Does electroencephalogram phase variability account for reduced P3 brain potential in externalizing disorders?
- Authors
- Burwell, Scott J; Malone, Stephen M; Bernat, Edward M; Iacono, William G
- Year
- 2014
- Journal
- Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
- PMID
- 24656843
- DOI
- 10.1016/j.clinph.2014.02.020
- PMCID
- PMC4156932
OBJECTIVE: Amplitude deficits of the P3 event-related potential (ERP) are associated with externalizing psychopathology but little is known about the nature of underlying brain electrical activity that accounts for this amplitude reduction. We sought to understand if group differences in task-induced phase-locking in electroencephalographic (EEG) delta and theta frequencies may account for P3-externalizing associations. METHODS: Adult males (N=410) completed a visual oddball task and frontal and parietal P3-related delta- and theta-band phase-invariant evoked energy and inter-trial phase-locking measures were investigated with respect to 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 P3 energy. RESULTS: Reductions in both evoked energy and phase-locking, in both frequency bands, at both scalp sites, were associated with greater odds of externalizing diagnoses. Generally, adding phase-locking to evoked energy came with better prediction model fit. Moreover, reduced theta-band phase-locking partially mediated the effects of within-frequency evoked energy on externalizing prediction. CONCLUSIONS: Inter-trial phase-locking underlying P3 appears to be an important distinction between externalizing and control subjects. SIGNIFICANCE: This cross-trial phase-variability for externalizing-diagnosed individuals might reflect deficient top-down "tuning" by neuromodulatory systems.
Does reduced intertrial phase-locking mediate energy deficits in evoked P3 energy?Most research showing P3-amplitude reductions with externalizing-diagnoses (EXT) uses the evoked event-related potential, which is composed of phase-locked energy (EVK). In a mediation framework, the contribution attributable to P3 amplitude can be thought of as the “total effect” of EVK on EXT, corresponding to path c in model A. Theoretically, a high-degree of phase-locking factor (PLF, phase-locking independent of energy) is necessary for large values of EVK, but large values of EVK are not necessary for a high-degree of PLF. This is reflected in the mediation model B where the total effect, has been partitioned into “direct” (path c’) and “indirect” (paths a and b, or ab) effects. Path c’ is the difference between the total effect of EVK and the indirect effect through PLF, which is the product of a and b. Partial mediation is inferred when a reduction in the magnitude of c to c’ has occurred; or equivalently, an indirect effect ab is significantly different from zero.
Grand averages, topographical distributions and group-differencesA) Time-domain group-averaged voltage waveforms at the parietal site for attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), adult antisocial behavior (AAB), nicotine dependence (NicD), alcohol dependence (AlcD), illicit substance dependence (DrgD), and externalizing diagnosis-free controls (Con). The adjacent head-plot displays the topographical distribution of grand-average P3 scores for all subjects. B) Grand-average time-frequency evoked energy (phase-invariant stimulus-locked energy, EVK; in Joules, or J) transform of the time-domain voltage waveforms and topographical distributions for mean P3-corresponding delta and theta scores (windows for time-frequency scores denoted by dotted boxes). C) Grand-average phase-locking factor (the degree to which intertrial EEG phases are consistent, PLF) loadings and topographical distributions of delta and theta scores. Figures D, E, and F display group differences between externalizing (any of the above disorders)and control groups on measures displayed in A, B, and C, respectively; “cooler” colors indicate topographical regions where reductions in externalizing groups relative to controls are greatest.
Theta phase-locking partially mediates the pathway between evoked energy and externalizing predictionMediation models with parietal theta-frequency evoked energy (EVK) and phase-locking factor (PLF) as dual predictors of externalizing composites for any childhood disruptive disorder (Any-CDD), any substance use disorder (Any-SUD), and any externalizing disorder (Any-EXT). The total effect of EVK on diagnostic composites (path c) became non-significant (path c’) while the effect of PLF remained significant in models predicting Any-SUD and Any-EXT. This mediating role of EVK by PLF (i.e. the indirect path ab) was also significant for these two models, suggesting that a reduction in P3-related theta phase-locking partially explains the total effect of reduced theta energy on externalizing diagnoses. ***p < .001, **p < .01, *p < .05 for path coefficients.
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