Project Summary and Abstract The standard paradigm for the detection of HIV-associated CNS impairment (HIVCI) involves protocols that require trained personnel, often impractical and unavailable in typical outpatient clinical settings. As a result, HIVCI is often undetected or detected late, leading to a lower quality of life and decreased survival. With the need for earlier detection and the availability of new medical billing codes, a recent push to change the paradigm towards earlier screening of cognitive impairment as a precursor to diagnostic testing is currently underway; however, severely limited in its capability and scope. Therefore, there is an urgent need to enable this new paradigm to detect HIVCI earlier in the disease course (a topic area of interest to NIMH’s Division of AIDS Research and HIV Neuropathogenesis Program): universal screening (not requiring trained staff) to reliably refer HIV+ patients to neuropsychometric (NP) diagnostic testing (by trained staff). This SBIR proposes a novel value proposition: A universal screening tool based on a known functional impairment - driving. Thus, the long-term goal of this SBIR is a new Virtual Driving and CNS Assessment System (VDCA) as a valid, low cost, easy-to-administer, universal screening system for HIV+ patients. To achieve these objectives and develop the VDCA, we will leverage (1) our commercially-successful virtual driving test (VDT) as a platform on which to develop the VDCA; (2) our team’s scientific know-how in utilizing driving to task cognitive, sensorimotor and memory systems (including those implicated in HIVCI); (3) our exclusive access to an established longitudinal cohort of HIV+ participants; and (4) novel neuroimaging methods to detect HIVCI pathogenesis. Our preliminary work using magnetoencephalography (MEG) supports the development of the VDCA as a meaningful probe of cognitive control and functional capacity that will become a universal screen for HIVCI. In this supplement, we propose one additional aim building off of the successful work conducted in parent SBIR award, before pursuing a larger Phase II project: Aim 1: Conduct a feasibility imaging study to quantify HIVCI pathogenesis in the executive network of the frontal cortex as measured by VDCA performance. These insights will provide support for the utility and feasibility of the VDCA as a universal screen and set the direction for future refinement, testing and evaluation in Phase II.