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Disrupted brain state dynamics in opioid and alcohol use disorder: attenuation by nicotine use


Substance use disorder (SUD) is a chronic relapsing disorder with long-lasting changes in brain intrinsic networks. While most research to date has focused on static functional connectivity, less is known about the effect of chronic drug use on dynamics of brain networks. Here we investigated brain state dynamics in individuals with opioid use (OUD) and alcohol use disorder (AUD) and assessed how concomitant nicotine use, which is frequent among individuals with OUD and AUD, affects brain dynamics. Resting-state functional magnetic resonance imaging data of 27 OUD, 107 AUD, and 137 healthy participants were included in the analyses. To identify recurrent brain states and their dynamics, we applied a data-driven clustering approach that determines brain states at a single time frame. We found that OUD and AUD non-smokers displayed similar changes in brain state dynamics including decreased fractional occupancy or dwell time in default mode network (DMN)-dominated brain states and increased appearance rate in visual network (VIS)-dominated brain states, which were also reflected in transition probabilities of related brain states. Interestingly, co-use of nicotine affected brain states in an opposite manner by lowering VIS-dominated and enhancing DMN-dominated brain states in both OUD and AUD participants. Our finding revealed a similar pattern of brain state dynamics in OUD and AUD participants that differed from controls, with an opposite effect for nicotine use suggesting distinct effects of various drugs on brain state dynamics. Different strategies for treating SUD may need to be implemented based on patterns of co-morbid drug use.

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Fig. 1: Recurrent brain states.
Fig. 2: Brain dynamics in OUD vs HC.
Fig. 3: The effect of nicotine dependence and alcohol use on brain state transition probabilities.
Fig. 4: Brain dynamics in AUD smokers vs non-smokers.


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We thank Michele Vera-Yonga, Veronica Ramirez, Jamie Burns, Christopher Kure Liu, Dani Kroll, Dana Feldman, Karen Torres, Christopher Wong, Amna Zehra, Lori Talagala, Myke Vandine and Minoo McFarland for their contributions.


This work was accomplished with support from the National Institute on Alcohol Abuse and Alcoholism (ZIAAA000550, PI: NDV and ZIAAA000125, PI: RM), the Division of Intramural Clinical and Biological Research, NIAAA, including the 1SE Inpatient Behavioral Health Unit and the 1SE Outpatient Clinic.

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RZ and NDV designed the research; RZ and WY analyzed the data; RZ and NDV interpreted the data; RZ, WY, ESK, PM, SBD, MS, LV, DS, DT, NG, GJW, ND, RM performed the research; RZ wrote the first draft. All authors revised and approved the final version.

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Correspondence to Rui Zhang or Nora D. Volkow.

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Zhang, R., Yan, W., Manza, P. et al. Disrupted brain state dynamics in opioid and alcohol use disorder: attenuation by nicotine use. Neuropsychopharmacol. (2023).

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