Neural response to working memory demand predicts neurocognitive deficits in HIV.

Human immunodeficiency virus (HIV) continues to have adverse effects on cognition and the brain in many infected people, despite a reduced incidence of HIV-associated dementia with combined antiretroviral therapy (cART). Working memory is often affected, along with attention, executive control, and cognitive processing speed. Verbal working memory (VWM) requires the interaction of each of the cognitive component processes along with a phonological loop for verbal repetition and rehearsal. HIV-related functional brain response abnormalities during VWM are evident in functional MRI (fMRI), though the neural substrate underlying these neurocognitive deficits is not well understood. The current study addressed this by comparing 24 HIV+ to 27 demographically matched HIV-seronegative (HIV-) adults with respect to fMRI activation on a VWM paradigm (n-back) relative to performance on two standardized tests of executive control, attention and processing speed (Stroop and Trail Making A-B). As expected, the HIV+ group had deficits on these neurocognitive tests compared to HIV- controls, and also differed in neural response on fMRI relative to neuropsychological performance. Reduced activation in VWM task-related brain regions on the 2-back was associated with Stroop interference deficits in HIV+ but not with either Trail Making A or B performance. Activation of the posterior cingulate cortex (PCC) of the default mode network during rest was associated with Hopkins Verbal Learning Test-2 (HVLT-2) learning in HIV+. These effects were not observed in the HIV- controls. Reduced dynamic range of neural response was also evident in HIV+ adults when activation on the 2-back condition was compared to the extent of activation of the default mode network during periods of rest. Neural dynamic range was associated with both Stroop and HVLT-2 performance. These findings provide evidence that HIV-associated alterations in neural activation induced by VWM demands and during rest differentially predict executive-attention and verbal learning deficits. That the Stroop, but not Trail Making was associated with VWM activation suggests that attentional regulation difficulties in suppressing interference and/or conflict regulation are a component of working memory deficits in HIV+ adults. Alterations in neural dynamic range may be a useful index of the impact of HIV on functional brain response and as a fMRI metric in predicting cognitive outcomes.

Test-retest reliability of high angular resolution diffusion imaging acquisition within medial temporal lobe connections assessed via tract based spatial statistics, probabilistic tractography and a novel graph theory metric.

This study examined the reliability of high angular resolution diffusion tensor imaging (HARDI) data collected on a single individual across several sessions using the same scanner. HARDI data was acquired for one healthy adult male at the same time of day on ten separate days across a one-month period. Environmental factors (e.g. temperature) were controlled across scanning sessions. Tract Based Spatial Statistics (TBSS) was used to assess session-to-session variability in measures of diffusion, fractional anisotropy (FA) and mean diffusivity (MD). To address reliability within specific structures of the medial temporal lobe (MTL; the focus of an ongoing investigation), probabilistic tractography segmented the Entorhinal cortex (ERc) based on connections with Hippocampus (HC), Perirhinal (PRc) and Parahippocampal (PHc) cortices. Streamline tractography generated edge weight (EW) metrics for the aforementioned ERc connections and, as comparison regions, connections between left and right rostral and caudal anterior cingulate cortex (ACC). Coefficients of variation (CoV) were derived for the surface area and volumes of these ERc connectivity-defined regions (CDR) and for EW across all ten scans, expecting that scan-to-scan reliability would yield low CoVs. TBSS revealed no significant variation in FA or MD across scanning sessions. Probabilistic tractography successfully reproduced histologically-verified adjacent medial temporal lobe circuits. Tractography-derived metrics displayed larger ranges of scanner-to-scanner variability. Connections involving HC displayed greater variability than metrics of connection between other investigated regions. By confirming the test retest reliability of HARDI data acquisition, support for the validity of significant results derived from diffusion data can be obtained.