motor synapse defect general features
reduction in response to AP. presynaptic defect –> increment response. postsynaptic –> decrement response.
Dystrophy generally
Active breakdown/regeneration (stops eventually) with scarring
Myopathy generally
intrinsic weakness, microscopic changes
Nemaline myopathy
defect of thin filaments (nebulin/actin). Mutx determines severity. thready redness on trichrome stain
Duchenne MD
XLR. Proximal/progressive weakness. pseudohypertrophy. elevated CK. cardiomyopathy and respiratory insufficiency. Gower’s/Trandelenburg. Dystrophin: large protein anchors sarcolemma
AMPA-R and antagonists
Glutamate-R Channel. Mediates fast excitation. Sensitive. Antagonists are anti-epileptic
NMDA-R and antagonists
Glutamate-R Channel. Slower kinetics than AMPAR. Normally Mg2+ clogs pore, depolarization removes. Ca2+ permeable –> second messengers. Antagonists cause halucinations
Safety Factor
EPP - (minimum change to cause contraction). When present, ensures that every AP triggers muscle
AChE
Degrades ACh in NMJ, terminating transmission
Basic functions of thalamus
Relay: sensory, motor, associative, limbic; under heavy cortical control. Gate: transitions between waking and sleeping states (mediated by neuromodulation).
Basic functions of cortext
Generate sensory and motor representations of the external/internal world. Generate conciousness (depends on thalamocortical loops)
Role of thalamus in sleep
Switches from single spike/tonic mode to bursting mode. Mediated by T-type Ca2+ channels which are active at hyper-polarized RMP (-80mV). Makes the whole brain rhythmic. Bursting incompatible with coding.
Role of neuromodulators in sleep
hyperpolarized RMP acheived by K+ leakage into cell, because neuromodulators (NE, 5HT, DA) are less active while entering sleep
rhythmic movements
generated by CPGs in spinal cord and brain stem. chewing, swallowing, walking, etc
Voluntary movements
goal-directed, generated internally, improve with practice
Feedback (voluntary movements)
“error signal” produces compensatory changes
Feedforward (voluntary movements)
Anticipatory contraction. Essential for rapid movements. Depends on ability to predict (experience). Cortical commands project to reticular formation (pontine/medullary) which modifies medial motor pathway in anticipation of lateral action.
Population encoding
Non-1-to-1 encoding (applies to motor cortex). “Each cell votes” (although there are “sweet spots” for certain muscles, e.g.)
Supplementary motor area (SMA)
Important for memorized sequential movements (instructed delay or internally initiated complex tasks). Planning
Lateral premotor areas
Movement triggered by sensory stimuli (integration). Anticipatory firing. Mental rehearsal or watching others (“mirror”) recapitulates firing.
Lateral motor system (cord)
controls distal limbs. dorso-lateral MNs (within ventral horn) lateral propriospinal/local interneurons (within intermediate zone)
Medial motor system (cord)
Controls posutral muscles. MNs located in antero-medial spinal gray. local propriospinal interneurons located medially in the intermediate spinal grey
Locomotor movement circuit
Cortex –> Mesencephalic Locomotor Region (MLR) –> reticular formation –> RST –> CPG. Excitatory output of MLR determines speed. Lots of feedback/adjustment. Isolated CPG capable of generating movement
Anatomical organization of cerebellum
primary fissure divides ant/post lobes. posterolateral fissure separate floculonodular lobe
functional organization of cerebellum
unrolled, central vermis, intermediate and lateral zones (each hemisphere). deep nuclei are output
cell types/circuit of cerebellum
climbing fibers (input 1) from olive wrap around Purkinge cells (1 fiber/PC, 5-10 PCs/fiber) high safety factor. Mossy fibers (input 2: cortical and sensory) terminate on GCs. GCs extend axons through molecular layer (highly convergent and divergent). Single output (except vestibulocerebellum): PCs –> DCNs –> descending motor systems
somatotopic organization and function of spinocerebellum
spinocerebellum = vermis + IZs. Makes corrections during movement. discontinuous maps (fractured somatotopy) with head/axial muscles in vermis and limbs in IZs.
inputs to spinocerebellum
Proprioceptive via spinocerebellar tracts, ICP. Motor via corticopontine fibers, MCP.
