The age-related trajectory of visual attention neural function is altered in adults living with HIV: A cross-sectional MEG study

Abstract

Background Despite living a normal lifespan, at least 35% of persons with HIV (PWH) in resource-rich countries develop HIV-associated neurocognitive disorder (HAND). This high prevalence of cognitive decline may reflect accelerated ageing in PWH, but the evidence supporting an altered ageing phenotype in PWH has been mixed. Methods We examined the impact of ageing on the orienting of visual attention in PWH using dynamic functional mapping with magnetoencephalography (MEG) in 173 participants age 22–72 years-old (94 uninfected controls, 51 cognitively-unimpaired PWH, and 28 with HAND). All MEG data were imaged using a state-of-the-art beamforming approach and neural oscillatory responses during attentional orienting were examined for ageing, HIV, and cognitive status effects. Findings All participants responded slower during trials that required attentional reorienting. Our functional mapping results revealed HIV-by-age interactions in left prefrontal theta activity, alpha oscillations in the left parietal, right cuneus, and right frontal eye-fields, and left dorsolateral prefrontal beta activity ( p <.005). Critically, within PWH, we observed a cognitive status-by-age interaction, which revealed that ageing impacted the oscillatory gamma activity serving attentional reorienting differently in cognitively-normal PWH relative to those with HAND in the left temporoparietal, inferior frontal gyrus, and right prefrontal cortices ( p <.005). Interpretation This study provides key evidence supporting altered ageing trajectories across vital attention circuitry in PWH, and further suggests that those with HAND exhibit unique age-related changes in the oscillatory dynamics serving attention function. Additionally, our neural findings suggest that age-related changes in PWH may serve a compensatory function. Funding National Institutes of Health, USA.

Three-year reliability of MEG resting-state oscillatory power

“…The test-retest reliability of oscillatory activity in pediatric populations may be very different, and it is widely known that such frequency-specific activity does change with development ( Fung et al, 2020 ; Heinrichs-Graham et al, 2020 ; Taylor et al, 2021 ; Uhlhaas et al, 2010 ; Whitford et al, 2007 ). Our sample also did not extend into older adult-hood, where either normative or pathologic aging may significantly alter the stability of these measurements ( Arif et al, 2020 ; Heinrichs-Graham et al, 2018 ; Spooner et al, 2019 ; Wiesman and Wilson, 2019 ). Additionally, long-term stability of activity may not generalize to clinical populations.…”

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

“…This testing was conducted across all participants and the entire frequency range (4 -100 Hz) and used an initial cluster threshold of p < 0.001 and 10,000 permutations. These methods are described in depth in our recent publications [11][12][13]65]. The resulting timefrequency clusters that survived permutation testing were selected for source imaging analyses.…”

“…To our knowledge, no study to date has directly linked accelerated biological aging in PWH to the neurofunctional changes that occur in cognitively impaired PWH, which include deficits in visuospatial processing, attention, working memory, and motor function networks [10][11][12][13][14][15][16][17][18][19]. This paucity of work linking biological aging and functional brain activity persists despite a growing body of research showing chronological age-and disease-specific alterations to these functional networks in PWH.…”

Neural dynamics of attention in HIV: A cognitive aging phenotype?

“…Focusing on specific cognitive systems, such as the attentional systems, may facilitate our understanding of the mechanisms leading to dysfunction and provide more narrowly defined treatment targets. In this issue of EBioMedicine, Arif and colleagues [1] aimed to identify the neural factors contributing to attention deficits in 79 PWH (28 with HAND) compared to 94 HIV-uninfected individuals. The clinical significance of a focus on attention is high, as deficits in this cognitive domain are central to cognitive aging in PWH [2] and can affect the ability to perform daily tasks such as poor HIV medication adherence [3].…”

“…However, the brain mechanisms underlying attention-deficits in PWH remain poorly defined. Arif et al [1] found that age differentially modulates the oscillatory dynamics underlying the attentional orienting processes in PWH and controls. They also reported an age-related increase in gamma oscillations in HAND vs. unimpaired PWH within three primary Ventral Attention Network nodes and attributed these findings to age-related compensation.…”