Cognitive and motor effects of dopaminergic medication withdrawal in Parkinson's disease.
OBJECTIVE
Recent evidence points towards dissociable effects of dopaminergic medication on motor function and cognitive function mediated by different fronto-striatal neural circuits. This study aimed to clarify the role of dopaminergic medication in spatial working memory, and reinforcement-based associative learning in relation to clinical changes in motor function in early Parkinson's disease (PD).


METHODS
We tested 14 patients with mild to moderate PD on and off dopaminergic medication, on a spatial delayed-response working memory task, and on spatial and non-spatial (visual) trial-and-error learning tasks based on reinforcement, carefully matched for motor requirements. In addition, we explored relationships between the effects of withdrawal on motor symptom expression and performance on the cognitive tasks.


RESULTS
Withdrawal from dopaminergic medication significantly exacerbated motor symptoms. This was related to spatial learning, but not visual learning, or delayed response accuracy. Moreover, medication withdrawal led to dissociable effects of response latency on the spatial learning and spatial delayed response tasks, with patients becoming faster after spatial learning, but relatively slower on the delayed response task. These changes in response latency were unrelated to motor symptom impairment.


CONCLUSIONS
Our findings suggest dissociable effects of dopamine medication withdrawal on cognitive processes putatively mediated by dorsal and ventral striatal regions.
Fern-Pollak
Liory
L
Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, London W12 0NN, UK.
Whone
Alan L
AL
Brooks
David J
DJ
Mehta
Mitul A
MA
D000368:Aged; D000704:Analysis of Variance; D001245:Association Learning / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D015259:Dopamine Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000188:drug therapy; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
D015259:Dopamine Agents