Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours

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Gouveia, Flavia Venetucci ; Germann, Jurgen ; Elias, Gavin J. B. ; Boutet, Alexandre ; Loh, Aaron ; Lopez Rios, Adriana Lucia ; Diaz, Cristina Torres ; Contreras Lopez, William Omar ; Ruiz Martinez, Raquel Chacon ; Fonoff, Erich Talamoni ; Benedetti-Isaac, Juan Carlos ; Giacobbe, Peter ; Arango Pava, Pablo M. ; Yan, Han ; Ibrahim, George M. ; Lipsman, Nir ; Lozano, Andres ; Hamani, Clement

• Tipo de documento: Artigo Científico
• Fonte: eLIFE; v. 12, p. 27-pg., 2023-05-22.

Resumo

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, 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 fiber tracts and functionally connected with 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 behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network. (AU)

• Processo FAPESP: 13/20602-5 - Análise prospectiva dos resultados funcionais da amigdalotomia bilateral assistencial em pacientes com agressividade refratária
• Beneficiário: Flavia Venetucci Gouveia
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/10466-8 - Desvendando agressividade: estudo de imagem do cérebro agressivo
• Beneficiário: Flavia Venetucci Gouveia
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 11/08575-7 - Papel da modulação dopaminérgica no núcleo lateral da amígdala sobre a resposta condicionada de esquiva
• Beneficiário: Raquel Chacon Ruiz Martinez
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores