Dynamic network dysfunction in cocaine dependence: Graph theoretical metrics and stop signal reaction time

Graphic theoretical metrics have become increasingly popular in characterizing functional connectivity of neural networks and how network connectivity is compromised in neuropsychiatric illnesses. Here, we add to this literature by describing dynamic network connectivities of 78 cocaine dependent (CD) and 85 non-drug using healthy control (HC) participants who underwent fMRI during performance of a stop signal task (SST). Compared to HC, CD showed prolonged stop signal reaction time (SSRT), consistent with deficits in response inhibition. In graph theoretical analysis of dynamic functional connectivity, we examined temporal flexibility and spatiotemporal diversity of 14 networks covering the whole brain. Temporal flexibility quantifies how frequently a brain region interacts with regions of other communities across time, with high temporal flexibility indicating that a region interacts predominantly with regions outside its own community. Spatiotemporal diversity quantifies how uniformly a brain region interacts with regions in other communities over time, with high spatiotemporal diversity indicating that the interactions are more evenly distributed across communities. Compared to HC, CD exhibited decreased temporal flexibility and increased spatiotemporal diversity in the great majority of neural networks. The graph metric measures of the default mode network negatively correlated with SSRT in CD but not HC. The findings are consistent with diminished temporal flexibility and a compensatory increase in spatiotemporal diversity, in association with impairment of a critical executive function, in cocaine addiction. More broadly, the findings suggest that graph theoretical metrics provide new insights for connectivity analyses to elucidate network dysfunction that may elude conventional measures.