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

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.

The "when" and "where" of the interplay between attentional capture and response inhibition during a Go/NoGo variant.

Inhibitory control relies on attention, inhibition, and other functions that are integrated across neural networks in an interactive manner. Functional MRI studies have provided excellent spatial mapping of the involved regions. However, finer temporal resolution is needed to capture the underlying neural dynamics and the pattern of their functional contributions. Here, we used anatomically-constrained magnetoencephalography (aMEG) which combines MEG with structural MRI to examine how the spatial ("where") and temporal ("when") processing stages and interregional co-oscillations unfold in real time to contribute to inhibitory control. Healthy participants completed a modified Go/NoGo paradigm in which a subset of stimuli was modified to be visually salient (SAL). Compared to the non-modified condition, the SAL manipulation facilitated response withholding on NoGo trials and hindered responding to Go stimuli, reflecting attentional capture effectuated by an orienting response to SAL stimuli. aMEG source estimates indicate SAL stimuli elicited the attentional "circuit breaker" effect through early activity within a right-lateralized network centered around the lateral temporal cortex with additional activity in the pre-supplementary motor area (preSMA) and anterior insula (aINS/FO). Activity of the bilateral inferior frontal cortex responded specifically to inhibitory demands and was generally unaffected by the attentional manipulation. In contrast, early aINS/FO activity was sensitive to stimulus salience while subsequent activity was specific to inhibitory control. Activity estimated to the medial prefrontal cortex including the dorsal anterior cingulate cortex and preSMA reflected an integrative role that was sensitive to both inhibitory and attentional stimulus properties. At the level of neurofunctional networks, neural synchrony in the theta band (4-7 Hz) revealed interactions between principal cortical regions subserving attentional and inhibitory processes. Together, these results underscore the dynamic, integrative processing stages underlying inhibitory control.

Binge drinking is associated with altered resting state functional connectivity of reward-salience and top down control networks.

Binge drinking is characterized by bouts of high-intensity alcohol intake and is associated with an array of health-related harms. Even though the transition from occasional impulsive to addictive alcohol use is not well understood, neurobiological models of addiction suggest that repeated cycles of intoxication and withdrawal contribute to the development of addiction in part through dysregulation of neurofunctional networks. Research on the neural sequelae associated with binge drinking is scant but resting state functional connectivity (RSFC) studies of alcohol use disorders (AUD) indicate that the development and maintenance of long-term excessive drinking may be mediated by network-level disruptions. The present study examined RSFC in young adult binge (BD) and light (LD) drinkers with seeds representing the networks subserving reward (the nucleus accumbens and caudate nucleus), salience (anterior cingulate cortex, ACC), and executive control (inferior frontal cortex, IFC). BDs exhibited enhanced connectivity between the striatal reward areas and the orbitofrontal cortex and the ACC, which is consistent with AUD studies and may be indicative of alcohol-motivated appetitive behaviors. Conversely, BDs demonstrated lower connectivity between the IFC and hippocampus which was associated with higher craving. This may indicate impaired ability to suppress unwanted thoughts and a failure to employ memory of the harmful consequences of heavy drinking in prospective plans and intentions. The observed greater connectivity of the reward/salience network and the lower prefrontal-hippocampal connectivity were associated with hazardous drinking levels indicating that dysregulation of neurofunctional networks may underlie binge drinking patterns.

Disruption of Frontal Lobe Neural Synchrony During Cognitive Control by Alcohol Intoxication.

Decision making relies on dynamic interactions of distributed, primarily frontal brain regions. Extensive evidence from functional magnetic resonance imaging (fMRI) studies indicates that the anterior cingulate (ACC) and the lateral prefrontal cortices (latPFC) are essential nodes subserving cognitive control. However, because of its limited temporal resolution, fMRI cannot accurately reflect the timing and nature of their presumed interplay. The present study combines distributed source modeling of the temporally precise magnetoencephalography (MEG) signal with structural MRI in the form of "brain movies" to: (1) estimate the cortical areas involved in cognitive control ("where"), (2) characterize their temporal sequence ("when"), and (3) quantify the oscillatory dynamics of their neural interactions in real time. Stroop interference was associated with greater event-related theta (4 - 7 Hz) power in the ACC during conflict detection followed by sustained sensitivity to cognitive demands in the ACC and latPFC during integration and response preparation. A phase-locking analysis revealed co-oscillatory interactions between these areas indicating their increased neural synchrony in theta band during conflict-inducing incongruous trials. These results confirm that theta oscillations are fundamental to long-range synchronization needed for integrating top-down influences during cognitive control. MEG reflects neural activity directly, which makes it suitable for pharmacological manipulations in contrast to fMRI that is sensitive to vasoactive confounds. In the present study, healthy social drinkers were given a moderate alcohol dose and placebo in a within-subject design. Acute intoxication attenuated theta power to Stroop conflict and dysregulated co-oscillations between the ACC and latPFC, confirming that alcohol is detrimental to neural synchrony subserving cognitive control. It interferes with goal-directed behavior that may result in deficient self-control, contributing to compulsive drinking. In sum, this method can provide insight into real-time interactions during cognitive processing and can characterize the selective sensitivity to pharmacological challenge across relevant neural networks.

Behavioral and Brain Activity Indices of Cognitive Control Deficits in Binge Drinkers.

Heavy episodic drinking is prevalent among young adults and is a public issue of increasing importance. Its initiation and maintenance are associated with deficits in the capacity to inhibit automatic processing in favor of non-habitual responses. This study used functional magnetic resonance imaging (fMRI) to examine behavioral and brain activity indices of cognitive control during the Stroop task as a function of binge drinking. Heavy episodic drinkers (HED) reported consuming 5+/6+ drinks in two hours at least five times in the past six months and were compared to light drinkers (LED) who reported two or fewer binge episodes but were matched on demographics, intelligence and family history of alcoholism. Greater conflict-induced activity in the ventrolateral prefrontal cortex (VLPFC) and thalamus was observed in HED participants and it was positively correlated with alcohol intake and alcohol-related harmful consequences. HEDs maintained intact accuracy but at a cost of prolonged reaction times to high-conflict trials and increased ratings of task difficulty. Greater activation of the areas implicated in cognitive control is consistent with compensatory network expansion to meet higher cognitive demands. These results provide further insight into degradation of cognitive control in HEDs which may benefit development of detection and prevention strategies.