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The phenomenon of brain recovery after long-term abstinence has been reported in substance use disorders. However, few longitudinal studies have been conducted to observe the potential recovery in heroin users, and little is known about the neural mechanism underlying the decreased craving after prolonged abstinence. The 8-month longitudinal study was carried out in 29 heroin users and 30 healthy controls. By choosing the L_DLPFC, which was activated by the heroin cue as the seeding region, different brain connection patterns were compared between healthy controls and heroin users by using Granger causality analysis (GCA) at baseline. Then, a paired t test was employed to detect the potential recovery of L_DLPFC circuits after prolonged abstinence. The visual analog scale (VAS) and trail-making test-A (TMT-A) were adopted to investigate craving and cognitive control impairment, respectively. The neuroimaging changes were then correlated with behavioral improvements. Similar analyses were applied for the mirrored right DLPFC to verify the lateralization hypothesis of the DLPFC in addiction. In the longitudinal study, enhanced GCA coefficients were observed in the L_DLPFC-R_insula circuit of heroin users after long-term abstinence and were associated with craving score changes. At baseline, decreased GCA coefficients from the left DLPFC to the bilateral SMA and right putamen, together with the reduced GCA strength from the bilateral OFC to the left DLPFC, were found between HUs and HCs. Our findings extended the brain recovery phenomenon into the field of heroin and suggested that the increased regulation of the L_DLPFC over the insula after prolonged abstinence was important for craving inhibition., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence., Method: 31 heroin users (age: 44.13±7.68 years, male: 18 (58%), duration of abstinence: 85.2 ± 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months., Results: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues., Conclusion: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The striatum mediates reward processing in addiction, and previous fMRI (functional Magnetic Resonance Imaging) studies have revealed abnormal striatofrontal functional connectivity in heroin addiction. However, little is known about whether there is abnormal structural connectivity of the striatal circuit in heroin addiction. This study investigated the structural connectivity of striatal circuits in abstinent heroin-dependent individuals (HDIs) without methadone treatment., Methods: Forty-three (age: 38.8 ± 7.1) male HDIs and twenty-one (age: 42.4 ± 7.9) matched healthy controls underwent high-resolution T1 and whole-brain diffusion tensor imaging (64 directions) magnetic resonance imaging. Connectivity-based seed classification probabilistic tractography was used to detect the tract strengths of striatal circuits with 10 a priori target masks. Tract strengths were compared between groups and correlated with impulsivity behavior, evaluated using the Barratt Impulsivity Scale (BIS), and craving, measured on visual analogue scale (VAS)., Results: HDIs showed significantly weaker tract strength of the left striatum-medial orbitofrontal cortex (mOFC) (Bonferroni corrected, p < 0.05/20 = 0.0025) and significantly higher BIS total, attention, motor, and non-planning scores (Bonferroni corrected, p < 0.05/4 = 0.0125) than controls. In HDIs, negative correlations were observed between the left striatum- mOFC tract strengths and the BIS total, attention and non-planning scores (r 1 =-0.410, p 1 = 0.005; r 2 =-0.432, p 2 = 0.003; r 3 =-0.506, p 3 <0.001) and between the right striatum-posterior cingulate cortex (PCC) tract strengths and craving scores (r=-0.433, p = 0.009) in HDIs., Conclusion: HDIs displayed decreased structural connectivity of the striatum-mOFC circuit and higher impulsivity. Higher impulsive behavior was associated with decreased left striatal circuit connectivity. These findings suggest that the striatal circuit tract strengths might be a novel potential biomarker in heroin and, potentially, general opioid addiction., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

As a critical component of cortico‐striato‐thalamo‐cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting‐state functional connectivity (RSFC) differences of the thalamus were investigated between age‐, gender‐, and alcohol‐matched 37 HU and 33 healthy controls (HCs). Trail making test‐A (TMT‐A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT‐A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU. [ABSTRACT FROM AUTHOR]

• Opioid use disorder demonstrated increased resting-state functional connectivity in the insular subdivisions after 8 months of abstinence. • Changes in RSFC within insular neurocircuits were correlated with reduced craving after protracted abstinence. • Neuroplasticity might exist after protracted abstinence, which might be helpful for the development of further therapeutic procedures in substance use disorders. The insular cortex plays a critical role in reward circuitry involved with drug craving in substance use disorders. This study aimed to investigate whether opioid use disorder exhibit functional alterations in the insular circuitry after abstinence. Sixty-one opioid use disorder underwent resting-state and 3D-T1-weighted magnetic resonance imaging and completed craving questionnaires at baseline and after 8 months of abstinence. Changes in resting-state functional connectivity in the insular cortex and their correlations with craving were analyzed. Craving was reduced at follow-up compared with baseline. Compared with that at baseline, there was significantly increased resting-state functional connectivity between the right insular cortex and the superior frontal gyrus/anterior cingulate gyrus (family-wise error corrected) at follow-up. Changes in the functional connectivity of the right dorsal anterior insula/posterior insula with the bilateral superior frontal gyrus were negatively correlated with changes in craving. Our results demonstrated the presence of changes in functional connectivity of the insula in opioid use disorder after protracted abstinence, providing novel evidence of a correlation between craving changes and changes in the neurocircuitry of insular cortex subdivision after abstinence. This study reveals the possibility of neuroplasticity after protracted abstinence, providing insight for future abstinence therapies and rehabilitation procedures for patients with substance use disorders. [ABSTRACT FROM AUTHOR]