Week 4 - Neuro Big Ideas Flashcards
(434 cards)
1
Q
carotid artery on ultrasound
A
laterally on neck, does not compress, pulses, can find bifercation superiorly - dark circle
2
Q
jugular vein on ultrasound
A
laterally on the neck, compresses, larger than carotid, gets larger when feet are elevated - dark circle
3
Q
thyroid on ultrasound
A
isthmus medially over trachea, lobes laterally, grainy gray
4
Q
trachea on ultrasound
A
medial, dark circle, can see cartilage rings
5
Q
clinical applications of neck ultrasound
A
anthosclerosis, putting in lines, cysts, tumors, thyroid / parathyroid / salivary gland abnormalities
6
Q
ultrasound usage
A
top of screen = superficial, bottom of screen = deep, orient green dot to same side of body, square probe = deep, rectangular probe = shallower, transvaginal probe = long and thin, increasing usage
7
Q
muscle receptors (sensory)
A
muscle spindles and golgi tendon organs
8
Q
muscle spindles
A
sensory afferent, in intrafusal muscle fibers parallel with extrafusal fibers, noncontractile core, attached to contractile units on either end, 2 receptor types in center - 1. primary Ia annulospiral endings, 2. secondary II flower spray, spindle is innervated by gamma motor neurons
9
Q
gogli tendon organ
A
sensory afferent, at junction of muscle and tendon, in series with extrafusal fibers
10
Q
extrafusal muscle fibers
A
normal contractile muscle fibers, innervated by alpha motor neurons
11
Q
intrafusal muscle fibers
A
contains muscle spindle, parallel to extrafusal fibers, innervated by gamma motor neurons
12
Q
muscle spindles
A
sensory mechanoreceptor, stretch reflex - muscle contracts in response to moderate stretch
13
Q
coactivation of alpha and gamma motorneurons
A
maintains activity in the spindle and tone in the muscle
14
Q
golgi tendon organ
A
sensory mechanoreceptor, inverse stretch reflex - strong contraction is followed by muscle relaxation due to GTO activation of inhibitory interneuron
15
Q
muscle spindle physiology
A
low activity if muscle is relaxed, muscle stretch causes spindle depolarization
16
Q
muscle spindle primary type Ia response to muscle stretch
A
detect velocity of stretch in dynamic muscle contraction, phasic graded potential that declines with adaptation and theoretically hyperpolarizes completely on muscle contraction release (prevented by gamma motor neurons)
17
Q
muscle spindle secondary type II response to muscle stretch
A
detect amplitude of stretch in static muscle contraction, graded potential that is tonic and does not adapt, does slightly hyperpolarize when contraction stops
18
Q
stretch reflex
A
muscle spindle, monosynaptic, muscle stretch causes muscle and spindle contraction, 1. muscle stretches, 2. depolarization of spindle afferent, 3. activation of alpha and gamma motor neurons, 4. contraction of extrafusal fibers via alpha motor neurons stimulation, 5. intrafusal fibers contract to keep tension in spindle (like hair cell tip link adaptation motor) via gamma motor neuron stimulation for continued response - the spindle afferent itself is not contractile but the intrafusal fibers it is in are contractile - key in maintaining muscle tone
19
Q
muscle tone
A
mediated by muscle spindle stretch reflex, tested by deep tendon reflex tests, if gamma motor neurons are defective = spastic effects
20
Q
golgi tendon organ physiology
A
inverse stretch reflex, 1. tendon stretch causes gogli tendon depolarization, 2. activation of inhibitory interneuron, 3. decreased alpha and gamma motor neuron activity, 4. muscle relaxation
21
Q
normal muscle spindle and golgi tendon organ function
A
systems work together to maintain muscle tone
22
Q
elimination of alpha motor neurons
A
causes falccid paralysis because muscle fibers are not stimulated to contract
23
Q
overactive gamma motor neurons
A
spastic paralysis due to muscle overcontraction, spindles tell alpha motor neurons to contract more
24
Q
elimination of descending inhibition from motor cortex
A
spastic paralysis, too much tone in muscles
25
spinal reflexes - final common pathway
alpha motor neuron, not truly final, creates a spindle and GTO feedback loop instead
26
alpha motor neuron - spindle and GTO feedback loop
need because muscles are nonlinear force generators (only create optimal force vs stretch for short time during contraction), reflexes keep muscle in optimal force vs stretch range
27
reflex arc
1. sensory receptor, 2. 1st order afferent neuron, 3. 1-3 CNS synapses, 4. motor neuron, 5. muscle - can have multiple components that create a complicated pathway and timed delay response in waves
28
stretch reflex
monosynaptic
29
inverse stretch reflex
trisynaptic
30
recurrent inhibition
afferent or motor neuron shuts itself off, ex: motor neuron making closed loop with renshaw cell that inhibits the motor neuron when the motor neuron sends an excitatory message - shuts off the original motor neuron and other touching the renshaw cell
31
scratch reflex in a dog
specific sensory stimulus is adequate for evoking a specific stereotyped response
32
lengthening reaction (contraction followed by relaxation)
light weight -> moderate stretch -> spindle fiber stretch reflex -> contraction that maintains the weight, heavier weight -> activated tendon receptors -> inverse stretch reflex -> muscle relaxation, modulated by gamma motor neurons, allows for controlled contraction with balanced tension
33
clasp knife reflex
problem in lengthening reaction (gamma motor neuron overactivity, spindle problem, decreased in descending inhibition)
34
withdrawal reflex
interaction between reflexes, noxious stimulus -> withdrawal of limb by contraction of flexors (monosynaptic pathway) and relaxation of extensors (disynaptic pathway with inhibitory interneuron)
35
crossed extensor
part of withdrawal reflex, extensors on other side of body contract to counter withdrawal reflex
36
reflex
first level of motor control, defined stimulus causing stereotyped response
37
spinal integration of motor control
built on underlying circuits
38
remove higher level motor control in circuit (upper motor neuron lesion)
behave of lower parts of the circuit becomes apparent, ex: descending control -> reflexes -> central pattern generator (stereotyped response) -> alpha motor neuron, remove higher CNS centers like motor cortex = reveals lower forms of control including nystagmus and clasp knife reflex
39
spinal cord lesion
reflexes and circuits below lesion remain intact, initially after spinal cord injury have period of spinal shock with no reflexes, eventually primitive and then more complicated reflexes return
40
Snellen test / chart
tests visual acuity with letter in rows of decreasing size, placed 20 ft from pt, tests cones in macula mostly
41
neurological injury and learning
easier to relearn something already learned than to learn for the first time after neurological injury
42
neurological injury and plasticity
plasticity - ability of brain to change or take on new function, highest at birth and decreases, improves recovery from neurological injury
43
ideal time for child neurological injury
3-7 years old, development and key learning have happened (language), plasticity is high
44
developmental stages
different anatomy, physiology, and disease onset - neonatal, toddler, childhood, adolescent, adult
45
timing of pediatric neurological lesions
congenital?, static?, progressive?, what is the lesion doing over time?
