Temporal processsing demands in the HIV-1 transgenic rat: Amodal gating and implications for diagnostics

Despite the success of combination antiretroviral therapy (cART), approximately 50% of HIV-1 seropositive individuals develop HIV-1 associated neurocognitive disorders (HAND). Unfortunately, point-of-care screening tools for HAND lack sensitivity and specificity, especially in low-resource countries. Temporal processing deficits have emerged as a critical underlying dimension of neurocognitive impairments observed in HIV-1 and may provide a key target for the development of a novel point-of-care screening tool for HAND. Cross-modal prepulse inhibition (PPI; i.e., auditory, visual, or tactile prepulse stimuli) and gap-prepulse inhibition (gap-PPI; i.e., auditory, visual or tactile prepulse stimuli), two translational experimental paradigms, were used to assess the nature of temporal processing deficits in the HIV-1 transgenic (Tg) rat. Cross-modal PPI revealed a relative insensitivity to the manipulation of interstimulus interval (ISI) in HIV-1 Tg rats in comparison to controls, regardless of prestimulus modality. Gap-PPI revealed differential sensitivity to the manipulation of ISI, independent of modality, in HIV-1 Tg rats in comparison to control animals. Manipulation of context (i.e., concurrent visual or tactile stimulus) in auditory PPI revealed a differential sensitivity in HIV-1 Tg animals compared to controls. The potential utility of amodal temporal processing deficits as an innovative point-of-care screening tool was explored using a discriminant function analysis, which diagnosed the presence of the HIV-1 transgene with 97.4% accuracy. Thus, the presence of amodal temporal processing deficits in the HIV-1 Tg rat supports the hypothesis of a central temporal processing deficit in HIV-1 seropositive individuals, heralding an opportunity for the development of a point-of-care screening tool for HAND.