Epigenetic aging is associated with aberrant neural oscillatory dynamics serving visuospatial processing in people with HIV

Abstract

Background: Despite effective antiretroviral therapy, cognitive impairment and other aging-related comorbidities are more prevalent in people with HIV (PWH) than in the general population. Previous research examining DNA methylation has shown PWH exhibit accelerated biological aging. However, it is unclear how accelerated biological aging may affect neural oscillatory activity in virally suppressed PWH, and more broadly how such aberrant neural activity may impact neuropsychological performance. Methods: In the present study, participants (n = 134) between the ages of 23 -72 years underwent a neuropsychological assessment, a blood draw to determine biological age via DNA methylation, and a visuospatial processing task during magnetoencephalography (MEG). Our analyses focused on the relationship between biological age and oscillatory theta (4-8 Hz) and alpha (10 -16 Hz) activity among PWH (n=65) and seronegative controls (n = 69). Results: PWH had significantly elevated biological age when controlling for chronological age relative to controls. Biological age was differentially associated with theta oscillations in the left posterior cingulate cortex (PCC) and with alpha oscillations in the right medial prefrontal cortex (mPFC) among PWH and seronegative controls. Stronger alpha oscillations in the mPFC were associated with lower CD4 nadir and lower current CD4 counts, suggesting such responses were compensatory. Participants who were on combination antiretroviral therapy for longer had weaker theta oscillations in the PCC. Conclusions: These findings support the concept of interactions between biological aging and HIV status on the neural oscillatory dynamics serving visuospatial processing. Future work should elucidate the long-term trajectory and impact of accelerated aging on neural oscillatory dynamics in PWH.

Oscillatory markers of neuroHIV-related cognitive impairment and Alzheimer’s disease during attentional interference processing

“…Further, aberrations in theta activity have also been linked to tau accumulation [46] in ADS cases, which is known to follow major amyloid accumulation. Although the cause of neural and cognitive deficits in HAND is uncertain, persistent neuroinflammation, mitochondrial dysfunction, and accelerated aging are all thought to play a major role [47][48][49][50][51][52][53], which separately or together may lead to altered theta oscillatory dynamics in attention circuitry. Regardless, our results suggest that theta oscillations are differentially affected across a network of brain regions in ADS compared to HAND, with the latter group exhibiting sharply decreased theta neural interference effects.…”

“…However, the neurobiological origins of these deficits may differ between those with HAND and ADS, as only ADS pathology has been linked to amyloid deposition whereas as HAND has been attributed to a family of interconnected causes (e.g., inflammation, mitochondrial redox environment, etc.) [6,8,[47][48][49][50][51][52][53].…”

Movement-related beta and gamma oscillations indicate parallels and disparities between Alzheimer's disease and HIV-associated neurocognitive disorder

“…Interestingly, disease-specific alterations in interference activity scaled with disease-specific metrics. In particular, those with HAND exhibited stronger beta interference effects in the left precentral cortex with lower CD4 nadir counts, which may reflect that those with the most severe legacy effects and/or weaker immune systems may utilize more compensatory mechanisms to overcome interference serving motor control ( Schantell et al, 2022b ). Further, those who have been on cART the longest had stronger gamma interference effects in the right pre-SMA, which may reflect the legacy effects of earlier antiretroviral treatment, which had more severe side effects, or the cumulative effects of cART exposure ( Schantell et al, 2022b ).…”

“…In particular, those with HAND exhibited stronger beta interference effects in the left precentral cortex with lower CD4 nadir counts, which may reflect that those with the most severe legacy effects and/or weaker immune systems may utilize more compensatory mechanisms to overcome interference serving motor control ( Schantell et al, 2022b ). Further, those who have been on cART the longest had stronger gamma interference effects in the right pre-SMA, which may reflect the legacy effects of earlier antiretroviral treatment, which had more severe side effects, or the cumulative effects of cART exposure ( Schantell et al, 2022b ). Among those on the ADS, poorer sleep quality was associated with stronger beta interference effects in the right superior temporal cortex during the planning period, along with weaker beta interference effects in the left prefrontal cortex during the movement execution period.…”

Stress and Psychosocial Distress Scale with Blunted Oscillatory Dynamics Serving Abstract Reasoning

“…Whole-Brain Statistics. To probe whole-brain associations between neural oscillatory power serving abstract reasoning and psychosocial distress, we computed voxel-wise correlations between psychosocial distress and spectrally specific maps of neural oscillatory activity [27,[48][49][50]. Pseudo-t values were extracted from the peak voxel of each significant cluster in the resulting maps (i.e., the voxel with the highest statistical value per cluster) in each participant.…”