46
pediatric neurological H & P
hard, nonverbal pt, very observation base, rely on eyes / ears
47
newborns and locating neurological lesions
extrapyramidal system is in control because pyramidal system is not fully developed, extra pyramidal system is dominant first and bilateral, lesion may not show until pyramidal system starts to take over, ex: congenital stroke may not show until 6-12 months old
48
distinguishing CNS and PNS lesions
in both cases muscle tone is low, reflexes are present with CNS lesion, reflexes are not present with PNS lesion
49
pediatric neurologist tools
reflex hammer, play sets, legos, chalk board, eyes - watch reach/draw/squat/walk, ears - listen to speech
50
gower sign
climbing / pushing on things to stand up due to proximal muscle weakness
51
traction pull
pull on lower extremity, baby responds by flexing knee and hip
52
head control
watch head position and ability to hold it up in baby
53
vertical suspension
looks for proximal muscle tone in baby, hang baby vertically and baby pulls legs into sitting position
54
horizontal suspension
looks at pelvic tone and head control, hold baby horizontally under belly, head and butt should be even
55
galant sign
sensory, spine, stroke one side of spine and back will curve in response, should be gone by 4mnths
56
grasping
finger in baby palm hand should clench, foot does same but must distinguish from Babinski sign
57
thumbs and fisting
bad, sign of upper motor neuron spasticity, thumb inside fist abnormal, fist should open with Marrow startle response
58
rooting reflex
run finger on cheek, turn head and start to pucker
59
morrow repsonse
startle response, limbs should go out
60
skin
pediatric neurological exam, tells you a lot, ex: neurofibromatosis with cafe spots in groin and axial areas, myelomeningeocele (tuft of hair), hypomelaninosis of Ito - whorls of white spots on skin, Sturge-Weber with port wine stain in trigeminal region
61
growth charts
pediatric neurological exam, tells you a lot, ex: hydrocephalus (feel for bulging fontaneles), Angelman syndrome (underweight - eat little), Prader-Wili (over weight - eat lots), failure to thrive
62
basic motor control system
primary motor cortex -> ventral horn cells -> muscle, there are many other parts
63
motor control circuits
influence corticospinal tract, cerebellum and basal ganglia, to cortex via thalamus and back from cortex
64
brainstem motor control centers
indirect motor control centers and pathways because cortical motor pathways pass through them, ex: rubrospinal, vestibulospinal, and reticulospinal, tonically activate lower motor neurons esp. to axial and antigravity muscles, neurons in medial ventral horn
65
corticospinal tract
main influence on motor neurons to distal extremities (like hand and foot in lateral ventral horn)
66
corticospinal tract collaterals
modulate and control brainstem centers to create right amount of supporting tone without stiffness
67
upper motor neuron lesion
corticospinal tract and collaterals to brain stem motor nuclei, loss of direct effect on lower motor neurons and loss of control and modulation in brainstem control centers
68
upper motor neuron lesion clinical findings
findings due to loss of direct effect on lower motor neurons -> loss of lower strength, loss of lower dexterity, positive Babinski sign; findings due to loss of control of brain stem centers -> increased tone, hyperreflexia, clasp-knife phenomenon
69
lower motor neuron lesion clinical findings
final common motor neuron pathway, loss of strength, tone, and reflexes with denervated muscle wasting and hypersensitivity fasciculations
70
upper motor neuron syndrome
combination of loss of direct corticospinal tract and indirect brainstem motor control centers
71
decorticate posture
upper motor neuron lesion above red nucleus, thumb tucked, fisted fingers, pronation of forearm, flexion of elbow, lower extremity extension, foot inversion - red nucleus reinforces antigravity flexions of arms
72
decerebrate posture
upper motor neuron lesion below red nucleus and above vestibulospinal and reticulospinal nuclei, arm pronated, arm extended, lower extremity extended - antigravity flexion of red nucleus is gone and reticulospinal/vestibulospinal tract reinforce extension tone in upper and lower extremities
73
lesion in medulla
acutely flaccid, all brainstem motor nuclei and corticospinal tracts cut off, if pt were to survive tone would return via interneuronal spinal cord activity
74
localizing upper motor neuron lesions
above decussation of pyramids (crossing of corticospinal tracts) gives contralateral findings, below decussation of pyramids in spinal cord gives findings on ipsilateral side
75
spinal cord lesions
give upper motor neuron signs below the level of the lesion from effect on corticospinal tract, lower motor neuron signs at level of lesion from effect on ventral horn / nerve root - lower motor neuron signs are good for locating the level of a spinal cord lesion
76
motor system clinical testing
muscle strength, tone, reflexes, pathological reflexes
77
spasticity (clasp-knife phenomena)
type of hypertonia, upper motor neuron lesion, rate dependent resistance with collapse of resistance at end of range of motion
78
rigidity (lead pipe or plastic-like)
type of hypertonia, upper motor neuron lesion, basal ganglia disease, resistance constant throughout range of motion
79
acute upper motor neuron lesions / upper motor neuron lesions in infants
can produce hypotonia first, followed by hypertonia
80
motor cortical areas
frontal lobe - primary motor cortex (area 4), premotor cortex (area 6), supplementary motor cortex (area 6), frontal eye fields (area 8) - internal motor commands, deficits include loss of voluntary movement, paresis, increased tone/stretch reflexes, only way we can communicate
81
motor projections from motor cortex
corticobulbar, corticopontine, corticoreticular, corticospinal - to brainstem and spinal cord
82
connected to motor cortical areas, help control muscle tone
cerebellum, basal ganglia, descending systems
83
motor cortex characteristics
1. agranular - poorly developed granular layers II and IV, well developed pyramidal layers III and V, giant pyramidal Betz cells in layer IV (cortex has 6 layers, sensory cortex has good granular layers), 2. low intensity stimulus evokes movement
84
functions of primary motor cortex
1. control individual muscles/force as shown in stimulation studies, 2. control global aspects of movement like direction and amplitude of force - debated
85
primary motor cortex homunculus
lateral/temporal to medial - mouth, face, hand, arm, trunk, hip, leg, foot
86
primary motor cortex columnar organization
vertical columns with sharp boundaries down into cortex, control specific actions, ex: thumb flexion / adduction / abduction
87
afferent input into primary motor cortex
dorsal column nuclei and ventral posterior lateral/medial thalamus, cerebellum, basal ganglia, primary somatosensory cortex, premotor cortex, supplementary motor cortex, posterior partietal cortex (areas 5 and 7)
88
afferent input from dorsal column nuclei and ventral posterior lateral/medial thalamus to primary motor cortex
joint afferents, muscle spindle receptors (type Ia and II) length and velocity of contralateral muscle, cutaneous input from glaborous skin, primary motor cortex intergrates sensory information to execute movements
89
primary motor cortex outputs
from pyramidal neurons in primary motor / premotor / supplementary motor / somatosensory / posterior parietal / frontal eye fields to basal ganglia / red nucleus / pontine nuclei / reticular formation / cranial nerve nuclei / spinal cord; many axons, few are giant Betz cells from cortical layer IV, passes through pyramidal decussation, to lower motor neurons, part of reflex circuits, part of motor programs
90
primary motor cortex to basal ganglia
corticostriate
91
primary motor cortex to red nucleus
corticorubral, involves cerebellum too
92
primary motor cortex to pontine nuclei
corticopontine, involves cerebellum too
93
primary motor cortex to reticular formation
corticoreticular, tone and reflex control
94
primary motor cortex to cranial nerve nuclei
corticobulbar, clinically useful for CNS lesions
95
primary motor cortex to spinal cord
corticospinal
96
corticobulbar tract to trigeminal motor nucleus (CN V)
controls muscles of mastication via V3, medial to trigeminal chief sensory nucleus, in the midpons
97
corticobulbar tract to facial nucleus (CN VII)
lower face controlled by contralateral motor cortex (affected by stroke), upper face controlled by ipsilateral and contralateral cingulate motor cortex (not affected by stroke), facial nucleus is in caudal pons, lower face portion lateral, upper face portion medial
98
corticobulbar tract to nucleus ambiguus
primary motor cortex to laryngeal and upper airway, vagus and glossopharyngeal, bilateral connections, located in rostral medulla dorsal to inferior olive
99
corticobulbar tract to spinal accessory nerve in cervical spine
trapezius and strernocleidomastoid, shrugging shoulders and turning head to side opposite SCM, stronger ipsilateral than bilateral, terminates on cells in medial ventral horn in upper cervical spinal cord
100
corticobulbar tract to hypoglossal nucleus
tongue muscles, nucleus in dorsal rostral medulla in floor of 4th ventricle, stronger contralateral, some bilateral parts, tongue will deviate toward defective side
101
lower quadrant of face affected
lesion in lower face portion of CN VII nucleus
102
upper half of face affected
lesion in upper face portion of CN VII nucleus
103
frontal eye field
project to brainstem gaze centers that project to CN III, IV, and VI nuclei, voluntary eye movement control
104
corticospinal tract
motor cortex to spinal cord, terminates on dorsal horn / intermediate gray / ventral horn, single corticospinal axon diverges into alpha motor neurons of many muscle, corticospinal fibers cross to contralateral at pyramidal decussation, passes through internal capsule, cerebral crus, basilar pons, ventral fasiculus of spinal cord
105
primary motor cortex cells encode for muscle activation/force
experiment - chimp with extensor and flexor loads, specific motor cortex neuron only fires with flexor load and responding flexor action
106
primary motor cortex cells encode for movement direction
