Abstract
To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in intellectually capable persons (IC-ASD). We searched peer-reviewed international literature to identify clinical trials investigating TMS as a treatment for behavioral and cognitive symptoms of IC-ASD. We identified sixteen studies and were able to conduct a meta-analysis on twelve of these studies. Seven were open-label or used neurotypical controls for baseline cognitive data, and nine were controlled trials. In the latter, waitlist control groups were often used over sham TMS. Only one study conducted a randomized, parallel, double-blind, and sham controlled trial. Favorable safety data was reported in low frequency repetitive TMS, high frequency repetitive TMS, and intermittent theta burst studies. Compared to TMS research of other neuropsychiatric conditions, significantly lower total TMS pulses were delivered in treatment and neuronavigation was not regularly utilized. Quantitatively, our multivariate meta-analysis results report improvement in cognitive outcomes (pooled Hedges’ g = 0.735, 95% CI = 0.242, 1.228; p = 0.009) and primarily Criterion B symptomology of IC-ASD (pooled Hedges’ g = 0.435, 95% CI = 0.359, 0.511; p < 0.001) with low frequency repetitive TMS to the dorsolateral prefrontal cortex. The results of our systematic review and meta-analysis data indicate that TMS may offer a promising and safe treatment option for pediatric and young adult patients with IC-ASD. However, future work should include use of neuronavigation software, theta burst protocols, targeting of various brain regions, and robust study design before clinical recommendations can be made.
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Availability of Data and Materials
Data regarding systematic review is attached to the submission. Further meta-analytic data than presented in this manuscript is available upon request.
Abbreviations
- rTMS :
-
Repetitive transcranial magnetic stimulation
- MDD :
-
Major depressive disorder
- HF-rTMS :
-
High frequency rTMS
- LtDLPFC :
-
Left dorsolateral prefrontal cortex
- TMS :
-
Transcranial magnetic stimulation
- LF-rTMS :
-
Low frequency rTMS
- RtDLPFC :
-
Right dorsolateral prefrontal cortex
- TBS :
-
Theta burst stimulation
- cTBS :
-
Continuous theta burst stimulation
- iTBS :
-
Inhibitory theta burst stimulation
- dTMS :
-
Deep TMS
- OCD :
-
Obsessive compulsive disorder
- mPFC :
-
Medial prefrontal cortex
- ACC :
-
Anterior cingulate cortex
- ASD :
-
Autism spectrum disorder
- RRB :
-
Restricted/repetitive behaviors
- EF :
-
Executive functioning
- IC-ASD :
-
Autism spectrum disorder in intellectually capable persons
- PRISMA:
-
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
- SMD :
-
Standardized mean differences
- REML :
-
Restricted maximum likelihood
- I2 JWR :
-
Jackson-White-Riley I2 index
- NT :
-
Neurotypical
- ADI-R :
-
Autism diagnostic interview-revised
- ADOS :
-
Autism diagnostic observation schedule
- SCL :
-
Skin conductance level
- HRV :
-
Heart rate variability
- BiDLPFC :
-
Bilateral DLPFC
- M1:
-
Primary motor cortex
- SMA :
-
Supplemental motor area
- pSTS :
-
Posterior superior temporal sulcus
- FDI :
-
First dorsal interossei muscle
- SRS-2:
-
Social responsiveness scale
- RBS-R :
-
Repetitive behavioral scale-revised
- ABC:
-
Aberrant behavioral checklist
- ERP :
-
Event related potentials
- BRIEF:
-
Behavioral Rating Inventory for Executive Function
- SR:
-
Self-Report
- VABS-II:
-
Vineland Adaptive Behavior Scale–II
- MRCP:
-
Movement-related cortical potentials
- PV:
-
Parvalbumin
- E/I:
-
Excitation-to-inhibition
- EEG:
-
Electroencephalogram
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This work is funded in part by the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under award numbers T32HD007475 in the Eunice Kennedy Shriver National Institute of Child Health and Human Development, K23MH100450, and the Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder. Dr. Joshi is specifically supported by the NIMH of the NIH under Award Number K23MH100450. Dr. Anteraper receives grant support from NIMH of the NIH under award number 1R03MH121879-01A1. Dr. Croarkin receives funding from the NIH under grants R01 MH113700 and R01 MH124655. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the NIMH or the NIH.
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JS: Conceptualization, Methodology, Investigation, Data Curation, Formal Analysis, Writing—Original Draft. MD: Conceptualization, Methodology, Investigation, Data Curation, Formal Analysis, Writing – Review and Editing. AG: Conceptualization, Methodology, Investigation, Writing – Review and Editing. AC: Conceptualization, Methodology, Investigation, Data Curation, Writing – Review and Editing. SA: Conceptualization, Writing – Review and Editing. PC: Conceptualization, Supervision, Writing – Review and Editing. GJ: Conceptualization, Methodology, Investigation, Data Curation, Formal Analysis, Supervision, Writing – Review and Editing.
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JRS is employed by Vanderbilt University Medical Center as a child and adolescent psychiatrist with no other financial relationships to disclose. AG and MD do not have financial relationships to disclose. AC reports personal fees from Massachusetts Department of Mental Health, non-financial support from NIH, personal fees from Pamlab, Inc., personal fees from US Department of Defense, non-financial support from Neurocentria, Inc., personal fees from Food and Drug Administration, non-financial support from Pfizer Pharmaceuticals, Inc., personal fees from Sunovion Pharmaceuticals, Inc., non-financial support from Roche TCRC, Inc. SA is employed by the Carle Foundation Hospital in Urbana, Illinois with no other financial relationships to disclose. PC has received research support from Pfizer, Inc. and equipment support from Neuronetics, Inc. and MagVenture, Inc. He has received grant in kind support from AssureRX for supplies and genotyping. He has been the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. He has served as a paid consultant for Engrail Therapeutics, Myriad Neuroscience, Procter and Gamble Company, and Sunovion. In the last year, GJ has received research support from the Demarest Lloyd, Jr. Foundation as a primary investigator (PI) for investigator-initiated studies. Additionally, GJ receives research support F. Hoffmann-La Roche Ltd. as a site PI for multi-site trials. In the past three years, GJ has received research support from Pfizer and the Simons Center for the Social Brain. In addition, GJ has received honorarium from the Governor's Council for Medical Research and Treatment of Autism in New Jersey and from NIMH for grant review activities. Finally, he received speaker’s honorariums from the American Academy of Child and Adolescent Psychiatry, The Israeli Society of ADHD, the Canadian Academy of Child and Adolescent Psychiatry, and the University of Jülich.
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Smith, J.R., DiSalvo, M., Green, A. et al. Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Neuropsychol Rev 33, 834–855 (2023). https://doi.org/10.1007/s11065-022-09564-1
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DOI: https://doi.org/10.1007/s11065-022-09564-1