Moxon-Emre Iska, Daskalakis Zafiris J, Blumberger Daniel M, Croarkin Paul E, Lyon Rachael E, Forde Natalie J, Tani Hideaki, Truong Peter, Lai Meng-Chuan, Desarkar Pushpal, Sailasuta Napapon, Szatmari Peter, Ameis Stephanie H
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.
Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Front Neurosci. 2021 Oct 6;15:711542. doi: 10.3389/fnins.2021.711542. eCollection 2021.
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 [ = 6.54, = 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 [ = 1.52, = 0.32, = 4.74, < 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. Clinicaltrials.gov (ID: NCT02311751), https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1; NCT02311751.
兴奋性和抑制性神经传递的改变与自闭症谱系障碍（ASD）有关。使用重复经颅磁刺激（rTMS）来增强或抑制皮质兴奋性的干预措施正在针对各种靶点进行研究，不过rTMS的作用机制尚未在ASD中得到检验。在此，我们研究了兴奋性rTMS治疗疗程是否会调节患有ASD的青少年的谷氨酸能（Glx）或γ-氨基丁酸（GABA）代谢物水平。28名患有ASD且有执行功能障碍的参与者[23.3±4.69岁；7名女性]接受了对左侧背外侧前额叶皮质（DLPFC）的两次磁共振波谱（MRS）扫描。在患有ASD的参与者被随机分配接受对DLPFC进行20次的主动或假rTMS疗程之前和之后进行MRS扫描。有19名发育正常的对照者[23.8±4.47岁；6名女性]的基线MRS数据。在基线时比较了ASD组和对照组之间Glx和GABA+的代谢物水平，并在接受主动与假rTMS的ASD参与者中比较了rTMS治疗前后代谢物水平的变化。主动rTMS组的Glx绝对变化大于假rTMS组[F = 6.54，p = 0.02]，不过GABA+的绝对变化在两组之间没有差异。我们还研究了在主动与假组中，基线代谢物水平与rTMS前后代谢物水平变化之间的关系。rTMS组调节了基线Glx与rTMS前后Glx变化之间的关系，以至于基线Glx仅预测主动rTMS组中的Glx变化[β = 1.52，SE = 0.32，t = 4.74，p < 0.001]；当基线水平较低时Glx水平升高，而当基线水平较高时Glx水平降低。我们的结果表明，对DLPFC进行兴奋性rTMS的干预疗程可能会调节患有ASD的青少年的局部Glx水平，并且与先前关于rTMS后谷氨酸能改变的报告一致。追踪谷氨酸能标志物的干预研究可能会为rTMS在ASD中的治疗潜力提供作用机制方面的见解。Clinicaltrials.gov（ID：NCT02311751），https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1；NCT02311751。
