Deep Brain Stimulation of the Nucleus Accumbens for Severe Self-Injurious Behavior in Children: A Phase I Pilot Trial

Carolina Gorodetsky¹, Karim Mithani², Sara Breitbart³, Han Yan⁴, Kristina Zhang⁵, Flavia Venetucci Gouveia⁶, Nebras Warsi², Hrishikesh Suresh², Simeon M Wong⁷, Joelene Huber⁸, Elizabeth N Kerr⁹, Abhaya V Kulkarni¹⁰, Margot J Taylor¹¹, Louis P Hagopian¹², Alfonso Fasano¹³, George M Ibrahim¹⁴

Affiliations

¹ Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
² Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
³ Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
⁵ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
⁶ Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
⁷ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
⁸ Division of Pediatric Medicine and Developmental Pediatrics, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁹ Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁰ Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, Ontario, Canada.
¹¹ Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
¹² Neurobehavioral Unit, Department of Behavioural Psychology, Kennedy Krieger Institute, Baltimore, Maryland.
¹³ Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Krembil Brain Institute, Toronto, Ontario, Canada.
¹⁴ Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: george.ibrahim@sickkids.ca.

PMID: 39645140
DOI: 10.1016/j.biopsych.2024.12.001

Clinical Trial

Deep Brain Stimulation of the Nucleus Accumbens for Severe Self-Injurious Behavior in Children: A Phase I Pilot Trial

Carolina Gorodetsky et al. Biol Psychiatry. 2025.

. 2025 Jun 15;97(12):1116-1126.

doi: 10.1016/j.biopsych.2024.12.001. Epub 2024 Dec 5.

Authors

Affiliations

¹ Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
² Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
³ Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
⁵ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
⁶ Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
⁷ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
⁸ Division of Pediatric Medicine and Developmental Pediatrics, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁹ Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁰ Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, Ontario, Canada.
¹¹ Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
¹² Neurobehavioral Unit, Department of Behavioural Psychology, Kennedy Krieger Institute, Baltimore, Maryland.
¹³ Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Krembil Brain Institute, Toronto, Ontario, Canada.
¹⁴ Division of Neurosurgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: george.ibrahim@sickkids.ca.

PMID: 39645140
DOI: 10.1016/j.biopsych.2024.12.001

Abstract

Background: Self-injurious behavior (SIB) consists of repetitive, nonaccidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB is prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviors.

Methods: We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov identifier NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB and SIB-associated behaviors, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS.

Results: Six children (ages 7-14 years) underwent NAc-DBS without serious adverse events. One child was found to have a delayed asymptomatic intracranial hemorrhage adjacent to a DBS electrode that did not require intervention, and 3 children experienced transient worsening in irritability or SIB with titration of stimulation parameters. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviors across multiple standardized scales, concurrent with clinically meaningful improvements in quality of life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex.

Conclusions: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.

Keywords: Autism spectrum disorder; Children; Clinical trial; Deep brain stimulation; Nucleus accumbens; Self-injurious behavior.

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Deep Brain Stimulation of the Nucleus Accumbens for Severe Self-Injurious Behavior in Children: A Phase I Pilot Trial

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Deep Brain Stimulation of the Nucleus Accumbens for Severe Self-Injurious Behavior in Children: A Phase I Pilot Trial

Authors

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Medical