Assessing and stabilizing atypical plasticity in autism spectrum disorder using rTMS: Results from a proof-of-principle study

Pushpal Desarkar; Tarek K Rajji; Stephanie H Ameis; Daniel M Blumberger; Meng-Chuan Lai; Yona Lunsky; Zafiris J Daskalakis

doi:10.1016/j.clinph.2021.03.046

Assessing and stabilizing atypical plasticity in autism spectrum disorder using rTMS: Results from a proof-of-principle study

Clin Neurophysiol. 2022 Sep:141:109-118. doi: 10.1016/j.clinph.2021.03.046. Epub 2021 May 5.

Authors

Pushpal Desarkar¹, Tarek K Rajji², Stephanie H Ameis³, Daniel M Blumberger², Meng-Chuan Lai⁴, Yona Lunsky⁵, Zafiris J Daskalakis⁶

Affiliations

¹ Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. Electronic address: pushpal.desarkar@camh.ca.
² Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
³ Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁴ Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁵ Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

PMID: 34011467
DOI: 10.1016/j.clinph.2021.03.046

Abstract

Objectives: Emerging evidence implicates atypical plasticity in the neurophysiology of autism spectrum disorder (ASD). Specifically, autistic people demonstrated hyperplasticity in response to theta-burst stimulation (TBS). We hypothesized that autistic adults would display hyperplasticity to TBS and that repetitive transcranial magnetic stimulation (rTMS) - which potentiates brain inhibitory mechanisms - would 'stabilize' hyperplasticity.

Methods: Using a randomized, cross-over design, plasticity was assessed using TBS in the left motor cortex (M1) in 31 autistic adults and 30 sex-, intelligence quotient-, and age-matched controls. Autistic adults (n = 29) were further randomized (1:1) to receive a single session of active (n = 14) or sham (n = 15) rTMS (6000 pulses at 20 Hz) over left M1 and plasticity was reassessed on the next day following rTMS.

Results: Both long-term potentiation (LTP) and long-term depression (LTD) were significantly increased in the ASD group, indicating hyperplasticity. Active, but not sham rTMS, attenuated LTD in autistic adults.

Conclusions: We provided further evidence for the presence of brain hyperplasticity in ASD. To our knowledge, this is the first study to show preliminary evidence that an excessive LTD in ASD can be 'stabilized' using rTMS. Such 'stabilizing' effect of rTMS on LTP was not observed, likely due to small sample size or a more specific 'attenuating' effect of rTMS on LTD, compared to LTP.

Significance: These findings indicate atypical brain inhibitory mechanisms behind hyperplasticity in ASD. Utilizing a larger sample, future replication studies could investigate therapeutic opportunities of 'mechanism-driven' rTMS.

Keywords: Autism spectrum disorder; Gamma-aminobutyric acid; Neurophysiology; Plasticity; Theta-burst stimulation; Transcranial magnetic stimulation.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Autism Spectrum Disorder* / diagnosis
Autism Spectrum Disorder* / therapy
Autistic Disorder*
Cross-Over Studies
Female
Humans
Male
Motor Cortex* / physiology
Neuronal Plasticity / physiology
Transcranial Magnetic Stimulation / methods

Grants and funding

R01 MH114879/MH/NIMH NIH HHS/United States