Neuromodulation for treatment resistant autism: systematic review

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social-communication impairment, restricted interests, repetitive behaviors, and, in a subset of individuals, severe aggression, self-injurious behavior (SIB), and obsessive-compulsive symptoms. Traditional behavioral and pharmacological approaches often provide limited benefit. Neuromodulation and ablative neuropsychiatric procedures have emerged as potential therapeutic strategies targeting the neural circuits implicated in ASD.

To systematically review the existing clinical literature on neuromodulatory and neurosurgical interventions for ASD, including deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS), transcranial direct current stimulation (tDCS), low-frequency electromagnetic stimulation, and stereotactic radiosurgery.

A comprehensive search of PubMed, Embase, and Cochrane Library was performed from inception through December 2025. Studies were included if they involved individuals with ASD undergoing any neuromodulation or ablative procedure and reported clinical outcomes.

Sixteen studies met inclusion criteria. DBS targeting the nucleus accumbens, amygdala, or internal capsule produced substantial reductions in aggression, SIB, and obsessive-compulsive symptoms, with long-term improvements observed for up to several years. rTMS and iTBS targeting the pSTS, DLPFC, or medial prefrontal regions improved social responsiveness, emotion recognition, and aspects of executive function with minimal adverse effects. tDCS demonstrated benefits for social cognition, executive functioning, and behavioral regulation. Radiosurgery targeting limbic structures resulted in durable reductions in pathological aggression in highly refractory cases. Across modalities, adverse events were mild and transient.

Neuromodulatory and ablative interventions demonstrate promising therapeutic potential for individuals with treatment-resistant ASD, particularly those with aggression, SIB, and profound social-cognitive deficits.