Unit III week 1 Flashcards
1
Q
Brainstem Function (3)
A
1) Conduit functions
2) Integrative functions
3) Cranial nerve functions
2
Q
Conduit function of brainstem
A
transit and processing stations for ascending and descending pathways between cerebrum, cerebellum, and spinal cord
3
Q
Integrative Functions of brainstem
A
“Keeps you alive” - integrative functions, consciousness, sleep-wake cycle, muscle tone, posture, respiratory and cardiovascular control
4
Q
Cranial Nerve Functions of brainstem
A
home of cranial nerves 3-12 and their nuclei
5
Q
Local signs
A
clues to where lesion in brainstem is based on the levels CNs exit brainstem
Long tracts = meridians of longitude, CNs are parallels of latitude
Can figure out lesion based on long tract deficits + CN deficit
CN SIGN appears IPSILATERAL to lesion, LONG TRACT signs are CONTRALATERAL
Lesions in medial part of brainstem result in completely different deficits than a lateral lesion
6
Q
Inferior cerebellar peduncle
A
conveys spinal cord information to cerebellum and interconnects cerebellum with vestibular nucleus and inferior olive
Carries contralateral inferior olive, ipsilateral spinocerebellar, and ipsilateral vestibular
7
Q
Middle cerebellar peduncle
A
route by which information from cerebral cortex gets to cerebellum via pontine nuclei
carries info from contralateral pontine nuclei to dentate nuclei
8
Q
Superior cerebellar peduncle
A
route by which the cerrebellum gets information back to the cerebral cortex via the thalamus
Carries info from dentate nuclei to contralateral thalamus
9
Q
Cerebral peduncle
A
structures at the front of the midbrain which arise from the front of the pons and contain the large ascending (sensory) and descending (motor) nerve tracts that run to and from the cerebrum from the pons
10
Q
Medial and lateral division of the spinal cord:
Alar vs. Basal plate
Visceral vs. non-visceral portion
A
Alar plate → sensory, more lateral basal plate → motor, more medial
Visceral portion: closest to sulcus limitans
Visceral motor → lateral to somatic motor, medial to somatic sensory
Non-visceral portion: lateral to visceral portion
11
Q
Corticospinal tract review
A
Internal capsule → corticospinal tract in cerebral peduncles → split up in pons, separated by pontine nuclei, and then come together again to reform corticospinal tract → Medulla, corticospinal tract in pyramid → decussation at spinomedullary junction → ventral horn of spinal cord to a-motor neurons
12
Q
Dorsal Column-Medial Lemniscus review
A
Sensory info comes in → Fasciculus gracilis (legs), Cuneatus (arms) → first synapses in medulla at nucleus gracilis/cuneatus → cross → pons, ML slips and forms a mustache (upper arms more medial), just below mustache is trapezoid body (crossing fibers of auditory pathway) → VPL of thalamus
13
Q
Anterolateral (spinothalamic) review
A
Synapse in spinal cord dorsal horn, cross in spinal cord, and then doesn’t stop until it reaches the top → pain is more lateral than other tracts in medulla → spinothalamic tract is lateral to medial lemniscus thalamus
14
Q
Sound
A
series of pressure waves of alternating compression (increased density) and rarefaction (decreased density) of air molecules
Tells us WHAT and WHERE (direction and distance)
15
Q
Intensity
A
increase of intensity in a sound is when the air is compressed more forcefully during peak compression each cycle → increased density of air
“Loudness” = pressure at peak of compression
16
Q
dB SPL = decibels of sound pressure level
equation
A
dB SPL = 20 x Log (P1/P2)
P2 = standardized reference pressure, 20x10^-6 (micro Pascals)
P1 = pressure of the tested sound
Sound above 120 dB → permanent hearing loss
17
Q
Frequency
A
number of times per second that a sound wave reaches peak of rarefaction (or compression)
18
Q
Quantification of hearing loss
A
determining for each ear, and at different frequencies, the smallest dB SPL a subject can just detect
19
Q
External ear
A
pinna, external auditory meatus, bounded by tympanic membrane
20
Q
Function of external ear
A
Pinna collects sound, funnels it toward auditory meatus, provides acoustical cues to spatial location of sound source
Pressure waves then move tympanic membrane
Rarefaction → TM bulges out
Compression → TM presses in
21
Q
Middle ear
A
ossicular chain (malleus, incus, stapes)
Moved by movement of tympanic membranes
22
Q
Inner ear includes the _______ and _________
A
cochlea and semicircular canal
23
Q
Acoustic impedance mismatch
A
Air-fluid boundary causes most acoustic energy to be reflected away, water → high impedance, air → low impedance
24
Q
What allows us to overcome the acoustic impedance mismatch
A
Middle ear allows us to overcome impedance mismatch
1) P=F/A → Area of tympanic membrane 20x that of stapes → low amplitude vibrations falling onto large tympanic area concentrated into large amplitude motions of much smaller stapes footplate
2) Orientation of middle ear bones confer levering action resulting in larger force
→ almost completely overcomes air-fluid impedance mismatch problem
Impedance mismatch is a problem if fluid fills middle ear → otitis media
25
Sensorineural hearing loss
damage to or loss of hair cells and/or nerve fibers
involves cochlea
26
Common causes of sensorineural hearing loss (4)
1) Excessively loud sounds
2) Exposure to ototoxic drugs (diuretics, aminoglycoside antibiotics, ASA, cancer therapy drugs)
3) Age (presbycusis) - lose high frequency hearing, as we age
4) Genetic causes
27
Conductive hearing loss
degraded mechanical transmission of sound energy through middle ear.
Areas involved: external ear, tympanic membrane, middle ear
28
Common causes of conductive hearing loss (7)
1) Filling of middle ear with fluid during otitis media
2) Otosclerosis - arthritic bone growth impedes ossicle movement
3) Malformation of ear canal (swimmer’s ear, cauliflower ear)
4) Perforation/rupture of tympanic membrane
5) Interruptions of ossicular chain
6) Static pressure in middle
7) cholesteatoma (skin cyst that acts in tumor-like way)
29
How can you differentiate conductive vs. sensorineural hearing loss?
Can overcome conductive hearing loss by placing tuning fork against bone
30
Tonotopic map
frequency-wise arrangement of tones or frequencies along length of BM (and is preserved through the auditory pathway into the primary auditory cortex)
Key for determining IHC sensitivity at different spots along BM → each IHC will respond best to a certain frequency determined by mechanical properties of BM at that particular location
Sound FREQUENCY = primary stimulus attribute mapped along cochlea
31
BM at apex vs. base
BM more flexible, wider, and thicker at APEX
→ LOW FREQUENCY VIBRATION
BM thinner narrower, and more rigid near oval and round window at BASE of cochlea
→ HIGH FREQUENCY VIBRATION
32
3 compartments of the cochlea
scala vestibuli, scala media, scala tympani
33
Basilar membrane (BM)
separates scala media and scala tympani
Mechanical properties of BM key for discrimination of sound frequency
IHCs attached to BM
34
Organ of corti
sits on top of BM and in scala media
Contains inner hair cells (IHC) attached to BM that transduce sound into electrical signals
Each cross section = 1 IHC and 3 outer hair cells (OHC)
35
Helicotrema
hole in BM at apex of cochlea, connects scala tympani to scala vestibuli, relieves pressure → both have perilymph
36
How sound elicits movement of BM
1) Stapes hits OVAL WINDOW (during peak of compression) → oval window bulges into SCALA VESTIBULI = “traveling wave”
2) → downward movement of BM to relieve compression
3) → compress fluid in SCALA TYMPANI → ROUND WINDOW bulges out towards middle ear (pressure relief)
Opposite happens with rarefaction - round bulges in, oval bulges out
37
What is the "traveling wave"
generated by stapes hitting oval window - reaches max amplitude at certain location along length of BM
Particles itself are NOT traveling with wave, just going up and down
38
Hair cell:
sensory receptor responsible for detecting sound pressure and converting mechanical vibration into a membrane potential change (transduction)
16,000 hair cells per cochlea
Arranged in 4 rows - row of 3,500 IHCs, 3 outer rows with 12,55 OHCs
39
Stereocilia
located on apical surface of IHC
Change membrane potential of hair cell
Bending of stereocilia → altered gating of transduction channels near tips of individual hairs
Connected by tip links
40
Resting potential of IHC, driving potential of IHC and mechanism of depolarization vs. hyperpolarization
Resting potential of IHC = -50mV, never “at rest”
Push stereocilia bundle in direction TOWARD longest stereocilia, pull trap door open with tip links → DEPOLARIZATION
Push stereocilia bundle in direction AWAY from longest stereocilia, slams trap door shut with tip links → HYPERPOLARIZATION
Driving potential of 130 mv (-50 → +80 mV)
41
Endolymph
K+ rich fluid filling scala media, bathes stereocilia on apical end of hair cells
42
Stria vascularis
epithelium on side of scala media, actively pumps K+ into endolymph to maintain high [K+] → ENDOCOCHLEAR POTENTIAL
(+80mV positive potential in scala media, endolymph positive with respect to perilymph)
43
MUTATION in gap junction subunit, connexin 32 causes what?
