title: Putative cortical dopamine levels affect cortical recruitment during planning.
abstract: Planning, the decomposition of an ultimate goal into a number of sub-goals is critically dependent upon fronto-striatal dopamine (DA) levels. Here, we examined the extent to which the val158met polymorphism in the catechol O-methyltransferase (COMT) gene, which is thought to primarily alter cortical DA levels, affects performance and fronto-parietal activity during a planning task (Tower of London). COMT genotype was found to modulate activity in the left superior posterior parietal cortex (SPC) during planning, relative to subtracting, trials. Specifically, left SPC blood oxygenation level-dependent (BOLD) response was reduced in groups with putatively low or high cortical DA levels (COMT homozygotes) relative to those with intermediate cortical DA levels (COMT heterozygotes). These set of results are argued to occur either due to differences in neuronal processing in planning (and perhaps subtracting) caused by the COMT genotype and/or the cognitively heterogeneous nature of the TOL, which allows different cognitive strategies to be used whilst producing indistinguishable behavioural performance in healthy adults. The implications of this result for our understanding of COMT's effect on cognition in health and disease are discussed.
authors.affiliation: Medical Research Council Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, United Kingdom; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlands. Electronic address: seaneyjames@gmail.com.
authors.forename: S J
authors.initials: SJ
authors.lastname: Fallon
authors.forename: A
authors.initials: A
authors.lastname: Hampshire
authors.forename: C H
authors.initials: CH
authors.lastname: Williams-Gray
authors.forename: R A
authors.initials: RA
authors.lastname: Barker
authors.forename: A M
authors.initials: AM
authors.lastname: Owen
mesh_terms: D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011340:Problem Solving / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology
chemical_list: D002394:Catechol O-Methyltransferase; D004298:Dopamine
keywords: Catechol O-methyltransferase (COMT); Dopamine; Inverted-U; Planning; fMRI
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