Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory.
Previous data suggest that methylphenidate can have variable effects on different cognitive tasks both within and between individuals. This is thought to be underpinned by inverted U-shaped relationships between cognitive performance and dopaminergic activity in relatively separate fronto-striatal circuits and reflected by individual differences in trait impulsivity. Direct evidence for this is currently lacking. In this study, we demonstrate for the first time that therapeutic doses of oral methylphenidate administered to young healthy subjects result in different sized changes in D(2)/D(3) receptor availability in different regions of the human striatum and that the change in receptor availability within an individual subregion predicts cognitive performance on a particular task. Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals. Performance on the reversal learning task was predicted by the drug-induced change in D(2)/D(3) receptor availability in postcommissural caudate, measured using [(11)C]-raclopride radioligand PET imaging, whereas performance on the spatial working memory task was predicted by changes in receptor availability in the ventral striatum. Reversal learning performance was also predicted by subjects' trait impulsivity, such that the most impulsive individuals benefited more from methylphenidate, consistent with this drug's beneficial effects on cognition in attention deficit hyperactivity disorder.
Clatworthy
Philip L
PL
Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom.
Lewis
Simon J G
SJ
Brichard
Laurent
L
Hong
Young T
YT
Izquierdo
David
D
Clark
Luke
L
Cools
Roshan
R
Aigbirhio
Franklin I
FI
Baron
Jean-Claude
JC
Fryer
Timothy D
TD
Robbins
Trevor W
TW
D000328:Adult; D001931:Brain Mapping / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008774:Methylphenidate / Q000008:administration & dosage*; D010775:Photic Stimulation / Q000379:methods; D011237:Predictive Value of Tests; D012193:Reversal Learning / Q000187:drug effects / Q000502:physiology*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
D008774:Methylphenidate; D004298:Dopamine