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Previously, we applied a meta\u2010analytical approach to define a network\u2010level target for connectivity\u2010based rt\u2010fMRI NF in substance use disorders. The analysis yielded consistent connectivity alterations between the insula and anterior cingulate cortex (ACC) as well as the dorsal striatum and the ACC. In the current investigation, we addressed the feasibility of regulating this network and its functional relevance using connectivity\u2010based neurofeedback. In a double\u2010blind, sham\u2010controlled design, 60 nicotine users were randomly assigned to the experimental or sham control group for one NF training session. The preregistered primary outcome was defined as improved inhibitory control performance after regulation of the target network compared to sham control. Secondary outcomes were (1) neurofeedback\u2010specific changes in functional connectivity of the target network; (2) changes in smoking behavior and impulsivity measures; and (3) changes in resting\u2010state connectivity profiles. Our results indicated no differences in behavioral measures after receiving feedback from the target network compared to the sham feedback. Target network connectivity was increased during regulation blocks compared to rest blocks, however, the experimental and sham groups could regulate to a similar degree. Accordingly, the observed activation patterns may be related to the mental strategies used during regulation attempts irrespective of the group assignment. We discuss several crucial factors regarding the efficacy of a single\u2010session connectivity\u2010based neurofeedback for the target network. This includes high fluctuation in the connectivity values of the target network that may impact controllability of the signal. To our knowledge, this investigation is the first randomized, double\u2010blind controlled real\u2010time fMRI study in nicotine users. This raises the question of whether previously observed effects in nicotine users are specific to the neurofeedback signal or reflect more general self\u2010regulation attempts.<\/jats:p>","DOI":"10.1002\/hbm.70077","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T09:37:06Z","timestamp":1732009026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Connectivity\u2010Based Real\u2010Time Functional Magnetic Resonance Imaging Neurofeedback in Nicotine Users: Mechanistic and Clinical Effects of Regulating a Meta\u2010Analytically Defined Target Network in a Double\u2010Blind Controlled Trial"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-2890","authenticated-orcid":false,"given":"Arezoo","family":"Taebi","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine RWTH Aachen 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