Function/dysfunction of cerebellum and basal ganglia Flashcards
What is the feedback analogy?
heater that turns on when temp drops below certain threshold
What is feedforward control?
using sensory data to predict a state
How a target value achieved and maintained?
Correct prediction (feedforward) + accurate corrections (feedback)
What is the role of feedforward/feedback mechanisms in motor control?
important in “recalibrating” simple movements to adjust to novel circumstances (injuries, strength increase/decrease, new physical maneuvers, etc)
Where is position sense encoded?
S1 in post-central gyrus
How is info about the location in space of visual stimuli encoded?
“Where” pathway: visual info –> occipital lobe –> dorsally to parietal cortex
What info is required for guided movement of limb to target?
Parietal association corticies: “where” pathway + joint proprioceptive info –> premotor cortex (Brodmann’s area 6)
How is the cerebellum involved in adaptation for effector targeting?
recalibrates via pathways connecting parietal and premotor corticies. Adaptive feedforward control
Describe the cerebellar pathway for recalibration of accurate effector targeting
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
What is the significance of mossy fiber input in the relationship between joint position sense and visual coordiates?
reflects current state of parietal cortical mapping between visual and proprioceptive signals
How is the olivary nucleus involved in cerebellar recalibration of accurate effector targeting?
Simultaneous discharge of olivary climbing fibers and parallel fibers –> network reconfiguration. Occurs only when feedback is different than expected –> error signal by ION
Why is the ION known as a comparator?
compares expected state (conveyed by deep cerebellar nuclei as a reflection of parietal network) with observed state (visual and proprioceptive feedback)
What happens when the ION senses feedback different than expected?
error signal by ION –> climbing fibers –> cerebellar cortex –> complex spikes in purkinje cells
How is long-term depression initiated, what what is its role in recalibration of accurate effector targeting?
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
How do dopaminergic neurons initially react to an unexpected reward?
Spikes in action potentials
How do dopaminergic neurons react after the behavior that elicits the reward has been learned?
Cease dopamine release
Where are the dopaminergic “reward” neurons located?
Ventral tegmental area (VTA) of the thalamus and substantia nigra pars compacta (SNc)
In what way are the SNc/VTA neurons similar to ION neurons?
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
What group of neurons convey a reflection of the current state of the cortico-striatal network to SNc/VTA neurons?
Patch (striosome) neurons. Similar to mossy fibers’ reflection of state of visual/parietal network
How would you assess dysmetria on physical exam?
Finger-nose-finger test (intention tremor), Heel-shin test
How would you assess dysdiadochokinesia on physical exam?
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)
Describe pronator drift
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
How would you assess speech coordination on exam?
Repeat LaLaLa rapidly –> CN XII test
PaPaPa –> CN VII test
KaKaKa –> CN X test
LaPaKaLaPaKa –> ability to switch rapidly between these
How would you assess station and gait?
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
What are the steps in dopamine synthesis?
Tyrosine (tyrosine hydroxylase) –> L-DOPA (dopa decarboxylase) –> dopamine
What are the steps in dopamine breakdown?
Dopamine (MAO) –> DOPAC (COMT) –> HVA
A mutation in what protein confers autosomal dominant Parkinson’s disease?
alpha-synuclein
Where is alpha synuclein found in patients without alpha synuclein mutation?
Lewy bodies
What is the primary medication used in treatment of parkinson’s?
Levodopa-carbidopa (Sinemet)
What are the pros and cons of dopamine receptor agonist use in Parkinson’s?
Pro: less risk of dyskinesia than sinemet
Con: not a substitute for sinemet (patients will still ultimately need sinemet)
What drug facilitates the release of endogenous dopamine?
amantadine (also a glutamate receptor antagonist)
What is the role of anticholinergics in treatment of parkinsons?
For the initial treatment of tremor (Trihexyphenidyl, benztropine, diphenhydramine)
Which drug is useful in counteracting toxic metabolite formation from MPTP-induced parkinsonism?
Selegiline (Deprenyl)
What is the mechanism of action of MAO inhibitors in treatment of parkinsons?
prevent dopamine breakdown. MAO-B = safer
What is the role of COMT inhibitors in treatment of Parkinsons?
prevents breakdown of L-DOPA and dopamine (Tolcapone, Entacapone)
What common drug class can lead to drug-induced parkinsonism?
Neuroleptics