collapse of endocochlear potential, congenital deafness
44
Perilymph
ionic composition similar to blood (high Na, low K+), fills scala vestibuli and scala tympani
45
Tip-Links
connect apex of stereocilia to shank of next (taller one) - key role in opening and closing of mechanically gated channels at tips of stereocilia
46
Tectorial membrane
Generates shearing force (between basilar and tectorial membrane) that results in bending of hair cells
Directly attached to outer hair cells
47
Auditory nerve fibers
afferent fibers located at basal end of hair cells
Cell bodies in SPIRAL GANGLION
Project to cochlear nucleus of brainstem
Hair cell depolarizes → open Ca2+ basolateral channels → synaptic vesicles release glutamate → excitation of afferent axon → AP sent to second order neurons in brainstem
48
Cochlear amplifier
Efferent innervation from central auditory system act upon OHCs to amplify movements of BM
OHCs respond to changes in voltage with a change in length = “Electromotile”
49
mechanism of cochlear amplifier
OHCs respond to changes in voltage with a change in length = “Electromotile”
Voltage sensitive PRESTIN protein → change length of OHC
→ OHC pulls BM toward or away from tectorial membrane → changes mechanical frequency selectivity of BM
→ Contributes 50 dB of cochlea’s sensitivity to sound
OHC enhances movement of BM in a frequency dependent manner
50
Medial olivocochlear neurons (MOC)
efferent neurons, innervate OHCs
Sense context of sound environment
Act as feedback control to change cochlear sensitivity via OHCs
*Use ACh
Adjust sensitivity of cochlea by changing properties of OHCs so you can function with correct auditory sensitivity in loud vs. quiet environment
51
Clinical importance of OHCs
Sensorineural deafness due to damage of OHCs
OHCs more sensitive to damage from abx and loud sound
Streptomycin, gentamycin → block transduction channel of OHCs and can kill OHCs, resulting in deafness
52
Spiral Ganglion Cells
aka auditory nerve (8th CN), innervates hair cells
53
Type I ANFs
innervate IHC, myelinated
Make up 95% of ANFs
10-30 ANFs innervate a single IHC
54
Type II ANFs
innervate OHC, not myelinated
1 ANFs innervate 10 OHCs
55
Frequency tuning curve
sound response of a single ANF where the number of APs fired per sec plotted vs. sound frequency
56
Characteristic frequency
sound to which fiber is maximally sensitive, dictated by place on BM
Fibers have specific frequency selectivity
57
Four properties of ANFs
1) frequency of sound encoded by place along cochlear BM where afferent fiber innervates an IHC (ANFs have topographic map of sound frequency)
2) Rate code
3) Phase lock
4) Temporal pattern of APs
58
Rate code property of ANFs
sound intensity encoded via increases in NT release and increases in rate neuron fires APs
59
Phase lock property of ANFs
neurons tend to fire APs only at particular phases of ongoing sound waveform, only LOW frequency sounds (below 1.5kHz)
Important for pitch perception
60
What two properties of ANFs are crucial for pitch perception?
pitch perceived by place of stimulation along basilar membrane and by phase locking (timing of APs with waves)
61
Auditory neuropathy
patients have normal hearing, but can’t hear with ambient noise
Normal OHC function, but absent/abnormal auditory brainstem response
Problem with neural transmission from IHC to ANFs or in ANF function
ANFs have lost ability to phase lock → deficit in discriminating/understanding speech
62
Temporal pattern property of ANFs
Temporal pattern of AP in ANFs determine pitch of sounds with frequencies below 1 kHz
63
otoacoustic emissions
outer hair cells also produce sounds that can be detected in the external auditory meatus with sensitive microphones
used to screen newborns for hearing loss
64
General pathway of the auditory system
Information proceeds from the _________ to __________ cells and the VIIIth nerve afferents in the ear
→ _________ nuclei
→ many cross in the ___________ to the ________ in brain stem
→ Then all ascending fibers stop in the _____________ in the midbrain and the _____________ in the thalamus
→ cortex in the ____________ gyrus.
*All auditory afferents synapse in cochlear nuclei and thalamus.
Information proceeds from the ORGAN OF CORTI to SPIRAL GANGLION cells and the VIIIth nerve afferents in the ear
→ COCHLEAR nuclei
→ many cross in the TRAPEZOID BODY to SUPERIOR OLIVE in the brain stem
→ Then all ascending fibers stop in the INFERIOR COLLICULUS in the midbrain and the MEDIAL GENICULATE BODY in the thalamus
→ cortex in the SUPERIOR TEMPORAL gyrus.
*All auditory afferents synapse in cochlear nuclei and thalamus.
65
Cochlear nuclei (2)
located where in brainstem?
position in pathway of auditory information
spiral ganglion cells bifurcate upon entering brainstem to innervate nuclei on dorsal and lateral aspects of INFERIOR CEREBELLAR PEDUNCLE of ROSTRAL MEDULLA
1) Branch innervates VENTRAL COCHLEAR NUCLEUS (VCN)
- -> Some then cross midline to trapezoid body
2) Branch innervates DORSAL COCHLEAR NUCLEUS (DCN)
- -> Some then cross midline to dorsal acoustic stria
66
After synapsing in the cochlear nuclei, the auditory tracts regroup as ________ and ascend to ________________
Tracts regroup as lateral lemniscus → ascend to inferior colliculus of midbrain
67
Inferior colliculus
receives direct projections from cochlear nuclei and multisynaptic input from pontine nuclei (superior olivary complex) = obligatory relay center of ascending auditory info
Right IC represents sound on LEFT side of body
68
Along the way up to midbrain, many axons terminate in various nuclear complexes in pons
These pontine regions are known as what?
Superior Olivary Complex
69
After synapsing in the inferior colliculus, auditory nerve fibers do what?
Inferior colliculus → ipsilateral medial geniculate in thalamus and contralateral inferior colliculus and medial geniculate
Medial geniculate → primary auditory cortex (A1)
70
Primary auditory cortex (A1)
- Part of superior temporal gyrus
- Cochleo-topic (tonotopic) map found on cortical surface
-gets input from the MGN of thalamus
Brodmann's area 41
Tonotopic map
- Neurons responding to lower frequencies located anteriorly
- Neurons responding to higher frequencies located posteriorly
71
Unilateral lesions ROSTRAL to cochlear nuclei cause what?
Lesions CAUDAL to cochlear nucleus and those including the CN produce what?
Unilateral lesions ROSTRAL to cochlear nuclei do NOT produce unilateral deafness
CAUDAL lesions and those including the CN produce unilateral deafness
72
Sound localization
computed centrally in auditory system based on neural representations of spectral and temporal characteristics of acoustic stimuli arriving at the two ears
73
Three main acoustical cues for sound source localization
1) Interaural time differences (ITD)
2) Interaural level differences (ILD)
3) Spectral cues (monoaural spectral shape)
74
Interaural time differences (ITD)
physical separation in space of ears → different times of arrival of sound at two ears
Cue to horizontal location of sound
encoded in Medial Superior Olive
75
Interaural level differences (ILD)
ears separated by an obstacle (the head) → acoustic shadow for high frequencies
encoded in Lateral Superior Olive
76
Duplex theory of sound localization:
Low frequencies → ITDs
| High frequencies → ILDs
77
Spectral cues - Monaural spectral shape
arise from direction and frequency dependent reflection and diffraction of pressure waveforms of sounds by pinna that result in broadband spectral patterns, or shapes, that change with location
Primarily for high frequency sounds
78
Medial superior olive (MSO)
ITDs encoded in Medial superior olive (MSO) - nucleus of superior olivary complex
MSO contains input from CONTRALATERAL ear (already crossed in trapezoid body), so projects IPSILATERALLY up to auditory midbrain
MSO receives excitatory input from both ears via cells of anteroventral cochlear nucleus (AVCN)
79
anteroventral cochlear nucleus (AVCN)
AVCN receive excitatory inputs from ANFs
AVCN organized tonotopically
sends output to MSO and LSO
80
3 properties of input to MSO neurons
1) Phase-locked neural responses of ANF/AVCN neurons carry timing info to MSO
2) MSO neurons = coincidence detectors
3) Axons of AVCN cells input to MSO form delay lines
81
MSO neurons as coincidence detectors
maximal response when AP from AVCN cells from L ear coincides with R ear
82
MSO and delay lines
Axons of AVCN cells input to MSO form delay lines due to differences in neural path length from AVCN to MSO → differences in neural conduction times to MSO
Projection to contralateral MSO = longer path length than ipsilateral MSO
83
These 3 properties of input to MSO allows for what?
