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Cerebral Cortex Advance Access first published online on February 5, 2008
This version published online on February 9, 2008
Cerebral Cortex, doi:10.1093/cercor/bhm240
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© 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

COMT val158met Genotype Affects Recruitment of Neural Mechanisms Supporting Fluid Intelligence

Sonia J. Bishop1,2, John Fossella3, Camilla J. Croucher2 and John Duncan2

1 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK, 2 Medical Research Council, Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF, UK, 3 Department of Psychiatry, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA

Address correspondence to Sonia J. Bishop at email: sb445{at}cam.ac.uk.

Fluid intelligence (gf) influences performance across many cognitive domains. It is affected by both genetic and environmental factors. Tasks tapping gf activate a network of brain regions including the lateral prefrontal cortex (LPFC), the presupplementary motor area/anterior cingulate cortex (pre-SMA/ACC), and the intraparietal sulcus (IPS). In line with the "intermediate phenotype" approach, we assessed effects of a polymorphism (val158met) in the catechol-O-methyltransferase (COMT) gene on activity within this network and on actual task performance during spatial and verbal gf tasks. COMT regulates catecholaminergic signaling in prefrontal cortex. The val158 allele is associated with higher COMT activity than the met158 allele. Twenty-two volunteers genotyped for the COMT val158met polymorphism completed high and low gf versions of spatial and verbal problem-solving tasks. Our results showed a positive effect of COMT val allele load upon the blood oxygen level–dependent response in LPFC, pre-SMA/ACC, and IPS during high gf versus low gf task performance in both spatial and verbal domains. These results indicate an influence of the COMT val158met polymorphism upon the neural circuitry supporting gf. The behavioral effects of val allele load differed inside and outside the scanner, consistent with contextual modulation of the relation between COMT val158met genotype and gf task performance.

Key Words: COMT • fMRI • g • genotype • intelligence • prefrontal cortex


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