Neural indices of heritable impulsivity: Impact of the COMT Val158Met polymorphism on frontal beta power during early motor preparation

Abstract

Studies of COMT Val¹⁵⁸Met suggest that the neural circuitry subserving inhibitory control may be modulated by this functional polymorphism altering cortical dopamine availability, thus giving rise to heritable differences in behaviors. Using an anatomically-constrained magnetoencephalography method and stratifying the sample by COMT genotype, from a larger sample of 153 subjects, we examined the spatial and temporal dynamics of beta oscillations during motor execution and inhibition in 21 healthy Met¹⁵⁸/Met¹⁵⁸ (high dopamine) or 21 Val¹⁵⁸/Val¹⁵⁸ (low dopamine) genotype individuals during a Go/NoGo paradigm. While task performance was unaffected, Met¹⁵⁸ homozygotes demonstrated an overall increase in beta power across regions essential for inhibitory control during early motor preparation (∼100 ms latency), suggestive of a global motor "pause" on behavior. This increase was especially evident on Go trials with slow response speed and was absent during inhibition failures. Such a pause could underlie the tendency of Met¹⁵⁸ allele carriers to be more cautious and inhibited. In contrast, Val¹⁵⁸ homozygotes exhibited a beta drop during early motor preparation, indicative of high response readiness. This decrease was associated with measures of behavioral disinhibition and consistent with greater extraversion and impulsivity observed in Val homozygotes. These results provide mechanistic insight into genetically-determined interindividual differences of inhibitory control with higher cortical dopamine associated with momentary response hesitation, and lower dopamine leading to motor impulsivity.

Keywords: COMT; Dopamine; Magnetoencephalography; Response inhibition.

Fig. 1.. Go/NoGo task.

The task consisted of “X” and “Y” letters presented in an alternating (80%, Go) or repeated (20%, NoGo) manner. Participants were instructed to make a button press with their right index finger for every alternation and inhibit their response for each repetition. A total of 685 trials were presented in rapid succession every 1400 ± 150 ms with each letter being presented for 230 ms before being replaced by a central fixation dot for the remainder of the trial.

Fig. 2.. Task performance.

As expected, response accuracy was higher on Go trials compared to NoGo trials overall. However, genotype groups did not differ on accuracy, reaction times, and premature responses. ***p < .001.

Fig. 3.. Overall pattern of beta dynamics during motor execution and inhibition.

Greatest changes in beta power were observed over the left sensorimotor area (sMOT), which controls the responding right hand. Beta power began to decrease prior to stimulus onset in anticipation of making a response. Beta diverged at ~200 ms to NoGo trials, reflecting successful response inhibition. It continued decreasing on Go trials, with the nadir approximately corresponding to reaction times (marked with a vertical bar). A similar, but weaker effect was observed within the right sMOT, ipsilateral to the responding hand. Activity maps represent the contrast of NoGo > Go beta power averaged across all participants during the 250–400 ms time window.

Fig. 4.. Impact of genotype on overall beta dynamics.

During early motor preparation (60–110 ms, yellow shading), Val¹⁵⁸ homozygotes exhibited a precipitous drop in overall beta power which is suggestive of greater behavioral disinhibition. In contrast, Met¹⁵⁸ homozygotes displayed an “uptick” at ~100 ms (marked with black arrows) that may reflect transient inhibition. It was particularly evident in the left frontal areas. Subsequent activity at the beta nadir (250–400 ms, blue shading) similarly demonstrated overall lower beta power in the Val¹⁵⁸ group relative to Met¹⁵⁸ homozygotes. This effect was similar in both hemispheres. Time courses and bar graphs represent beta power averaged across Go and NoGo trials within the early time window (60–110 ms, marked in yellow) and around the nadir (250–400 ms, marked in light blue). Activity maps represent the Met¹⁵⁸/ Met¹⁵⁸ > Val¹⁵⁸/ Val¹⁵⁸ contrast of trial-averaged beta power. ^&p < .07; *p < .05; ***p < .001.

Fig. 5.. Genotype differentially impacts early beta dynamics on trials with fast vs. slow reaction times.

To examine how genotype modulates preparatory beta power during successful Go responses, trials were stratified according to whether the reaction time was slow (SRT) or fast (FRT) for the individual. During early motor preparation (60–110 ms), Met¹⁵⁸ homozygotes exhibited an uptick in beta power relative to Val¹⁵⁸ homozygotes on the trials with slow response latencies. In contrast, early beta power did not differ between slow and fast responses for Val¹⁵⁸ homozygotes. Bar graphs represent average beta power within the 60–110 ms time window ± SEM. Vertical black bars on sMOT-lh time courses represent average fast (FRT) and slow (SRT) response latencies. sMOT: left sensorimotor cortex, dACC: left dorsal anterior cingulate cortex. ^&p < .07 *p < .05; **p < .01.

Fig. 6.. Impact of genotype on early beta dynamics as a function of NoGo errors.

During successful response inhibition (i.e., correct NoGo trials), Met¹⁵⁸ homozygotes displayed an “uptick” in beta power relative to Val¹⁵⁸ homozygotes. However, when Met¹⁵⁸ homozygotes made an error and were unable to withhold their response, no such beta increase was observed, particularly within the right rostral anterior cingulate (rACC). Bar graphs represent average beta power within the time window ± SEM. *p < .05.