Journal Article

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

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

2023

Overview

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.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Aggression - psychology / Aggressive behavior / aggressive behaviour / Aggressiveness / Alzheimer's disease / Behavior / Brain / Child / Datasets / Deep brain stimulation / Deep Brain Stimulation - methods / Epilepsy / Genes / Genetic research / Genomics / Humans / Hypothalamus / Hypothalamus, Posterior - physiology / imaging connectomics / imaging transcriptomics / Inflammation / Intellectual disabilities / Localization / Lozano, Andrés / Magnetic Resonance Imaging / Neural networks / Neurobiology / Neuroimaging / Neuroscience / Neuroses / Obsessive compulsive disorder / Patients / Pediatrics / Periaqueductal gray area / Post traumatic stress disorder / Sensorimotor system / Transcriptomics / Treatment Outcome