Personalized repetitive transcranial magnetic stimulation guided by the spectral electroencephalogram may enhance and democratize therapy for autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a genetically heterogeneous group of neurodevelopmental disorders that affect 1 in 36 children (CDC data) and have recognizable core deficits in common, including repetitive stereotyped behaviors and difficulties in social interaction and communication. Pharmacological interventions moderate some ASD comorbidities, but do not alleviate core deficits and have significant side effects. While many behavioral therapies are inadequate, a very intensive form called applied behavioral analysis (ABA) is demonstrably effective. ABA is based on graded progression and immediate feedback. ABA has raised concerns over its intensive nature and has triggered unease about being too harsh. One solution may derive from a widespread hypothesis of ASD pathogenesis, which posits that the brain in ASD is overexcited, i.e., excitation dominates over inhibition, and electroencephalographic (EEG) alpha band oscillatory activity is altered, which degrades sensory input and task management. This may also disrupt the brain mesolimbic dopaminergic reward cascade causing social interactions to be unrewarding, leading to deleterious social behavior and poor communication. We hypothesize that a comprehensive, personalized form of spectral EEG guided repetitive transcranial magnetic stimulation that we term PrTMS, can normalize alpha EEG oscillations, E/I balance, and dopaminergic reward signaling, to facilitate improved psychosocial behavior. The goal is for PrTMS to synergize with behavioral interventions, so that ABA for example, could be less intensive. This may hold the promise of making self-determination more readily attainable for ASD persons, and could also democratize ASD therapy by rendering it more affordable.