Prefrontal gating of sensory input differentiates cognitively impaired and unimpaired aging adults with HIV

Abstract

Despite effective therapies that have extended the life expectancy of persons living with HIV, 35-70% of these adults still develop some form of cognitive impairment, and with a growing population of aging adults with HIV, the prevalence of these cognitive deficits is likely to increase. The mechanisms underlying these HIV-associated neurocognitive disorders remain poorly understood but are often accelerated by the aging process and accompanied by disturbances in sensory processing, which may contribute to the observed cognitive decline. The goal of the current study was to identify the impact of aging on HIV-related alterations in inhibitory processing and determine whether such alterations are related to cognitive impairment in neuroHIV. We used magnetoencephalographic imaging, advanced time series analysis methods, and a paired-pulse stimulation paradigm to interrogate inhibitory processing in 87 HIV-infected aging adults and 92 demographically matched uninfected controls (22-72 years old). Whole-brain maps linking age and neural indices were computed for each group and compared via Fisher's Z transformations. Peak voxel time-series data were also extracted from the resulting images to quantify the dynamics of spontaneous neural activity preceding stimulation onset in each group. Whole-brain analyses using the somatosensory gating index, a metric of inhibitory processing and age distinguished impaired adults with HIV from unimpaired HIV-infected adults and controls. Briefly, younger cognitively impaired adults with HIV strongly utilized the prefrontal cortices to gate somatosensory input, and the role of this region in gating was uniquely and significantly modulated by aging only in impaired adults with HIV. Spontaneous neural activity preceding stimulus onset was also significantly elevated in the prefrontal cortices of those with HIV-associated neurocognitive disorder, and this elevation was significantly related to the CD4 nadir across both HIV-infected groups. This is the first study to examine the impact of aging on inhibitory processing in HIV-infected adults with and without cognitive impairment. Our findings suggest that young adults with HIV-associated neurocognitive disorder utilize the prefrontal cortices to gate (i.e. suppress) redundant somatosensory input, and that this capacity uniquely diminishes with advancing age in impaired adults with HIV.