outputs from spinocerebellum
limbs: interposed N –> SCP–> VL –> M1 (contralateral). Axial: fastigial N –> medial motor systems
function and ouput of cerebrocerebellum
active before movement, during planning. Dentate N –> SCP –> VL –> association, premotor, M1 (contralateral). Also has cognitive functions (judging time, tactile identification)
Function, input, and output of vestibulocerebellum (floculonodular lobe)
coordinates eye movements during head movements, maintains balance. Input from vestibular system. Output to MLF, vestibulospinal
General basal ganglia function
movement (posture, speed, tone), cognition, behavior. Feedback/Modulatory loop with thalamus/cortex
Input to basal ganglia
Cortext –> striatum
output from basal ganglia
GP + SN –> VA/VL –> frontal cortex
pharmacology of SNc
dopaminergic input from SNc facilitates direct/inhibits indirect –> enhanced motor output
Hallmarks of basal ganglia disease
Bradykinesia, Rigidity, postural instability, hyperkinetic abnormal movements (chorea, tremor)
Treatment of PD
Levodopa (crosses BBB) and is substrate for rate-limiting step of DA synthesis. Combined with peripheral DDCis.
Types of thalamic cells
Thalamocortical: lots of dendrites and send excitatory output to cortex. Reticular nucleus cells: surround thalamus and recieve colateral input from descending cortical axons. send inhibitory projections into rest of thalamus
Types of cortical cells
Granular cells (spiny stellate): L4, receive input from thalamus and project to layers 2/3, most prominant in sensory areas. Pyramidal cells: 80%, output to other areas, heavily interconnected (local interaction/parallel processing), apical dendrite, basal dendrites, lots of spines. Oodles of different kinds of inhibitory cells (feedforward/back inhibition, prevent seizures)
Basic cortical circuit
Thalamus –> L4 –> L2/3 (output to other cortices) –> L5 (output to non-cortical areas) –> L6 (output to thalamus and other non-cortical areas)
functional organization of cortex
Columns!
adaptation
rate at which firing decrements with constant stimulation. for somatosensory receptors, determines firing properties of efferent neurons
Surround (lateral) inhibition
allows for sharpening of receptive field and detection of contrast.
Relay station for information destined for S1
VPL/VPM
basic organization of S1
“looking at the body from multiple perspectives:” different regions specialized for different types of sensory input, within regions subregions represent body parts with different densities (homunculus). Columnar organization (with rapid-adapting and slow-adapting columns) allows for integration
Mechanism of plasticity in S1
“unmasking” of normally dormant connectivity (theory)
Perceived intensity of pain vs affective intensity
perceived in S1 not necessarily equivalent to unpleasantness (different area)
Signs/symptoms of cerebellar disease
Cerebellar ataxia (DNE sensory ataxia), nystagmus, dysmetria, titubation, scanning speech, disdiadohokinesis. Romberg sign
Principles of cerebellar disease
isolated syndrome rare, often seen with other brainstem problems. Recovery can be rapid, but slow progress can be missed b/c of redundancy. transient hypotonia with acute, normal tone with chronic
occlusion of distal basilar artery
Weber/Medial Midbrain syndrome. Bangs out CNIII ipsilaterally with contralateral hemiparesis (CST, CBT)
Occlusion of proximal or midbasilar arter
Pontine/Locked in syndrome
occlusion of PICA (or VA)
Wallenberg/Lateral Medullary syndrome: Horner’s, crossed face/body sensory loss, ataxia, vertigo
MCA occlusion
contralateral hemiparesis (face+arm>leg) (frontal lobe, cortical and/or subcortical region) (the lateral portion of the motor homunculus is the face and arm), aphasia (dominant hemisphere, Broca/Wernicke areas), neglect (non-dominant hemisphere), contralateral visual hemifield or quadrant defect (optic radiations), deviation of gaze (frontal eye fields), cortical sensory deficits (parietal lobe), and other cortical symptoms.
ACA occlusion
contra hemiparesis (leg), sensory loss, behavior (?)
