COGNITIVE IMPAIRMENT IN LONG COVID: NEUROBIOLOGICAL INSIGHTS FROM RESTING-STATE FMRI IN A LARGE-SCALE COHORT

Introduction: Cognitive impairment (CI) is a common and debilitating consequence of COVID-19 and may persist for more than one year following the acute infection. Previous neuroimaging studies in COVID-19 survivors with CI have reported widespread alterations in functional connectivity (FC), particularly within fronto-parietal circuits and subcortical regions, including the hippocampus, basal ganglia, and thalamus. This study investigates the neural correlates of CI in individuals who recovered from COVID-19 and examines the relationship between FC patterns and specific cognitive domains.
Methods: Resting-state functional MRI data from 136 participants were analyzed using a ROI-to-ROI approach across 246 brain regions defined by the Human Brainnetome Atlas. Group comparisons were conducted based on the presence or absence of CI, and correlation analyses assessed associations between FC and scores from a comprehensive neuropsychological test battery.
Results: Whole-brain FC did not differ between participants with and without CI. Across the entire cohort, hypoconnectivity between two basal ganglia regions and two frontal motor regions was associated with poorer performance in the cognitive domain “Reasoning and Problem-Solving”, whereas hyperconnectivity between the prefrontal thalamus and the postcentral gyrus was also linked to impairments in the same domain.
Conclusions: These findings suggest that FC alterations within cortico-striatal and thalamo-cortical circuits may underlie deficits in higher-order executive functions in post-COVID-19 patients and underscore the importance of evaluating discrete cognitive domains in relation to brain connectivity.