Modulation of Dorsolateral Prefrontal Cortex Glutamate/Glutamine Levels Following Repetitive Transcranial Magnetic Stimulation in Young Adults With Autism

Frontiers in Neuroscience, Vol. 15 (2021)

Mots clés
Auteurs
  • Iska Moxon-Emre
  • Cundill Centre for Child and Youth Depression, The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Zafiris J. Daskalakis
  • Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Zafiris J. Daskalakis
  • Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
  • Daniel M. Blumberger
  • Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Daniel M. Blumberger
  • Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
  • Paul E. Croarkin
  • Division of Child and Adolescent Psychiatry, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States
  • Rachael E. Lyon
  • Cundill Centre for Child and Youth Depression, The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Natalie J. Forde
  • Cundill Centre for Child and Youth Depression, The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Natalie J. Forde
  • Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands
  • Hideaki Tani
  • Cundill Centre for Child and Youth Depression, The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Peter Truong
  • Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Meng-Chuan Lai
  • Cundill Centre for Child and Youth Depression, The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Meng-Chuan Lai
  • Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
  • Meng-Chuan Lai
  • Department of Psychiatry, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada
  • Meng-Chuan Lai
  • Department of Psychology, University of Toronto, Toronto, ON, Canada
  • Pushpal Desarkar
  • Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Pushpal Desarkar
  • Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
  • Napapon Sailasuta
  • Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Peter Szatmari
  • Cundill Centre for Child and Youth Depression, The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Peter Szatmari
  • Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
  • Peter Szatmari
  • Department of Psychiatry, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada
  • Stephanie H. Ameis
  • Cundill Centre for Child and Youth Depression, The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Stephanie H. Ameis
  • Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
  • Stephanie H. Ameis
  • Department of Psychiatry, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada

Résumé

Altered excitatory and inhibitory neurotransmission has been implicated in autism spectrum disorder (ASD). Interventions using repetitive transcranial magnetic stimulation (rTMS) to enhance or inhibit cortical excitability are under study for various targets, though the mechanistic effects of rTMS have yet to be examined in ASD. Here, we examined whether an excitatory rTMS treatment course modulates glutamatergic (Glx) or γ-aminobutyric acid (GABA) metabolite levels in emerging adults with ASD. Twenty-eight participants with ASD and executive function impairment [23.3 ± 4.69 years; seven-female] underwent two magnetic resonance spectroscopy (MRS) scans of the left dorsolateral prefrontal cortex (DLPFC). MRS scans were acquired before and after participants with ASD were randomized to receive a 20-session course of active or sham rTMS to the DLPFC. Baseline MRS data was available for 19 typically developing controls [23.8 ± 4.47 years; six-female]. Metabolite levels for Glx and GABA+ were compared between ASD and control groups, at baseline, and metabolite level change, pre-to-post-rTMS treatment, was compared in ASD participants that underwent active vs. sham rTMS. Absolute change in Glx was greater in the active vs. sham-rTMS group [F(1,19) = 6.54, p = 0.02], though the absolute change in GABA+ did not differ between groups. We also examined how baseline metabolite levels related to pre/post-rTMS metabolite level change, in the active vs. sham groups. rTMS group moderated the relation between baseline Glx and pre-to-post-rTMS Glx change, such that baseline Glx predicted Glx change in the active-rTMS group only [b = 1.52, SE = 0.32, t(18) = 4.74, p < 0.001]; Glx levels increased when baseline levels were lower, and decreased when baseline levels were higher. Our results indicate that an interventional course of excitatory rTMS to the DLPFC may modulate local Glx levels in emerging adults with ASD, and align with prior reports of glutamatergic alterations following rTMS. Interventional studies that track glutamatergic markers may provide mechanistic insights into the therapeutic potential of rTMS in ASD.Clinical Trial Registration:Clinicaltrials.gov (ID: NCT02311751), https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1; NCT02311751.

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