UC San Diego

Rationale: Inhibitory control is an executive function essential for flexible and adaptive behavior. This 3-paper dissertation examined its spatio- (“where”) temporal (“when”) neural dynamics with inhibitory Go/NoGo paradigms. A multimodal anatomically-constrained magnetoencephalography (aMEG) method combined the temporal precision and distributed source modeling of MEG with structural MRI and provided insight into the anatomical distribution of the engaged areas and their functional interdependence.Study 1 examined the relative contributions of attentional and inhibition-related processes using a modified Go/NoGo task in a cohort of healthy participants (N=26). Attentional capture was subserved by early activity within right-lateralized temporoparietal areas followed by activation of a “braking” network comprised of ventrolateral prefrontal areas responding specifically to inhibitory demands. Medial prefrontal areas supported integrative processing of inhibitory and attentional stimulus properties. Study 2 explored how genetically-determined cortical dopamine availability in individuals genotyped for the COMT Val158Met polymorphism (Met/Met: N=21; Val/Val: N=21) modulated neural activity of response preparation, inhibition, and execution. Met homozygotes (high dopamine) exhibited an increase in beta power during early motor preparation suggestive of a transient “pause,” which could underlie the tendency of Met homozygotes to be more cautious and inhibited. In contrast, Val homozygotes (low dopamine) commonly endorse higher impulsivity. They exhibited greater beta decrease during early motor preparation, indicative of high response readiness. Study 3 evaluated the effects of alcohol intoxication on the neurocircuitry of inhibitory control in social drinkers with (FHP) or without (FHN) a family history of alcoholism (N=19 per group), a heritable, multifaceted risk factor for the development of alcohol use disorder (AUD). In FHP, lower inhibition-induced oscillatory power was associated with extraversion. Converging evidence across behavioral and neural indices supports low responsivity of FHP to alcohol intoxication, which may mediate the development of AUD. The multimodal aMEG method can provide high-resolution insight into the neural underpinnings of inhibitory control with implications for healthy behavior and genetically-determined interindividual differences in impulsivity. Because of their sensitivity to synaptic signaling, these indices can reveal neural signature of the acute and persistent impact of alcohol on self-regulatory functions, and may serve as endophenotypes of disinhibitory disorders, including the vulnerability to AUD.