PCA occlusion
Occlusion of the PCA results in occipital infarction and therefore contralateral visual field loss (hemianopsia). Sometimes PCA occlusion may also result in contralateral hemiparesis and behavior changes because of the thalamic and capsular involvement.
subarachnoid hemorrhage
WHOL, +/- focal signs, 95% caught on CT, xanthochromic/bloody CSF, aneurism (branch points) or AVM
Intracerebral hemorrhage
Hypertension, hypertension, hypertension! microvasculature, charcot-bouchard aneurysms
hallmark of brainstem lesion (and exceptions)
alternating hemiplegia except CN IV nuc and CNIII subnucleus for sup. rectus
hallmark of para-brainstem lesion
CN palsy w/o weakness
Taste coding vs Olfactory coding
Labelled line coding (non overlapping modalities) for taste (preserved in insular cortex) vs combinatorial code for olfaction
Taste receptors vs olf receptors
Salty/Sour = ion channels; sweet/umami/bitter = GPCRs. smell = many GPCRs
Taste transduction vs olf transduction
Direct depol or GPCR-linked TRP channel (taste) vs CNG Na+/Ca++/Cl- channels (olf)
Pupillary light reflex circuit
Photoreceptors (hyperpolarized) –> ganglion cells –> optic nerve –> chiasm –> tract (bilateral) –> branchium of sup colliculus –> pretectal nuclei –> E-W nuc –> ciliary ganglion (parasympathetics, bilateral –> pupilary sphincter (short ciliary nerves)
Afferent pupil defect
affected eye dilates in swinging light test
Function of middle ear
amplifies vibrations of tympanic membrane, counteracting air–>fluid phase transition
Function of cochlea
houses basilar membrane, IHCs and OHCs. Allows for conversion of vibration into neural firing. Spectral decomposition!
IHC transduction
positive displacement (toward large cilium) opens K+ channels –> Ca2+ influx, vesicle release
Frequency vs intensity coding in 8th nerve
Frequency is labeled line: each cell has characteristic frequency (due to basilar membrane) vs intensity is coded by multiple neurons receiving input from single hair cell; larger synapses repond at lower intensities (so also labelled line, in a way).
How is location of sound computed by brain?
MSO: Interaural time difference (know circuit). LSO: interaural level difference (don’t worry about circuit). Inferior colliuclus integrates with vertical position (pinna-dependent) and tuning data
Paths in auditory cortex
Dorsal stream: where. Ventral stream: what. percept generally represented early in stream, categorization/association late in stream
Organization of auditory cortex
core–> belt –> parabelt :: simple –> complex –> more complex
Embryology of eye
ectoderm: neuro (retina, optic nerve, iris), neural crest (cornea, sclera, melanocytes), surface (conjunctiva, lens) + mesoderm: EOMs
Circuit for saccade movements
command generated by FEF (voluntary) or Sup Col (express) –> PPRF generates “pulse”/integrator generates “step” –> ipsilateral nuc VI (lat rectus) –> MLF –> contra nuc III (medial rectus).
VOR circuit
CN VIII –> vest nuc –> inhibits ipsi nuc VI/MLF and activates contra nuc VI/MLF. also projects to VPM (concious perception)
Gain adjustment of VOR
CN VIII has direct input to cerebellar cortex, which projects to vestibular nuc
transduction in retina
rhodopsin aborbs photos –> inhibits phosphodiesterases –> cGMP reduced –> Na+ channels close, cell hyperpolarized –> glutamate interrupted –> activation of ganglion cells
sensation of increment/decrement in retina
2 bi-polar cells per rod/cone. One is inhibited by glutamate, other is activated. Yields two separate channels
Contrast sensation in retina
first computation of visual system: lateral inhibition by horizontal cells in outer plexiform layer. turns ganglion cells into contrast sensors
Types of ganglion cells
M-Cells sense motion; poor spatial resolution and contrast detection; input from many bipolar cells. P-cells sense color; high spatial resolution and contast detection; input from single bipolar cell
projections of optic nerve
suprachiasmatic nuc, pretectal nuc, sup coll, acc. optic nuc, LGN
Retinal field vs brain field.
L presented to R brain, R presented to L brain (nasal fibers cross, temporal don’t). Retina is upside-down and flipped relative to focal point, so inferior cortex gets superior field and superior cortex gets inferior field
Organization of LGN
Each layer is retinotopic but distorted. M/P info and ipsi/contra info in separate layers. no interaction between layers. minor processing (same RFs as retina)
M-cell information in V1
LGN neurons synapse in IVc-alpha, then diverge in IVB (many-to-1 and 1-to-many). 1st point of binocular integration. feature sensitive (orientation, direction, movement, depth).
