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White matter disconnection in acquired criminality

Molecular Psychiatry (2025)Cite this article

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Abstract

Structural brain imaging is increasingly introduced as evidence in criminal trials. A key imaging abnormality identified in criminal populations is alteration to the right uncinate fasciculus but it remains unclear whether these changes play a causal role in criminal behavior. Lesion studies of acquired criminality offer the opportunity to assess the causal role of focal disruption of specific white matter connections in criminal behavior. We studied lesion locations of focal brain damage associated with new onset criminal behavior compared to lesions associated with 21 diverse neuropsychiatric symptoms. First, we analyzed the intersection of lesion locations with an atlas-based right uncinate fasciculus. Second, we assessed the intersection of lesion locations with all white matter tracts from this atlas. Third, we performed a connectome-based analysis of all possible white matter connections with each lesion ___location, without a priori assumptions regarding specific tracts. We repeated all analyses limited to subjects who committed violent crimes. Lesions associated with criminality intersected the right uncinate more than lesions associated with other neuropsychiatric symptoms (p = 4.78 × 10−8). Compared to other tracts, the right uncinate fasciculus was the tract most strongly associated with lesion-induced criminality followed by the forceps minor. An unbiased connectome-based analysis confirmed these findings. Among subjects who committed violent crimes the right uncinate was the key tract identified. Lesions associated with criminality intersect the right uncinate fasciculus more than other lesions and more than other white matter tracts. Damage to the right uncinate may play a causal role in criminal behavior, especially violent crime.

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Fig. 1: Structural connectivity mapping of criminality versus controls. Left: Lesion locations.
Fig. 2: Lesions locations associated with criminality intersect the right uncinate.
Fig. 3: Lesions associated with criminality intersect multiple white matter tracts compared to controls.

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Data availability

The networks from the analyses (Fig. 3) are publicly available at: https://identifiers.org/neurovault.collection:15236. The code to prepare structural connectivity maps is available at: https://storage.googleapis.com/bcblabweb/index.html and the structural connectivity data is available at: https://www.humanconnectome.org/study/hcp-young-adult/document/1200-subjects-data-release. Statistical analyses were performed in MatLab (version 2019b), FSL (version 6.0.4) and SPSS (version 28.0.0.0).

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Acknowledgements

Data were provided, in part, by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University.

Funding

IK receives funding from NIH NINDS L30 NS134024. AC was funded by NIH/NIMH K23MH120510, the Child Neurology Foundation, and the Simons Foundation Autism Research Initiative Bridge to Independence Fellowship. MDF was supported by the Nancy Lurie Marks Foundation, the Mather’s Foundation, the Ellison / Baszucki Foundation, the Kaye Family Research Endowment and National Institutes of Health grants R21 MH126271, R56 AG069086, R01 MH113929, R01 MH115949, and R01 AG060987. RRD was supported by National Institutes of Health, National Institute on Aging grant K23 AG070320-01A1.

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Author notes

  1. These authors contributed equally: R. Ryan Darby, Michael D. Fox.

Authors and Affiliations

  1. Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA

    Isaiah Kletenik, William Drew & Michael D. Fox

  2. Center for Brain Circuit Therapeutics, Brigham and Women’s Hospital, Boston, MA, USA

    Isaiah Kletenik, Alexander L. Cohen, William Drew & Michael D. Fox

  3. Harvard Medical School, Boston, MA, USA

    Isaiah Kletenik, Alexander L. Cohen & Michael D. Fox

  4. Departments of Neurology and Psychiatry, and Behavioral Neurology Section, University of Colorado School of Medicine, Aurora, CO, USA

    Christopher M. Filley

  5. Department of Neurology, Computational Radiology Laboratory, Department of Radiology, Boston Children’s Hospital, Boston, MA, USA

    Alexander L. Cohen

  6. Department of Philosophy, University of California San Diego and Salk Institute, San Diego, CA, USA

    Patricia S. Churchland

  7. Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA

    R. Ryan Darby

  8. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA

    Michael D. Fox

  9. Departments of Psychiatry, and Radiology, Brigham and Women’s Hospital, Boston, MA, USA

    Michael D. Fox

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Contributions

IK, CMF, RRD and MDF conceived and designed the work; IK, RRD and MDF acquired the data; IK, ALC, WD, RRD and MDF analyzed and interpreted data; IK, CMF, PSC, RRD and MDF drafted the work; IK, CMF, ALC, PSC, RRD and MDF revised the manuscript critically for important intellectual content.

Corresponding author

Correspondence to Isaiah Kletenik.

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Competing interests

MDF is a consultant for Magnus Medical and Soterix and holds intellectual property on using connectivity imaging to guide brain stimulation. RRD served as an expert witness in a criminal case mentioned in this article; all data described in reference to this case was gathered independently by IK from publicly available resources. The other authors report no competing interests.

Ethics approval

The study was approved by Mass General Brigham/Partners Institutional Review Board Protocol 2020P002987 in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We analyzed previously published, publicly available images with informed patient consent per individual journal requirements.

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Kletenik, I., Filley, C.M., Cohen, A.L. et al. White matter disconnection in acquired criminality. Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-03076-z

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