No abstract

One of the hallmarks of anxiety disorders is impaired cognitive control, affecting working memory (WM). The dorsolateral prefrontal cortex (dlPFC) is critical for WM, however it is still unclear how dlPFC activity relates to WM impairments in patients. Forty-one healthy volunteers and 32 anxiety (general and/or social anxiety disorder) patients completed the Sternberg WM paradigm during safety and unpredictable shock threat. On each trial a series of letters was presented, followed by brief retention and response intervals. On low and high load trials, subjects retained the series (5 and 8 letters, respectively) in the original order, while on sort trials subjects rearranged the series (5 letters) in alphabetical order. We sampled BOLD activity during retention using a bilateral anatomical dlPFC mask. Compared to controls, patients showed increased reaction time during high load, greater right dlPFC activity, and reduced dlPFC activity during threat. These results suggest that WM performance for patients and controls may rely on distinct patterns of dlPFC activity with patients requiring bilateral dlPFC activity. These results are consistent with reduced efficiency of WM in anxiety patients. This reduced efficiency may be due to an inefficient allocation of dlPFC resources across hemispheres or a decreased overall dlPFC capacity.

Background For individuals with Alcohol Use Disorder (AUD), long‐term recovery is difficult in part due to symptoms of anxiety that occur during early abstinence and can trigger relapse. Research in rodent models of AUD has identified the bed nucleus of the stria terminalis (BNST), a small, sexually dimorphic, subcortical region, as critical for regulating anxiety‐like behaviors during abstinence, particularly in female mice. Furthermore, prolonged alcohol use and subsequent abstinence alter BNST afferent and efferent connections to other brain regions. To our knowledge, however, no studies of early abstinence have investigated BNST structural connectivity in humans during abstinence; this study addresses that gap. Methods Nineteen participants with AUD currently in early abstinence and 20 healthy controls completed a diffusion tensor imaging (DTI) scan. BNST structural connectivity was evaluated using probabilistic tractography. A linear mixed model was used to test between‐groups differences in BNST network connectivity. Exploratory analyses were conducted to test for correlations between BNST connectivity and alcohol use severity and anxiety within the abstinence group. Sex was included as a factor for all analyses. Results The BNST showed stronger structural connectivity with the BNST network in early abstinence women than in control women, which was not seen in men. Women also showed region‐specific differences, with stronger BNST‐hypothalamus structural connectivity but weaker vmPFC‐BNST structural connectivity than men. Exploratory analyses also demonstrated a relationship between alcohol use severity and vmPFC‐BNST structural connectivity that was moderated by sex. Conclusions This study is the first to demonstrate BNST structural connectivity differences in early abstinence and revealed key sex differences. The sex‐specific differences in BNST structural connectivity during early abstinence could underlie known sex differences in abstinence symptoms and relapse risk and help to inform potential sex‐specific treatments.