Multivariate patterns of brain functional connectome associated with COVID-19-related negative affect symptoms

Severe mental health problems with the representation of negative affect symptoms (NAS) have been increasingly reported during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore the multivariate patterns of brain functional connectome predicting COVID-19-related NAS. This cohort study encompassed a group of university students to undergo neuroimaging scans before the pandemic, and we re-contacted participants for 1-year follow-up COVID-related NAS evaluations during the pandemic. Regularized canonical correlation analysis was used to identify connectome-based dimensions of NAS to compute pairs of canonical variates. The predictive ability of identified functional connectome to NAS dimensional scores was examined with a nested cross-validation. Two dimensions (i.e. mode stress and mode anxiety) were related to distinct patterns of brain functional connectome (r² = 0.911, P_FDR = 0.048; r² = 0.901, P_FDR = 0.037, respectively). Mode anxiety was characterized by high loadings in connectivity between affective network (AFN) and visual network (VN), while connectivity of the default mode network with dorsal attention network (DAN) were remarkably prominent in mode stress. Connectivity patterns within the DAN and between DAN and VN, ventral attention network, and AFN was common for both dimensions. The identified functional connectome can reliably predict mode stress (r = 0.37, MAE = 5.1, p < 0.001) and mode anxiety (r = 0.28, MAE = 5.4, p = 0.005) in the cross-validation. Our findings provide new insight into multivariate dimensions of COVID-related NAS, which may have implications for developing network-based biomarkers in psychological interventions for vulnerable individuals in the pandemic.