Function/dysfunction of cerebellum and basal ganglia

Question 1

What is the feedback analogy?

Answer 1

heater that turns on when temp drops below certain threshold

Question 2

What is feedforward control?

Answer 2

using sensory data to predict a state

Question 3

How a target value achieved and maintained?

Answer 3

Correct prediction (feedforward) + accurate corrections (feedback)

Question 4

What is the role of feedforward/feedback mechanisms in motor control?

Answer 4

important in “recalibrating” simple movements to adjust to novel circumstances (injuries, strength increase/decrease, new physical maneuvers, etc)

Question 5

Where is position sense encoded?

Answer 5

S1 in post-central gyrus

Question 6

How is info about the location in space of visual stimuli encoded?

Answer 6

“Where” pathway: visual info –> occipital lobe –> dorsally to parietal cortex

Question 7

What info is required for guided movement of limb to target?

Answer 7

Parietal association corticies: “where” pathway + joint proprioceptive info –> premotor cortex (Brodmann’s area 6)

Question 8

How is the cerebellum involved in adaptation for effector targeting?

Answer 8

recalibrates via pathways connecting parietal and premotor corticies. Adaptive feedforward control

Question 9

Describe the cerebellar pathway for recalibration of accurate effector targeting

Answer 9

Parietal cortex –> cortico-pontine fibers –> internal capsule –> contralateral pontine gray –> cerebro-cerebellum mossy fibers –> granule cells –> parallel fibers –> Purkinje cells –> dentate nucleus –> VL of the thalamus –> motor and premotor corticies

Question 10

What is the significance of mossy fiber input in the relationship between joint position sense and visual coordiates?

Answer 10

reflects current state of parietal cortical mapping between visual and proprioceptive signals

Question 11

How is the olivary nucleus involved in cerebellar recalibration of accurate effector targeting?

Answer 11

Simultaneous discharge of olivary climbing fibers and parallel fibers –> network reconfiguration. Occurs only when feedback is different than expected –> error signal by ION

Question 12

Why is the ION known as a comparator?

Answer 12

compares expected state (conveyed by deep cerebellar nuclei as a reflection of parietal network) with observed state (visual and proprioceptive feedback)

Question 13

What happens when the ION senses feedback different than expected?

Answer 13

error signal by ION –> climbing fibers –> cerebellar cortex –> complex spikes in purkinje cells

Question 14

How is long-term depression initiated, what what is its role in recalibration of accurate effector targeting?

Answer 14

Initiated by parallel fibers synapsing on purkinje cells that were active at the same time as climbing fiber-induced spikes. LTD –> deactivated “erroneous” network, formation of new network

Question 15

How do dopaminergic neurons initially react to an unexpected reward?

Answer 15

Spikes in action potentials

Question 16

How do dopaminergic neurons react after the behavior that elicits the reward has been learned?

Answer 16

Cease dopamine release

Question 17

Where are the dopaminergic “reward” neurons located?

Answer 17

Ventral tegmental area (VTA) of the thalamus and substantia nigra pars compacta (SNc)

Question 18

In what way are the SNc/VTA neurons similar to ION neurons?

Answer 18

they both act as comparators. Unpredicted reward leads to strong activation of SNc/VTA, just like new visual-motor stimuli leads to strong activation of ION

Question 19

What group of neurons convey a reflection of the current state of the cortico-striatal network to SNc/VTA neurons?

Answer 19

Patch (striosome) neurons. Similar to mossy fibers’ reflection of state of visual/parietal network

Question 20

How would you assess dysmetria on physical exam?

Answer 20

Finger-nose-finger test (intention tremor), Heel-shin test

Question 21

How would you assess dysdiadochokinesia on physical exam?

Answer 21

Rapid precision hand movements (quickly tap thumb to each of other 4 digits in sequence), rapid alternating foot movements (patient taps your hand with their foot, alternating plantar-and dorsiflexion)

Question 22

Describe pronator drift

Answer 22

Patient stands with eyes closed, arms extended forward with palms up. Positive result = affected limb pronates and drifts downward. Pyramidal tract or parietal lobe dysfunction = contralateral lesion. Cerebellar disease = ipsilateral lesion

Question 23

How would you assess speech coordination on exam?

Answer 23

Repeat LaLaLa rapidly –> CN XII test
PaPaPa –> CN VII test
KaKaKa –> CN X test
LaPaKaLaPaKa –> ability to switch rapidly between these

Question 24

How would you assess station and gait?

Answer 24

Romberg test (unsteadiness standing with eyes closed), Pull test (pull back on patient’s shoulders, leading to patient step backward), Observation of casual and forced gait

Question 25

What are the steps in dopamine synthesis?

Answer 25

Tyrosine (tyrosine hydroxylase) –> L-DOPA (dopa decarboxylase) –> dopamine

Question 26

What are the steps in dopamine breakdown?

Answer 26

Dopamine (MAO) –> DOPAC (COMT) –> HVA

Question 27

A mutation in what protein confers autosomal dominant Parkinson’s disease?

Answer 27

alpha-synuclein

Question 28

Where is alpha synuclein found in patients without alpha synuclein mutation?

Answer 28

Lewy bodies

Question 29

What is the primary medication used in treatment of parkinson’s?

Answer 29

Levodopa-carbidopa (Sinemet)

Question 30

What are the pros and cons of dopamine receptor agonist use in Parkinson’s?

Answer 30

Pro: less risk of dyskinesia than sinemet
Con: not a substitute for sinemet (patients will still ultimately need sinemet)

Question 31

What drug facilitates the release of endogenous dopamine?

Answer 31

amantadine (also a glutamate receptor antagonist)

Question 32

What is the role of anticholinergics in treatment of parkinsons?

Answer 32

For the initial treatment of tremor (Trihexyphenidyl, benztropine, diphenhydramine)

Question 33

Which drug is useful in counteracting toxic metabolite formation from MPTP-induced parkinsonism?

Answer 33

Selegiline (Deprenyl)

Question 34

What is the mechanism of action of MAO inhibitors in treatment of parkinsons?

Answer 34

prevent dopamine breakdown. MAO-B = safer

Question 35

What is the role of COMT inhibitors in treatment of Parkinsons?

Answer 35

prevents breakdown of L-DOPA and dopamine (Tolcapone, Entacapone)

Question 36

What common drug class can lead to drug-induced parkinsonism?

Answer 36

Neuroleptics