experiment - chimp with target in different directions, specific motor cortex neuron only fires in directional movement on one side of circle
107
population code and primary motor cortex
neurons broadly tuned to a movement parameter, fire as a population, each cell contributes to movement
108
robotic prosthetic arm and primary motor cortex
can use muscle and direction coding groups of cells to control robotic prosthetic arm via thoughts from motor cortex - without seeing the monkey can know what the monkey is doing
109
premotor cortex afferent input
prefrontal cortex, supplementary motor area, posterior parietal (area 5 and 7), cingulate motor area, cerebellum and basal ganglia via thalamus
110
premotor cortex efferent output
primary motor cortex (area 4), supplementary motor area, posterior parietal cortex, prefrontal cortex, basal ganglia, red nucleus in brainstem, corticospinal tract
111
premotor cortex stimulation
coordinates turning of contralateral eye and head, eyes go and head follows, synergistic movement - contralateral hand reaches and head turns to watch
112
premotor cortex functions
sensorimotor transformation (sensory cue into motor action), planning and learning, dorsal portion for arm, ventral portion for hand,
113
premotor cortex function experiment
monkey sees yellow block and plans to put hand on it when stimulus light goes on, while planning neurons fire and firing decreases after stimulus light goes on, same neuron is not involved in planning to move hand other direction
114
dorsal strea
pathway by which visual information moves from posterior to anterior via the occipital lobe / posterior parietal lobe / premotor and primary motor cortexes; allows for sensory cues to guide movement
115
ventral premotor cortex (hand)
controls higher levels of grasping, contains mirror neurons that fire when pt grasps or when pt watches another person grasp same object
116
mirror neurons
found in ventral premotor cortex, fire when pt grasps or when pt watches another person grasp same object, functions - imitation, action understanding (use motor system to understand actions of another person), intention (harmful?)
117
mirror neurons experiment
ventral premotor neurons fire when monkey grasps and when monkey watches another monkey or human grasp same object
118
supplementary motor cortex afferents
primary motor cortex (area 4), prefrontal cortex, posterior parietal, basal ganglia, cerebellum
119
supplementary motor cortex efferents
primary motor cortex (area 4), striatum, brainstem, corticospinal tract
120
supplementary motor cortex stimulation
contralateral limb movement across joints, related to postural changes
121
supplementary motor cortex functions
internal generation of movement, sequences of learned movements
122
supplementary motor cortex homunculus
leg most posterior, arm, face most anterior
123
experiment - involved in learned motor sequences
primary motor cortex, supplementary motor area - internally driven movement - part of muscle memory - athletes stimulate the supplementary motor area when they visualize doing something
124
experiment - not involved in motor action after sensory cue
primary motor cortex, premotor area - sensory driven movement
125
supplementary motor area and internally driven learned movements
neuron fires with specific learned sequence but not with same parts of sequence in different order
126
highly proficient tasks and supplementary motor area
as tasks become more proficient and better learned, supplementary motor area reduces activity and primary motor cortex assumes control
127
cerebellar vermis
along midline in cerebellum
128
cerebellar intermediate zone
lateral to vermis in cerebellum
129
cerebellar lateral zone
lateral to intermediate zone in cerebellum
130
deep cerebellar nuclei
lateral to medial - dentate, emboliform, globose, fastigial - don't eat green frogs - also connected with vestibular nucleus
131
cerebellar peducles
superior, middle, inferior
132
cerebellar cortical layers
outer to inner, molecular, purkinje cell, granular
133
purkinje cells
output neuron of cerebellum, sends inhibitory GABA messages to cerebellar nuclei and vestibular nuclei, receives parallel (excitatory from granule cells) and climbing fiber input (excitatory from inferior olive), dendrites in molecular layer and cell body in purkinje cell layer
134
granule cells
cell body in granular cell layer with parallel fibers to purkinje cells, 1/2 of neurons in the brain, parallel fibers are excitatory with glutamate
135
inhibitory interneurons of cerebellum
Stellate, basket, and Golgi cells - all give off GABA - all excited by parallel fibers with glutamate
136
carabellar circuits
1. mossy fibers -> granule cells -> purkinje cells, 2. cotralateral inferior olive -> climbing fiber -> purkinje cell, 3. purkinje cell -> cerebellar nuclei and medial / lateral vestibular nucleus, 4. cerebellar nuclei -> many CNS targets
137
cerebellar afferents
mossy fibers afferents and climbing fiber afferents
138
mossy fiber cerebellar afferents
many spinal and brainstem sites of origin, excitatory glutamate synapse with granular cells, produce simple spikes in purkinje cells, high firing frequency, encode temporal and intensity infromation, run in groups horizontally across cerebellum
139
climbing fiber cerebellar afferents
sole source is inferior olive, monosynaptic with purkinje cell, powerful excitation, produces complex spikes in purkinje cell, fires less often, encodes teaching signal, run in vertical groups on cerebellum
140
cerebellar organization
ipsilateral, left cerebellum = left side of body, right cerebellum = right side of body
141
cerebellar functional divisions
vestibulocerebellum, spinocerebellum, cerebrocerebellum
142
vestibulocerebellum
flocculonodular lobe and vermis zone
143
vestibulocerebellum afferents
via mossy fibers, semicircular canals, otoliths, visual (parietal/occipital to pontine nuclei)
144
vestibulocerebellum efferents
1. medial / lateral vestibular and fastigial nuclei, 2. medial vestibulospinal tract (trunk/neck muscles), 3. lateral vestibulospinal tract (limb muscles), 4. gaze centers in brainstem (eye movements)
145
spinocerebellum
intermediate zone of cerebellum
146
spinocerebellum afferents / inputs
via mossy fibers to granular cells to parallel fibers, vestibular visual/auditory input, spinocerebellar tract inputs, facial somatosensory and proprioceptive input
147
dorsal spinocerebellar tract
spinocerebellar input, peripheral feedback - re-afferent information, in dorsal lateral fasiculus of spinal cord
148
ventral spinocerebellar tract
spinocerebellar input, provides info about state of spinal circuitry - efferent copy, relays muscle motor commands to other parts of nervous system, ventral lateral fasiculus of spinal cord
149
dorsal spinocerebellar tract path
cell body in Clark's nucleus of dorsal horn, ascends on ipsilateral side into cerebellum via inferior cerebellar peduncle, ascends from cerebellum to ventral lateral and anterior thalamic nuclei to cerebral cortex
150
ventral spinocerebellar tract path
cell body in ventral horn, crosses to contralateral via anterior white commissure in spinal cord, ascends to rostral pons, crosses back to ipsilateral, descends to cerebellum in the superior cerebellar peduncle
151
rubrospinal tract
branch off dorsal spinocerebellar tract as it ascends from cerebellum, goes to red nucleus, descends in dorsal horn
152
spinocerebellum efferents / outputs - vermis
vermis projects to fastigial nucleus, enters reticulospinal tract and vestibulospinal tract
153
spinocerebellum efferents / outputs - intermediate zone
intermediate zone projects to globose and emboliform nuclei, which go to red nucleus that controls rubrospinal tract, goes ventral lateral thalamus and motor cortex that controls that corticospinal tract
154
cerebrocerebellum
lateral zones of cerebellar hemispheres
155
cerebrocerebellum afferents / inputs
pontine nuclei, sensory / motor / premotor / parietal cortices
156
cerebrocerebellum efferents / outputs
to dentate nuclei, projects to ventral lateral thalamic nucleus to motor and premotor cortex (controls corticospinal tract), to prefrontal cortex, to red nucleus (controls rubrospinal tract)
157
climbing fibers
from contralateral superior olive to purkinje cells in cerebellum, orthoganal (right angle) to parallel fibers, run in parasagittal (vertical), projections in cerebellum, source of complex spikes that are teaching signals
158
functions of the cerebellum
produces smooth/coordinated movement (problems in cerebellum cause decomposition of movements and dysmetria), times movements, motor learning, predicts consequences of motor action by receiving information about effects of movements and intended movement
159
motor learning in cerebellum
when presented with new motor learning, climbing fibers stimulate parallel fiber - purkinje cell synapse until learning has happened for a long time and then climbing fiber stimulation decreases giving way to long term depression
160
motor learning with vestibulo-oculo reflex
reflex allows eyes to stays on target even though head is moving, 2x magnifying glasses causes world to move more than head and world slips off fovea (retinal slip), climbing fibers are activated to vestibulocerebellum to reteach reflex, vestibulo-ocular reflex adjusts to magnifying glasses, during learning period climbing fibers cause vestibulo-oculo reflex to have an increased amplitude
161
long term depression of parallel fibers in cerebellum
after climbing fiber teaching for a long time climbing fiber stimulation decreases at synapse of parallel fiber - purkinje cell and synapse gets weaker
162
dorsal spinocerebellar tract
re-afferent about effect of movement, arises from Clarke's nucleus, from legs and trunk, enters cerebellum through inferior cerebellar peduncle
163
ventral spinocerebellar tract
efference copy (info about intended movement to other parts of brain), arise from ventral horn, from legs and trunk, enters cerebullum through superior cerebellar peduncle
164
cuneocerebellar tract
re-afferent (effect of movement), arises from external cuneate nucleus, from arms, enters cerebellum through the inferior cerebellar peduncle
165
rostral spinocerebellar tract
efference copy (information about intended movement to rest of body), arises from ventral horn, from arms, enters cerebellum through interior cerebellar peduncle
166
cerebellum predicts consequences of motor action by...
