Drinking reduction during cognitive behavioral therapy for alcohol use disorder is associated with a reduction in anterior insula-bed nucleus of the stria terminalis resting-state functional connectivity

Abstract

Background: Connectivity between the anterior insula (AI) and the bed nucleus of the stria terminalis (BNST) may play a role in negative emotions that drive compulsive drinking in patients with alcohol use disorder (AUD). We hypothesized that reductions in drinking during cognitive behavioral therapy (CBT), an effective treatment that teaches regulation (coping) skills for managing negative emotions during abstinence, would be associated with reductions in resting-state functional connectivity (RSFC) between the AI and the BNST.

Methods: We included 18 patients with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition diagnosis of AUD who were (1) seeking treatment and (2) drinking heavily at baseline. We measured RSFC as Pearson's correlation between the BNST and multiple regions of interest in the insula at baseline and after completion of 12 weeks of a single-arm clinical trial of outpatient CBT. We also assessed the number of heavy drinking days over the previous 28 days (NHDD) at both time points. We used 1-sample t-tests to evaluate AI-BNST RSFC at baseline, paired t-tests to evaluate changes in AI-BNST RSFC from pre-CBT to post-CBT, and linear regression to evaluate the relationship between changes in AI-BNST RSFC and NHDD.

Results: We found a significant positive RSFC between the AI and the BNST at baseline (p = 0.0015). While there were no significant changes in AI-BNST RSFC from pre- to post-CBT at the group level (p = 0.42), we found that individual differences in reductions in AI-BNST RSFC from pre- to post-CBT were directly related to reductions in NHDD from pre- to post-CBT (r = 0.73, p = 0.0008).

Conclusions: These findings provide preliminary evidence that reduced AI-BNST RSFC may be a mechanism of drinking reduction in AUD and that AI-BNST RSFC may be a target for CBT and possibly other treatments.

Trial registration: ClinicalTrials.gov NCT02316574.

Keywords: BNST; CBT; functional connectivity; insula; negative affect.

Figure 1:

Insula regions of interest (ROIs). A: BNST ROI shown in coronal section. B. Surface map showing left cortical surface with insula ROIs shown, and also the A-P position of the coronal slice in A. C. Close-up of the left insula. D. Close-up of the right insula. AL= anterior long gyrus, PL = posterior long gyrus, PS = posterior short gyrus, MS = middle short gyrus, AS = dorsal anterior short gyrus, DAC = dorsal accessory gyrus, VAC = ventral accessory gyrus, VS = ventral anterior short gyrus, BNST=bed nucleus of the stria terminalis

Figure 2:

CONSORT diagram for the trial. CIWA-AR = Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised

Figure 3:

Left insula-BNST RSFC patterns. A. RSFC between insula ROIs and ipsilateral BNST at baseline (pre-CBT). Only the left DAC showed significant positive RSFC with the ipsilateral BNST at baseline, after correcting for multiple comparisons. B. Changes in RSFC between left dorsal anterior insula (DAC) and ipsilateral BNST, pre- and post-CBT. Points represent individual patients, with lines connecting pre- and post-CBT RSFC values. AL= anterior long gyrus, PL = posterior long gyrus, PS = posterior short gyrus, MS = middle short gyrus, AS = dorsal anterior short gyrus, DAC = dorsal accessory gyrus, VAC = ventral accessory gyrus, VS = ventral anterior short gyrus. BNST=bed nucleus of the stria terminalis. *significant at p<0.003, NS=not significant at p<0.05.

Figure 4:

Relationship between NHDD (pre-CBT – post-CBT) and Left DAC-BNST RSFC (pre-CBT – post-CBT). Scatterplot and best fit line of linear regression model. BNST=bed nucleus of the stria terminalis. DAC=dorsal accessory gyrus. NHDD= Number of heavy drinking days