Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men reported at twice the rate for women. Using a controlled, cross-sectional, age-matched (18–56 y) design to better understand the cognitive neuroscience of OUD, we evaluated the electroencephalographic (EEG) responses of male and female participants with OUD vs. age- and gender-matched non-OUD controls during a simple visual object recognition Go/No-Go task. Overall, women had significantly slower reaction times (RTs) than men. In addition, EEG N200 and P300 event-related potential (ERP) amplitudes for non-OUD controls were significantly larger for men, while their latencies were significantly shorter than for women. However, while N200 and P300 amplitudes were not significantly affected by OUD for either men or women in this task, latencies were also affected differentially in men vs. women with OUD. Accordingly, for both N200 and P300, male OUD participants exhibited longer latencies while female OUD participants exhibited shorter ones than in non-OUD controls. Additionally, robust oscillations were found in all participants during a feedback message associated with performance in the task. Although alpha and beta power during the feedback message were significantly greater for men than women overall, both alpha and beta oscillations exhibited significantly lower power in all participants with OUD. Taken together, these findings suggest important gender by OUD differences in cognitive processing and reflection of performance in this simple visual task.

Background: Opioid use disorder (OUD) and associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men consistently reported at twice the rate for women. We have recently reported sex-specific differences in electrocortical activity in persons with OUD in a visual object recognition task. The mesolimbic dopamine (DA) system is implicated in OUD but also plays a critical role in some disorders of visual attention and a modulatory role in the processing of visual stimuli in the blue cone pathway of the retina. We hypothesized that electrocortical responses to color stimuli would be affected differentially in men and women with OUD. Methods: Using a controlled, cross-sectional, age-matched (18–56 years) design, we evaluated color processing in male and female subjects recruited from a community-based, high-intensity residential substance abuse and detoxification treatment program. We evaluated electroencephalogram (EEG) event-related potentials (ERPs) and reaction time (RT), in male and female participants with OUD (n = 38) vs. sex- and age-matched non-OUD control participants (n = 37) in a simple color recognition Go/No-Go task, as well as perceptual and behavioral responses in physiological and neuropsychological tests. Results: N200, P300, and late potential (LP) Relevant stimulus-induced ERPs were evoked by the task and were well-differentiated from Irrelevant distractor stimuli. P300 amplitudes were significantly greater and N200 and LP latencies were significantly shorter in male vs. female non-OUD controls in this task. There were significant sex differences in N200, P300, and LP amplitudes and latencies between male vs. female non-OUD subjects and OUD differences with blue color as the Relevant stimulus. In the Binocular Rivalry Test, there were shorter dwell times for perceiving a blue stimulus in male OUD subjects and there were significant sex and OUD differences in neuropsychological tests including Finger Tapping, Trails A/B, and Symbol Digit Modalities Test. Conclusions: These findings suggest that there are significant sex-related physiological, perceptual, and cognitive differences in color processing that may result from deficits in DA production in the retina that mirror deficits in mesolimbic DA transmission correlating with OUD, suggesting that blue color processing has the potential to be an effective biomarker for brain DA and for diagnosis and monitoring of treatment efficacy in substance use disorders.