Oct17 M1-Basal Ganglia Flashcards
classification of movement disorders
- hypokinetic
- PD and variants (MSA, PSP, etc.) - hyperkinetic (everything else) (are usually but not always basal ganglia dz)
- tremor
- chorea, athetosis, ballism
- myoclonus
- dystonia
- tics and stereotypy
bradykinesia def
small movements (ROM), fatigue (ROM decreasing as do the mvmt) for ANY movement (steps, voice, handwriting)
beats up their family + chorea = think of what dz
Huntington’s dz (HD).
-frontal deficiency
(imp) structures of the basal ganglia
- caudate and putamen (forming dorsal striatum) separated by anterior limb of internal capsule
- globus pallidus externa and interna (GPe and GPi). very close but very diff fcts.
- substantia nigra pars compacta (SNpc). (affected in PD) (note: SN pars reticula is functionally* part of the GPe)
- SN is in the midbrain* just lat to mamillary bodies
- subthalamic nucleus (STN) is above SN
functions of the basal ganglia
- circuits for modulation of movement (tone and motivation) as part of focusing actions (picking the correct ones)
- govern output. yes or no signal (likelihood). more generally (not fine things of movement which are controlled by cortex and cerebellum)
- not emotional**
what are the loops or circuits in the basal ganglia
diff pathways of connections
- from SN to ventral striatum to dorsal lateral prefrontal cortex
- from SN to premotor cortex
- from SN to motor cortex
- etc
names of the 4 main loops in the basal ganglia (which all regulate tone and motivation)
- motor (move or not) (involved in hyperkinetic disorders and parkinsonism)
- cognitive (which areas to activate? task switching and focusing priorities)
- visual (oculomotor)
- limbic (to act or not) (apathy (limbic loop working too much) vs impulse control (impulse disorder = limbic loop working less**)
main ntr in basal ganglia loops
dopamine
dopamine fct
- reward ntr. is a reward prediction error signal
- shown not to be ntr for ‘‘happy’’ bc increases before something good so more for showing ‘‘reward is coming’’
- dopamine stops = signal to brain to not do anything, there’s nothing there
2 main structures controlling the motor, cognitive and limbic loops
- SN (1) connects to caudate (association cortex) and putamne (motor areas)
- SN also connects to the ventral tegmental area (2) which connects to limbic areas of the ventral striatum including the nucleus accumbens
SNc to putamen = what loop
motor (SNc to motor areas of cortex)
is a dorsal loop
SNc to caudate = what loop
cognitive (SNc to association cortex)
is a dorsal loop
VTA to ventral striatum = what loop
emotive (limbic) (VTA to ventral striatum nucleus accumbens)
- is a ventral loop*
- D2Rs in this loop*
main cause of motor sx in PD
- dopamine problem bc of a lesion in SN (which controls the direct pathway which increases movement)
- lose SN = less stim of direct pathway (loop) (D1 Rs in striatum) = less movement
- less inhibition of indirect loop (D2 Rs in striatum) (meaning it works more intensely) (which normally inhibits movement) = less movement
SN charact
- appears as black line on gross pathology
- has melanin in its dopaminergic neurons
- in Parkinson’s dz (hypokinetic), it appears lighter on gross patho bc these neurons died
why PD fixable
- levodopa (dopamine precursor)
- other dopamine agents
- neurosurgery (targeting SNc and GPi)
why dopamine works as tx for PD
- mimics what SN normally does
- inhibits the normally indirect (inhibiting) pathway = more movement
- stim the direct (stim) pathway = more movement
2 neurosurgical tx for PD
- hole in GPi (the endpoint of both D1 and D2 pathways) which normally inhibits movement
- hole in STN (of indirect D2 pathway) = less inhibition
pathophgy of HD (Huntington’s dz)
main problem in HD = frontal degeneration
selective degeneration of indirect pathway (D2). D1 is working fine
-result = move more
-mvmts are excessive and unforced
-center-surround system (fact of having 2 systems) for focusing mvmts stopped working
dyskinesia def
abnormal mvmt
PD patient moving too much, what might be the cause
got a dose of meds that was too high
tx of HD (chorea and dyskinesia)
- dopamine blockade (neuroleptics, dopamine depletors)
* note chorea is the least of the pts problems*
consequence of dopamine agonist dose being too high in a PD pt
on top of the motor benefits and better mood, pt starts spending, hypersexuality, etc. becomes excessive
- dopamine agonist fixed the SNc (dorsal loops)
- dopamine agonist stimulated the D2Rs in the ventral loop (VTA to ventral striatum) = this loop became excessive
consequence of suddenly stopping meds in a PD pt
severe depression (apathy, anhedonia, nothing is worth it, suicidal)