All 3 → *Allows for a place code for the horizontal location of sounds in terms of timing between the two ears
84
Lateral superior olive (LSO)
ipsilateral vs. contralateral LSO inpus
ILDs encoded by Lateral superior olive (LSO) - nuclei of superior olivary complex
Ipsilateral ear input to LSO conveyed via ANF synapses with AVCN cells → ipsilateral LSO
Contralateral ear input to LSO conveyed from AVCN → across midline to neurons of medial nucleus of trapezoid body (MNTB)
85
calyx of Held
AVCN synapse onto MNTB = calyx of Held = LARGEST synapse in entire CNS
86
medial nucleus of trapezoid body (MNTB) neurons
Contralateral ear input to LSO conveyed from AVCN → across midline to neurons of medial nucleus of trapezoid body (MNTB)
AVCN synapse onto MNTB = calyx of Held = LARGEST synapse in entire CNS
MNTB neurons = glycinergic → inhibitory effect on LSO
87
Net result of LSO inputs...
ipsilateral excitation and contralateral inhibition of LSO neurons allowing computation of difference between intensity of sounds present at the two ears
88
Dorsal Cochlear Nucleus
what happens if you lesion this?
Spectral cues encoded in Dorsal Cochlear Nucleus → across midline to excitatory synapse on inferior colliculus
Lesion → can’t tell if sound is above or below you, but can still localize in horizontal plane
89
Inferior colliculus represents sound where?
IC represents sound in contralateral hemisphere, and MSO, LSO and DCN reconverge at contralateral IC
Unilateral lesions in IC or above → deficits in sound source localization for sources contralateral to lesion
90
Secondary auditory cortex A2
Brodmann’s area 42
Surrounds A1
Does not have tonotopic organization
Includes Wernicke's Area → understanding and processing spoken language
→ Wernicke's Aphasia = general impairment in language comprehension but not language production
91
Mental status exam includes:
1) Arousal and attention - level of consciousness, digit span, serial events
2) Memory - orientation, three words at 5 minutes, remote events
3) Language - fluency, comprehension, repetition, naming, reading, writing
4) Visuospatial function - clock drawing tests for hemineglect
5) Mood and affect - inquiries about feelings, observations of affect
6) Complex cognition - executive function, similarities, proverbs, judgement, insight
92
Aphasia
acquired disorder of language resulting from damage to brain areas subserving linguistic capacity
93
Dysarthria
disorder of speech due to motor system involvement
94
Dysphonia
disorder of voice related to laryngeal disease
95
Amnesia
impaired recent memory, with deficit new learning
96
Handedness and cerebral language dominance
Language is lateralized usually to LEFT hemisphere - 99% of right handers and 67% of left handers are left dominant → great majority of people are left dominant for language
Ambidextrous people may have mixed language dominance
97
Right hemisphere contributions to language
Automatic speech - expletives, angry outbursts
Prosody - inflection of speech with emotion
Music - subserved by right hemisphere > left
Humor, Metaphor
Recovery - mediated in part by right hemisphere - can rewire itself to become linguistically competent again
98
Assessment of aphasia includes assessment of... (5)
Spontaneous speech - nonfluency is characterized by labored, effortful speech and less than 6-word phrases
Auditory comprehension - poor comprehension is defined by performing less than 4 step verbal commands
Repetition - “No ifs, ands, or buts”
Naming - Common (e.g. pen) and less common (e.g. crystal of a watch) objects
Reading/writing - a short passage or sentence
99
All patients with aphasia have what kind of impairment?
All patients with aphasia have NAMING impairment - inability to name common items = most sensitive indicator of language impairment
100
Broca’s aphasia
repetition, naming, comprehension, and fluency
"non-fluent" aphasia
aphasia with nonfluent speech and good comprehension
Poor repetition and naming
Left hemisphere - Broca’s area
101
Wernicke's aphasia
repetition, naming, comprehension, and fluency
fluent aphasia
fluent speech and poor comprehension
Poor repetition and naming
Left hemisphere - Wernicke’s area
102
Conduction aphasia
repetition, naming, comprehension, and fluency
where is the lesion?
loss of repetition and naming in presence of preserved fluency and comprehension
Left hemisphere - Arcuate fasciculus - white matter tract connecting Wernick’es and Broca’s areas
103
Global aphasia
repetition, naming, comprehension, and fluency
where is the lesion?
disabling disruption of all aspects of language
Left hemisphere - Perisylvian region
104
Panic Disorder
sudden overwhelming episodes of anxiety that include both somatic and psychic elements, along with worry about either the implication of the attack or about having future attacks
Can occur with or without agoraphobia (fear to leave the house)
Onset typically early adulthood, 2x more in females
105
Symptoms of panic disorder
palpitations, pounding heart, tachycardia, SOB, sensation of smothering, sweating, trembling/shaking, feeling of choking, chest pain/discomfort, nausea, dizziness, feeling faint, paresthesias, chills/hot flashes, derealization/depersonalization, fear of losing control or going crazy, fear of dying
106
Differential diagnosis - what else could be causing panic disorder?
```
Hyper/hypothyroidism
Hyperparathyroidism
Mitral valve prolapse, cardiac arrhythmias, coronary insufficiency
Pheochromocytoma
Hypoglycemia
True vertigo
Drug/alcohol withdrawal
Cannabis intoxication
```
107
Treatments of panic disorder
```
Benzodiazepines
Tricyclic antidepressants
Monoamine oxidase inhibitors
SSRIs, SNRIs
Cognitive behavioral therapy
```
108
Generalized Anxiety Disorder
excessive worry and more generalized somatic symptoms of anxiety (worry, anxiety, tension)
75-90% comorbid with other psych disorders
109
Treatments of GAD
Benzos, Buspirone, TCAs, MAOIs, SNRIs, SSRIs, CBT
110
Social Phobia
overwhelming anxiety in situations where one would have to interact with others, be center of attention, or perform in front of others - NOT “shyness”
111
Treatment of social phobia
benzos, B-blockers, MAOIs, SSRIs, CBT
112
Obsessive-Compulsive Disorder
Obsessions: recurrent, persistent thoughts, images, or impulses that are intrusive and cause anxiety
Compulsions: repetitive behaviors or mental acts that are performed in order to reduce anxiety
High comorbidity with Tourette’s Disorder
113
Pathophysiology of OCD
relative imbalance between direct and indirect basal ganglia pathways, with tendency toward greater direct basal ganglia tone
→ thalamic disinhibition → further activation of orbitofrontal cortex → push even more toward direct pathway tone
→ driven circuit which leads to “capture” of cognitions and behaviors
114
Treatment of OCD
Clomipramine, SSRIs, atypical antipsychotics, CBT, neurosurgery
115
Biological theories of anxiety (2)
Dysregulated sympathetic system - locus coeruleus, dysregulated noradrenergic function
GABA-benzodiazepine system - Decreased BZD receptor binding in hippocampus and prefrontal cortex
116
Neurocircuitry of fear in anxiety
1) Fear generation → amygdalo cortical interactions
Anxiety = fear generation is trigger happy
2) Fear extinction → orbitofrontal cortex and prefrontal cortex
Anxiety = fears never extinguished
117
Characteristic audiogram in conductive hearing loss
shows DIFFERENCE between air conduction line and bone conduction line** → how we distinguish a conductive hearing loss
118
Neural hearing loss
causes and areas involved
Causes:
1) 8th nerve tumors - vestibular schwannoma (acoustic tumor)
- 6% of all intracranial tumors
2) Auditory neuropathy
3) Multiple sclerosis
Areas involved: 8th cranial nerve, central pathways
119
Neural hearing loss
signs/audiogram
Asymmetry of hearing between two ears, and reduced speech perception scores
120
Audiogram - what to look for, what is normal
0 = normal hearing threshold of a young adult
1) Should have normal bone conduction and air conduction
2) Should have good clarity at decibel level adequate for patient → if not, then probably something neural wrong (schwannoma, etc.)
3) Should have symmetry between ears
121
Presbycusis
gradual, progressive, bilateral hearing loss caused by degenerative physiologic changes associated with aging
Decreased hearing threshold sensitivity
Decreased ability to understand suprathreshold speech
Central auditory process impairment
**most significant drop off is at high frequencies
122
Noise exposure causes what pattern on audiogram
baseline, then a drop, and then return to baseline at high frequency
123
are syndromic or non-syndromic mutations more common in congenital hearing loss?
non-syndromic (Connexin26/GJB2)
124
Endolymphatic hydrops
Pathologic condition, idiopathic
Expansion/distension of endolymphatic compartment of inner ear
Recurrent episodes of vertigo, sensorineural hearing loss, tinnitus, and aural fullness
125
Disordered inner ear fluid homeostasis
some causes
causes dysfunction of stria vascularis and loss of endocochlear potential
1) Vascular dysfunction and/or vasculitis
2) Systemic metabolic disorders: DM, hyperthyroidism, renal failure, arteriosclerosis
3) Immune system disorders: lupus, Cogan's syndrome, sarcoidosis, Wegener's granulomatosis, autoimmune inner ear disease
126
What are the two otolith organs?
1. Utricle
| 2. Saccule
127
What are the sensory epithelia of the otolith organs?
