Executive function deficit in betel quid-dependence: Evidence from functional and effective connectivity of executive control network

Betel quid (BQ) ranks fourth in global self-administered psychoactive agents, after caffeine, alcohol and nicotine, with 600 million consumers. Patients with BQ dependence (BQD) disorder demonstrate deficits in executive function. However, the neural correlates of the resting-state executive control network (ECN) and BQD-related pathopsychological characteristics still remain unclear. The present study aimed to assess the functional and effective connectivity of the ECN using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-five BQD individuals and 54 healthy controls (HCs) were recruited in this study. The executive function of all participants was tested by three tasks. Independent component and Granger causal analysis were employed to investigate the functional connectivity within ECN and ECN-related directional effective connectivity, separately. Behavioural results suggested a marked deficit of executive function in BQD individuals. Compared with HCs, BQD individuals showed overall weaker functional connectivity in the ECN, mainly including dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (IPL) and middle frontal gyrus (MFG). We observed decreased outflow of information from the right DLPFC and IPL to the precentral/pre-supplement motor area (SMA) and increased outflow of information from the MFG to the middle occipital gyrus in BQD individuals. Correlation analysis revealed that the effective connectivity from IPL to precentral/pre-SMA was negatively correlated to the BQD scales in BQD individuals. Our findings revealed impaired executive function, functional connectivity of the ECN and causal interaction between networks in patients with BQD. These results could potentially direct future targets for the prevention and intervention of BQD.