Phase I clinical trial findings published in Biological Psychiatry show that deep brain stimulation of the reward-related region of the brain is relatively safe and may improve quality of life

Philadelphia, March 20, 2025 – Severe self-injurious behavior in children with autism spectrum disorder (ASD) poses a significant risk of permanent physical injury. Not all children respond to behavioral therapies. Findings from a pilot trial in Biological Psychiatry, published by Elsevier, show that deep brain stimulation (DBS) of the nucleus accumbens (NAc), the reward-related region of the brain, in children with severe self-injurious behavior and ASD is relatively safe and feasible and may have notable benefits.

John Krystal, MD, Editor of Biological Psychiatry, says, “Repetitive self-injurious behavior is a terribly dangerous and potentially life-threatening condition for which there are limited treatment options. This report describes a novel neurosurgical approach to treatment involving DBS of a brain reward center. While the findings are extremely preliminary, they suggest that stimulation of this reward-related region of the brain may reduce self-injurious behavior, justifying further study.”

Lead investigator George M. Ibrahim, MD, PhD, Division of Neurosurgery, Department of Surgery and Program in Neuroscience and Mental Health, The Hospital for Sick Children; Institute of Biomedical Engineering; Institute of Medical Science, University of Toronto, notes, "Children with severe self-injurious behavior represent an exquisitely vulnerable population, often with limited treatment options. Our extensive experience with pediatric DBS and brain network mapping provided an opportunity to develop the evidence base for a novel therapy for affected children. In this study, we showed that DBS targeting the NAc is relatively safe and may improve quality of life."

Researchers performed a regulated, Health Canada-monitored phase I clinical trial for safety and feasibility in six children aged 7–14 years, supporting families with a multidisciplinary medical team. Using wearable technology to quantify movements and PET scans to assess changes in brain circuitry, investigators observed reductions in self-injurious behavior concurrent with improvement in quality of life and changes in brain metabolism in relevant neural circuits.

Dr. Ibrahim explains, "Several non-specific psychopharmacological therapies are frequently administered in the setting of severe self-injurious behavior based on low-level evidence and predominantly off-label prescriptions. These have been associated with limited efficacy and can have considerable side effects. There is, therefore, a critical and unmet need to develop effective treatments for children with severe, refractory self-injurious behavior."

Situated within the ventral striatum, the NAc presents a compelling target for neuromodulation of cortical-striatal circuitry to reduce the severity of self-injurious behavior in children. The NAc is a central structure in the mesolimbic reward pathway and plays a critical role in integrating dopaminergic reinforcement signals. DBS of the NAc has shown promise in normalizing frontostriatal dynamics and reducing the severity of obsessive-compulsive disorder in adults, a condition also characterized by impaired inhibitory control. The safety and feasibility of NAc-DBS for the treatment of self-injurious behavior in children has not been rigorously investigated before.

Dr. Ibrahim notes, "Although DBS is extensively studied in adults with numerous neurological and neuropsychological conditions, its applications in children are limited. The current work represents the first clinical trial of DBS for any neurodevelopmental disorder in childhood. It encourages larger studies to demonstrate efficacy and tolerability."