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C534 Lecture 6 Basal ganglia: pathology. BG regulate the drive to action Hyperkinetic disorders Huntington’s chorea (striatum-GPe pathway lost) Tourette’s (abnormal BG activity in some imaging studies, but specific pathology unclear. Tourette’s syndrome Excessive, repeated actions
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BG regulate the drive to action • Hyperkinetic disorders • Huntington’s chorea (striatum-GPe pathway lost) • Tourette’s (abnormal BG activity in some imaging studies, but specific pathology unclear
Tourette’s syndrome • Excessive, repeated actions • Action is executed correctly • But context is “inappropriate”
BG regulate the drive to action • Hypokinetic disorders • Parkinson’s disease. • Loss of nigrostriatal dopaminergic neuromodulatory input
Loss of nigrostriatal dopaminergic neuromodulatory input • Pharmacological therapies • L-DOPA • Neurosurgical therapies (DBS) • Lesion/stimulate • STN • GPi (pallidotomy)
What’s NOT affected by BG lesions? Same action pattern/”motor programme” Less motor drive Horak FB, Anderson ME (1984) Influence of globus pallidus on arm movements in monkeys. I. Effects of kainic acid-induced lesions.J Neurophysiol. 1984 Aug;52(2):290-304
What’s NOT affected by BG lesions? Same action pattern/”motor programme” Less motor drive McLennnan et al (1972) J Neurol Sci, 15, 141-152.
Agonist burst amplitude(mV) What’s is affected by BG lesions? Muscle activity (“agonist burst”) has correct timing But low amplitude: motor areas Not sending sufficiently strong Signal to muscles Agonist burst not scaled up for Larger movements All movements are hypometric
What’s is affected by BG lesions? • Internally-generated movements • Reduced SMA readiness potentials in PD patients
Parkinson’s Normal • PET scans • Internally-generated - rest • Reduced SMA activity in PD patients
What’s is affected by BG lesions? Move1, pause, move2 Movement times longer Pause time also longer! Cognitive components of Action as well as motor Components are affected Benecke R, Rothwell JC, Dick JP, Day BL, Marsden Disturbance of sequential movements in patients with Parkinson's disease.Brain. 1987,110:361-79.
Internally-generated vs externally-triggered movements • Reduced SMA readiness potentials in PD patients • Externally-triggered movements are intact
Actions guided by an External stimulus Are relatively preserved Are these mediated by a non-BG pathway (cerebellum?)