Neural correlates of proactive avoidance deficits and alcohol use motives in problem drinking

Abstract

Physical pain and negative emotions represent two distinct drinking motives that contribute to harmful alcohol use. Proactive avoidance, in contrast, can reduce consumption in response to these motives but appears to be impaired in those with problem drinking. Despite such evidence, proactive avoidance and its underlying neural deficits have not been assessed experimentally. How these deficits inter-relate with drinking motives to influence alcohol use also remains unclear. The current study leveraged neuroimaging data in forty-one problem and forty-one social drinkers who performed a probabilistic learning go/nogo task featuring proactive avoidance of painful outcomes. We identified the brain responses to proactive avoidance and contrasted the neural correlates of drinking to avoid negative emotions vs. physical pain. Behavioral results confirmed proactive avoidance deficits in problem drinking individuals' learning rate and performance accuracy, both which were associated with greater alcohol use. Imaging findings in the problem drinking group showed that negative emotions as a drinking motive predicted attenuated right anterior insula activation during proactive avoidance. In contrast, physical pain motive predicted reduced right putamen response. These regions' activations as well as functional connectivity with the somatomotor cortex also demonstrated a negative relationship with drinking severity and positive relationship with proactive avoidance performance. Path modeling further delineated the pathways through which physical pain and negative emotions influenced the neural and behavioral measures of proactive avoidance. Taken together, the current findings provide experimental evidence for proactive avoidance deficits in alcohol misuse and establish the link between their neural underpinnings and drinking behavior.

Fig. 1. Behavioral design.

Probabilistic learning go/nogo task (PLGT): Participants learned to respond to four cue categories to avoid electric shocks (i.e., go-to-avoid, nogo-to-avoid) and gain monetary rewards (i.e., go-to-win, nogo-to-win), with two different images per cue category. Correct responses yielded favorable outcomes 80% of the times whereas incorrect responses yielded unfavorable outcomes 80% of the times. Shocks were only delivered in 50% of the shock feedback instances to reduce head movement.

Fig. 2. Behavioral performance and drinking characteristics.

A Problem drinking (in purple) performed significantly worse than social drinking (in blue) participants in Go-to-avoid trials. Problem drinking participants’ Go-to-avoid performance accuracy showed a significant negative correlation with B drinking severity as measured by AUDIT scores, C Negative emotions drinking motive, and D Physical discomfort drinking motive score. All correlation plots show regression residuals with the effects of sex, age, education, and smoking status removed. **p < 0.01.

Fig. 3. Task performance and drinking behavior relationship.

In those with problem drinking proactive avoidance learning rate showed significant correlations with (A) Go-to-avoid performance accuracy, (B) drinking severity, (C) Negative emotions, and (D) Physical discomfort drinking motives.

Fig. 4. Neural correlates of drinking severity and drinking motives during proactive avoidance (Go-to-avoid > Nogo-to-avoid).

A AUDIT scores predicted lower activations in the right putamen and right anterior insula. B Negative emotions drinking motive scores predicted lower activations in the right insula, and C and Physical discomfort drinking motive predicted lower activations in the right putamen and left caudate.

Fig. 5. Path models.

A Negative emotions motivated drinking, both of which reduced insular activity during proactive avoidance. Attenuated anterior insular activity worsened behavioral performance during proactive avoidance via lowered learning rate. B Physical discomfort motivated drinking, both of which reduced putamen activity during proactive avoidance. Attenuated putamen activity worsened behavioral performance during proactive avoidance via lowered learning rate. Both models showed a good fit. *p < 0.05, **p < 0.01.

Fig. 6. Connectivity results.

A Regions involved in proactive avoidance were identified in social drinkers: bilateral but primarily left pre/postcentral gyri, bilateral insula, left middle frontal gyrus, dorsal anterior cingulate cortex, supplementary motor area, left thalamus, and right cerebellum. We focused on the left pre/postcentral gyrus (in green circle) for subsequent functional connectivity analyses. In problem drinking participants, proactive avoidance performance accuracy showed significant and positive correlations with B insula-pre/postcentral gyrus connectivity and C putamen-pre/postcentral gyrus connectivity. In contrast, drinking severity showed significant and negative correlations with D insula-pre/postcentral gyrus connectivity and E putamen-pre/postcentral gyrus connectivity.