Testing the effects of adolescent alcohol use on adult conflict-related theta dynamics

Abstract

Objective Adolescent alcohol use (AAU) is associated with brain anomalies, but less is known about long-term neurocognitive effects. Despite theoretical models linking AAU to diminished cognitive control, empirical work testing this relationship with specific cognitive control neural correlates (e.g., prefrontal theta-band EEG dynamics) remains scarce. A longitudinal twin design was used to test the hypothesis that greater AAU is associated with reduced conflict-related EEG theta-band dynamics in adulthood, and to examine the genetic/environmental etiology of this association. Methods In a large (N = 718) population-based prospective twin sample, AAU was assessed at ages 11/14/17. Twins completed a flanker task at age 29 to elicit EEG theta-band medial frontal cortex (MFC) power and medial–dorsal prefrontal cortex (MFC-dPFC) connectivity. Two complementary analytic methods (cotwin control analysis; biometric modeling) were used to disentangle the genetic/shared environmental risk towards AAU from possible alcohol exposure effects on theta dynamics. Results AAU was negatively associated with adult cognitive control-related theta-band MFC power and MFC-dPFC functional connectivity. Genetic influences primarily underlie these associations. Conclusions Findings provide strong evidence that genetic factors underlie the comorbidity between AAU and diminished cognitive control-related theta dynamics in adulthood. Significance Conflict-related theta-band dynamics appear to be candidate brain-based endophenotypes/mechanisms for AAU.

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

“…Finally, findings from a recent large-scale genome-wide association study of alcohol dependence suggest that pathological alcohol use and measures of normative alcohol consumption are only modestly genetically correlated (Walters et al, 2018). As the liability underlying clinically problematic alcohol use (e.g., AUD) and phenotypes of normative drinking patterns (such as those used in our previous report; Harper et al, 2017a) only partially overlap, it is not clear whether our prior theta-adolescent drinking findings will extend to AUD measures. Hence, investigating how pathological alcohol use that extends into emerging adulthood affects neurodynamics has substantial public health significance.…”

“…This finding is consistent with two high-risk family studies linking familial risk of alcohol dependence and reduced theta during a monetary gambling task (Kamarajan et al, 2015) and a response inhibition task (Kamarajan et al, 2006). The results from Harper et al (2017a) provided initial evidence that conflict-related midfrontal theta is a potential endophenotype for alcohol misuse.…”

“…In a recent report (Harper, Malone, & Iacono, 2017a), we investigated the association between adolescent alcohol use (a quantitative index of alcohol consumption/exposure) and adult conflict-related frontal theta in a large prospective twin sample. Results of that report indicated that greater drinking in adolescence (ages 11–17) was associated with reduced response conflictrelated theta power in adulthood (age 29).…”

“…Results of that report indicated that greater drinking in adolescence (ages 11–17) was associated with reduced response conflictrelated theta power in adulthood (age 29). The CTC design and biometric modeling offered evidence suggesting that the reduction in frontal theta was not a consequence of adolescent drinking, but was instead primarily due to common genetic factors underlying individual differences in both adolescent drinking and frontal theta activity (Harper et al, 2017a). This finding is consistent with two high-risk family studies linking familial risk of alcohol dependence and reduced theta during a monetary gambling task (Kamarajan et al, 2015) and a response inhibition task (Kamarajan et al, 2006).…”

“…The current report was designed as an extension of the previous analyses in Harper et al (2017a) to evaluate, in the same prospective twin sample, the etiological effects of cumulative lifetime pathological alcohol use (i.e., AUD) past age 17 and up to age 29 on cognitive controlrelated theta dynamics. The vulnerability of the prefrontal cortex to the possible neurotoxic effects of drinking continues as the brain matures during early adulthood (Bennett & Baird, 2006).…”