Citation

Venetucci Gouveia F, Germann J, Elias GJB, Boutet A, Loh A, Lopez Rios AL, Torres Diaz C, Contreras Lopez WO, Martinez RCR, Fonoff ET, Benedetti-Isaac JC, Giacobbe P, Arango Pava PM, Yan H, Ibrahim GM, Lipsman N, Lozano A, Hamani C. Elife 2023; 12: e84566.

Copyright

(Copyright © 2023, dLife Sciences Plublications, Ltd)

DOI

10.7554/eLife.84566

PMID

37212456

Abstract

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behaviour, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating the volume of activated tissue modelling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fibre tracts and interconnected brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas - together with patient age - were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behaviour, neuronal communication, plasticity and neuroinflammation might underlie this functional network.

Language: en

Keywords

human; neuroscience