Elevated inflammation in people with HIV is associated with aberrant neural oscillations serving selective attention

Modern medicine has greatly extended the lifespan of people with HIV (PWH), but the risk of cognitive decline remains sharply elevated. Such impairments have been linked to aberrant neural oscillations across multiple brain regions, particularly attention-related cortices, with persistently high inflammatory levels widely thought to be central. While a few studies have linked elevated inflammation with cognitive impairment in PWH, none have extended this link to the underlying neurophysiology. 88 PWH and 91 controls underwent dynamic functional mapping with magnetoencephalography (MEG) during an attention task, a blood draw, and neuropsychological testing. Using multiplex immunoassays, we quantified inflammatory markers implicated in CNS function (i.e., TNF-α, CRP, IP-10) and derived a neuroinflammation index. Whole-brain functional maps of neural oscillatory activity were subjected to linear mixed effect modeling to identify the relationships between inflammation and task-related oscillations that differed by group (p < .005, corrected). PWH performed more poorly than controls on the MEG selective attention task and on neuropsychological tests. PWH also had elevated neuroinflammatory index scores compared to controls, which were correlated with attentional performance. Significant condition-by-group-by-inflammation interactions in the theta (4–8 Hz) and alpha (8–14 Hz) ranges were detected across frontoparietal cortices, with greater inflammation scaling with stronger theta responses in PWH in multiple regions. Further, parietal responses were significantly correlated with clinical indices of HIV. These findings provide the first direct link between neurophysiological dysfunction and elevated inflammation in virally suppressed PWH, suggesting that interventions targeting inflammation may be highly promising in mitigating cognitive decline.