Parietal Default Mode Network Connectivity is Associated with Tobacco Use in Psychosis

Abnormal default mode network (DMN) connectivity was observed in both tobacco use and psychotic spectrum disorders, but it remains unknown how psychosis impacts the relationship between connectivity and tobacco use. Interventions targeting the left lateral parietal DMN node (LLP _DMN ) have modulated DMN connectivity and nicotine craving in psychosis. We aimed to investigate relationships between DMN connectivity, psychotic illness, and tobacco use.

336 participants (psychosis: n=161, control: n=175) reported their tobacco use history and underwent resting-state functional magnetic resonance imaging. We calculated connectivity within DMN and salience network (SN), between DMN-SN, and from LLP _DMN to other DMN and SN nodes. Logistic and LASSO regression with bootstrapping were performed to investigate diagnosis-by-connectivity interactions on lifetime tobacco use. Exploratory brainwide analysis was conducted by regressing brainwide connectivity to LLP _DMN against daily cigarette use.

We observed a significant diagnosis-by-DMN connectivity interaction for lifetime tobacco use (p=0.0281, coefficient=0.457, OR=1.579, 95% CI=[1.063, 2.411]); in the psychosis group, higher DMN connectivity was associated with higher odds of lifetime tobacco use. LASSO regression yielded four predictors of lifetime tobacco use: age, diagnosis, LLP _DMN connectivity to a prefrontal SN node, and the interaction between diagnosis and LLP _DMN connectivity to a right parietal DMN node. Brainwide analysis identified bilateral somatomotor clusters where higher connectivity to LLP _DMN correlated with higher daily cigarette use (voxel-wise p<0.001, cluster p<0.05).

Psychosis diagnosis modified relationship between DMN connectivity and tobacco use. Modulating DMN connectivity may provide a psychosis-specific treatment target for tobacco dependence.