Temporal instability in brain activation: a novel paradigm for evaluating the maintenance of attention among substance dependent patients.

Abstract

Prior studies have demonstrated statistically significant but subtle differences in brain function between patients with a history of substance dependence (SD) and control groups. The goal of the present study was to show that variability in brain activation over the trials of a cognitive task is more useful for revealing the putative impact of SD than analyses focusing on the amplitude of activation averaged over trials. The study also tested the additional contribution of antisocial personality disorder (ASPD)-a prevalent comorbidity that promotes both an early onset and more severe course of SD. Two hundred eleven adults performed two selective attention tasks while P300 event-related electroencephalographic potentials were recorded. They were assigned to one of 3 mutually exclusive groups: no lifetime history of SD or ASPD (n = 67), a SD history but no ASPD (n = 68), or both SD and ASPD (n = 76). The major finding was a statistically significant elevation of P300 amplitude inter-trial variability (ITV) in the SD plus ASPD group in comparison to the group with neither attribute. The elevation was detected during both selective attention tasks and most prominent at electrodes sites located over the frontal brain. There were no group differences in P300 amplitude averaged over trials. We conclude from these findings that the ITV of P300 amplitude is an efficient and sensitive biomarker of the maintenance of attention. It is valuable for revealing group differences associated with substance dependence and ASPD. It may ultimately be valuable for detecting improvements resulting from psychostimulant treatment or other interventions, including cognitive remediation.