Maculae
128
Utricle location
Floor of vestibule
129
Saccule location
hangs vertically on lateral wall of vestibule
130
The utricle senses what?
portion of the head with respect to gravity
131
The saccule senses what?
linear acceleration in vertical direction
132
Maculae contain ___ cells and ____ overlaid with ___
contain hair cells and supporting cells, with apical surface overlaid with gelatinous mass (otolithic membrane)
133
Name of crystals that overlie hair cells in maculae and what are they composed of?
Otoconia
Composed of calcium carbonate
134
Maculae assist with ___ detection and ____ changes= "___" receptors
gravity
postural
"static" receptors
135
Epithelia of utricle and saccule are oriented at ___ angles of one another
right angles
| Therefore, they are activated buy different signals
136
Hair cell axes of polarity in utricle and saccule
Hair cell axes of polarity are opposite in utricle and saccule
→ maximum excitation (depolarized) of one group of hair cells, while opposing hair bundle orientations maximally inhibited (hyperpolarized)
137
Saccule hair bundles oriented facing ____ from _____ (central region of epithelium) while utricle hair bundles face ____
AWAY
Striola
TOWARDS
138
Function of Maculae
Detect linear acceleration (change in velocity) of head and position with respect to gravity
139
Semicircular canal organs
3 - horizontal, anterior, and posterior canals
organized in orthogonal planes to each other and allow detection of movements in yaw, pitch, and roll axes (angular acceleration)
140
How do semicircular canals on one side work with those on the contralateral side? (2)
1. Horizontal canals on L and R work together - while one is maximally stimulated the other is maximally inhibited
2. Posterior canal on one side works with anterior canal from other side
141
Ampulla
welling at one end of each canal with specialized patch of epithelium, “crista” → contain sensory hair cells
142
Hair bundles of the ampulla project into ___ (gel like substance)
cupula
143
____ moves cupula and stimulates hair cells in the __________→
i.Firing rate will increase, and then adapt (due to _________)
Endolymph
crista ampullaris
endolymph inertia
144
Function of semicircular canals
Detect angular accelerations and decelerations
Does NOT sense continued motion (adaptation)
- Because cupula has returned to its normal position
145
Membranous labyrinth
connective tissue surrounds sensory organs, which in turn is encased by the bony labyrinth within petrous portion of temporal bone
146
Each hair cell has bundle of ___ filled ____ projecting from apical surface in staircase like pattern
actin filled stereocilia
147
Kinocilium
Tallest cilium within on one side of hair bundle
a.Give the hair cell directional polarity - towards kinocilium is depolarization, away is hyperpolarization
148
Tip Links
connect adjacent cilia, and their lower end to an ion channel
149
Hair bundle bathed in ____ (___ K+, ___ Na and Ca2+), but base of hair cell bathed in _____ (____ K+, ____ Na and Ca2+)
endolymph
High, Low
Perilymph
Low, High
150
Hair cells are found where?
Ampulla of semicircular canals, saccule, and utricle
151
Types of hair cells in vestibular system
Type I hair cells: have an afferent nerve terminal encasing most of the basolateral surface of the cell
Type II hair cells: bouton type synapses and efferent innervation that innervates hair cells
152
Vestibular pathway
movement accessory structure (cupula in semicircular canal, otoliths in saccule/utricle) pushes on hair bundle → depolarize → modulate release of NT from hair cell → act on afferent vestibular nerves, cause APs to fire at higher frequency in nerve fiber
Vestibular nerve --> flocculonodular lobe and vestibular nuclei
153
Vestibular afferent nerves at rest
fire APs even at rest
154
Cell bodies of vestibular afferent nerves located in ______ ganglion → project to ______
Scarpa's
ipsilateral vestibular nucleus
155
Location of vestibular nuclei
located at border of caudal pons and rostral medulla
156
Four vestibular nuclei
1. Superior
2. Inferior
3. Medial
4. Lateral
157
Superior and medial vestibular nuclei receive fibers from
Semicircular canals
158
Superior and medial vestibular nuclei project to what?
What is the function of these neurons?
ascending information via medial longitudinal fasciculus (MLF) →
1) oculomotor nuclei
2) trochlear nucleus
3) abducens nucleus
4) cervical motor neurons of neck musculature
Coordinates eye and head movements
-Gaze control
159
Descending/inferior vestibular nuclei receive inputs from (5)
saccule, utricle, and semicircular canals, spine, and cerebellum
160
Descending/inferior vestibular nuclei project to
vermal cerebellum, reticular formation, and other brainstem centers
161
Utricles project to (3)
lateral, medial, inferior vestibular nucleus
162
Spine and cerebellum project to which vestibular nucleus?
lateral
163
Semicircular canals project to which vestibular nuclei?
medial and superior
164
Second order cells in vestibular nuclei project to what three main places
1) flocculo-nodular lobe of cerebellum
2) Ascend via MLF (to occulomotor, abducens, and trochlear nuclei)
3) Descend via MLF and LATERAL VESTIBULOSPINAL TRACT --> ventral horn of spinal cord (postural reflexes)
165
Vestibular Occular Reflex (VOR)
during head rotation, vestibular system signals how fast head is moving and oculomotor system responds to keep visual field stable
166
VOR:
Move head left → endolymph ____-> hair cells excited on ____, inhibited on ____
endolymph moves in opposite direction to rotation → hair cells excited on LEFT, inhibited on RIGHT
167
VOR: (moving head to LEFT)
Vestibular afferent fibers synapse in _____ nucleus
______ nerve innervates medial rectus on _____ side (excite, contract)
At same time, get excitatory signal from ____ horizontal canal via ____ nerve to excite lateral rectus muscle on ____ eye
Vestibular
Occulomotor
LEFT
LEFT
6th (Abducens)
Right
168
Nystagmus
involuntary eye movements that occur during the VOR
169
Neurochemistry of Parkinson’s Disease
Loss of substantia nigra dopaminergic cells → reduce dopamine input to striatum
-dopamine = excitatory to striatal neurons → reduce inhibitory input to globus pallidus and thus lose “disinhibition” thalamus
Loss of dopamine synthesis
Loss of regulated release
“Lewy Bodies” with a-synuclein protein precipitate
170
L-Dopa
Provides useful clinical benefit for 5-20 years after diagnosis
--> Early smooth motor control produced by L-Dopa is replaced by fluctuations in clinical state, ranging from freezing spells, to wild dyskinetic movement
When quality of L-Dopa response fails, other drugs provide only partial improvement
Oral absorption, crosses BBB
Converted to dopamine in brain, but much of L-Dopa systemically is decarboxylated in intestine, liver, and peripheral organs
**→ take L-Dopa with carbidopa
171
Carbidopa
peripheral decarboxylase inhibitor
blocks decarboxylase in intestine and peripheral organs, but does NOT cross BBB
→ Reduces L-dopa requirements by 90%
172
Dopamine Receptor Agonists
directly stimulate dopamine receptors in caudate/putamen - most are D2 agonists
173
Dopamine Receptor Agonists drug names (2)
Pramipexole (Mirapex) - D2 + D3 agonist
| Ropinirole (Requip) - D2 agonist
174
Drugs that facilitate release of endogenous dopamine:
Amantadine
175
Anticholinergic drugs for Parkinson's
Less effective than L-Dopa
Used for initial therapy of tremor
Balance the overactivity of inhibitory cholinergic interneurons in striatum caused by lack of dopamine
176
Drug names of Anticholinergic drugs for Parkinson's (3)
Benztropine
Diphenhydramine (Benadryl)
Trihexyphenidyl
*can make you constipated and cause difficulty to empty your bladder
177
Monoamine oxidase inhibitors for Parkinson's
2 drug names also
prevent breakdown of dopamine → prolong D action
Selegiline
Rasagiline
178
Catechol-o-methyltransferase inhibitors for Parkinson's
2 drug names also
Prevent breakdown of L-dopa and dopamine by COMT
Drug Name:
Tolcapone
Entacapone
179
Surgical treatment for Parkinson's (2)
1) Fetal dopamine cell transplants to treat Parkinson’s
2) Placing pacemaker stimulating electrodes in certain basal ganglia nuclei, including globus pallidus, subthalamic nucleus, and thalamus
180
Ways to treat Parkinson's
1) L-DOPA + Carbidopa **most important
2) Dopamine receptor agonists
3) Facilitate endogenous release of dopamine
4) Anticholinergic drugs
5) Monoamine oxidase inhibitors
6) Catechol-o-methyltransferase (COMT) inhibitors
7) Surgical treatment
181
How does dopamine deficiency block movement?
No dopamine for D1 Receptors?
No dopamine for D2 Receptors?
