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      Recovery of superior frontal gyrus cortical thickness and resting‐state functional connectivity in abstinent heroin users after 8 months of follow‐up

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          Abstract

          Compared with healthy controls, heroin users (HUs) show evidence of structural and functional brain alterations. However, little is known about the possibility of brain recovery after protracted heroin abstinence. The purpose of this study was to investigate whether brain recovery is possible after protracted abstinence in HUs. A total of 108 subjects with heroin addiction completed structural and functional scans, and 61 of those subjects completed 8‐month follow‐up scans. Resting‐state data and 3D‐T1 MR images were collected for all participants, first at baseline and again after 8 months. Cognitive function and craving were measured by the Trail Making Test‐A (TMT‐A) and Visual Analog Scale for Craving, respectively. The cortical thickness and resting‐state functional connectivity (RSFC) differences were then analyzed and compared between baseline and follow‐up, and correlations were obtained between neuroimaging and behavioral changes. HUs demonstrated improved cognition (shorter TMT‐A time) and reduced craving at the follow‐up (HU2) relative to baseline (HU1), and the cortical thickness in the bilateral superior frontal gyrus (SFG) was significantly greater at HU2 than at HU1. Additionally, the RSFC of the left SFG with the inferior frontal gyrus (IFG), insula, and nucleus accumbens and that of the right SFG with the IFG, insula and orbitofrontal cortex (OFC) were increased at HU2. The changes in TMT‐A time were negatively correlated with the RSFC changes between the left SFG and the bilateral IFG, the bilateral caudate, and the right insula. The changes in craving were negatively correlated with the RSFC changes between the left OFC and the bilateral SFG. Our results demonstrated that impaired frontal‐limbic neurocircuitry can be partially restored, which might enable improved cognition as well as reduced craving in substance‐abusing individuals. We provided novel scientific evidence for the partial recovery of brain circuits implicated in cognition and craving after protracted abstinence.

          Highlights

          • Improved cognition and reduced craving were observed in heroin users (HUs) after 8 months of abstinence.

          • HUs demonstrated increased superior frontal gyrus (SFG) cortical thickness after 8 months of abstinence.

          • Increased resting‐state functional connectivity within SFG circuits was correlated with improved cognition and reduced craving; Brain circuit recovery was detected as a result of protracted abstinence in HUs.

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          Most cited references59

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          Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications.

          The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.
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            Neurobiology of addiction: a neurocircuitry analysis.

            Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.
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              Neurocircuitry of addiction.

              Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: 'binge/intoxication', 'withdrawal/negative affect', and 'preoccupation/anticipation' (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex-dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.
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                Author and article information

                Contributors
                kyuan@xidian.edu.cn
                junliu123@csu.edu.cn
                Journal
                Hum Brain Mapp
                Hum Brain Mapp
                10.1002/(ISSN)1097-0193
                HBM
                Human Brain Mapping
                John Wiley & Sons, Inc. (Hoboken, USA )
                1065-9471
                1097-0193
                24 March 2022
                July 2022
                : 43
                : 10 ( doiID: 10.1002/hbm.v43.10 )
                : 3164-3175
                Affiliations
                [ 1 ] Department of Radiology Second Xiangya Hospital of Central South University Changsha China
                [ 2 ] School of Life Science and Technology Xidian University Xi'an China
                [ 3 ] Engineering Research Center of Molecular and Neuroimaging Ministry of Education Xi'an China
                [ 4 ] Hunan Judicial Police Academy Changsha China
                [ 5 ] Xi'an Key Laboratory of Intelligent Sensing and Regulation of Trans‐Scale Life Information, School of Life Science and Technology Xidian University Xi'an China
                [ 6 ] Inner Mongolia Key Laboratory of Pattern Recognition and Intelligent Image Processing, School of Information Engineering Inner Mongolia University of Science and Technology Baotou China
                Author notes
                [*] [* ] Correspondence

                Kai Yuan, School of Life Science and Technology, Xidian University, Xi'an China.

                Email: kyuan@ 123456xidian.edu.cn

                Jun Liu, Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, China.

                Email: junliu123@ 123456csu.edu.cn

                Author information
                https://orcid.org/0000-0001-8690-6847
                https://orcid.org/0000-0002-3098-1124
                Article
                HBM25841
                10.1002/hbm.25841
                9188969
                35324057
                db190b52-d707-4d31-8e24-38f8b2401c32
                © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 11 February 2022
                : 22 November 2021
                : 06 March 2022
                Page count
                Figures: 7, Tables: 3, Pages: 12, Words: 8452
                Funding
                Funded by: National Key Research and Development Program of China , doi 10.13039/501100012166;
                Award ID: 2016YFC0800908
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 61971451
                Award ID: 81871426
                Award ID: 81671671
                Funded by: Key R&D projects in Hunan Province
                Award ID: 2019SK2131
                Funded by: Fundamental Research Funds for the Central Universities of Central South University
                Award ID: 2021zzts0378
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2021JJ40839
                Funded by: Leading talents of scientific and technological innovation in Hunan Province in 2021
                Award ID: 2021RC4016
                Funded by: Clinical Research Center For Medical Imaging In Hunan Province
                Award ID: 2020SK4001
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                July 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:12.06.2022

                Neurology
                abstinence,addiction,brain recovery,cognitive function,craving,heroin
                Neurology
                abstinence, addiction, brain recovery, cognitive function, craving, heroin

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