Drossel, Gunner2025-02-142025-02-142024-09https://hdl.handle.net/11299/269984University of Minnesota Ph.D. dissertation. September 2024. Major: Neuroscience. Advisor: Anna Zilverstand. 1 computer file (PDF); x, 294 pages + 3 supplementary files.Rates of return to use in addiction treatment remain high. We argue that the development of improved treatment options will require advanced understanding of individual heterogeneity in Substance Use Disorders (SUDs). In Chapter one, we hypothesized that considerable individual differences exist in the three functional domains underlying addiction—approach-related behavior, executive function, and negative emotionality. We included N = 593 participants from the enhanced Nathan Kline Institute-Rockland Sample (ages 18–59, 67% female; N = 420 Controls; N = 173 with past SUDs [54% female]). To test our a priori hypothesis that distinct neuro-behavioral subtypes exist within individuals with past SUDs, we conducted a latent profile analysis with all available phenotypic data as input and characterized resting-state brain function for each discovered subtype. In Chapter two, we aimed to validate these subtypes in a sample with a current Cocaine Use Disorder (CocUD). We included N=109 participants from the SUDMEX CONN dataset (ages 22-39, 15% female; N=48 Controls; N=61 with CocUD [30% female]). We conducted a latent profile analysis with all phenotypic data as input and characterized resting-state brain function per subtype. In Chapter three, we investigated translational preclinical results. We summarized the effects of acute or chronic drug (self-) administration on brain function for various classes of drugs and determined consistency with human literature. We performed a systematic literature search and identified 116 studies on in vivo rodent resting-state functional magnetic resonance imaging (n=84) or positron emission tomography (n=41) spanning depressants (n=27), opioids (n=23), stimulants (n=72), and cannabis (n=3). Results overall supported functionally derived subtypes, demonstrating considerable individual heterogeneity in the multi-dimensional impairments in addiction. Additionally, results from reviewing preclinical studies of drug (self-) administration provided evidence of altered resting-state brain function in rodents upon drug administration, implicating the brain’s reward network analogue to human studies. However, alterations were more dynamic than previously known, with dynamic adaptation depending on the length of drug administration. Further incorporation of relevant preclinical findings with neurobehavioral assessment and mechanism-based subtyping of human participants diagnosed with and in treatment for SUDs can aid in contributing to the betterment of interventions and therapies for personalize addiction medicine.enaddictionneuroimagingpsychiatrysubstance use disordersubtypingtranslationalThesis or Dissertation