No dopamine for D1 Receptors → reduces GABA in striatum → more GABA in GP interna → thalamus inhibited → movement blocked in cortex
No dopamine for D2 receptors → striatum releases more GABA → reduces GABA in GP externa → increases GABA release in GP interna → thalamus inhibited → movement blocked
182
Dopamine normally does what in regards to movement
Normally dopamine turns up direct pathway and turns down indirect pathway
→ Dopamine facilitates movement
183
Hyperkinesis
moving too much
Chorea, tics, dystonia, restless legs, myoclonus
Tremor
184
Tremor
rhythmic oscillatory movement produced by alternating or synchronous contraction of antagonist muscles
Positional: resting, action (intentional), postural (with sustained posture)
Frequency: fast or slow
Regular or jerky
185
Hypokinesia
not moving enough
| Parkinsonism
186
Most common movement disorders in adults and in kids
Adults: Restless leg syndrome, essential tremor, parkinson disease
Children: Tics
187
Dystonias
[esp. Wilson’s disease]
Pathophysiology:
-Co-contraction of muscle agonists and antagonists → sustained muscle contractions causing twisting, abnormal postures
Can be associated with tremor
Mobile, static, task specific, exercise induced, diurnal
Can be task specific: e.g. writers cramp
188
Treatment of dystonias (5)
```
Anticholinergic
Muscle relaxants
Benzos
Botulinum toxin injections
Deep brain stimulation
```
189
Tics
brief intermittent movements or sounds
Sudden, abrupt, transient
Repetitive and coordinated
Vary in intensity, repeated at irregular intervals
May resemble gestures, normal behavior
Most common in children
190
Essential tremor
Postural and kinetic tremor (NOT at rest)
Affects hands, arms, head, voice
191
Treatment of essential tremor (6)
B-blockers, primidone, topiramate, gabapentin, clonazepam, deep brain stimulation
192
Tourette’s syndrome
Diagnostic criteria (3)
1) Age of onset less than 16 years
2) Motor and vocal tics
Motor = grimacing, blinking, nose twitching, hopping, clapping, throwing, head banging
Vocal = grunts, throat clearing, barks, sniffing, shouting
3) Lasts > 1 year
193
Treatment of Tourette's Syndrome
Educate family, patient, school
Support groups
Treat OCD, ADHD, tics (only if interfering with life)
CBT
194
Motor symptoms of Parkinson's
```
Resting tremor (may not have tremor!)
Bradykinesia/akinesia
Rigidity
Postural instability
Hypophonia, dysphagia
DOES NOT involve muscle weakness!
```
195
Some nonmotor symptoms of Parkinson's
Depression, anxiety, cognitive impairment
Autonomic instability (orthostatic hypotension, bladder dysfunction, constipation, erectile dysfunction)
Sleep disturbances
Sensory changes (muscle cramps, pain, paresthesias)
196
Atypical parkinsonian disorders include...
1) Lewy Body Dementia
2) Progressive supranuclear palsy
3) Multiple systems atrophy
4) Drug-induced parkinsonism
5) Vascular parkinsonism
6) Posttraumatic parkinsonism
7) Postinfectious parkinsonism
197
Chorea
irregular, brief, dancing-like, jerky
198
Huntington's disease key findings
Chorea-athetosis, dementia and psychiatric illness
199
Progressive supranuclear palsy
Progressive, onset >50 years
Impaired eye movements = CANNOT DOWNGAZE
Early onset of postural instability
200
Psychogenic movement disorders are characterized by what? (9)
1) SUDDEN ONSET
2) waxing and waning
3) Do not respond to meds, but DO respond to placebo/psychotherapy
4) Selective disability
Inconsistent - changing movement amplitude, frequency, and direction
5) Combination of movement disorders
6) Movement increases with attention and decreases with distractibility
7) Evidence of depression or somatization
8) History of similar disorder in family
9) Medical professional
201
Motor unit
a-motor neuron and the muscle fibers it innervates
Each muscle fiber only innervated by one motor neuron
Muscle fibers in a motor unit are the same type
202
Small motor unit
Small a-motor neuron → innervate small number of muscle fibers → small force
Preferentially innervate slow twitch muscle fibers
Requires less input to cause a depolarization and AP
Important for sustained activities (maintaining posture)
Degenerate in ALS
203
Large motor unit
a-motor neuron → innervate many muscle fibers → large force
Preferentially innervate fast twitch glycolytic muscle fibers, quick to fatigue (running, jumping)
Require more input to drive them - recruited later with larger currents
204
Motor neuron pool
population of a-motor neurons that innervate the muscle fibers within a single muscle
205
Size principle for recruitment of muscles
Systemic recruitment of smaller to larger motor units - generates graded forces
Orderly recruitment of increasingly forceful motor units because small neurons have HIGH input resistances
→ given synaptic current induces larger voltage change in a small motor neuron compared to a large motor neuron
206
Types of muscle cells (4)
1) Tonic
2) Slow twitch
3) Fast twitch oxidative
4) Fast twitch glycolytic
207
Tonic muscle fibers
non-spiking muscle fibers, shorten extremely slowly, efficiently generate isometric tension with low fatigability
208
Slow twitch muscle fibers
generate APs to twitch, fatigue very slowly, high concentration of myoglobin and many mitochondria
209
Fast twitch oxidative muscle fibers
activate quickly, many mitochondria so fatigue moderately slowly
Make up the “Fast Fatigue-Resistant” Motor units
210
Fast twitch glycolytic muscle fibers
activate quickly, fatigue rapidly, few mitochondria - depend on anaerobic glycolysis ATP generation
Make up the “Fast Fatigable” Motor units
211
Exercise/Chronic stimulation can effect muscle fibers how?
can shift motor unit phenotype from fast to slow → slows fatigability, increases endurance capacity
212
A-motor neurons
output of local circuits that control muscle = final common pathway
Innervate striated muscle
Cell bodies in ventral horn of spinal cord and brainstem cranial motor nuclei
Have somatotopic organization
213
Somatotopy of a-motor neurons
Medial-Lateral somatotopy:
- Lateral musculature innervated by laterally situated motor neurons
- medial musculature innervated by medially situated motor neurons
Rostrocaudal somatotopy: Cervical and lumbar enlargements due to more muscles innervated at those levels
214
Muscle tone
stretch reflex influence on tone?
Y-motor neuron activation influence on tone?
defined as resistance to muscle stretch - important for walking, standing, running, etc.
Stretch reflex provides resistance to stretch → enhances tone
Y-motor neuron activation → top-down regulation of muscle tone
215
Hypotonia
condition of decreased muscle tone due to damage to Ia sensory afferents innervating spindles or a-motor neurons innervating muscle
216
Hypertonia
due to damage to descending motor pathways that influence spinal cord premotor circuits
217
Muscles Spindles
proprioceptor embedded within a muscle, composed of muscle fibers
Aka intrafusal muscle fiber - runs PARALLEL with force-generating extrafusal muscle fibers
Preferentially signals muscle stretch
Important for maintaining muscle tone - Feedback system for maintaining muscle strength
Use group Ia and group II fibers (large, fast)
Innervated by y-motor neurons
218
Group Ia fibers synapse on ___________ in the spinal cord and cause ______________ in response to stretch
Ia → synapse on a-motor neurons in spinal cord → trigger muscle contraction of homonymous muscle fiber in response to stretch
219
Group Ia fibers
large and fast
used by muscle spindles
Have a non-zero firing rate under baseline conditions → maintenance of muscle tone
Can signal passive stretch by increasing firing rate and passive shortening by decreasing firing rate
220
Y-motor neurons
special motor neurons that innervate intrafusal muscle fibers
During voluntary contraction, a and y motor neurons fire together → shorten extrafusal AND intrafusal muscle fibers together → maintains spindle sensitivity to stretch
Do not directly interact with Ia fibers→ not engaged during reflexive contractions
221
Golgi tendon organs
collagen structures at junction of muscle and tendon
-made up of capsule and collagen fibrils
Innervated by Ib fibers
In SERIES with muscle and tendon
Important for stabilizing contractions
Not contractile, not innervated (by y-motor neurons)
Feedback system for maintaining muscle force
Preferentially sensitive to muscle TENSION rather than passive stretch
222
How are golgi tendons activated?
Preferentially sensitive to muscle tension rather than passive stretch:
Passive stretch lengthens muscle before straining the tendon
During muscle contraction, force increases tension on collagen strands → causes them to fire AP
Participate in negative feedback regulation of muscle tension
223
Stretch Reflex Circuit
“knee-jerk” reflex
Monosynaptic
Hammer tap → stretch muscle spindle→ stimulate Ia sensory axons → activate a-motor neuron in spinal cord → contract stretched muscle
224
Reciprocal innervation of Ia fibers
Ia fibers also innervate other inhibitory interneurons → inhibit other motor neurons → inhibit opposing antagonist muscle
--> activate contraction in one muscle, and relaxation in opposing muscle
225
Rapid error correction in movements
mismatch between expected and actual muscle stretch detected rapidly and used to correct errors in motor output
226
what would happen if you picked up a big box, labeled "Books" that you expected to be be heavy but was actually really light?
→ exert lots of force, highly active firing of a/y motor neurons and shortening of muscle and spindle
BUT if box is actually empty, muscles would shorten too quickly relative to spindle (spindle is floppy) and mismatch will cause Ia spindle afferent to drop firing rate
→ rapid reduction in a-motor neuron drive → reduce muscle contraction
227
What happens if the box is heavier than we expect?