comparing re-afferent messages from dorsal spinocerebellar tract (legs/trunk) and cuneocerebellar tract (arms) with efference copy (intended movement) information from ventral spinocerebellar tract (legs/trunk) and rostral spinocerebellar tract (arms) - learning via climbing fibers improves predictions
167
ethical obligation in field of medicine
Huntington case - state law that says that you are obligated to report pt who is a surgeon with Huntington, other law says that we are allowed to break confidentiality when there is a risk to public health (ex: bus driver with HD)
168
cerebellar output
from purkinje cells, has inhibitory synapse on deep cerebellar nuclei
169
layer V of primary motor cortex
contains medium-large pyramidal cells that give rise to corticospinal and corticobulbar axons that pass through ventral pons
170
neurological exam - station
pt should be able to stand with feet less than shoulder width apart
171
neurological exam - gait
normal walk, should be smooth and coordinated, upper extremities should move with walk
172
neurological exam - heel and toe walks
tests balance and strength in distal lower extremities
173
neurological exam - tandem gait
heel to toe walk on straight line, pt should be able to balance without falling or stepping aside
174
hemiplegic/hemiperetic gait
all on one side, extension of leg with internal rotation, shoulder adducted, elbow flexed, wrist pronated, fist with thumb tucked in
175
diplegic/diperetic gait
on both sides of body, flexion at hip and knee, ankles extended and internally rotated, knees adducted, arms flexed - looks like swinging side to side, ex: cerebral palsy
176
neuropathic gait - distal lower extremities effected
on both sides, inability to dorsiflex the foot (foot drop/drag if don't step high enough), must raise foot high to clear floor, if unilateral is peripheral nerve injury, if bilateral is something like ALS
177
myopathic gait
inability to stabilize the pelvis, pelivis dips toward nonweight bearing leg and hips look tilted, body/head leans toward weight bearing leg to centralize weight, aslo called Trendelenberg, can be caused by muscular dystrophy
178
parkinson gait
hypokinetic gate, stooped, bent at waist, trouble initiating gate, small/shuffle steps that speed up to a finestrated gait, hands tremor, turn as though on a block in one place with little shuffles
179
huntington gait
hyperkinetic gate, head randomly side to side, arms moving randomly, finger curling, shoulders up and down, legs kicking out to sides, back and forth at the hip
180
ataxic gait
wide stance (trouble with normal narrow station), small jerks especially above waist, trouble with tandem walk - falling to sides, cerebellar lesion or drunken
181
neuroaxis
all levels contribute to gait, look at upper and lower extremities,
182
neurological exam - upper extremities
inspect for bulk and fasciculations, palpate for tenderness/consistency/contractures, tone - passive range of motion (flexion/extension at wrist/elbow), strength from proximal to ditsal and grade 0-5
183
upper extremity strength testing
C5 - should extension, C6 - arm flexion, C7 - arm extension, C8 - wrist extension, T1 - hand grasp
184
muscle strength grading
0 - no contraction, 1 - slight contraction no movement, 2 - full ROM without gravity, 3 - full ROM with gravity, 4 - full ROM and some resistance, 5 - full ROM and full resistance
185
biceps DTR
C5-6
186
brachioradialis DTR
C5-6
187
triceps DTR
C7
188
finger flexors
C8
189
grading deep tendon reflexes
0 - absent, 1 - decreased, 2 - normal, 3 - brisk and excessive, 4 - with clonus
190
pronator drift
extend arms in front with palms up and eyes closed, watch for pronation or downward drift of arm, indicates corticospinal tract disease if present
191
neurological exam - lower extremities
inspect (bulk/fasciculation), palpate (tenderness/consistency/contractures), tone (passive range of motion in flexion/extension of ankle/knee), strength (proximal to distal, graded 0-5), deep tendon reflexes
192
lower extremity strength testing
L2 - hip flexion, L3 - knee extension, L4 - knee flexion, L5 - ankle dorsiflexion, S1 - ankle plantar flexion
193
lower extremity deep tendon reflex
L2-4 - patellar reflex, S1-2 achilles reflex
194
plantar reflex
stroke skin on lateral sole heel to ball to great toe, flexion of all toes is normal, Babinski sign - abnormal extension of great toe and fanning of other toes
195
pathological reflexes
reflex pattern that appears when there is damage to frontal lobes and inhibition of primitive reflex is absent
196
snout reflex
press tongue blade against lips, abnormal - pouting of lips
197
root reflex
stroke lateral upper lip, abnormal - move mouth toward stimuli
198
palmomental reflex
stroke palm of hand, abnormal - contraction of ipsilateral mentalis muscle in lower lip
199
lower extremities - upper leg and girdle strength
tested by squating and rising
200
lower extremities - foreleg strength
tested by heel and toe walks
201
skin sensation dermatomes
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202
muscle dermatomes
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203
neurological exam parts
mental status, cranial nerves, motor, sensory, reflexes, coordination, gait
204
mental status exam
judgement (what would you do if...), orientation (person, place, time), intellect (name last presidents), memory (recall 3 words now and later), remote memory (past event), appearance (hygiene and dress), calculation (serial 3s)
205
upper extremities muscle strength
bicep, tricep, deltoid, grip, wrist extension, thumb opposition, intrinsic hand muscles
206
lower extremities muscle strength
hip flexion/extension, hip adduction/abduction, knee flexion/extension, foot dorsiflexion/plantar flexion
207
deep tendon reflexes
bicep, tricep, brachioradialis, patellar, achilles
208
Babinski
if present is positive, stroke lateral sole to ball to great toe, toes should flex, abnormal - toes flare/extend
209
sensory
spinothalamic tract (pain and temp) - sharp/dull or coolness; dorsal column (touch, vibration, proprioception) - vibration with tuning fork or position of finger
210
coordination
finger-nose-finger, heel-to-shin, rapid alternating movements
211
gait
station, normal, tandem, heel, toe
212
Romberg
standing with eyes closed for 20 sec w/out support, see if pt waivers to one side
213
pronator drift
arms outstretched palms up, drift down suggests corticospinal defect, drift upward suggests position sense problem
214
parts of basal ganglia
neostriatum, globus pallidus, substantia nigra, subthalamic nucleus
215
neostriatum
receives major inputs, part of basal ganglia, made up of caudate and putamen nuclei - both have spiny neurons
216
spiny neurons
in neostriatum (caudate, putamen), have many dendrites, receive major input, primary output, GABA neurotransmitter, two kinds - GABA/substance P and GABA/enkephalin
217
afferent from cortex to neostriatum (corticostriate pathway)
cortex has excitatory effect on GABA/SP and GABA/ENK spiny cells in caudate/putamen with glutamate, afferent from premotor/primary motor/supplementary motor area cortices
218
aspiny neurons
function as interneurons in neostriatum
219
striatum to thalamus projection (direct pathway) - allows thalamus to act
cortex (glutamate/excitatory) -> striatal GABA/SP (GABA /inhibitory) -> globus pallidus internus (GABA/inhibitory) -> ventral anterior and ventral lateral thalamic nuclei via lenticular fasciculus -> returns to cortex as excitatory feedback loop
220
striatum to brainstem projection
cortex (glutamate/excitatory) -> striatal GABA/SP (GABA /inhibitory) -> substantia nigra pars reticulata -> ventral anterior and ventral lateral thalamic nuclei via lenticular fasciculus and to brainstem -> superior colliculus for eye movements and pedunculopontine nuclei for locomotion (believed to be part of eye movement problem in parkinson)
221
striatum to thalamus (indirect pathway) - suppresses thalamus
cortex (glutamate/excitatory) -> striatum GABA/ENK (GABA/inihibitory) -> globus pallidus externus (GABA/inhibitory) -> subthalamic nucleus (glutamate/excitatory) -> globus pallidus internus / substantia nigra reticulata (GABA/inhibitory) -> thalamus -> excitatory feedback loop to cortex
