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Despite effective treatments for attaining sobriety, the majority of patients relapse within a year, making relapse a substantial barrier to long\u2010term treatment success. A major factor contributing to relapse is heightened negative affect that results from the combination of abstinence\u2010related increases in stress\u2010reactivity and decreases in reward sensitivity. Substantial research has contributed to the understanding of reward\u2010related changes in AUD. However, less is known about anxiety during abstinence, a critical component of understanding addiction as anxiety during abstinence can trigger relapse. Most of what we know about abstinence\u2010related negative affect comes from rodent studies which have identified key brain regions responsible for abstinence\u2010related behaviors. This abstinence network is composed of brain regions that make up the extended amygdala: the nucleus accumbens (NAcc), the central nucleus of the amygdala (CeA), and the bed nucleus of the stria terminalis (BNST). More recently, emerging evidence from rodent and human studies suggests a fourth brain region, the anterior insula, might be part of the abstinence network. Here, we review current rodent and human literature on the extended amygdala's role in alcohol abstinence and anxiety, present evidence for the anterior insula's role in the abstinence network, and provide future directions for research to further elucidate the neural underpinnings of abstinence in humans. A better understanding of the abstinence network is critical toward understanding and possibly preventing relapse in AUD.<\/jats:p>","DOI":"10.1111\/adb.12861","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T19:23:05Z","timestamp":1580239385000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Anxiety during abstinence from alcohol: A systematic review of rodent and human evidence for the anterior insula's role in the abstinence network"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0192-0496","authenticated-orcid":false,"given":"Elizabeth A.","family":"Flook","sequence":"first","affiliation":[{"name":"Vanderbilt Center for Addiction Research Vanderbilt University School of Medicine  Nashville TN USA"},{"name":"Vanderbilt Brain Institute Vanderbilt University School of Medicine  Nashville TN USA"},{"name":"Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Luchsinger","sequence":"additional","affiliation":[{"name":"Vanderbilt Center for Addiction Research Vanderbilt University School of Medicine  Nashville TN USA"},{"name":"Vanderbilt Brain Institute Vanderbilt University School of Medicine  Nashville TN USA"},{"name":"Vanderbilt J.F. 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