Heavier than we expect → muscle spindle stretches more than muscle fibers → increase Ia spindle firing → increase contraction of muscle fibers via a-motor neurons
228
Extensor-flexor coupling circuits
Ib afferents innervate GTOs → GTOs directly innervate inhibitory and excitatory interneurons in spinal cord
Protects musculature from over exertion by relaxing the synergist (homonymous) muscle and contracting the antagonist
229
Crossed-extensor reflex
-what happens when you step on a tack?
Cutaneous sensory receptors (nociceptors in case of stepping on a tack) innervate spinal interneuron motor networks
→ coordinate extensor relaxation and flexor contraction on same side as stimulus and converse extensor contraction and flexor relaxation on contralateral side
230
Central Pattern Generator
what do you not need for central pattern generation?
Where is the "control center"
neural networks that can produce patterned, rhythmic outputs in absence of sensory or central input - coordinate complex movements
Used in locomotor patterning
Sensory and descending input from upstream motor centers can modify CPG output, BUT SENSORY is NOT NECESSARY for CPGs to generate organized rhythmic motor output
Resides in mesencephalic locomotor center
231
Reticular formation
where does the reticulospinal tract project?
collection of loosely connected areas in midbrain tegmentum (ventral midbrain)
Reticulospinal tract: send axons ipsilaterally and innervate medial part of ventral horn
232
Modulatory functions of reticular formation
Modulatory functions: cardiovascular, respiratory control, and sensorimotor reflexes, eye movement, sleep-wake regulation, and coordination of limb/trunk movement
233
Premotor functions of reticular formation (3)
1) Regulate locomotor speed via Input from mesencephalic locomotor region - initiator of CPG activity
2) Anticipatory responses to voluntary movement (e.g. flex legs before lifting weight, anticipating change in center of balance)
3) Important for posture, balance and anticipatory movements
234
Vestibulospinal tract/Vestibular nuclei
informs brain of what? (4)
Sensory info detected by ___________ and sent via _____________ to ________________
informs brain of head position, orientation, and motion - important for protective responses to falls
Sensory info detected by semicircular canals and sent via 8th cranial nerve to vestibular nuclei
235
Vestibular nuclei sends info via what 3 pathways?
Each pathway is responsible for what?
1) Medial vestibulospinal tract to medial spinal cord
→ regulate head orientation and neck muscle activation
2) Lateral vestibulospinal tract to lateral motor pools
→ control proximal limb musculature
3) descending projections to cranial nuclei III (oculomotor), IV (trochlear, and VI (abducens)
→ regulate eye movement
236
Vestibulo-Occular-Reflex
produces eye movements that counter head movements to keep gaze fixed
Absent VOR indicates brainstem damage
237
VOR pathway:
Vestibular nuclei --> projects __________ to ___________
Abducens nuclei ________
On side contralateral to activated vestibular neuron/ nucleus what happens?
On side ipsilateral to activated vestibular neuron/ nucleus what happens?
Vestibular nuclei → project BILATERALLY to ABDUCENS NUCLEI
Abducens nuclei CROSS again:
On side contralateral to activated vestibular neuron/ nucleus...
-axons excite motor neurons that contract lateral rectus of contralateral eye and medial rectus of ipsilateral eye
On side ipsilateral to activated vestibular neuron/ nucleus
-axons inhibit motor neurons that control medial rectus muscle of contralateral eye and lateral rectus of ipsilateral eye
238
Superior colliculus/Tectospinal tract
| aka colliculospinal tract
midbrain structure responsible for orienting gaze and body position
Computes a map merging auditory and visual space onto body coordinates
Descending projections of colliculospinal tract target motor neurons that control axial musculature of neck (e.g. turn head/upper torso towards siren going off)
239
Descending pathways for control of finger movement
Descending pathways for control of axial musculature
Lateral corticospinal tract
Ventral corticospinal tract
240
Primary Motor Cortex (M1)
Brodmann’s Area 4 in precentral gyrus of cerebral cortex
Pyramidal neurons of layer five → spinal cord via corticospinal tract
Critical for voluntary action
241
Corticospinal tract pathway
Internal capsule → cerebral peduncle (ventral midbrain)
→ collateralize (branch while continuing their course) in pons
→ pyramids (caudal medulla), where most axons cross
→ lateral corticospinal tract or ventral corticospinal tract:
242
lateral corticospinal tract
→ direct synapse on a-motor neurons for hand and finger movement
→ spinal cord local circuit interneurons to innervate motor neurons in ventral horn
243
ventral corticospinal tract
axons remain ipsilateral, innervate ipsilateral axial and proximal limb muscles
244
Premotor Cortex
just anterior to primary motor cortex
Fewer descending projections, but still make up 25% of corticospinal tract
Involved when movement is initiated by an external cue
245
Supplementary motor cortex
involved in self-cued movements
| Highly active during mental rehearsal of movement
246
“Mirror neuron” activity
selective neural responses in response to subject watching an action with an intended consequence
Role in empathy and learning
247
Organizational principle of motor cortex
“Motor Maps”
1) Disproportionate M1 Surface area devoted to controlling musculature used in fine motor tasks
2) Movements, not muscles are mapped
248
Motor cortical plasticity is used in stroke recovery how?
Stroke → damage motor cortex → acute impairments in ability to control affected area
Over time, areas adjacent to damaged cortical region can sprout new connections and subserve motor control of affected body part → functional recovery
249
Practice and motor cortical plasticity
repeated performance of a given action leads to expansion of that region of cortex
250
Three functional divisions of the cerebellum
1) Cerebrocerebellum = lateral hemispheres
2) Spinocerebellum = vermal and paravermal regions
3) Vestibulocerebellum = flocculo-nodular lobe
251
Three main fiber bundles of cerebellum
Inferior Cerebellar Peduncle: major input
Middle Cerebellar Peduncle: major input
Superior Cerebellar Peduncle: major output
252
Three cortical layers of cerebellum
molecular
purkinje
granule
253
Paired central nuclei of deep cerebellum (4)
1-3) Interposed nucleus - dentate, globose, emboliform
4) Fastigial nucleus
254
Three main deficits with cerebellar lesion
synergy, equilibrium, tone
NO loss of muscle strength or sensation
255
Flocculo-Nodular Lobe: aka vestibulocerebellum
receives input from __________ and outputs to _____________
Important for what main functions (2)
vestibular nuclei and 8th cranial nerve directly (NO connection to deep cerebellar nuclei)
vestibular nuclei of brainstem
Important for axial control, vestibular control (balance, eye movements, VOR, VCR, VSR)
256
Vermis projects to _________ nucleus → ________ and ___________
Information then descends via the ____________
Fastigial nucleus (DCN)
Vestibular nucleus and pontine reticular formation (bilaterally)
medial descending system
257
Medial descending system is made up of the ______________ and ___________.
It carries information form the _______ to control what?
lateral vestibulospinal tract and pontine reticulospinal tract
carries information from the vermis
→ control of axial musculature, posture, and balance, and integration of head and eye movements
(Axial (trunk) musculature represented along vermis)
258
Paravermis projects to the ____________ nuclei and then travels via the ______________ to the ___________ and _________
interpositus nuclei →
via Superior Cerebellar Peduncle
contralateral red nucleus and Va/Vl Thalamus
259
The paravermis sends descending motor output via what?
Paravermis receives input from where?
LATERAL descending system - rubrospinal tract
Input from spinal cord
260
Function of paravermis
→ Fine tune movement of limbs
Distal limbs represented stretching out into paravermal regions
**right cerebellum controls right hand
261
Flocculonodular lobe
```
functional region?
Principal input?
Deep nucleus?
Principal destination?
function?
```
functional region - vestibulocerebellum
Principal input - vestibular sensory cells
Deep nucleus - vestibular
Principal destination - axial motoneurons
function - axial control, vestibular reflex (balance, eye movement)
262
Vermis
```
functional region?
Principal input?
Deep nucleus?
Principal destination?
function?
```
functional region - spinocerebellum
Principal input - Visual, auditory, vestibular, somatosensory
Deep nucleus - Fastigial
Principal destination - medial systems
function - axial motor control (posture, locomotion, gaze)
263
Paravermis
```
functional region?
Principal input?
Deep nucleus?
Principal destination?
function?
```
functional region - spinocerebellum
Principal input - spinal afferents
Deep nucleus - interposed
Principal destination - lateral system, red nucleus
function - distal motor control
264
Lateral hemisphere
```
functional region?
Principal input?
Deep nucleus?
Principal destination?
function?
```
functional region - cerebrocerrebellum
Principal input - cortical afferents
Deep nucleus - dentate
Principal destination - integration areas
function - initiation, planning timing
265
The cerebellar deep nuclei carry what information
Provide major output pathway of cerebellum
Cerebellar outputs from deep nuclei of medial regions (vermis, vestibulocerebellum) → modulate medial descending pathways (vestibulospinal tracts, reticulospinal tracts, tectospinal tracts)
Cerebellar outputs from deep nuclei of lateral regions (paravermis and vestibulocerebellum) → modulate rubrospinal and corticospinal outputs
266
Neocerebellum (aka cerebrocerebellum) projects to the ___________ nucleus and then to _____________ to influence what cortical regions?
