Intermittent Theta Burst Stimulation Improves Sleep in Autism Spectrum Disorder by Reorganizing Overlapping Brain Networks With Neurochemical and Transcriptomic Signatures: A Randomized Controlled Trial
In brief
Intermittent theta-burst stimulation reduces insomnia severity in autism after eight weeks
In a randomized trial of 70 adults with autism and chronic insomnia, daily left-orbitofrontal iTBS for eight weeks lowered Insomnia Severity Index scores and altered brain network overlap in 13 cortical regions. The network changes aligned with glutamate and GABA receptor maps and gene signatures of adolescent excitatory neurons, suggesting a neurochemical basis for the sleep benefit. Further work is needed to confirm durability and optimal dosing.
- Journal
- CNS neuroscience & therapeutics (Q1)
- Published
- 1 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Huashuang Zhang, Bincan Xiong, Hongchi Liu, Yilin Huang, Jingwen Zhang, Ruimin Yu, et al.
- PMID
- 42590803
- DOI
- 10.1002/cns.71041
Why clinicians should know about it
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (top studies of the week, 16 August 2026): Ranked by evidence level and journal quartile
Abstract
BACKGROUND: Overlapping network architecture supports functional integration and multifunctional regional engagement in the brain, and may serve as a candidate biomarker for interventions in autism spectrum disorder (ASD). However, the biological context underlying intermittent theta-burst stimulation (iTBS)-related changes in overlapping network architecture remains poorly understood. METHODS: Seventy patients with ASD and chronic insomnia were randomly assigned to receive either real or sham iTBS targeting the left orbitofrontal cortex, administered once daily for 8 weeks. The Insomnia Severity Index (ISI) and resting-state functional magnetic resonance imaging (fMRI) data were collected at baseline and after the intervention. The Shannon-entropy diversity coefficient was calculated to characterize overlapping network architecture. The JuSpace toolbox was used to assess spatial correspondence between iTBS-related network changes and neurotransmitter systems. Transcriptomic-neuroimaging association analyses were then performed using gene-expression data from the Allen Human Brain Atlas. RESULTS: Sleep improvement following real iTBS was accompanied by changes in overlapping network architecture across 13 cortical regions. These changes showed spatial correspondence with mGluR5 and GABA_A receptor density maps. Regions showing iTBS-related network changes were associated with glutamatergic synaptic transmission and calcium-dependent signaling, enriched for cortical excitatory neuronal signatures with peak expression during adolescence, and organized into a highly interconnected protein-protein interaction network centered on the Ca2+-PKA signaling axis. CONCLUSIONS: This study provides multiscale evidence for the biological context underlying iTBS-related changes in overlapping network architecture in ASD with chronic insomnia.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.