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Here, we investigated neural network responses to reward and punishment and the molecular profiles of the connectivity features predicting alcohol use severity in young adults. We curated the Human Connectome Project data and employed connectome-based predictive modeling (CPM) to examine how functional connectivity (FC) features during wins and losses are associated with alcohol use severity, quantified by Semi-Structured Assessment for the Genetics of Alcoholism, in 981 young adults. We combined the CPM findings and the JuSpace toolbox to characterize the molecular profiles of the network connectivity features of alcohol use severity. The connectomics predicting alcohol use severity appeared specific, comprising less than 0.12% of all features, including medial frontal, motor\/sensory, and cerebellum\/brainstem networks during punishment processing and medial frontal, fronto-parietal, and motor\/sensory networks during reward processing. Spatial correlation analyses showed that these networks were associated predominantly with serotonergic and GABAa signaling. To conclude, a distinct pattern of network connectivity predicted alcohol use severity in young adult drinkers. These \u201cneural fingerprints\u201d elucidate how alcohol misuse impacts the brain and provide evidence of new targets for future intervention.<\/jats:p>","DOI":"10.3390\/brainsci14060610","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T11:47:17Z","timestamp":1718797637000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Functional Networks of Reward and Punishment Processing and Their Molecular Profiles Predicting the Severity of Young Adult Drinking"],"prefix":"10.3390","volume":"14","author":[{"given":"Yashuang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology, 100 Pingleyuan, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology, 100 Pingleyuan, Beijing 100124, China"},{"name":"Beijing International Science and Technology Cooperation Base for Intelligent Physiological Measurement and Clinical Transformation, Beijing 100124, China"},{"name":"BJUT-UPV Joint Research Laboratory in Biomedical Engineering, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-5930","authenticated-orcid":false,"given":"Dongmei","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology, 100 Pingleyuan, Beijing 100124, China"},{"name":"Beijing International Science and Technology Cooperation Base for Intelligent Physiological Measurement and Clinical Transformation, Beijing 100124, China"},{"name":"BJUT-UPV Joint Research Laboratory in Biomedical Engineering, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-4693","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyao","family":"Ye-Lin","sequence":"additional","affiliation":[{"name":"BJUT-UPV Joint Research Laboratory in Biomedical Engineering, 46022 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n e Innovaci\u00f3n en Bioingenier\u00eda, Universitat Polit\u00e8cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9393-1212","authenticated-orcid":false,"given":"Chiang-Shan Ray","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA"},{"name":"Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06520, USA"},{"name":"Wu Tsai Institute, Yale University, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology, 100 Pingleyuan, Beijing 100124, China"},{"name":"Beijing International Science and Technology Cooperation Base for Intelligent Physiological Measurement and Clinical Transformation, Beijing 100124, China"},{"name":"BJUT-UPV Joint Research Laboratory in Biomedical Engineering, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of addiction: A neurocircuitry analysis","volume":"3","author":"Koob","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100089","DOI":"10.1016\/j.addicn.2023.100089","article-title":"Appetitive and aversive cue reactivities differentiate neural subtypes of alcohol drinkers","volume":"7","author":"Chen","year":"2023","journal-title":"Addict. 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