P cell information in V1
LGN neurons synapse in IVc-beta (RFs preserved) axons project to II and III (mix of center-surround/orientation-selective cells). stays separate from M info.
Organization of V1 generally
Above IVc, binocular input, but ocular dominance columns still aparant. Color organized in CO blobs in II/III. Orinetation columns ordered into pinwheels. Lateral connectivity (pyramidal cells, excitatory) –> Kanzina triangle!
Ventral stream in vision
“What, Who”: P-cells –> LGN (3,4,5) –> Layer IVcbeta –> CO blobs –> V2 (thin stripes) –> V4 (orientation and color-selective cells, color constancy) –> ITC
Dorsal stream in vision
“Where, Action”: M-cells –> LGN(1,2) –> Layer IVcalpha –> Layer IVB –> V2 (thick stripes) –> MT/V5 (direction/velocity sensitive, aperture problem, structure-from-motion) –> PPC
Basic categories of learning
non-associative: sensitization/habituation. associative: classical conditioning. stimulus-response: operant conditioning
Short-term/long-term results and implications from Aplysia
Short-term sensitization of withdrawal by shock (5HT neuron increases Ca++ in pre-synaptic terminal via cAMP, phosphorylation dependent). After multiple trials, response persists (cAMP activates genes leading to changes in synaptic strength)
molecular basis of LTP
NMDA receptor is blocked by Mg at RMP. permeable to Ca++ when depolarized (is molecular coincedence detector: depolarization + glutamate). leads to up-regulation of AMPA and long-term changes in a synapse-specific way.
Laterality of speech and language (anatomy)
Left hemisphere in RH adults. Broca’s (ventrolateral frontal) and Wernicke’s (dorsolateral temporal) and arcuate fasciculus (skirts silvian fissure). More likely bilateral in LH adults
Broca’s aphasia
non-fluent, intact single word comprehension, poor repetition, mildly impaired naming. Concepts intact but central processing disorder: trouble putting words together meaningfully
Wernicke’s aphasia
fluent but empty speech, poor comprehension and repitition, poor naming. Concepts underlying words are gone
Conduction aphasia
Fluent speech, intact comprehension and naming. Poor repitition. Arcuate fasciculus banged out.
Global aphasia
Non-fluent, poor comprehension, impaired repirtion, poor naming. Carotid occlusion
Problems with connection model of aphasia
aphasia also possible in right hemisphere stroke, neurodegeneration, subcortical lesions, dementia (e.g. expressive deficits, grammatical comprehension deficits)
Alexia (peripheral vs central)
Difficulty reading. Peripheral: letter-by-letter reading (alexia w/o agraphia–splenium of corp callosum). central: difficulty putting letters into words
Agraphia (peripheral vs central)
Disorder of writing. Peripheral: motor formation (apractic agraphia). Central: spelling
Episodic memory (and sub-divisions)
autonoetic conciousciousness, mental time travel. item vs associative, recollection vs familiarity
Fuctions and lesions of perirhinal cortex, parahippocampal cortex, hippocampus
PRC is “what” (item memory), PHC is “where” (context memory), HP is integrator (item-in-context). Lesions of extrahippocampal structures results in familiarity defect. Lesions to HP result in recollection defect. Forming new semantic memories is dependent on episodic memory
Papez circuit
HP–>Fornix –> mamm bod –> ATN –> internal capsul –> cingulate gyrus –> cingulum –> PHG –> HP
Frontal lobe lesion effect on memory
free recall, recollection impaired; potential for false memory; item familiarity and cued recall often normal; enhanced performance with environmental support
Pathophys, genetics of Alzheimer’s
Amyloid plaques “set stage,” NF tangles are injury. Hippocampus decoupled from inputs early. Memory loss unresponsive to environmental support. Progressive dementia. Basal forebrain ACh reduced (Tx: cholinesterase inhibitors)
Temporal distinction in memory
Working memory (DLPFC, MTL) = minutes. Remote memory (gradual transfer to neocortex) = days, months, years
Classical conditioning brain area
cerebellum (eyeblink, rabbits)
