The catechol-o-methyltransferase Val158Met polymorphism modulates organization of regional cerebral blood flow response to working memory in adults

• COMT Val158Met polymorphism and co-activation of brain areas during working memory
• 129 participants, aged 35 to 70 years
• rCBF to performance correlations differ regionally for different genotypes.
• Degree of shared activation and importance for performance is genotype specific.
• Dopamine availability may alter brain networks to achieve comparable performance.

This study examined the effect of catechol-o-methyltransferase (COMT) Val158Met genotypes on the co-activation of brain areas involved in cognition during a working memory (WM) task. The pattern of concomitant region of interest (ROI) activation during WM performance varied by genotype: Val/Val showing the least and Met/Met the most covariance. There were no differences of performance on the WM task between the COMT genotypes. However, relatively better performance was associated with less concomitance of dorsolateral prefrontal cortex (DLPFC) and cingulate cortex for Val/Val, but more concomitance of DLPFC with AH for Met/Met. Within genotypes WM performance was significantly correlated with rCBF to the amygdala/hippocampus (AH) for Val/Val (r = 0.44, p = 0.009), to the parietal lobe for Val/Met (r = 0.29, p = 0.03), and to the thalamus for Met/Met (r = 0.32, p = 0.04). Different genotypes showed different regional specificity and concomitant activation patterns suggesting that varying dopamine availability induces different brain processing pathways to achieve similar WM performance.