Deficits in proactive avoidance and neural responses to drinking motives in problem drinkers

Abstract

Physical pain and negative emotions represent two distinct drinking motives that contribute to harmful alcohol use. Proactive avoidance which can reduce problem drinking in response to these motives appears to be impaired in problem drinkers. However, 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 collected in forty-one problem and forty-one social drinkers who performed a probabilistic learning go/nogo task that involved proactive avoidance of painful outcomes. We characterized the regional brain responses to proactive avoidance and identified the neural correlates of drinking to avoid physical pain and negative emotions. Behavioral results confirmed problem drinkers' proactive avoidance deficits in learning rate and performance accuracy, both which were associated with greater alcohol use. Imaging findings in problem drinkers showed that negative emotions as a drinking motive predicted attenuated right 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, along with alcohol use severity, influenced the neural and behavioral measures of proactive avoidance. Taken together, the current findings provide experimental evidence for proactive avoidance deficits in problem drinkers and establish the link between their neural underpinnings and alcohol misuse.

Figure 1

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.

Figure 2

Behavioral performance and drinking characteristics. (A) Problem drinkers (in purple) performed significantly worse than social drinkers (in blue) in Go-to-avoid trials. Problem drinkers’ 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 < .01.

Figure 3

In problem drinkers, 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.

Figure 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 insula. Negative emotions and Physical discomfort drinking motive scores predicted lower activations in the right insula (B) and right putamen and left caudate (C), respectively.

Figure 5

Path analysis. (A) Negative emotions motivated drinking, both of which reduced insular activity during proactive avoidance. Attenuated 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 < .05, ** p < .01

Figure 6

(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 drinkers, 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.