Deep brain stimulation for severe autism: from pathophysiology to procedure

Abstract

Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.

Keywords: AF = arcuate fasciculus; BLA = basolateral nucleus of the amygdala; DBS = deep brain stimulation; DMN = default mode network; ECoG = electrocorti-cography; EEG = electroencephalography; OCD = obsessive-compulsive disorder; PFC = prefrontal cortex; SIB = self-injurious behavior; UF = uncinate fasciculus; amygdala; autism; autistic spectrum disorder; basolateral nucleus; deep brain stimulation; fMRI = functional MRI; mPFC = medial PFC; neurodevelopmental disorders.