The role of the COMT val158met polymorphism in mediating aversive learning in visual cortex

Abstract The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (SNP) alters metabolic activity of the COMT enzyme regulating catecholamines, with the Val (valine) allele resulting in 40% greater enzymatic activity than the Met (methionine) allele. Previous research has identified systematic inter-individual differences in cognitive and behavioral phenotypes related to this polymorphism, often attributed to the fact that extracellular dopamine in the prefrontal cortex is strongly affected by the COMT enzyme. The neurophysiological mechanisms mediating these inter-individual differences in specific brain systems and task contexts remain to be established however. In the current study, we examined the extent to which physio-mechanistic differences by COMT genotype affect somato-visceral and visual cortical responses to learned threat cues. Classical aversive differential conditioning was implemented using rapidly phase-reversing grating stimuli, previously shown to engage retinotopic visual cortex. Differential response patterns in sensory and autonomic systems were elicited by pairing one grating (CS +, conditioned stimulus), but not the other (CS −), with a noxious stimulus. Dense-array electroencephalography and somato-visceral measures of defensive reactivity were recorded in addition to self-report data. Individuals of the Val/Val genotype, compared to Met allele carriers, reliably showed greater initial enhancement in their visuocortical response to the CS +, accompanied by stronger defensive engagement, indexed by heart rate acceleration and startle potentiation. The finding that COMT polymorphism status affects threat cue reactivity at the visuocortical level is consistent with the notion that sensory processing of threat is facilitated by strong re-entrant bias signals from anterior areas, including the prefrontal cortex.