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.

Keywords: Adolescent alcohol use; Cognitive control; Cotwin control; Endophenotype; Functional connectivity; Theta.

Figure 1

Time-frequency theta-band (3–8 Hz) EEG dynamics. (A) Left: The grand average time-frequency plots of stimulus-locked (time = 0, dashed line) medial frontal power at channels FCz/Cz for incongruent and congruent conditions. Note the strong increase in theta-band power following incongruent stimuli. Right: The response conflict effect (difference between incongruent and congruent trials) on time-frequency power. The time-frequency plot of the response conflict effect for power pooled across FCz/Cz (white electrodes) and the associated topographic distribution of theta-band power show robust theta power enhancement over the medial frontal cortex for incongruent trials. (B) Left: Same as (A), but for FCz–seeded (purple electrode) functional connectivity as measured by the weighted phase lag index (wPLI). These plots illustrate enhanced connectivity between a medial frontal cortex channel (FCz) and a cluster of dorsal medial and dorsolateral prefrontal channels (dPFC; white electrodes), which is augmented during incongruent trials. The black outline boxes denote the region of interest used for statistical analyses.

Figure 2

Graphical depiction of a general ACE bivariate model illustrating the variance in each individual observed phenotype (indicated in rectangular boxes) parsed into that explained by latent variables (indicated in circles) reflecting additive genetic (A), shared environmental (C), and nonshared environmental (E) effects, and the associated genetic (rA), shared environmental (rC), and nonshared environmental (rE) correlations, between adolescent alcohol use and incongruent theta-band power. The rE correlation is analogous to the within-pair exposure effect in the cotwin control analysis, while rA and rC capture the familial risk effect.