Altered angular gyrus activation during the digit symbol substitution test in people living with HIV: beyond...

Speed-of-information processing (SIP) is often impaired in people living with HIV (PLWH), typically assessed through tests such as the digit symbol (DS) and symbol search, which also rely on motor and executive functions. This study aims to disentangle SIP deficits from other cognitive impairments in PLWH using an MRI-adapted digit symbol substitution test (mDSST). Fifty-seven PLWH (34.7 ± 11.2 years) and 50 age-matched people living without HIV (PLWoH, 31.8 ± 9.9 years) completed standardized neuropsychological tests and the mDSST. Behavioral performances and brain activations were compared, with correlations drawn between group-differentiating brain activations and clinical ratings of cognitive domains. Results showed that PLWH performed worse in DS and symbol search, made fewer responses, and was slower in mDSST, with performances correlating to SIP and motor ratings. Notably, PLWH showed greater deficits in attention compared to PLWoH, rather than in SIP or motor. PLWH also exhibited greater primary motor cortex activation and reduced right angular gyrus activation. These findings suggest that slower performances on SIP-related tests in PLWH may be partially linked to abnormal visuospatial attention, as reflected by reduced angular gyrus activation, with higher motor cortex activation potentially serving as a compensatory mechanism. Future studies should explore whether prefrontal regions implicated in SIP are impaired in more severely affected PLWH.