Neural correlates of maintenance working memory, as well as relevant structural qualities, are associated with earlier antiretroviral treatment initiation in vertically transmitted HIV.

There is evidence of HIV affecting cognitive functioning across age groups, with adult studies showing related deficits in frontostriatal and hippocampal regional activity. Additionally, delayed initiation of antiretroviral treatment (ART) has been associated with poorer cognitive outcomes in HIV-infected youth. Little is known, however, of the neural correlates underlying such cognitive deficits in youth populations. We investigated maintenance working memory-related brain activity in South African HIV-infected youth and controls, and the effect of ART initiation age on underlying structures. Sixty-four perinatally infected youth (ages 9-12) and 20 controls (ages 9-13) underwent functional magnetic resonance imaging (fMRI) while completing 1-back and 0-back blocks of the N-back task. At an uncorrected p value threshold of 0.001, the HIV-infected group showed decreased activation in the left superior temporal gyrus, pre- and postcentral gyri, insula, and putamen as well as bilateral hippocampus, and mid cingulum. The HIV patients with delayed ART initiation showed less activation during processing conditions in the mid cingulum; left inferior parietal gyrus; and right inferior frontal, bilateral thalamic, and superior temporal regions. When these regions were tested for structural differences, the mid cingulum and right inferior frontal gyrus, insula, and thalamus were found to have less cortical thickness, surface area, or volume in the group with delayed ART initiation. Regional differences between HIV-infected youth and controls noted in the N-back task are consistent with impairments in structures involved in maintenance working memory. These data support earlier ART initiation in perinatally infected individuals

Tracking Real-Time Changes in Working Memory Updating and Gating with the Event-Based Eye-Blink Rate

Effective working memory (WM) functioning depends on the gating process that regulates the balance between maintenance and updating of WM. The present study used the event-based eye-blink rate (ebEBR), which presumably reflects phasic striatal dopamine activity, to examine how the cognitive processes of gating and updating separately facilitate flexible updating of WM contents and the potential involvement of dopamine in these processes. Real-time changes in eye blinks were tracked during performance on the reference-back task, in which demands on these two processes were independently manipulated. In all three experiments, trials that required WM updating and trials that required gate switching were both associated with increased ebEBR. These results may support the prefrontal cortex basal ganglia WM model (PBWM) by linking updating and gating to striatal dopaminergic activity. In Experiment 3, the ebEBR was used to determine what triggers gate switching. We found that switching to an updating mode (gate opening) was more stimulus driven and retroactive than switching to a maintenance mode, which was more context driven. Together, these findings show that the ebEBR - an inexpensive, non-invasive, easy-to-use measure - can be used to track changes in WM demands during task performance and, hence, possibly striatal dopamine activity

Tracking Real-Time Changes in Working Memory Updating and Gating with the Event-Based Eye-Blink Rate

Effective working memory (WM) functioning depends on the gating process that regulates the balance between maintenance and updating of WM. The present study used the event-based eye-blink rate (ebEBR), which presumably reflects phasic striatal dopamine activity, to examine how the cognitive processes of gating and updating separately facilitate flexible updating of WM contents and the potential involvement of dopamine in these processes. Real-time changes in eye blinks were tracked during performance on the reference-back task, in which demands on these two processes were independently manipulated. In all three experiments, trials that required WM updating and trials that required gate switching were both associated with increased ebEBR. These results may support the prefrontal cortex basal ganglia WM model (PBWM) by linking updating and gating to striatal dopaminergic activity. In Experiment 3, the ebEBR was used to determine what triggers gate switching. We found that switching to an updating mode (gate opening) was more stimulus driven and retroactive than switching to a maintenance mode, which was more context driven. Together, these findings show that the ebEBR - an inexpensive, non-invasive, easy-to-use measure - can be used to track changes in WM demands during task performance and, hence, possibly striatal dopamine activity