Emotional conditioning, brain area, and lesion
Attaching emotions to objects. Amygdala for fear. Also glutamatergic input to HP (?). Lesion results in Kluver-Bucy
Operant conditioning and brain areas
Predictive memory for actions/consequences (Law of Effect). VTA/lymbic system and dorsal medial frontal cortex
Procedural learning, brain area, and lesion
“practice makes perfect” unconcious learning. Cerebellum, SMA, BG. Lesions in PD, movement disorders, depression
Basic L/R functional divide in parietal lobes
L: language, praxis, counting/arithmetic. R: prosody, spatial representation, attention, subitizing, estimating
Apraxia
Acquired deficit in learned or skilled movements in the presence of normal strength and sensation. Bilateral: L inferior parietal lobe lesion (unable to judge the movements of others, limb-as-tool error). Unilateral: Contra premotor cortex lesion (able to judge movements of others)
L parietal lesion
Apraxia, Gerstmann’s syndrome: agraphia, acalculia, finger agnosia, R/L confusion, “general body schema disturbance”
Bilateral parietal lesion
Balint’s syndrome: “reaching and looking” optic ataxia, ocular apraxia, simultagnosia
Neglect (hallmarks, subtypes)
Left-sided from right MCA stroke. Extinction, subtle disctinction (neglected information propogating through other areas). Hemispace neglect is more dorsal lesion (inferior parietal) closer to “where”. Hemi-object is more ventral (superior temporal gyrus) closer to “what” pathway
Corticobulbar lesion
No signs! (bilateral innervation) EXCEPTION: UMN to CNVII will give lower face paralysis CONTRALATERALLY
Mechanisms for injury recovery
sprouting, axonal regeneration, cell replacement
impediments to regeneration in CNS
limited cell regrowth (limited data suggest endogenous SCs can contribute). anti-trophic factors expressed by oligodendrocytes–nogo, omgp, mag. signal through Rho
cognitive changes with normal aging
forgetfulness, multi-tasking, slower processing, problem solving. highly variable
mild cognitive impairment (types)
day-to-day generally preserve. Amnestic = memory impairment (single or multiple) can progress to AD. nonamnestic= higher function w/o memory problems (progress to non-AD dementia)
FTD
cortical function. disinhibition, personality, emotion, nonfluent aphasia, semantic dementia. art! tau/TDP-43 aggregates
Dementia with Lewy Bodies
progressive, attention/executive function, hallucinations, REM sleep disorder. alpha-synuclein aggregates.
VaD
vascular injury (cortical territories or subcortical). small infarcts in fronto-subcortical communication areas.
Coma
No response to external stimuli other than reflex. Eyes closed and sleep-wake cycle absent
Coma exam
Exclude mimics, localize: cortex (systemic) or brainstem (structural). 1) pupils (brainstem) 2) eye movements (roving = cortex). 3) reflexes (oculocephalic. oculovestibular: cold water is analogous to head turn toward opposite side; slow deviation absence = brainstem; corrective nystagmus absence = cortex)
Cheyne-stokes breathing
bilateral thalamic
hyperventilation
pontomesencephalic
apneustic (yawns)
lateral tegmentum of the lower pons
ataxic breathing (gasps)
lower dorsomedial medulla
subfalcine herniation
compresses contra ACA
uncal herniation
ipsilateral CN III palsy, contralateral/ipsilateral hemiparesis
central herniation
progression of brainstem symptoms
tonsilar herniation
“talk and die”
Pathophys of migraine
susceptibility (channelopathy) leads to wave of CSD (aura) which triggers trigeminal meningial afferents, release of substance P (pain). TRIGGERS VASODILATION
Migraine therapy
increase 5-HT (inhibiting CNV). Triptans: SSAs. CGRPs: good for hypertension
Causes of stroke
Pump (cardioembolism), Pipes (large artery disease–recurrent events!), Pressure (watershed/border zone–man in barrel), Platelets (lacunar–absence of cortical and visual signs!)
acute stroke therapy
save the penumbra! give t-PA (risk is hemorrhage), mechanical thrombolysis
stroke prevention
modify risk factors, prevent thromboembolism
Venous thromboembolism
doesn’t respect arterial territories
