Addiction: A striatal roller-coaster On the neural and associative-learning mechanisms underlying gambling and alcohol use disorder

Many theories of addiction distinguish different stages in the addiction cycle, with associated transitions at the neurobiological level – both in relation to habitual control of behavior and reward processing. In this thesis, Tim van Timmeren investigated the role of several proposed mechanisms underlying compulsive behavior in addiction, with a specific focus on neurocognitive associative-learning mechanisms (such as cognitive flexibility, reward processing, and habits) and addiction-chronicity. Across several studies, patients with alcohol use disorder (AUD) and gambling disorder (GD) were compared to matched controls. Neuroimaging techniques were used to measure brain function and structure.
The main findings presented in this thesis can be summarized as follows: first, GD is characterized by deficits in performance on neurocognitive tasks linked to compulsivity, such as cognitive inflexibility. Second, contrary to our hypotheses, no clear pattern of an increased reliance on habits or environmental stimuli was found in either AUD or GD. These results were surprising given the strong evidence from animal studies for the role of habits in addiction, but indicate that generally increased propensity for habit-formation is not a risk factor for addiction. Third, marked but heterogeneous striatal dysfunction during reward processing was found across both gambling and AUD, with a crucial role for addiction-related cues. Finally, impaired structural corticostriatal connectivity and increased insular functional connectivity were found in patients with GD. These altered connectivity profiles may represent a neurobiological basis for decreased cognitive flexibility and increased craving and gambling distortions, respectively; both key defining characteristics of GD.