Projects to dentate nucleus → contralateral ventrolateral thalamus → influence cortex regions (primary motor and premotor cortex)
→ higher level coordination of movements (planning, initiation of movement)
267
The cerebrocerebellum receives input form where?
pontine gray matter:
Axons from cortex synapse on ipsilateral neurons in basal pons → pontine neurons send axons contralaterally to cerebellar hemispheres
268
Sensory input into cerebellum and descending cerebellar output are __________, while tracts between cerebellum and cortex __________
Thus, the right cerebellum deals with what side of the body and what side of the motor cortex?
uncrossed
decussate
→ Right cerebellum deals with right (ipsilateral) body, and must communicate with left (contralateral) motor cortex
269
Cerebellar lesions result in loss of __________ but NOT _______ or __________
Cerebellar lesions result in loss of coordination but NOT sensation or strength
270
Modest lesion to cerebellar cortex vs. lesion of large region of cortex or deep nuclei
Modest lesions to cerebellar cortex have little obvious motor effect and to do so, must involve large regions of cortex or lesion underlying deep nuclei
271
Deficits that arise from cerebellar damage (6)
HANDS Tremor
Hypotonia: anterior lobe injury
Ataxia: loss of coordination or timing of muscles
Nystagmus - Extraocular muscle deficit → nystagmus
Dysarthria - Slurred speech
Stance and gait problems
Tremor
272
Ataxia
Loss of coordination or timing of muscles
Dysmetria: inability to bring limb to required/desired point in space
Dysdiadochokinesia: impaired rapid alternating movements
Decomposition of movements
273
Tremor associated with cerebellar damage
Intention tremors perpendicular to direction of limb motion, increasing oscillations as limb approaches target
274
Cellular constituents of cerebellar cortex (5)
Stellate cells, Basket cells, Purkinje cells, Granule cells, and Golgi cells - divided into three layers
275
Cerebellar cortex:
Molecular layer
uppermost layer
contains large numbers of:
1) parallel fibers
2) dendrites of Purkinje cells
3) scattered inhibitory neurons (Stellate cells and basket cells)
Parallel fibers interact with dendrites of multiple Purkinje cells
Each purkinje cell is in contact with many parallel fibers
276
Cerebellar cortex:
Purkinje Cell Layer
contains cell bodies of Purkinje cells
ONLY output from cerebellar cortex is via Purkinje cells
Purkinje cell output inhibits cells of deep nuclei
277
Cerebellar cortex:
Granular Layer
many small granule cells whose processes extend superficially to become parallel fibers in molecular layer
278
Stellate Cells and Basket Cells
excitation of basket and stellate cells by parallel fibers results in inhibition of neighboring Purkinje cell = Lateral Inhibition
Inhibition of Purkinje cell → disinhibition of deep cerebellar neurons
279
Purkinje cells are inhibitory or excitatory?
Purkinje cell output inhibits cells of deep nuclei
280
Input to the cerebellar cortex comes from ____________ and ___________
mossy fibers and climbing fibers
281
Mossy fibers come from where?
arise from several different sources (depends on functional zone they innervate)
1) Clarke's column (nucleus gracilis) in spinal cord - relay proptioceptive information from lower extremities
2) Lateral cuneate nucleus in caudal medulla (relaying proprioceptive information from upper extremities
3) Vestibular nuclei
4) Pontine nuclei (pontine nuclei send axons to contralateral middle cerebral peduncle --> cerebral cortex)
282
Mossy fibers
Come from three functional regions to innervate cerebellar cortex
Diverge extensively, excite large number of granule cells that then excite Purkinje cells, Stellate cells, and Basket cells via parallel fibers
Many parallel fibers must sum to generate a single AP in a Purkinje cell = Simple Spike
283
Simple spike
Many parallel fibers must sum to generate a single AP in a Purkinje cel
Generated by mossy fiber input
284
Climbing fibers originate in __________ and travel via _________ cerebellar penduncle to make direct contact with _________
CONTRALATERAL inferior olivary nucleus
CONTRALATERAL inferior
Purkinje cells
285
Climbing fiber and Purkinje cell interaction
Each climbing fiber contacts one Purkinje cell - very powerful synaptic contact
Single AP in climbing fiber → burst of spikes in Purkinje cell = Complex Spike
286
Complex Spike
Single AP in climbing fiber → burst of spikes in Purkinje cell
287
Cerebellar cortex has cells that receive two distinct inputs
1) One is modality-specific input (i.e. balance, limb position, eye-hand coordinates) that represent a copy of the reflex input
→ MOSSY FIBERS
2) Another input from the inferior olivary nucleus, signals errors and unexpected responses in reflex activity
→ CLIMBING FIBERS
288
Together, the input from the mossy fibers (modality specific) and climbing fibers (unexpected responses) generate what?
→ together generate an output that modifies the gain of the reflex in question
289
what happens when a purkinje cell is simultaneously depolarized by a mossy fiber and a climbing fiber?
Plasticity:
If there is simultaneous depolarization of Purkinje cell between mossy fiber (copy of sensory signal) and climbing fiber (inferior olivary nucleus) there is a WEAKENING of a signal (LTD) and modulation of cerebellar output
290
When ________ detects a discrepancy between planned and actual motor performance, it generates what?
INFERIOR OLIVE
generates climbing fiber activity (error signal) that modulates cerebellar function
→ Long-term depression of sensitivity to mossy fiber input (reduced simple spike frequency)
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Putamen
Sensorimotor cortex projects to putamen
Projects to its own subsection of GP → VA thalamus → motor cortex, especially supplementary motor area (SMA)
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Caudate
Input widely from frontal association cortex (frontal lobes)
Sends info to its own region of GP → dorso-medial thalamus → association cortex
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Nucleus Accumbens
caudal juncture between caudate and putamen
Processes info from paleo-cortex
Part of limbic system - emotional and drive-related behavior
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What happens when Dopamine stimulates D1 receptors?
Dopamine stimulates D1 receptors in striatum → releases GABA in striatum → reduces GABA in GP interna → disinhibit thalamus → movement allowed in cortex
= direct pathway
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What happens when dopamine stimulates D2 receptors?
D2 dopamine receptors project to GP externa (inhibits)→ stops inhibiting STN → STN excited → activates GPi → inhibits thalamus → turns of thalamo-cortical activity (decreases movement)
= Indirect Pathway
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Substantia nigra
dopamine rich
Receives projections from striatum (C and P)
-Striatum releases GABA and inhibits substantia nigra
Projects back to caudate and putamen via PARS COMPACTA neurons that contain and release dopamine
Projects to thalamus via PARS RETICULA
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Substantia nigra and parkinson's
Dopamine in striatum is EXCITATORY
Parkinson’s = degeneration of substantia nigra, loss of dopamine input = paucity of movement
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Subthalamic nucleus
Input from external segment of GP → release GABA, inhibit subthalamic nucleus
Projects to external and internal segment of GP → excitation of internal segment of GP
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Major source of input to basal ganglia?
Cerebral cortex
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Parkinson's vs. Huntington's
direct vs. indirect pathway activity
Direct pathway facilitates movement, indirect pathway inhibits movement
Parkinson’s = activity in direct pathway reduced relative to indirect pathway → paucity of movement
Huntington’s = activity in indirect pathway reduced → hyperkinetic disorder
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Out put of basal ganglia
Basal ganglia output via thalamus which inhibits motor cortex function, until thalamus is "disinhibited" by GP
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Huntington's disease symptoms
Chorea: continuous rapid movements of face, tongue, or limbs
Athetosis: slow, writhing, ceaseless movements of hand, lips, tongue, neck, and foot
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Huntington's disease pathophysiology
AD mutation on 4th chromosome, CAG triplet repeat 17 to 34 times
Possible due to too much dopamine or glutamate excitotoxicity
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Direct path from cortex to basal ganglia
Cortex → input nuclei (Caudate and Putamen) → output nucleus (Globus Pallidus interna) → Thalamus (VA/VL for motor portion, DM for cognitive/associational)
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Cellular actions in basal ganglia
activation of motor control signal is achieved by release from inhibition (disinhibition), NOT by direct excitation
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Cells in layer ________ of cerebral cortex send axons to synapse in _______________ where they release ___________
Cells in layer 5 of cerebral cortex (output cells) send axons to synapse in basal ganglia → release GLUTAMATE to excite cells in Caudate or Putamen
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(direct pathway)
Cells in caudate or putamen send axons to __________ where they release _______ and cause what?
GP cells → send axons to ________ → release _________ --> _________ thalamus → thalamus _______ firing and ________ cortical neurons
Cells in C or P send axons to globus pallidus → release GABA, inhibit GP cells
GP cells → send axons to thalamus → release LESS GABA, disinhibit thalamus → thalamus increases firing and excites cortical neurons
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GP cells are continuously acting on the thalamus how?