222
cortex to thalamus (hyperdirect pathway - bypasses striatum) - fast way for cortex to suppresses thalamus
cortex (glutamate/excitatory) -> subthalamic nucleus (glutamate/excitatory) -> globus pallidus internus and substantia nigra reticulata (GABA/inhibitory) -> ventral anterior and ventral lateral thalamic nuclei -> excitatory feeback loop to cortex
223
substantia nigra reticulata
GABA inhibitory to thalamus
224
substania nigra compacta (dopamine loop)
striatum GABA/SP (GABA/inhibitory) via striatonigral projection -> substantia nigra compacta (dopamine) -> excitatory on striatum GABA/SP D1 receptors and inhibitory on striatum GABA/ENK D2 receptors
225
dopamine and GABA/SP D1 receptors
excitatory, stimulates the direct pathway from striatum to thalamus allowing thalamus to act on movement, stimulates inhibition of dopamine loop
226
dopamine and GABA/ENK D2 receptors
inhibitory, blocks indirection pathway from striatum to thalamus that inhibits the thalamus - allowing the thalamus to act on movement
227
globus pallidus internus / substantia nigra reticulata
inhibitory to thalamus, tonically suppresses thalamus and motor activity
228
motor activity
requires decreased globus pallidus internus activity so that thalamus is no longer inhibited
229
direct pathway
facilitates movement by inhibiting globus pallidus internus that would normally inhibit the thalamus, cortex -> striatum -> globus pallidus internus
230
indirect pathway
suppresses movement by suppressing the thalamus, cortex -> striatum -> globus pallidus externus -> subthalamic nucleus -> globus pallidus internus -> thalamus
231
hyperdirect pathway
suppresses movement quickly by suppressing the thalamus, cortex -> subthalamic nucleus -> globus pallidus internus -> thalamus
232
basal ganglia circuit example - eye movement via
frontal eye fields (excitatory/glutamate) -> caudate nucleus GABA/SP (GABA/inhibitory) -> substantia nigra reticulata (GABA/inhibitory) -> superior colliculus uninhibited (glutamate/excitatory) -> gaze centers in brainstem stimulated (saccade)
233
effect of increased dopamine on direct pathway
inhibits GABA/ENK striatum, increasing globus pallidus externus output inhibitory output, excitatory action of subthalamic nucleus on globus pallidus internus decreased, globus pallidus internus is not stimulated to inhibit thalamus, thalamus is allowed to act on movement
234
effect of increased dopamine on indirect pathway
excites GABA/SP striatum, increasing inhibition of globus pallidus internus, decreasing inhibition of thalamus - allowing thalamus to act on movement
235
normal globus pallidus internus activity
creates inhibitory tonic balance in ventral anterior and ventral lateral thalamus
236
increased dopamine levels (methanphetamine)
less excitation of globus pallidus internus by subthalamic nucleus, more inhibition of globus pallidus internus by striatum (putamen), overall less inhibition of ventral anterior and ventral lateral thalamus by globus pallidus internus = MORE MOTOR ACTIVITY
237
movement selection and basal ganglia
basal ganglia circuit used to select movement based on reward, dopamine neurons provide estimate of reward
238
postural tone
tonic muscle activity that opposes gravity, lower limb extensors, upper limb flexors, due to tonic activity of alpha motor neurons on extrafusal fibers, keep center of gravity directly above support surface, descending tracts and spinal reflexes work together to maintain center of mass
239
increases tone
direct increased alpha motor neuron activity, increased gamma motor neuron activity in intrafusal spindle reflex causes increased alpha motor neuron activity via IA fibers
240
vestibulospinal tract and postural tone
increases/decreases alpha motor neuron activity directly, medial vestibulospinal tract to axial muscles (neck/spine), lateral vestibulospinal tract to limb muscles, input from vestibular organs and cerebellum
241
medial vestibulospinal tract
axial tonic muscle control via direct alpha motor neurons stimulation, starts in medial vestibular nucleus, decends in medial vestibulospinal tract, synpases on alpha motor neuron cell body in medial ventral horn
242
lateral vestibular tract
appendicular tonic muscle control via direct alpha motor neurons stimulation, starts in lateral vestibular nucleus, decends in lateral vestibulospinal tract, synpases on alpha motor neuron cell body in lateral ventral horn
243
alpha motor neuron
direct tonic muscle control, cell body in ventral horn
244
reticulospinal tract
increases/decreases gamma and alpha motor neuron activity (gamma activity causes spindle to fire which causes alpha to fire), two descending systems - pontine reticular formation and medullary reticular formation - activity in this tract explains hypertonic/hyperreflexive changes in upper motor neuron syndrome
245
pontine reticular formation
premotor/primary motor/primary sensory cortices -> contralateral pontine reticular formation -> descends in medial reticulospinal tract -> excitatory on gamma motor neuron in ventral horn
246
medullary reticular formation
premotor/primary motor/primary sensory cortices -> contralateral medullary reticular formation -> descends in lateral reticulospinal tract -> inhibitory on gamma motor neurons; controls extensors - prevents from being hypertonic
247
tilt head/surface up
example of vestibulospinal reflex, vestibulocollic refelxes act on neck, vestibulospinal reflexes act on limbs, neck flexion, arm flexion, extension of legs
248
tilt head/surface down
extension of neck, extension of arms, flexion of legs
249
rotation around spinal axial
vestibulospinal reflex
250
head / body rolled to right
head rotates left, right limbs extend, left limbs flex
251
head / body rolled to left
head rotates to right, left limbs extend, right limbs flex
252
vestibulospinal reflex circuit
vestibular afferents -> vestibular nuclei -> vestibulospinal (limbs) and vestibulocollic (neck) tracts -> alpha motor neurons of neck and limbs
253
spinal cord transection (spinal cord injury or cerebral palsy)
descending corticospinal/vestibulospinal/reticulospinal tracts cut, 1-2 months flaccid and no reflexes, after 2 months hyperreactive reflexes and hypertonic muscles (increased extensor tone), caused by denervation hypersensitivity and spinal interneurons filling void left by inactive descending neurons
254
denervation hypersensitivity
leads to hyperreflexia and hypertonia with spinal cord transection, alpha motor neuron receptors upregulated and phosphorylated
255
interneurons filling descending innervation void
leads to hyperreflexia and hypertonia with spinal cord transection, interneuron fron muscle spindle to alpha motor neuron grows more sprouts
256
decerebration
lesion below red nucleus in spinal cord (mid-collicular), prevents cortex from inhibiting pontine reticular formation (excites gamma motor neuron) and stimulating medullary reticular formation (inhibits gamma motor neuron), allows pontine reticular formation to excite gamma motor neurons -> activating muscle spindle IA fibers -> activating alpha motor neurons -> tensing extensors in arms/legs/neck, sing of increasing pressure in brain, must relieve pressure, emergency
257
removal of cerebral cortex control
increases gamma motor neuron activity because the pontine reticular formation is no longer inhibited and has an excitatory effect on gamma motor neurons, overactive stretch reflex and extensors tensed
258
relief of abnormal tone
cut dorsal root where muscle spindle IA fiber enters to synapse with alpha motor neuron, used in cerebral palsy
259
decortication
lesion above red nucleus, extension of legs, flexion of arms, disinhibition of red nucleus increases flexor motor neuron activity in cervical spine
260
huntington epidemiology
1/10,000, white, 35-50 yrs, 1/3 clinical, 2/3 carriers, most common inherited neurodegenerative disorder, 100% penetrance, 15-20 year life expectancy after onset, causes of death - pneumonia, heart disease, falls, suicide, violence
261
huntington gene (Htt)
large, widespread in peripheral tissue, expressed in neurons, essential for embyronic development, on chromosome 4
