A selective insular perfusion deficit contributes to compromised salience network connectivity in recovering alcoholic men

Abstract

Background: Alcoholism can disrupt neural synchrony between nodes of intrinsic functional networks that are maximally active when resting relative to engaging in a task, the default mode network (DMN) pattern. Untested, however, are whether the DMN in alcoholics can rebound normally from the relatively depressed task state to the active resting state and whether local perfusion deficits could disrupt network synchrony when switching from conditions of rest to task to rest, thereby indicating a physiological mechanism of neural network adaptation capability.

Methods: Whole-brain, three-dimensional pulsed-continuous arterial spin labeling provided measurements of regional cerebral blood flow (CBF) in 12 alcoholics and 12 control subjects under three conditions: pretask rest, spatial working-memory task, and posttask rest.

Results: With practice, alcoholics and control subjects achieved similar task accuracy and reaction times. Both groups exhibited a high-low-high pattern of perfusion levels in DMN regions during the rest-task-rest runs and the opposite pattern in posterior and cerebellar regions known to be associated with spatial working memory. Alcoholics showed selective differences from control subjects in the rest-task-rest CBF pattern in the anterior precuneus and CBF level in the insula, a hub of the salience network. Connectivity analysis identified activation synchrony from an insula seed to salience nodes (parietal, medial frontal, anterior cingulate cortices) in control subjects only.

Conclusions: We propose that attenuated insular CBF is a mechanism underlying compromised connectivity among salience network nodes. This local perfusion deficit in alcoholics has the potential to impair ability to switch from cognitive states of interoceptive cravings to cognitive control for curbing internal urges.

Keywords: Alcohol; MRI; arterial spin labeling; brain; connectivity; perfusion; working memory.

Figure 1

Brain regions showing DMN pattern.

Figure 2

Brain regions showing task-activated pattern.

Figure 3

Top: Alcoholic pattern evident from ANOVA. Bottom: Interaction pattern evident from ANOVA.

Figure 4

Relations between rCBF at each rest condition and the task condition for the controls (left panel) and alcoholics (right panel).

Figure 5

Insula seed-to-ROI-connectivity results in controls (green) and between-groups comparison (red). Please refer to Table S3 in Supplement 1 for statistics.