GP cells continuously inhibit thalamus in absence of cortical input = emergency brake on your car - must release break and “disinhibit” car when you want to go
“Disinhibit” ONLY those specific corticospinal commands appropriate to behavioral task
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Stroke in subthalamic nucleus → ?
hemiballismus
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hemiballismus
Lose excitation to inhibitory neurons of globus pallidus → thalamus disinhibited → motor programs inappropriately initiated
Symptoms: flailing movements of arm and leg on one side
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Deep stimulation treatment of Parkinson patients
Implantation of electrodes into subthalamic nucleus or into internal segment of globus pallidus to stimulate the neurons in these parts of the basal ganglia
Used to treat patients who still receive benefit from meds, but are disabled by fluctuations between their on and off medication states
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Feedback controller
e.g. thermostat with heater and cooler turned on when temp crosses a certain threshold
Slow, tends to overshoot the mark in both directions
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Feedforward controller
system that predicts change in room temperature → activate heater preemptively, counteracting coming temperature drop
Involves using sensory data to calculate a state coming at some future time
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Adaptive feedforward control
feedforward system with error signal information
Error signal:
EX) window is opened→ predicts temp drop, heats house. Then measure temperature, and if it is off from desired → ERROR SIGNAL
Instructs system to perform more or less heating for the same inputs the next time around
Calibration process continues in case the system changes
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Parietal Association Cortex
Visual “Where” pathway (from dorsal stream from occipital visual cortex) provides visual info about target/limb position and joint position sense information from somatosensory cortex combine → integrated by parietal cortex
- This integrated information is fed to premotor cortices (frontal lobe) → calculate difference between current and desired location → issue command for desired changes in joint angles to primary motor cortex
- Contains an internal model that specifies certain PREDICTIONS
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Prism Adaptation
effect of prisms on a reaching movement
Changes system such that predictions of the system are no longer valid → system must be RECALIBRATED
CNS able to adapt to this change
Adaptation takes only a few trials when prisms are applied for a short time, but correcting post adaptation after effect can take much longer if prisms are worn for weeks or months
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Prism adaptation in patients with cerebellar damage
fail to show this adaptation
When prisms on → consistently point beyond target
When taken off → no post-adaptation after effect, right back on target
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Corticopontine fibers descend via _____________ → pontine grey →________ fibers that travel via _________ cerebellar peduncle and innervate _________________
(LEFT) internal capsule
mossy
middle
contralateral (RIGHT) cerebrocerebellum
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Parietal cortex role in mossy fiber input to cerebral cortex
Parietal cortex contributes a large amount to these corticopontine fibers
→ mossy fiber input is a reflection of current state of parietal cortical mapping between visual and proprioceptive signals
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Mossy fibers in right cerebrocerebellum synapse with ________ cells --> __________ that synapse with array of _______ cells
--> output to __________ via ________ cerebellar peduncle
--> ____________ and then __________
Mossy fibers synapse with granule cells → parallel fibers that synapse with array of Purkinje Cells
→ output to (RIGHT) dentate nucleus via superior cerebellar peduncle
→ across decussation to (LEFT) VA/VL thalamus
--> (LEFT) motor and premotor cortices
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Inferior olivary nucleus sends ________ fibers to _______ cells via the ________ cerebellar peduncle
climbing
Purkinje cells
Inferior
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Climbing fibers from ION generate burst of complex spikes in response to __________
unexpected change - spike activity returns to normal once you adapt
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Simultaneous discharge of olivary climbing fibers and parallel fibers leads to...
changes in synaptic strengths (Long Term Depression) of parallel-Purkinje synapses
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Inferior olivary nucleus as a comparator
Compares expected state (conveyed by deep cerebellar nuclei as a reflection of parietal network) with the observed state (conveyed by visual/proprioceptive feedback)
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NO CHANGE in ION activity would result if…
Proprioceptive and visual feedback are exactly what current parietal network predicts → reflection of parietal network conveyed to ION would cancel out proprioceptive and visual feedback
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Error signal from ION would result if…
Feedback was different from expected state
Error signal proportional to magnitude of difference between observed and expected states
Conveyed via climbing fibers to cerebellar cortex → complex spikes in Purkinje cells
Parallel fiber synapses that are active simultaneously with climbing fiber-induced complex spike undergo Long Term Depression
→ the ensemble that was active in erroneous movement has been deactivated and new ensemble conveys revised reflection of parietal cortex’s mapping of visual/proprioceptive coordinates to motor cortices
→ Predictions about which limb position will achieve which visual coordinate has been updated and motor system has adapted to new conditions
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Reflex error correction - picking up something heavier than expected
Muscle will be stretched and muscle spindle will discharge in proportion to magnitude of error
→ discharge signal conveyed to inferior olivary nucleus and transmitted to cerebellum as error signal that reconfigures the network that uses perceptions of object to generate predictions about motor commands required to lift it
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Reward activates _______ cells in ___________ and __________
dopaminergic cells
substantia nigra and VTA
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Dopamine in the substantia nigra and VTA does what?
→ dopamine facilitates and strengthens activity in specific circuit between cortex, striatum, GP, thalamus, and cortex
Symbol that anticipates reward can come to drive dopamine release
Prediction area about reward in substantia nigra is used to modify connectivity of cortico-striatal circuits - reinforce certain networks to exclusion of others
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How does SN and VTA know about what to expect in reward?
Splotches in striatum correspond to striosomes with separate projections from direct/indirect pathway that project to dopaminergic cells in SN
-these are GABAergic cells, so striosome inhibits dopaminergic cells in SN = Efference Copy
SN is mirror of striatal activity
Compares current vs. expected conditions
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Comparator in basal ganglia vs. cerbellum
Basal ganglia:
comparator = Substantia Nigra and VTA
Cerebellum:
comparator = Inferior olivary nucleus
Comparator generate a signal (Error signal) if observed outcome differs from predicted → uses signal to instruct and change circuit
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Mismatch between expected and observed rewards causes what?
Unpredicted reward STRONGLY activates medium spiny neurons
→ increase dopamine release into striatum → alter plasticity of cortico-striatal networks so networks that correctly predicted the error will be reinforced and those that do not correctly predict error will be diminished
→ recalibration of direct and indirect pathways so that revised network conveyed to VTA/SNc will now predict the reward and VTA/SNc will no longer discharge in response to discrepancy until next unexpected reward occurs
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Cerebellum and basal ganglia both have _________ projection neurons that act as pattern recognizers
Cerebellum = ?
Basal ganglia = ?
GABAergic
Cerebellum → Purkinje cells of cerebellar cortex
Basal ganglia → medium spiny cells of striatum
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Medium spiny cells of striatum
Medium spiny cells project directly to SNc/VTA (ventral tegmental area) dopaminergic neurons and convey a reflection of the current state of the corticostriatal network to the SNc/VTA dopaminergic neurons
Convey network’s current predictions about reward
Similar to GABAergic cells from deep cerebellar nuclei in cerebellar pathway
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Extrapyramidal signs
abnormal movement, posture, or muscular tone, NOT paresis or sensory loss
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Basal ganglia disorders result in what deficits? (3)
1) Tremor (resting)
2) Hypokinetic - rigidity, bradykinesia
Rigidity → lead pipe or cogwheel feeling
3) Hyperkinetic - chorea, athetosis, akathisia
- Spasticity → “clasp-knife”, velocity dependent increase in tension
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What happens with a lesion of midline cerebellum?
Lesions of midline (vermis) → impair coordination of stance and gait, axial truncal posture, and equilibrium
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What happens with cerebeller lesion of paravermis?
Lateral lesions impair the ipsilateral limb
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Stroke in paramedian branches of anterior spinal artery or vertebral artery causes what symptoms?
MEDIAL deficits
1) Motor (contralateral hemiparesis)
2) Medial lemniscus (contralateral deficit in vibration and touch)
3) Hypoglossal ipsilateral tongue deviation
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PICA stroke causes what symptoms (4)
LATERAL deficits
1) Spinocerebellar --> ataxia, dysmetria
2) Sympathetic dysfunction --> Horner syndrome (ipsilateral)
3) Dysphagia/Hoarsness (Nucleus Ambiguus, Vagal nerve problem)
4) Spinothalamic --> contralateral body, ipsilateral face pain and temperature deficit
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AICA stroke causes what symptoms (5)
LATERAL deficits
1) Facial nucleus --> ipsilateral facial paralysis
2) Cochlear nucleus --> ipsilateral hearing loss
3) Spinothalamic --> contralateral body, ipsilateral face pain and temperature deficit
4) Vestibular nucleus --> ipsilateral vestibular problems
5) Ataxia (spinocerebellum)
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Basilar artery stroke causes what symptoms?
Causes locked in syndrome
Complete paralysis except vertical eye movements
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Interposed nucleus of cerebellum --> ___________ --> _________ and ________
CONTRALATERAL red nucleus
inferior olive and rubrospinal tract
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Fastigial nucleus of cerebellum --> _________ and _________ and gets input from _________
BILATERAL vestibular nuclei and reticular formation
input from vestibular afferents
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Dentate nucleus of cerebellum --> _________
Input to dentate nucleus from ______
CONTRALATERAL VA/VL thalamus
input form pontine nuclei
