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. 

A coherent sense of self is crucial for social functioning and mental health. The N-methyl-D-aspartate antagonist ketamine induces short-term dissociative experiences and has therefore been used to model an altered state of self-perception. This randomized double-blind placebo-controlled cross-over study investigated the mechanisms for ketamine's effects on the bodily sense of self in the context of affective touch. Thirty healthy participants (15 females/15 males, age 19-39) received intravenous ketamine or placebo while performing self-touch and receiving touch by someone else during functional MRI - a previously established neural measure of tactile self-other-differentiation. Afterwards, tactile detection thresholds during self- and other-touch were assessed, as well as dissociative states, interoceptive awareness, and social touch attitudes. Compared to placebo, ketamine administration elicited dissociation and reduced neural activity associated with self-other-differentiation in the right temporoparietal cortex, which was most pronounced during other-touch. This reduction correlated with ketamine-induced reductions in interoceptive awareness. The temporoparietal cortex showed higher connectivity to somatosensory cortex and insula during other- compared to self-touch. This difference was augmented by ketamine, and correlated with dissociation strength for somatosensory cortex. These results demonstrate that disrupting the self-experience through ketamine administration affects neural activity associated with self-other-differentiation in a region involved in touch perception and social cognition, especially with regard to social touch by someone else. This process may be driven by ketamine-induced effects on top-down signaling, rendering the processing of predictable self-generated and unpredictable other-generated touch more similar. These findings provide further evidence for the intricate relationship of the bodily self with the tactile sense.

Insula responses to drug cues are correlated with cravings, and lesions in this area reduce nicotine seeking. Here, we investigated the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) targeting the insula in alcohol addiction. Treatment-seeking alcohol-dependent patients (Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition; N = 56) participated in this double-blind, sham-controlled, randomized trial. Participants received 10 Hz rTMS or sham using an H8 coil, 5 days a week for 3 weeks. Stimulation targeted insular cortex and overlaying regions bilaterally, while excluding anterior prefrontal areas. Craving and self-reported as well as biomarker-based drinking measures were collected at baseline, during treatment, and through 12 weeks. Resting-state magnetic resonance imaging (rsMRI) data were collected before and after treatment. Task-based MRI was used to probe brain correlates of reward processing, affective responses, and alcohol following completion of treatment. A marked overall decrease in craving and drinking measures was observed during treatment, but did not differ between rTMS or sham stimulation. Both groups equally increased their alcohol use following completion of treatment and through the 12-week follow-up. Analysis using seeds in the insula identified differences in resting-state connectivity between active and sham groups at completion of treatment, potentially indicating an ability of treatment to modify insula function. However, while each task robustly replicated brain responses established in the literature, no effects of rTMS were found. Collectively, this study does not support efficacy of rTMS targeting the insula in alcohol addiction.