ObjectiveTo investigate whether aging differentially affects neural activity serving visuospatial processing in a large functional neuroimaging study of HIV-infected participants and to determine whether such aging effects are attributable to differences in the duration of HIV infection.MethodsA total of 170 participants, including 93 uninfected controls and 77 HIV-infected participants, underwent neuropsychological assessment followed by neuroimaging with magnetoencephalography (MEG). Time-frequency analysis of the MEG data followed by advanced image reconstruction of neural oscillatory activity and whole-brain statistical analyses were used to examine interactions between age, HIV infection, and cognitive status. Post hoc testing for a mediation effect of HIV infection duration on the relationship between age and neural activity was performed using a quasi-Bayesian approximation for significance testing.ResultsCognitively impaired HIV-infected participants were distinguished from unimpaired HIV-infected and control participants by their unique association between age and gamma oscillations in the parieto-occipital cortex. This relationship between age and gamma was fully mediated by the duration of HIV infection in cognitively impaired participants. Impaired HIV-infected participants were also distinguished by their atypical relationship between alpha oscillations and age in the superior parietal cortex.ConclusionsImpaired HIV-infected participants exhibited markedly different relationships between age and neural responses in the parieto-occipital cortices relative to their peers. This suggests a differential effect of chronological aging on the neural bases of visuospatial processing in a cognitively impaired subset of HIV-infected adults. Some of these relationships were fully accounted for by differences in HIV infection duration, whereas others were more readily associated with aging.

HIV infection is associated with increased age-related co-morbidities including cognitive deficits, leading to hypotheses of HIV-related premature or accelerated ageing. Impairments in selective attention and the underlying neural dynamics have been linked to HIV-associated neurocognitive disorder; however, the effect of ageing in this context is not yet understood. Thus, the current study aimed to identify the interactive effects of ageing and HIV on selective attention processing. A total of 165 participants (92 controls, 73 participants with HIV) performed a visual selective attention task while undergoing magnetoencephalography and were compared cross-sectionally. Spectrally specific oscillatory neural responses during task performance were imaged and linked with selective attention function. Reaction time on the task and regional neural activity were analysed with analysis of covariance (ANCOVA) models aimed at examining the age-by-HIV interaction term. Finally, these metrics were evaluated with respect to clinical measures such as global neuropsychological performance, duration of HIV infection and medication regimen. Reaction time analyses showed a significant HIV-by-age interaction, such that in controls older age was associated with greater susceptibility to attentional interference, while in participants with HIV, such susceptibility was uniformly high regardless of age. In regard to neural activity, theta-specific age-by-HIV interaction effects were found in the prefrontal and posterior parietal cortices. In participants with HIV, neuropsychological performance was associated with susceptibility to attentional interference, while time since HIV diagnosis was associated with parietal activity above and beyond global neuropsychological performance. Finally, current efavirenz therapy was also related to increased parietal interference activity. In conclusion, susceptibility to attentional interference in younger participants with HIV approximated that of older controls, suggesting evidence of HIV-related premature ageing. Neural activity serving attention processing indicated compensatory recruitment of posterior parietal cortex as participants with HIV infection age, which was related to the duration of HIV infection and was independent of neuropsychological performance, suggesting an altered trajectory of neural function.

Key Points Question Are DNA methylation–based metrics of biological age associated with cortical thickness, and does a biological age acceleration index capture unique changes in cortical thinning compared with chronological age measures? Findings In this cross-sectional study of 82 healthy adults, both biological and chronological age were associated with widespread cortical thinning, but biological age acceleration was also associated with additional changes in cortical morphological features. Older biological age relative to chronological age was associated with accentuated thinning within prefrontal and temporal regions. Meaning These findings suggest that DNA methylation–based biological age may yield additional insight into healthy and pathological cortical aging compared with chronological age alone.

Key points Visual attention involves discrete multispectral oscillatory responses in visual and ‘higher‐order’ prefrontal cortices. Prefrontal cortex laterality effects during visual selective attention are poorly characterized. High‐definition transcranial direct current stimulation dynamically modulated right‐lateralized fronto‐visual theta oscillations compared to those observed in left fronto‐visual pathways. Increased connectivity in right fronto‐visual networks after stimulation of the left dorsolateral prefrontal cortex resulted in faster task performance in the context of distractors. Our findings show clear laterality effects in theta oscillatory activity along prefrontal–visual cortical pathways during visual selective attention. Abstract Studies of visual attention have implicated oscillatory activity in the recognition, protection and temporal organization of attended representations in visual cortices. These studies have also shown that higher‐order regions such as the prefrontal cortex are critical to attentional processing, but far less is understood regarding prefrontal laterality differences in attention processing. To examine this, we selectively applied high‐definition transcranial direct current stimulation (HD‐tDCS) to the left or right dorsolateral prefrontal cortex (DLPFC). We predicted that HD‐tDCS of the left versus right prefrontal cortex would differentially modulate performance on a visual selective attention task, and alter the underlying oscillatory network dynamics. Our randomized crossover design included 27 healthy adults that underwent three separate sessions of HD‐tDCS (sham, left DLPFC and right DLPFC) for 20 min. Following stimulation, participants completed an attention protocol during magnetoencephalography. The resulting oscillatory dynamics were imaged using beamforming, and peak task‐related neural activity was subjected to dynamic functional connectivity analyses to evaluate the impact of stimulation site (i.e. left and right DLPFC) on neural interactions. Our results indicated that HD‐tDCS over the left DLPFC differentially modulated right fronto‐visual functional connectivity within the theta band compared to HD‐tDCS of the right DLPFC and further, specifically modulated the oscillatory response for detecting targets among an array of distractors. Importantly, these findings provide network‐specific insight into the complex oscillatory mechanisms serving visual selective attention.

Chronological age remains an imperfect measure of accumulated physiological stress. Biological measures of aging may provide key advantages, allowing scientists focusing on age-related functional changes to use metrics derived from epigenetic factors like DNA methylation (DNAm), which could provide greater precision. Here we investigated the relationship between methylation-based age and an essential cognitive function that is known to exhibit age-related decline: selective attention. We found that DNAm-age predicted selective attention abilities and fully mediated the relationship between selective attention and chronological age. Using neuroimaging with magnetoencephalography, we found that gamma activity in the anterior cingulate was robustly predicted by DNAm-derived biological age, revealing the neural dynamics underlying this DNAm age-related cognitive decline. Anterior cingulate gamma activity also significantly predicted behavior on the selective attention task, indicating its functional relevance. These findings suggest that DNAm age may be a better predictor of cognitive and brain aging than more traditional chronological metrics.