Conflict-related medial frontal theta as an endophenotype for alcohol use disorder

Abstract

Diminished cognitive control in alcohol use disorder (AUD) is thought to be mediated by prefrontal cortex circuitry dysregulation. Research testing the relationship between AUD and specific cognitive control psychophysiological correlates, such as medial frontal (MF) theta-band EEG power, is scarce, and the etiology of this relationship is largely unknown. The current report tested relationship between pathological alcohol use through young adulthood and reduced conflict-related theta at age 29 in a large prospective population-based twin sample. Greater lifetime AUD symptomatology was associated with reduced MF theta power during response conflict, but not alpha-band visual attention processing. Follow-up analyses using cotwin control analysis and biometric modeling suggested that genetic influences, and not the consequences of sustained AUD symptomatology, explained the theta-AUD association. Results provide strong evidence that AUD is genetically related to diminished conflict-related MF theta, and advance MF theta as a promising electrophysiological correlate of AUD-related dysfunctional frontal circuitry.

Target‐related parietal P3 and medial frontal theta index the genetic risk for problematic substance use

“…Thus, at both the phenotypic and genetic level, individual differences in target‐related midfrontal theta accounted for unique variance in PSU, suggesting that deviations in medial frontal activity may reflect a core risk factor for substance use problems (Zucker et al, ) that is partially independent of the risk conferred by P3AR or RTV. This provides further evidence that theta indexes a familial vulnerability for SUDs (Harper, Malone, & Iacono, , ; Rangaswamy et al, ). Taken together, these findings are in line with current theories of PSU/SUDs, which propose a premorbid genetic risk for problematic use that is expressed, in part, by individual differences in cognitive processes, such as attentional allocation/bias and decision making, and prefrontal cortex functioning (Goldstein & Volkow, ; Iacono et al, ; Zucker et al, ).…”

“…While prior work has reported a common genetic association between reduced target‐related P3, parietal delta power, and SUDs (Gilmore et al, ), it remains unknown whether midfrontal theta during rare target detection is sensitive to genetic vulnerability for PSU. There is evidence that reductions in theta during other cognitive processes, such as response conflict (Harper, Malone, & Iacono, , ), response inhibition (Kamarajan et al, ), and loss/gain feedback processing (Kamarajan et al, ), reflect putative endophenotypes for alcohol use.…”

Parietal P3 and midfrontal theta prospectively predict the development of adolescent alcohol use

“…Theta is associated with normative and pathological alcohol use (Jones et al ., 2006; Andrew and Fein, 2010; Yoon et al ., 2013; Harper et al ., 2019); heritable (Harper et al ., 2019); diminished in first-degree relatives with AUD (Rangaswamy et al ., 2007); shares genetic variance with alcohol use (Harper et al ., 2019); and predicts alcohol use development (as shown here); all of which are important criterion for an endophenotype (Gottesman and Gould, 2003; Iacono et al ., 2017). Midfrontal theta elicited by other experimental tasks and cognitive processes, such as inhibitory control (Kamarajan et al ., 2006; however, see Harper et al ., 2018 b ), response conflict (Harper et al ., 2017 a , 2018 a ), and feedback processing (Kamarajan et al ., 2015) may also reflect candidate endophenotypes for clinical and non-clinical drinking. This is consistent with the hypothesis that variations in midfrontal theta across varied cognitive demands reflect a generic and reactive processing mechanism to facilitate successful action monitoring and cognitive control (Cavanagh et al ., 2012; Cavanagh and Frank, 2014; Cohen, 2014 b ).…”

Brain Structure and Function in Recovery

“…Similar observations across numerous studies have led to the proposal that P3 aberrations, particularly blunted P3 amplitudes, constitute a possible AUD endophenotype. 10,45,46 Using a cross-sectional design, Fein and colleagues 47 investigated the effect of abstinence on neurobiological variables, comparing individuals with AUD who were long-term abstinent (abstinence ≥ 6 months, mean abstinence > 6 years) and community controls. The investigators examined the P160-an ERP component with demonstrated sensitivity to face processing and reaction time-using an emotional face expression task.…”

“…Similar observations across numerous studies have led to the proposal that P3 aberrations, particularly blunted P3 amplitudes, constitute a possible AUD endophenotype. 10 , 45 , 46 …”