Does electroencephalogram phase variability account for reduced P3 brain potential in externalizing disorders?

Abstract

Background. Amplitude deficits of the P3 event-related brain potential (ERP) are associated with externalizing psychopathology but little is known about nature of the underlying brain electrical activity that accounts for this amplitude reduction. P3 amplitude is partially determined by electroencephalographic (EEG) frequencies in delta and theta bands and differences in phase-invariant stimulus-evoked energy and task-induced phase-locking associated with these frequencies may account for the P3-externalizing association.Methods. Adult males (N = 410) completed a visual oddball task and frontal and parietal ERPs were analyzed as P3-related (300 to 600 milliseconds post-stimulus) evoked energy and inter-trial phase-locking measures in the delta (1 - 3.5 Hz) and theta-frequency (3.5 - 8 Hz) bands. We investigated how the delta and theta activity underlying P3 varies with disorders in the externalizing spectrum, including substance dependence, adult antisociality, and childhood disruptive disorders. We hypothesized that P3-related phase-locking is weaker in externalizing-diagnosed individuals and this might mediate prior findings of reduced evoked P3energy. Results. Reductions in both evoked energy and phase-locking, in both frequency bands, at both scalp sites, were associated with greater odds of having an externalizing disorder. In most cases, adding phase-locking to evoked energy came with better prediction model fit. Moreover, reduced theta- but not delta-band phase-locking partially mediated the effects of within-frequency evoked energy on externalizing prediction.Conclusions. These results suggest that phase-locking of inter-trial EEG during the P3 time-window is an important distinction between externalizing-prone individuals and control subjects. This cross-trial phase-variability for externalizing-diagnosed individuals might reflect deficient top-down "tuning" by neuromodulatory systems.