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.

Multimodal Imaging Evidence for a Frontoparietal Modulation of Visual Cortex during the Selective Processing of Conditioned Threat

“…As expected, the ssVEP amplitude, generated in early visual peri-calcarine cortical areas, increased for CS+ relative to CS- trials, as participants acquired the CS+ and US contingencies (Gruss et al, 2016; Keil et al, 2013; Miskovic & Keil, 2012; Moratti & Keil, 2009; Moratti, Keil, & Miller, 2006). Consistent with a large body of hemodynamic neuroimaging research, these differences in visual cortical electrophysiology were accompanied by CS+ specific BOLD activation in visual cortical areas (Carter, O’Doherty, Seymour, Koch, & Dolan, 2006; Cheng, Knight, Smith, Stein, & Helmstetter, 2003; Klucken et al, 2009; Knight, Cheng, Smith, Stein, & Helmstetter, 2004; Tabbert, Stark, Kirsch, & Vaitl, 2005).…”

Catechol‐O‐methyltransferase Val158Met polymorphism associates with affect and cortisol levels in women

“…These data agree with previous findings that the Val allele associates panic disorder in women (Domschke et al, 2004;Hamilton et al, 2002). In further agreement, an additional study composed predominantly of female participants found that, relative to Val homozygotes, Met allele carriers had smaller visuocortical activation, lower heart rate, and decreased startle potentiation to aversive stimuli (Gruss, Langaee, & Keil, 2016). Another study compared allele status to behavioral risk taking propensity in adolescents and found risk taking to be higher in females, but not males, who were Met allele carriers.…”

Single-session label training alters neural competition between objects and faces.

“…Top-down modulation of face specific neural activity is consistent with previous FFA activity and N170 ERP responses (Gazzaley et al, 2005). Fur-thermore, the results presented here converge with work in other areas of associative learning, most notably Pavlovian conditioning (Gruss et al, 2016). Specifically, conditioning-induced changes in competition have been shown to prompt reentrant fronto-parietal signals that enhance or suppress information in occipital-temporal regions, which are capacity limited (Petro et al, 2017).…”