Abstract
Substance use disorders are associated with neuroimaging abnormalities, but results are heterogeneous across studies and vary across substances, and the causal interpretation of these abnormalities is unknown. We have used network mapping approaches and a functional connectome from a large cohort of healthy participants (n = 1,000) to test whether neuroimaging abnormalities across substance use disorders map to a common brain network. Starting with coordinates of regional brain atrophy from 45 studies (3,791 participants), we found that 91% of the neuroimaging findings mapped to a common brain network. This network was specific to substance use disorder compared to atrophy associated with normal aging and neurodegenerative disease (PFWE < 0.05). Coordinates of functional MRI abnormalities from 99 studies (5,256 participants) mapped to a similar brain network. We found no differences in networks across different substance use categories. We combined all substance use disorder data (144 studies, 9,047 participants) to generate an overall coordinate-based network for substance use disorder, which included positive connectivity to the anterior cingulate, bilateral insulae, dorsolateral prefrontal cortices and thalamus, and negative connectivity to the medial prefrontal and occipital cortices. Lesions resulting in remission from nicotine use disorder (n = 34) intersected this network significantly more than control lesions (n = 69; P < 0.0084). We conclude that neuroimaging abnormalities across substance use disorders map to a common brain network that is similar across imaging modalities, substances and lesion locations that cause remission from substance use disorders.
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Data availability
All atrophy and fMRI coordinates used in our study are available in published studies as identified in previous meta-analyses9,10,27. De-identified lesion masks of stroke lesions causing remission from nicotine use disorder are publicly available25,56, and clinical data from the patients may be shared upon request to the corresponding author of the original lesion network mapping study25. A version of the connectome along with preprocessing details is publicly available47. Voxel-wise imaging results were projected onto a publicly available ultrahigh-resolution ex vivo brain aligned to MNI space58.
Code availability
Code to conduct connectivity analyses is available as part of the open-access Lead-DBS software package (https://lead-dbs.org)57, and supporting code for this study is available at https://github.com/nimlab/NMH_Stubbs2023/.
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Acknowledgements
We thank Drs. A. Boes, J. Bruss and E. van Wijngaarden for sharing the lesion and clinical data included in the lesion validation analysis and Fig. 5, and we thank Dr. J. Joutsa for sharing the lesion case study data included in Supplementary Fig. 5. J.L.S. was supported by a Canadian Institutes of Health Research Vanier Scholarship and a University of British Columbia Friedman Award for Scholars in Health. J.J.T. was supported by the National Institute of Mental Health (K23MH129829), the Brain and Behavior Research Foundation, Sidney R. Baer Foundation, the Baszucki Brain Research Fund and Harvard Medical School. F.L.W.V.J.S. was supported by the NIH (R01NS127892). A.C. was supported by the NIH (K23MH120510), the Child Neurology Foundation and the Simons Foundation. Data from the Rochester cohort was supported in part by the National Heart, Lung and Blood Institute Preventive Cardiology Training (grant no. T32 HL007937) and by the Clinical and Translational Science Institute (grant no. UL1 RR024160) from the National Institutes of Health. W.G.H. was supported by the Jack Bell Chair in Schizophrenia. M.D.F. was supported by grants from the NIH (R01MH113929, R21MH126271, R56AG069086, R21NS123813 and R01NS127892), the Kaye Family Research Endowment, the Ellison/Baszucki Family Foundation and the Manley Family.
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J.L.S., J.J.T. and M.D.F. designed the study. J.L.S. and W.D. processed the data. J.L.S., J.J.T., S.H.S., F.L.W.V.J.S., A.L.C., W.D. and M.D.F. conducted and interpreted analyses. J.L.S., J.J.T., S.H.S., F.L.W.V.J.S., A.L.C., W.D., C.A.H., A.A., H.Z.W., W.G.H., W.J.P. and M.D.F. contributed to the interpretation of the results and writing of the manuscript.
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C.H. is employed by BrainsWay and has financial interest in the company. S.H.S. is a scientific consultant for Magnus Medical, and a clinical consultant for Acacia Mental Health, Kaizen Brain Center and Boston Precision Neurotherapeutics. S.H.S. has received investigator-initiated research funding from Neuronetics and BrainsWay. S.H.S. has served as a speaker for BrainsWay (branded) and PsychU.org (unbranded, sponsored by Otsuka). S.H.S. owns stock in BrainsWay (publicly traded) and Magnus Medical (not publicly traded). S.H.S. owns intellectual property involving the use of functional connectivity to target TMS. M.D.F. is a consultant for Magnus Medical, Solaris and Boston Scientific, and has intellectual property using connectivity imaging to guide brain stimulation. The remaining authors declare no competing interests.
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Stubbs, J.L., Taylor, J.J., Siddiqi, S.H. et al. Heterogeneous neuroimaging findings across substance use disorders localize to a common brain network. Nat. Mental Health 1, 772–781 (2023). https://doi.org/10.1038/s44220-023-00128-7
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DOI: https://doi.org/10.1038/s44220-023-00128-7
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