262
huntington protein (Htt)
unique, found in many tissues and parts of cell, striatal neurons vulnerable, undergoes post-translational modifications, many functions of wild-type protein (transport, anchoring, signaling)
263
huntington gene mapping project
1980s, Lake Maracaibo, Venezuela, Nancy Wexler - her mother had disease
264
huntington gene mutation (Htt)
autosomal dominant, expanded CAG repeat in exon 1, CAG codes for glutamine (Q) - poly Q, mutation in germline but continues in somatic cells, normal poly Q < 35, 36-41 poly Q incomplete penetrance, 40-60 poly Q adult onset, >60 poly Q juvenile onset
265
anticipation in huntington
age of onset decreases with successive generations, CAG repeat instability during meiosis (egg/sperm) and mitosis (sperm), anticipation more likely with paternal carrier due to higher rate of mutation in sperm
266
huntington modifier genes
mostly size of CAG repeat dictates age of onset, but some modifier genes affect age of onset, GluR6 (kainate receptor) = 5 years earlier, ApoE modifies severity, E4 protectively increases age of onset, NMDA receptor variants influence severity
267
sex of parent with huntington
earlier onset with paternal transmission
268
environmental factors and huntington
omega-3 fish fatty acids protective, omega-6 red meat increased susceptibility, enrichment slows disease
269
triple repeat diseases
9 neurodegenerative diseases with polyQ, all auto dominant except one, polyQ protein undergoes proteolytic cleavage liberatining toxic fragements, protein folding defects leading to inclusion aggregates, inverse correlation between number of repeats and age of onset
270
cleavage of huntington protein Htt
cleaved by proteases, expanded polyQ in exon 1 enhances rate of protein cleavage nearby, cleaved wildtype Htt is degraded in cytoplasm, cleaved mutant Htt tranlocates to nucleus becoming trapped and forming protein aggregates from remaining toxic fragment, basketlike aggregate traps other proteins
271
neurological inclusion bodies in huntington
protein aggregates, in striatum / cortex, appear before symptoms, possible protective against cell death, protective, or just end stage byproduct
272
neurotoxic effects of huntington
transcription dysregulation, altered neurotransmitters and excitotoxicity, interferes with wildtype Htt, apoptosis, oxidative stress from mito dysfunction and altered metabolism, gain of function and loss of wildtype function (vesicle transport, synaptic function)
273
clinical timeline in huntington
neuronal dysregulation long before motor defects which are long before cell death - psychiatric symptoms may preceded motor onset and cell death by 20 years
274
dysregulation of transcription in huntington
altered transcription precedes neurodegeneration, mutant Htt inhibits DNA binding and transactivation of different transcription factors, major target is CBP (histone acetyltransferase) which inhibits transcription, possible Tx histone deacetylase inhibitor to counter effect of mutant Htt on chromatin condensation
275
effects of huntington on neurons and neurotransmitters
NT alteration, loss of spiny neurons with GABAergic deficiency, upregulation of NMDA receptors causes exototoxicity (due to chronic glutamate exposure), neuronal cell death from overstimulation
276
increased excitotoxicity in huntington
1. increased glutamate, 2. reduced glia glutamate uptake, 3. hypersensitivity to NMDARs or increased mGluR signaling, 4. altered Ca intracellularly, 5. mitochondrial dysfunction
277
interference with wildtype Htt in huntington
Htt needed for embyronic development, mutant can trap wildtype in nucleus or bind in cytoplasm, wildtype function loss leads to defected axonal transport and synaptic dysfunction
278
apoptosis in huntington
end stage result, induced by mutant Htt, inhibition of mutant Htt cleavage reduces cell death
279
oxidative stress and huntington
excitotoxicity causes huge release of Ca -> mitochondrial dysfunction -> release of cytochrome C -> caspase activation -> cell death, mutant Htt interfers with PGC-1alpha in mitochondrial membrane - may explain metabolic dysfunction of losing weight despite normal caloric intake
280
huntington Tx strategies
inhibit protease, inhibit proteasome, inhibit misfolded protein, inhibit protein aggregation, inhibit autophagy of aggregates
281
allele specific siRNA potential tx for huntington
siRNA can selectively degrade mRNAs that differe by one nucleotide, 3/4 HD pts heterozygous for panel of SNPs in Htt gene
282
triple repeat diseases
9 neurodegenerative diseases with polyQ, all auto dominant except one, polyQ protein undergoes proteolytic cleavage liberatining toxic fragements, protein folding defects leading to inclusion aggregates, inverse correlation between number of repeats and age of onset
283
cleavage of huntington protein Htt
cleaved by proteases, expanded polyQ in exon 1 enhances rate of protein cleavage nearby, cleaved wildtype Htt is degraded in cytoplasm, cleaved mutant Htt tranlocates to nucleus becoming trapped and forming protein aggregates from remaining toxic fragment, basketlike aggregate traps other proteins
284
neurological inclusion bodies in huntington
protein aggregates, in striatum / cortex, appear before symptoms, possible protective against cell death, protective, or just end stage byproduct
285
neurotoxic effects of huntington
transcription dysregulation, altered neurotransmitters and excitotoxicity, interferes with wildtype Htt, apoptosis, oxidative stress from mito dysfunction and altered metabolism, gain of function and loss of wildtype function (vesicle transport, synaptic function)
286
clinical timeline in huntington
neuronal dysregulation long before motor defects which are long before cell death - psychiatric symptoms may preceded motor onset and cell death by 20 years
287
dysregulation of transcription in huntington
altered transcription precedes neurodegeneration, mutant Htt inhibits DNA binding and transactivation of different transcription factors, major target is CBP (histone acetyltransferase) which inhibits transcription, possible Tx histone deacetylase inhibitor to counter effect of mutant Htt on chromatin condensation
288
effects of huntington on neurons and neurotransmitters
NT alteration, loss of spiny neurons with GABAergic deficiency, upregulation of NMDA receptors causes exototoxicity (due to chronic glutamate exposure), neuronal cell death from overstimulation
289
increased excitotoxicity in huntington
1. increased glutamate, 2. reduced glia glutamate uptake, 3. hypersensitivity to NMDARs or increased mGluR signaling, 4. altered Ca intracellularly, 5. mitochondrial dysfunction
290
interference with wildtype Htt in huntington
Htt needed for embyronic development, mutant can trap wildtype in nucleus or bind in cytoplasm, wildtype function loss leads to defected axonal transport and synaptic dysfunction
291
apoptosis in huntington
end stage result, induced by mutant Htt, inhibition of mutant Htt cleavage reduces cell death
292
oxidative stress and huntington
excitotoxicity causes huge release of Ca -> mitochondrial dysfunction -> release of cytochrome C -> caspase activation -> cell death, mutant Htt interfers with PGC-1alpha in mitochondrial membrane - may explain metabolic dysfunction of losing weight despite normal caloric intake
293
huntington Tx strategies
inhibit protease, inhibit proteasome, inhibit misfolded protein, inhibit protein aggregation, inhibit autophagy of aggregates
294
allele specific siRNA potential tx for huntington
siRNA can selectively degrade mRNAs that differe by one nucleotide, 3/4 HD pts heterozygous for panel of SNPs in Htt gene
295
human genome project ELSI
ethical, legal, and social implications - use of info, privacy, confidentiality, stigam, reproductive issues, clinical concerns, testing and therapies, commercialization, patents
296
sequence of events for child born to parent with huntington
diagnosis of parent, awareness of risk status, recognition of disease in older relatives, care for children and affected parent, death of effected parent and disability of pt if HD positive, observe siblings develop disease and manage own behavior if HD positive, surviving parent helps care for affected adult child and total dependence if HD positive, birth of pt's grandchildren and pt's death
