Deep brain stimulation for extreme behaviors associated with autism spectrum disorder converges on a common pathway: a systematic review and connectomic analysis

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  • 1 Division of Neurosurgery, Department of Surgery, University of Toronto;
  • | 2 Division of Neurosurgery, The Hospital for Sick Children, Toronto;
  • | 3 Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario;
  • | 4 Division of Neurosurgery, McGill University, Montreal, Quebec;
  • | 5 Biological Sciences, Sunnybrook Research Institute, Toronto;
  • | 6 Divisions of Paediatric Medicine and Developmental Paediatrics, Department of Paediatrics, The Hospital for Sick Children, Toronto;
  • | 7 University Health Network, Toronto, Ontario, Canada;
  • | 8 Stereotactic and Functional Neurosurgery Division, International Misericordia Clinic, Barranquilla, Colombia;
  • | 9 Department of Stereotactic and Functional Neurosurgery, Jaslok Hospital and Research Centre, Mumbai, India;
  • | 10 Department of Neurosurgery, University Hospital La Princesa, Madrid, Spain;
  • | 11 Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts;
  • | 12 Joint Department of Medical Imaging, University of Toronto;
  • | 13 Edmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto;
  • | 14 Division of Neurology, University of Toronto;
  • | 15 Krembil Brain Institute, Toronto;
  • | 16 Institute of Biomedical Engineering, University of Toronto; and
  • | 17 Institute of Medical Science, University of Toronto, Ontario, Canada
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OBJECTIVE

Individuals with autism spectrum disorder (ASD) may display extreme behaviors such as self-injury or aggression that often become refractory to psychopharmacology or behavioral intervention. Deep brain stimulation (DBS) is a surgical alternative that modulates brain circuits that have yet to be clearly elucidated. In the current study the authors performed a connectomic analysis to identify brain circuitry engaged by DBS for extreme behaviors associated with ASD.

METHODS

A systematic review was performed to identify prior reports of DBS as a treatment for extreme behaviors in patients with ASD. Individual patients’ perioperative imaging was collected from corresponding authors. DBS electrode localization and volume of tissue activated modeling were performed. Volumes of tissue activated were used as seed points in high-resolution normative functional and structural imaging templates. The resulting individual functional and structural connectivity maps were pooled to identify networks and pathways that are commonly engaged by all targets.

RESULTS

Nine patients with ASD who were receiving DBS for symptoms of aggression or self-injurious behavior were identified. All patients had some clinical improvement with DBS. Connectomic analysis of 8 patients (from the systematic review and unpublished clinical data) demonstrated a common anatomical area of shared circuitry within the anterior limb of the internal capsule. Functional analysis of 4 patients identified a common network of distant brain areas including the amygdala, insula, and anterior cingulate engaged by DBS.

CONCLUSIONS

This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD. Using network mapping, the authors identified key circuitry common to DBS targets.

ABBREVIATIONS

ALIC = anterior limb of the internal capsule; ASD = autism spectrum disorder; DBS = deep brain stimulation; GPi = globus pallidus internus; JHMRS = Johns Hopkins motor stereotypy rating scale; NAcc = nucleus accumbens; OAS = Overt Aggression Scale; OCD = obsessive-compulsive disorder; pHyp = posterior hypothalamus; SIB = self-injurious behavior; VC/VS = ventral capsule/ventral striatum; VTA = volume of tissue activated.

Schematics of transseptal interforniceal resection of a superiorly recessed colloid cyst. ©Mark Souweidane, published with permission. See the article by Tosi et al. (pp 813–819).

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