Gender-Specific Interactions in a Visual Object Recognition Task in Persons with Opioid Use Disorder

Abstract

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.

Keywords: alpha and beta brain oscillations; electroencephalogram (EEG); event-related potentials (ERP); gender-specific differences; opioid use disorder (OUD); substance use disorder (SUD); visual attention; visual cognitive processing; visual evoked potential (VEP).

Figure 1

Gender-specific differences in event-related potentials in a visual object recognition task. Insets show the Standard, Irrelevant, and Relevant stimuli (50 ms) that were randomly presented at 2–4 s intervals over 10 min. Participants responded to the Relevant oddball open diamond “pop out” stimuli. (A,B) Each graph depicts superimposed grand-average visual event potentials (VEPs; N50, P100, N100, P200, N200, and P300) in response to Standard, Irrelevant, and Relevant stimuli during the Go/No-Go visual object recognition tasks. VEPs were recorded at electrode Pz in males (A) and females (B). Time of stimulus presentation is noted by dashed lines. Average Go Response reaction time (RT) is also noted by arrows. Of particular note is the stimulus-specific difference in P300 ERPs for the Relevant condition (vs. Irrelevant and Standard) in both men and women. The 128 sensor topo maps (colored circles) represent grand-averaged potentials obtained from across the head for all men compared to all women participants at 349 ms (P300) after the presentation of the stimuli. These maps are oriented as if looking down on the head from above (top of circle = front of head, bottom of circle = back of head). Extreme negative potentials are depicted in violet, and extreme positive potentials are shown in red. Again, note the differentiation across stimuli conditions of the P300 ERPs associated with the Relevant stimulus in both men and women on the topo maps and their prominence in the back of the head for the men but not for women. (C,D) These composite plots give a summary of descriptive statistics for ERP amplitude and latency measurements taken at location Pz for Relevant stimuli only across back of the head electrodes. They show the data points for each of the 38 participants by gender and ERP component. Male non-OUD subjects were characterized by significantly larger N200 and P300 amplitudes and shorter latencies than female non-OUD subjects. Note ** p < 0.001; *** p < 0.0001.

Figure 2

Effects of opioid use disorder on event-related potentials in a visual object recognition task. (A) Grand averaged visual event potentials (VEPs) obtained at Pz in men and women non-OUD controls vs. men and women with OUD for the Relevant stimulus. Compared to controls, those with OUD were characterized by smaller P300s on the grand-averaged waveform. (B) This graph summarizes ERP amplitude measurements in men and women and those with OUD. Scatter plots represent all the values in each group. Men had significantly greater N200 and P300 amplitudes compared to women regardless of OUD. However, there was a significant decrease in P300 ERP amplitudes for women with OUD. (C) This graph summarizes ERP latency measurements in men and women and those with OUD. Men had significantly shorter N200 and P300 latencies compared to women. Most interestingly, those with OUD had significantly longer N200 and P300 latencies in men, but shorter latencies in women. (D,E) In order to better demonstrate this double dissociation, standardized values for all participants by latency vs. amplitude are plotted in vectors to show the differential contrast between OUD and gender for N200 (D) and P300 (E).Note * p < 0.05; ** p < 0.001; *** p < 0.0001.

Figure 3

Gender differences in alpha and beta oscillations in a visual object recognition task. (A) This is a representative 2 s trace of raw electroencephalogram (EEG) data obtained in one non-OUD male participant at Pz for a Relevant stimulus. Note the feedback oscillations that occurred at around 1200 ms after the stimulus, when the feedback message was delivered to the subject. (B) Raw EEG data from a Relevant stimulus epoch in the same subject in (A) for all electrodes on the head. Top is front and bottom is back of the head. Note the oscillations that appeared during the feedback stimulus all around the head, but most evident at the back of the head. (C) Raw EEG epoch from one back of the head electrodes in (B) showing the robust oscillations during the feedback message as a Raster color plot of individual traces obtained for each of the 154 stimuli presented in one session for this representative participant. Red represents high positive amplitudes and violet represents low. Note that the oscillations are present for most of the epochs. (D) Wavelet analysis of a Relevant stimulus epoch from the same electrode shown in (C). Red indicates positive power while violet indicates negative. Note that in this subject there is robust theta, alpha, and beta power during the feedback stimulus. (E) This graph shows wavelet analysis of the average power for 4 bands during the feedback Relevant stimulus in this subject. Note that the feedback oscillation is dominated by alpha and beta activity. (F) Superimposed grand-averaged wavelets of alpha (8–13 Hz; above) and beta (13–30 Hz; below) activity in males vs. females for the Relevant stimuli. Note that alpha and beta activity is high around 1200 ms after the stimulus, which reflects the raw waveforms and wavelet analysis in (B–D). The dashed-line box indicates the window during the feedback stimulus which was used for determination of alpha and beta power. (G) This graph shows alpha and beta power (trapezoidal integration of area in dashed boxes shown in (C,D) over the epoch) for all men compared to all women for the Relevant stimulus condition across back of the head electrodes. Note that both alpha and beta power are significantly higher in men overall than for women Note * p < 0.05.

Figure 4

Effects of opioid use disorder (OUD) on alpha and beta oscillations in a visual object recognition task. (A) Superimposed grand-averaged alpha and beta (B) power determined with wavelet analysis comparing men vs. women and OUD vs. non-OUD participants. There appears to be a tendency for men’s waveforms to be greater than those for women during the feedback stimulus shown during the dashed-lined box corresponding to the feedback stimulus. (C) This graph shows alpha and beta power measurements for all men compared to all women and OUD vs. non-OUD. Although the trend was for OUD male and female subjects to have lower have lower alpha power, it was not significant. However, beta power was significantly lower in men and women participants with OUD vs. non-OUD controls. Note * p < 0.05.