297
suicidal ideation
peaks prior to diagnosis by symptoms and again when managing HD behaviors
298
predictive genetic testing
assess risk, intended to reduce morbidity and mortality, valuable if there is prevention or tx , can be pre-natal to assure non-affected child
299
huntington predictive testing
38+ repeats of Htt gene = 100% chance of getting HD, no tx, personal choid with psycho-social implications, pre and post counseling needed, only 5% choice predictive test
300
huntington exclusionary testing
embryos created in vitro, only unaffected embryos implanted, mother/father is never told their HD status
301
clincal issues with huntington
pregnancy/children, psychological, family dynamics, advice/counseling
302
huntington and beneficence
do good when possible, knowledge is power, planning life
303
huntington and non-maleficence
do no harm, emotional, family, social, privacy, confidentiality, indeterminate tests (lower number of CAG repeats <38), when will disease develop
304
huntington and autonomy
informed consent before testing, only test after age 18, prenantal testing - mother decides what happens to her body
305
huntington and justice
do greatest good for greatest number, is it ethical to test for disease that has no cure, cost of test ($300 diagnostic, $1000 predictive), genetic discrimination
306
triad of huntington symptoms
motor - chorea/impersistence/hypotonia/hyperreflexia/dystonia/akinetic-rigid; psychiatric - irritability/depression/agitation/delusions/personality change/suicidal ideation (7% of HD pts); cognitive - dementia/loss of processing speed/executive dysfunction/attention/retrieval/visual-spatial
307
huntington clinical additional symptoms
impaired visual saccades with normal smooth pursuit, weight loss, cachexia
308
juvenile huntington symptoms
myoclonus, seizures, like parkinsons, cognitive change, chorea often absent
309
huntington diagnosis
family hx - none in 8% of cases, paternal anticipation, physical exam, genetic testing, neuroimaging - caudate atrophy
310
huntington tx
there are no disease modifying agents, but there are tx given to lessen symptoms
311
memory enhancing drugs
amphetamines, aderol
312
synapse development
do form in absence of transmission (as in fetus), but transmission is needed to establish final connections
313
strengthen synapses
presynaptic and postsynaptic neurons firing simultaneously
314
weakens synapses
presynaptic and postsynaptic activities not linked
315
main learning and memory neurotransmitter
glutamate
316
main learning and memory receptors
metabotrophic glutamate receptor, ionotrophic - AMPA and NMDA receptors
317
NMDA receptors
blocked by Mg2+ at neg resting potential, if presynaptic glutamate release and postsynaptic depolarization coincide Mg2+ is displaced and Ca2+ enters cell - enhances synaptic effectiveness
318
long term potentiation
post synpatic response increases to new level following NMDA receptor stimulation because additional AMPA receptors are trafficked to the cell membrane/synapse
319
long term depression
weak NMDA receptor activation causes AMPA receptors to be internalized from cell membrane/synapse
320
memory and learning
adaptive change in response to environmental input
321
learning
acquisition of new information
322
memory
retention of learned information
323
memory consolidation
sensory input -> short term memory -> consolidation -> long term memory; process of protein synthesis that is inhibited by protein synthesis inhibitors
324
engrum
location where memory is residing, some area of brain important to memory formation, memory is an assembly of connected cells
325
H.M. case study
seizures, removed hippocampus and rhinal cortex in medial temporal lobe - lost a lot of memory
326
animal memory models
sea slugs and fruit flies, identified gene mutations in fruit flies that prevented learning, Ddc, amnesiac, rutabaga, dunce
327
Dcd mutation
prevents conversion of L-DOPA into dopamine and 5-hydroxytryptophan into serotonin
328
rutabaga mutation
prevents ATP being turned into cAMP
329
dunce mutation
prevents cAMP being turned into AMP by phosphodiesterase - which prevents the activation of protein kinase
330
molecular short term memory
5HT binds receptor, cAMP phosphorylates protein kinase which opens K+ and Ca2+ channels
331
molecular long term memory
transcription factor CREB1 is activated by phosphorylation by protein kinase and removal of CREB2 by MAP kinase, the gene CRE is transcribed early, the genes CAAT and TAAC are transcribed late, proteins are produced for synaptic growth
332
over expression of CaM kinase II
enhances activity of protein kinase A, more CREB1 transcription factor phosphorylated, smarter
333
protein kinase M zeta
involved in maintenance of late long term potentiation and memory, transcription of gene brought on by NMDA receptor stimulation, Ca inflow, and kinase activation
334
ZIP
peptide that abolishes long term potentiation in hippocampus by inhibiting protein kinase M zeta that acts at AMPA receptors, possible tx for PTSD
335
genes linked to intelligence in humans
IGF2R, higher IQ with mutation of cathespin D (CTSD), Alzheimers linked to CHRM2 (none = smarter, 1 copy = middle, 2 copies = lowest)
336
four questions for localizing lesions
what level is the lesion at - what side is the lesion on - mass / non-mass / indeterminate - pathology
337
what level is the lesion at
supratentorial (cerebral and diencephalon), posterior fossa (brainstem, cerebellum), spinal/vertebral, peripheral (plexus, nerves), multiple levels
338
what side is the lesion on
right focal, left focal, midline focal, diffuse non-focal
339
is the lesion mass
mass - focal and progressive, ex: hematoma / abscess / neoplasm, expansion and compression of tissues
340
is the lesion non-mass
focal and non-progressive ex: infarct OR diffuse and progressive ex: meningitis
341
is the lesion indeterminate
transient ex: transient ischemic attack
342
lesion temporal profile
time over which maximum signs and symptoms develop
343
vascular temporal profile
acute, < 24 hours, ex: hematoma
344
inflammatory temporal profile
subacute, 1 day - 1 month, ex: meningitis
345
neoplasm temporal profile
chronic, >1 month and focal, ex: astrocytoma
346
degenerative temporal profile
chronic > 1 month and diffuse, ex: parkinson
347
other causes of brain defects
intoxication, congenital, allergic/autoimmune, traumatic, endocrine/metabolic
348
acute, focal, progressive
mass, vascular, hematoma
349
subacute, focal, progressive
mass, inflammatory, abscess or granuloma
350
chronic, focal, progressive
mass, neoplasm
351
acute, focal, non-progressive
non-mass, vascular, infarct
352
acute, diffuse, progressive
non-mass, vascular, subarachnoid hemorrhage, anoxia
353
subacute, diffuse, progressive
non-mass, inflammatory, meningitis, encephalitis
354
chronic, diffuse, progressive
non-mass, degenerative
355
diffuse
suggest non-mass
356
intersegmetal findings
involve major sensory ascending or descending motor pathways, broader effect
357
segmental findings
specific components of CNS of PNS, localizing value
358
midbrain
CN III / IV
359
pons
CN V / VI / VII / VIII
360
medulla
CN IX / X / XI / XII
361
brachial plexus
C5-T1
362
sacral plexus
L2-S3
363
nipple
T4
364
umbillicus
T10
365
supratentorial
right / left cerebral hemispheres
366
posterior fossa
cerebellum and brainstem, cranial nerves
367
upper extremity segments
C5-T1
368
thoracic/abdominal segments
T1-T12
369
lower extremity segments
L2-S3
370
sphincter segments
S2-S4
371
supratentorial lesion
deficits on contralateral head and body
372
posterior fossa lesion
ipsilateral head and contralateral body
373
spinal cord lesion
ipsilateral (touch) and contralateral (pain/temp) body
374
peripheral nerve lesion
ipsilateral body
375
limbic system controls
mood, emotion, feelings, motivation, critical for memory
376
difficult to study limbic system
all structures anatomically interconnected, hard to measure physiological response
377
limbic system is clinically relevant because...
