Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/84566 |
| _version_ | 1827931580333555712 |
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| author | Flavia Venetucci Gouveia Jurgen Germann Gavin JB Elias Alexandre Boutet Aaron Loh Adriana Lucia Lopez Rios Cristina Torres Diaz William Omar Contreras Lopez Raquel Chacon Ruiz Martinez Erich Talamoni Fonoff Juan Carlos Benedetti-Isaac Peter Giacobbe Pablo M Arango Pava Han Yan George M Ibrahim Nir Lipsman Andres Lozano Clement Hamani |
| author_facet | Flavia Venetucci Gouveia Jurgen Germann Gavin JB Elias Alexandre Boutet Aaron Loh Adriana Lucia Lopez Rios Cristina Torres Diaz William Omar Contreras Lopez Raquel Chacon Ruiz Martinez Erich Talamoni Fonoff Juan Carlos Benedetti-Isaac Peter Giacobbe Pablo M Arango Pava Han Yan George M Ibrahim Nir Lipsman Andres Lozano Clement Hamani |
| author_sort | Flavia Venetucci Gouveia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:54:43Z |
| format | Article |
| id | doaj.art-4a1930d7fc5c47beb53ea4d7a0f5d818 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T06:54:43Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4a1930d7fc5c47beb53ea4d7a0f5d8182023-06-07T11:54:36ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.84566Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behavioursFlavia Venetucci Gouveia0https://orcid.org/0000-0003-0029-1269Jurgen Germann1https://orcid.org/0000-0003-0995-8226Gavin JB Elias2Alexandre Boutet3Aaron Loh4Adriana Lucia Lopez Rios5Cristina Torres Diaz6William Omar Contreras Lopez7Raquel Chacon Ruiz Martinez8Erich Talamoni Fonoff9Juan Carlos Benedetti-Isaac10Peter Giacobbe11Pablo M Arango Pava12Han Yan13George M Ibrahim14Nir Lipsman15Andres Lozano16Clement Hamani17Neuroscience and Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada; Sunnybrook Research Institute, Toronto, Canada; Division of Neuroscience, Sírio-Libanês Hospital, São Paulo, BrazilDivision of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, CanadaDivision of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, CanadaDivision of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Joint Department of Medical Imaging, University of Toronto, Toronto, CanadaDivision of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, CanadaDepartment of Functional and Stereotactic Neurosurgery, University Hospital San Vicente Fundación, São Paulo, Brazil; Department of Functional and Stereotactic Neurosurgery, San Vicente Fundación, Barranquilla, ColombiaDepartment of Neurosurgery, University Hospital La Princesa, Madrid, SpainNemod Research Group, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia; Division of Functional Neurosurgery, Department of Neurosurgery, FOSCAL Clinic, Bucaramanga, ColombiaDivision of Neuroscience, Sírio-Libanês Hospital, São Paulo, Brazil; LIM 23, Institute of Psychiatry, School of Medicine, University of São Paulo, São Paulo, BrazilDepartment of Neurology, Integrated Clinic of Neuroscience, School of Medicine, University of São Paulo, São Paulo, BrazilStereotactic and Functional Neurosurgery Division of the International Misericordia Clinic, Barranquilla, CanadaSunnybrook Research Institute, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, CanadaServicio de Neuocirugia Funcional y Esterotaxia, Clinica Comuneros Bucaramanga, Clinica Desa y Clinica Dime Neurocardiovascular de Cali; Clinica Nueva del Lago, Bucaramanga, ColombiaDivision of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, CanadaDivision of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, CanadaSunnybrook Research Institute, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, CanadaDivision of Neurosurgery, Department of Surgery, University Health Network, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, CanadaSunnybrook Research Institute, Toronto, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada; Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, CanadaDeep 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.https://elifesciences.org/articles/84566deep brain stimulationhypothalamusaggressive behaviourimaging connectomicsimaging transcriptomicsmagnetic resonance imaging |
| spellingShingle | Flavia Venetucci Gouveia Jurgen Germann Gavin JB Elias Alexandre Boutet Aaron Loh Adriana Lucia Lopez Rios Cristina Torres Diaz William Omar Contreras Lopez Raquel Chacon Ruiz Martinez Erich Talamoni Fonoff Juan Carlos Benedetti-Isaac Peter Giacobbe Pablo M Arango Pava Han Yan George M Ibrahim Nir Lipsman Andres Lozano Clement Hamani Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours eLife deep brain stimulation hypothalamus aggressive behaviour imaging connectomics imaging transcriptomics magnetic resonance imaging |
| title | Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours |
| title_full | Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours |
| title_fullStr | Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours |
| title_full_unstemmed | Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours |
| title_short | Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours |
| title_sort | multi centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours |
| topic | deep brain stimulation hypothalamus aggressive behaviour imaging connectomics imaging transcriptomics magnetic resonance imaging |
| url | https://elifesciences.org/articles/84566 |
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