People with HIV exhibit spectrally distinct patterns of rhythmic cortical activity serving cognitive flexibility

Abstract

Despite effective antiretroviral therapy, cognitive impairment remains prevalent among people with HIV (PWH) and decrements in executive function are particularly prominent. One component of executive function is cognitive flexibility, which integrates a variety of executive functions to dynamically adapt one's behavior in response to changing contextual demands. Though substantial work has illuminated HIV-related aberrations in brain function, it remains unclear how the neural oscillatory dynamics serving cognitive flexibility are affected by HIV-related alterations in neural functioning. Herein, 149 participants (PWH: 74; seronegative controls: 75) between the ages of 29-76 years completed a perceptual feature matching task that probes cognitive flexibility during high-density magnetoencephalography (MEG). Neural responses were decomposed into the time-frequency domain and significant oscillatory responses in the theta (4-8 Hz), alpha (10-16 Hz), and gamma (74-98 Hz) spectral windows were imaged using a beamforming approach. Whole-brain voxel-wise comparisons were then conducted on these dynamic functional maps to identify HIV-related differences in the neural oscillatory dynamics supporting cognitive flexibility. Our findings indicated group differences in alpha oscillatory activity in the cingulo-opercular cortices, and differences in gamma activity were found in the cerebellum. Across all participants, alpha and gamma activity in these regions were associated with performance on the cognitive flexibility task. Further, PWH who had been treated with antiretroviral therapy for a longer duration and those with higher current CD4 counts had alpha responses that more closely resembled those of seronegative controls, suggesting that optimal clinical management of HIV infection is associated with preserved neural dynamics supporting cognitive flexibility.

Keywords: Hierarchical cognitive control; Higher-order cognition; Magnetoencephalography; Oscillations; Perceptual feature matching.

Fig. 1.. Illustration of the perceptual feature matching task.

Trials had a fixation period lasting an average of 1700 ms and a stimulus presentation period of 2700 ms, during which, a set of three images were displayed. Participants matched the top image to one of the two bottom images based on either its pattern or shape, which was dictated by whether the top image was surrounded by a diamond or square. The meaning of diamond versus square was counterbalanced within each participant group. Participants indicated their choice via button press.

Fig. 2.. Behavioral performance on the MEG perceptual feature matching task.

People with HIV (PWH) were less accurate (A) and responded slower (B) on the perceptual feature matching task compared to controls. Accuracy, expressed as the percent correct, appears on the y-axis of (A) and reaction time, in ms, is displayed on the y-axis of (B), with group on the x-axes of both panels. Violin plots show the probability density per group, with the black bars indicating the group means. (C) Reaction time (y-axis) was also significantly correlated with HIV disease duration in PWH, with longer HIV disease durations (in years, x-axis) being associated with slower reaction times, controlling for the effect of age. The gray shading surrounding the trendline represents the standard error of the mean. **p < .01, *p < .05.

Fig. 3.. Neural oscillatory responses during the perceptual feature matching task.

Grand-averaged time-frequency spectrograms of MEG sensors exhibiting one or more significant oscillatory responses. Shown from top to bottom: gamma, early and late alpha, and theta activity. In each spectrogram, frequency (Hz) is shown on the y-axis, and time (ms) is shown on the x-axis. Signal power data are expressed as a percent difference from the baseline period, with color legends shown to the right of each spectrogram.

Fig. 4.. People with HIV exhibit altered oscillatory alpha and gamma activity during performance of the MEG task.

(A) The brain image on the left represents the voxel-wise group difference in oscillatory alpha activity during the early time window, with stronger alpha responses (i.e., more negative relative to baseline) in the right prefrontal cortex (PFC) of PWH compared to controls. (B—D) Similarly, voxel-wise group differences in oscillatory alpha activity during the late window were observed in the (B) left insula, (C) left anterior cingulate cortex (ACC), and in the (D) left ventral temporal cortex, with PWH having stronger oscillatory alpha activity relative to controls in all regions. (E) Group differences in gamma oscillations were also identified in the right cerebellum, with controls exhibiting stronger responses than PWH. In each panel, the peak voxel power values were extracted from the cluster depicted in the 3D rendition and are plotted to the right in the accompanying violin plots. *p < .005.

Fig. 5.. Clinical HIV metrics are related to alpha oscillations.

(A) People with HIV (PWH) who had been treated with ART for a longer duration had weaker (i.e., less negative; more optimal) oscillatory alpha responses in the left ventral temporal cortex, above and beyond the effects of age. (B) Higher current CD4 counts in PWH were associated with weaker alpha oscillations (i.e., more optimal) in the anterior cingulate cortex (ACC). The gray shading surrounding the trendline represents the standard error of the mean. *p < .05.

Fig. 6.. Oscillatory gamma and alpha power scale with behavioral measures.

(A) Regardless of HIV status, stronger gamma oscillations in the right cerebellum were associated with faster responses during the MEG task. (B-E) In contrast, stronger (i.e., more negative) alpha responses in the (B) left anterior cingulate and (C) left ventral temporal cortex were associated with slower reaction times, and stronger alpha oscillations in the (D) left insula and (E) left ventral temporal cortex were associated with lower accuracy on the task. Note that controls exhibited weaker alpha activity compared to PWH, and thus in all cases, poorer performance was associated with the neural response patterns observed in PWH. The gray shading surrounding the trendline represents the standard error of the mean. *p < .05, **p < .01.