>50% of pts Tx for mood disorder
378
structures of limbic system
amygdala, hippocampus, septal nuclei, nucleus accumbens, medial prefrontal cortex, anterior cingulate cortex, ventral tegmental area, anterior and dorsomedial thalamic nuclei, mammillary nuclei
379
hippocampus to mammillary bodies and septal nuclei
limbic pathway, large C shaped via the fornix
380
mammillary body to anterior thalamic nucleus
limbic pathway, mamilla-thalamic tract
381
amygdala to septal nuclei
limbic pathway, called stria terminalis
382
midbrain to forebrain
limbic pathway, via medial forebrain bundle
383
hypothalamus to brain stem / spinal cord
limbic pathway, via dorsal longitudinal fasciculus
384
anterior thalamic nuclei to anterior cingulate gyrus and medial prefrontal cortex
limbic pathway, via anterior limb of the internal capsule
385
all limbic circuits pass through...
hypothalamus, way to connect to autonomic and neuroendocrine pathways
386
limbic innervation
monoaminergic and cholinergic axons
387
norephinephrine in limbic system
released by locus ceruleus in pons, to cerebellum, brainstem, cortex
388
serotonin in limbic system
released by raphe nuclei in pons and midbrain, to cerebellum, brainstem, cortex
389
dopamine in limbic system
released by ventral tegmental area (VTA) in the mesolimbic system, from midbrain medial to substantia nigra to limbic system parts (nucleus accumbens, medial prefrontal cortex, amygdala, spetal nuclei)
390
dopamine
reward
391
addiction
dopamine plays a role due to role in reward
392
cocaine
blocks dopamine reuptake
393
amphetamine
blocks dopamine reuptake and increases dopamine release
394
lesion of ventral tegmental area / nucleus accumbens / dopamine receptor antagonist
decrease drug seeking behaviors
395
natural dopamine rewards
food, sex, exercise, produce dopamine reward through mesolimbic system
396
Tx addiction through mesolimbic reward system
reduces response to natural rewards
397
acetylcholine
released by nucleus basalis and septal nucleus in limbic system to hippocampus, loss of cholinergic neurons in early Alzheimers
398
amygdala
fear conditioning, increased activity with conditioned stimulus, lesion = no fear conditioning, inability to pair unconditioned and conditioned stimuli
399
prefrontal cortex
Phineas Gage, lesion = loss of goal directed behavior, increased impulsiveness, loss of moral reasoning, prefrontal cortex inhibits amygdala which excites the hypothalamus
400
dorsolateral prefrontal cortex
working memory for planning
401
orbital frontal cortex
inhibitory output to the amygdala for emotional control
402
hippocampus
lesion of hippocampus = anterograde amnesia (no new memories), temporally graded retrograde amnesia (lost memories 2-3 years before surgery, earlier memories intact), lost explicit/declarative memory (facts / events), did not lose implicit procedural nondeclarative memory (motor skills)
403
medial midbrain CN
CN III ventrally, CN IV dorsally
404
dorsal medial midbrain
CN III, descending pyramidal system with motor tracts, medial lemniscus with ascending sensory tracts
405
lateral midbrain
spinothalamic tract, reticulospinal tract
406
medial pons CN
CN VI
407
medial pons
CN VI, pyramidal system with descending motor tracts, medial lemniscus with ascending sensory tracts
408
lateral pons CN
CN V, CN VII, CN VIII
409
lateral pons
ascending spinothalamic tract, descending reticulospinal tract, spinal tract of CN V
410
medial medulla CN
CN XII
411
medial medulla
CN XII, descending pyramidal motor tracts, ascending medial lemniscus sensory tract
412
lateral medulla
CN IX, CN X, ascending spinothalamic tract, descending reticulospinal tract, descending spinal tract of CN V
413
rigidity
inflexibility and stiffness, resistance to passive stretch, clasp knife or lead pipe
414
dystonia
constant muscle contraction, often with pain
415
positive symptoms of parkinson / huntington
gain of function, lead pipe rigidity, cogwheel rigidity, athetosis (can't maintain posture), dystonia (involuntary contraction), chorea, ballismus (violent flinging of arms)
416
negative symptoms of parkinson / huntington
loss of function, akinesia, bradykinesia, masked facies, dystonia
417
schizophrenia postive symptoms
gain of function, hallucinations, dellusions
418
schizophrenia negative symptoms
loss of function, social withdrawal
419
resting tremor
parkinson, over-inhibition of thalamus by globus pallidus externus internus and substantia nigra reticulata, causes thalamic cells to go into osscilatory firing, disappears with action
420
intention tremor
MS, depressive substance withdrawal, with deliberate movement inadequate motor signaling during voluntary movement
421
nausea from parkinson tx (levodopa)
dopamine stimulates chemoreceptor trigger center in CNS, dopamine activates peripheral dopamine receptors - goes away with increased carbadopa
422
myerson's sign
normal - can stop blinking when tapping on forehead, abnormal - can't stop blinking when tapping on forehead
423
myerson's sign pathway
cortex -> basal ganglia -> cortex -> motor nuclei; basal ganglia normally inhibit, in parkinson basal ganglia inhibition is gone
424
direct basal ganglia motor circuit
increases motor activity by uninhibiting the thalamus
425
indirect basal ganglia motor circuit
decreases motor activity by inhibiting the thalamus
426
dopamine basal ganglia motor circuit
dopamine released by sunstantia nigra compacta, excites the direct pathway, inhibits indirect pathway - overall: motor activity increased with dopamine input
427
hyperkinetic disorder
direct pathway excited, indirect pathway inhibited, thalamus uninhibited = more motor activity, dyskinesia and ballismus, huntington
428
hypokinetic disorder
direct pathway inhibited, indirect pathway activated, thalamus inhibited = less motor activity, bradykinesia, akinesia, parkinson
429
parkinson tx model
imbalance of dopamine / ACh, low dopamine, can tx dopamine deficiency or use ACh receptor antagonist, interneurons signal spiny neurons with ACh, substantia nigra compacta signals spiny neurons with dopamine
430
hypothalamus functions
maintains homeostasis (receptor -> hypothalamus -> dorsal longitudinal fasciculus -> brainstem / spinal cord), integrate information for control of endocrine/autonomic/neural system - attached to pituitary gland
431
pituitary gland
sella turcica in sphenoid bone - stability
432
anterior pituitary gland
adenophysis - endoderm origin, pars tuberalis and distalis
433
posterior pituitary gland
neurophysis - ectoderm origin, infundibular stalk and posterior lobe
434
median eminence
infundibulum from hypothalamus to pituitary gland
