Resting-state functional connectivity and cognitive impairment after COVID-19 infection: Evidence from a large-scale fMRI study

Background: The development of cognitive impairment (CI) is a frequent and debilitating consequence of COVID-19 and can persist for more than 1 year after the acute infection stage. Previous neuroimaging studies in COVID-19 survivors with CI have revealed widespread alterations in functional connectivity (FC), particularly within fronto-parietal circuits and subcortical nuclei such as the hippocampus, basal ganglia, and thalamus. This study focuses on neural correlates of CI in subjects who recovered from COVID-19 and the relationship between FC patterns and discrete cognitive domains. Methods: Resting-state functional MRI data from 136 subjects were analyzed using a ROI-to-ROI approach across 246 brain regions derived from the Human Brainnetome Atlas. Group comparisons were performed based on the presence or absence of CI, and correlation analyses were conducted between FC and scores obtained from a comprehensive neuropsychological test battery. Results: Whole-brain FC showed no difference between patients with and without CI. In the whole study sample, hypoconnectivity between two basal ganglia regions and two frontal motor regions was associated with impaired performance in the cognitive domain "Reasoning and Problem-Solving," while hyperconnectivity between the prefrontal thalamus and the postcentral gyrus was associated with impaired performance in the same cognitive domain. Conclusions: Our findings indicate that FC alterations within the cortico-striatal and thalamo-cortical circuits may subtend deficits in higher-order executive functions in post-COVID-19 patients and highlight the importance of examining discrete cognitive domains in relation to brain connectivity.