STATIC AND DYNAMIC DISRUPTIONS OF SALIENCE-NETWORK FLEXIBILITY IN VETERANS WITH COMORBID MILD TBI AND ALCOHOL USE DISORDER

Mild traumatic brain injury (mTBI) and alcohol use disorder (AUD) commonly co-occur in Veterans, a comorbidity marked by poor outcomes and resistance to standard pharmacotherapy. Both conditions disrupt the salience network (SN), which coordinates transitions between default mode network (DMN) self-referential processing and cognitive control network (CCN) top-down engagement. When this switching mechanism fails, individuals may become stuck in internally focused states that sustain rumination, imp air cognitive flexibility, and amplify craving. Characterizing how mTBI+AUD jointly alter salience-network dynamics may reveal mechanistic targets for more precise pharmacological and neuromodulatory intervention in this treatment refractory population. Here, we examine static and dynamic SN interactions in 44 Veterans (22 mTBI+AUD; 22 age-and sex-matched controls) who completed 20 minutes of resting-state fMRI (TR=555 ms) and a post -scan Penn Alcohol Craving Scale. Data were preprocessed in CONN. Static functional connectivity was quantified as time -averaged coupling between the SN-CN and SN-DMN, using six a priori internetwork pairs per hemisphere derived from the Yeo-17 atlas. SNbias was summarized using a network orientation index (θ), defined as the inverse tangent of SN– CN relative to SN–DMN connectivity across the scan. To capture transient regulatory states, we applied seed-based co-activation pattern (CAP) analysis using a right anterior insula seed (a key SN node), identifying recurring SN-linked brain states and quantifying state persistence and entry frequency. CAP spatial maps were labeled by overlap with canonical Yeo -17 networks using the Dice coefficient. Group differences and craving effects across all subjects were tested using linear mixed-effects models with subject -level random intercepts, with FDR -correction applied. Compared with controls, Veterans with mTBI+AUD exhibited DMN -dominant salience network coupling: reduced SN –CN connectivity (p=0.009), increased SN –DMN connectivity (p=0.014 ), and lower network orientation values (p=0.005), indicating DMN-SN coupling dominance. Higher alcohol craving was independently associated with this same DMN -biased profile across all participants (all p < 0.05). Dynamic CAP analysis identified four reproducible recurring states across all subjects: DMN -SN, SN -dominant, SN –CN, and visual network configurations. The mTBI+AUD group persisted significantly longer in the DMN -SN state (β=3.54s, p < 0.001) and showed fewer state transitions overall (p < 0.05). A craving -by-state interaction linked higher craving to prolonged DMN -SN state persistence (β=1.58s, p < 0.001), independent of group. Together, these preliminary findings show that Veterans with mTBI+AUD exhibit convergent static and dynamic disruptions in SN regulation, marked by a trait-like bias toward DMN-dominant connectivity and prolonged occupancy of DMN -centered brain states. The alignment of time averaged connectivity biases with reduced moment -to-moment state switc hing suggests that mTBI+AUD may amplify impairments in SN -driven regulatory flexibility. Clinically, this may help explain why craving-related thoughts become overly salient and difficult to disengage from. Because SN interactions with the DMN and CN are k nown targets of pharmacologic and neuromodulatory interventions across addiction and mood disorders, these findings nominate specific circuit-level processes for future study. In particular, SN –DMN coupling and SN-DMNstate persistence emerge as testable n eural markers that may inform precision treatment development in this high-risk, underserved comorbid Veteran population.