From social drinking to alcohol addiction : Decision making and its neural substrates along a spectrum from social drinking to alcohol addiction

Abstract: For a minority of alcohol users, the initial sip of alcohol marks the start of a life-threatening process. This thesis studies cognitive mechanisms pertinent to alcohol addiction and its development, using a spectrum of individuals that range from healthy social drinkers, through people with hazardous use, to those suffering from alcohol addiction. Decision making can be altered in addiction, but less is known on the direct pharmacodynamic effects of alcohol intake in healthy people. Study 1 addressed decision making under the effects of moderate alcohol intoxication in healthy social drinkers using established behavioral economics tasks. The investigated processes encompassed both personal and social aspects of decision making. Within the personal domain, impulsivity and risk taking were investigated, while in the social domain, prosocial attitudes along with moral judgment were assessed. Moderate alcohol intoxication was found to impact only the social domain, leading to increased prosocial and utilitarian behaviors, but did not affect measures of impulsivity. Choosing alcohol over other natural rewards despite negative consequences is a central phenomenon of alcohol addiction. Two studies of this thesis investigated choice preference for alcohol compared to snack, using a cost manipulation paradigm, in light and heavy drinkers. Study 2 was a laboratory experiment whereas Study 3 was an imaging experiment for characterization of neural substrates. Cost was an important predictor of choice, as in both groups, alcohol choice was sensitive to cost in a parametric manner. This was mirrored in the brain by activity in value-based and salience regions, including orbitofrontal cortex and insula. In Study 2 we found that heavy drinkers showed generally higher alcohol choice preference and attenuated cost sensitivity. Failure to replicate this finding in Study 3, was possibly due to the artificial scanner environment. Craving is a key component in the cycle of addiction and a determinant of relapse, making it an important target for treatment interventions. Study 4 was a randomized sham-controlled trial using repetitive transcranial magnetic stimulation (rTMS) targeting the insula as a method to reduce craving and alcohol use in people suffering from alcohol addiction. An overall decrease in alcohol consumption and craving were seen, but did not differ between sham stimulation and rTMS targeting the insula. In summary, this thesis provides some insights into cognitive mechanisms related to alcohol addiction and processes that may be implicated in its development. During a moderate acute alcohol intoxication in healthy social drinkers, social decision-making is influenced, leading to increased utilitarian and altruistic behaviors. Thus, deficits in prosocial behaviors in people with alcohol addiction are unlikely to result from direct pharmacodynamic effects of alcohol, but are rather likely to reflect a selection of vulnerable individuals, consequences of the addictive process, or both. In individuals at risk of developing alcohol addiction, the sensitivity to the costs associated with choosing alcohol over an alternative reward is largely preserved, though it might be reduced compared to light, non-problem drinkers. Modulation of the insula cortex with TMS was not successful in decreasing alcohol use in individuals with alcohol addiction.