Dissociable neural substrates of opioid and cocaine use identified via connectome-based modelling


Opioid use disorder is a major public health crisis. While effective treatments are available, outcomes vary widely across individuals and relapse rates remain high. Understanding neural mechanisms of treatment response may facilitate the development of personalized and/or novel treatment approaches. Methadone-maintained, polysubstance-using individuals (n = 53) participated in fMRI scanning before and after substance-use treatment. Connectome-based predictive modeling (CPM)—a recently developed, whole-brain approach—was used to identify pretreatment connections associated with abstinence during the 3-month treatment. Follow-up analyses were conducted to determine the specificity of the identified opioid abstinence network across different brain states (cognitive vs. reward task vs. resting-state) and different substance use outcomes (opioid vs. cocaine abstinence). Posttreatment fMRI data were used to assess network changes over time and within-subject replication. To determine further clinical relevance, opioid abstinence network strength was compared with healthy subjects (n = 38). CPM identified an opioid abstinence network (p = 0.018), characterized by stronger within-network motor/sensory connectivity, and reduced connectivity between the motor/sensory network and medial frontal, default mode, and frontoparietal networks. This opioid abstinence network was anatomically distinct from a previously identified cocaine abstinence network. Relationships between abstinence and opioid and cocaine abstinence networks replicated across multiple brain states but did not generalize across substances. Network connectivity measured at posttreatment related to abstinence at 6-month follow-up (p < 0.009). Healthy comparison subjects displayed intermediate network strengths relative to treatment responders and nonresponders. These data indicate dissociable anatomical substrates of opioid vs. cocaine abstinence. Results may inform the development of novel opioid-specific treatment approaches to combat the opioid epidemic.

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This work was supported by grants K01DA039299, R21DA045969, P50DA09241 T32DA022975, and R01DA035058 from the National Institute on Drug Abuse. Data reported here have been presented at the American College of Neuropsychopharmacology’s 57th Annual Meeting, at the Collaborative Perspectives on Addiction 2019 Annual Meeting, and are scheduled for additional oral presentation at the Society for Biological Psychiatry’s 74th Annual Scientific Meeting, and the College on Problems of Drug Dependence (CPDD) 81st Annual Scientific Meeting.

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Correspondence to Sarah D. Lichenstein or Sarah W. Yip.

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SDL, DS, and SWY report no financial relationships with commercial interest. KMC has received multiple grants from NIDA and NIAAA. She is a member of CBT4CBT LLC; this is managed through University. MNP has received financial support or compensation for the following: MNP has consulted for and advised RiverMend Health and Opiant/Lakelight Therapeutics; has received unrestricted research support from Mohegan Sun Casino and grant support from the National Center for Responsible Gaming; and has consulted for legal and gambling entities on issues related to addictive disorders.

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Lichenstein, S.D., Scheinost, D., Potenza, M.N. et al. Dissociable neural substrates of opioid and cocaine use identified via connectome-based modelling. Mol Psychiatry (2019). https://doi.org/10.1038/s41380-019-0586-y

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