Neural oscillations serving abstract reasoning are differentially associated with inflammatory markers in people with...

Despite living a normal lifespan, people with HIV (PWH) are at a much greater risk of developing cognitive impairment. While the precise mechanisms are not fully understood, persistently high inflammation levels are thought to be a key contributor, as multiple studies have linked cognitive impairment and elevated inflammation. In contrast, evidence of a relationship between neural function and inflammatory activity is extremely limited in PWH and/or controls. Thus, in the current study, we integrate state-of-the-art dynamic functional brain mapping with measures of three inflammatory markers that have been widely reported as elevated in PWH.

A total of 142 participants (range: 20-66 years old; 64 PWH and 78 controls) completed a validated abstract reasoning task during magnetoencephalographic (MEG) imaging, underwent comprehensive neuropsychological testing, and provided a blood sample for plasma-based inflammatory marker analysis of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interferon γ-induced protein 10 (IP-10). The two groups were matched on age, sex, race/ethnicity, body-mass index (BMI), handedness, anxiety, substance use, and common medical conditions such as diabetes. Oscillatory neural responses supporting abstract reasoning were imaged by applying a beamformer to the processed MEG data, and whole-brain, voxel-wise analyses were conducted using each individual's CRP, TNF-α and IP-10 concentrations, controlling for age and BMI, to identify the differential impact of inflammation on oscillatory neural dynamics in PWH.

PWH exhibited significantly higher levels on each of the three inflammatory markers and performed more poorly on the abstract reasoning task than matched controls, with CRP levels being significantly related to performance across all participants. Critically, TNF-α levels were significantly related to the strength of theta oscillations during abstract reasoning in the left inferior frontal gyrus, with higher TNF-α scaling with weaker theta and the strength of this relationship differing by group. A similar relationship among increasing CRP levels and decreasing gamma oscillations was found in the left inferior parietal cortices, while increasing CRP was also associated with decreasing gamma in the right dorsolateral prefrontal cortex across both groups, with the latter being coupled to behavioral performance in controls.

These findings provide the first evidence linking elevated inflammatory levels to altered brain dynamics and performance in PWH. Such data provides crucial empirical evidence supporting the long-held view that elevated inflammation may be central to the higher rates of cognitive decline in PWH. Future work should examine whether decreasing these inflammatory levels leads to improvements in cognitive function in PWH.