Motor Cortex Excitation/Inhibition Imbalance in Young Adults With Autism Spectrum Disorder: A MRS-TMS Approach

Abstract

Excitatory/inhibitory imbalance has been suggested as a neurobiological substrate of the cognitive symptomatology in Autism Spectrum Disorder (ASD). Studies using magnetic resonance spectroscopy (MRS) attempted to characterize GABA and Glutamate brain levels in ASD. However mixed findings have been reported. Here, we characterize both neurochemical and physiological aspects of GABA system in ASD by implementing a more comprehensive approach combining MRS and transcranial magnetic stimulation (TMS). A group of 16 young ASD adults and a group of 17 controls participated in this study. We employed one MRS session to assess motor cortex GABA+ and Glutamate+Glutamine (Glx) levels using MEGAPRESS and PRESS sequences, respectively. Additionally, a TMS experiment was implemented including paired-pulse (SICI, ICF and LICI), input-output curve and cortical silent period to probe cortical excitability. Our results showed a significantly increased Glx, with unchanged GABA+ levels in the ASD group compared with controls. Single TMS measures did not differ between groups, although exploratory within-group analysis showed impaired inhibition in SICI5ms, in ASD. Importantly, we observed a correlation between GABA levels and measures of the input-output TMS recruitment curve (slope and MEP amplitude) in the control group but not in ASD, as further demonstrated by direct between group comparisons. In this exploratory study, we found evidence of increased Glx levels which may contribute to ASD excitatory/inhibitory imbalance while highlighting the relevance of conducting further larger-scale studies to investigate the GABA system from complementary perspectives, using both MRS and TMS techniques.

A bibliometric analysis of global research status and trends in neuromodulation techniques in the treatment of autism spectrum disorder

“…Green clustering includes Biological Psychiatry, Frontiers in Psychiatry, and Autism Research . These studies have mainly focused on the potential mechanisms of neuromodulation techniques in the treatment of autism [ 48 ]. Blue clustering includes Applied Psychophysiology and Biofeedback, The Journal of Autism and Developmental Disorders, and Autism .…”

“…This may limit research progress on the treatment of ASD using neuromodulation techniques. The top 10 journals in terms of number of publications and citations were mainly involved in the fields of neuromodulation, neuroscience, and mental cognition, which showed that neuromodulation techniques have received extensive attention in neuropsychiatric disorders, especially in improving the psychological and cognitive impairment of patients with ASD [ 47 , 48 , 76 , 83 , 91 ].…”

“…Previous studies have shown that mental disorders such as ASD may arise from an imbalance of E/I in the neural microcircuit, whereas the compensatory increase in the excitability of inhibitory cells partially alleviates the social defects caused by the increase in E/I balance [ 55 , 128 , 129 ]. Recent studies have shown that non-invasive neuromodulation techniques can regulate the distribution of neurotransmitters and metabolites in the brain [ 47 , 48 , 55 ], and improve the social and cognitive functions of patients with autism by altering the excitability of the cortex and neural circuits [ 39 , 51 , 79 ], which provides a theoretical basis for follow-up research in the treatment of ASD. The burst keywords in the most recent five years mainly focus on “obsessive–compulsive disorder,” “transcranial direct current stimulation,” “working memory,” “double blind” and “adolescent”.…”

“…In recent years, high-frequency theta-burst stimulation protocols to the motor cortex was also tested in children and adults [ 45 , 46 ]. Previous studies have shown that rTMS can affect cortical excitability by altering the glutamatergic (Glx) or γ-aminobutyric acid (GABA) metabolite levels [ 47 ], and reducing irritability, hyperactivity, and stereotyped behavior in autistic children [ 43 , 48 , 49 ]. In addition, it also has a positive impact on children’s error monitoring and correction function [ 50 ].…”

Glutamate, GABA and glutathione in adults with persistent post-concussive symptoms

“…Similarly, general data analysis for advanced MRS methods such as HERMES continue to evolve, including modeling the baseline and data fitting. The tissue correction methods carried out in this study include an α-correction to account for higher GABA in GM than WM as this method is widely used in studies examining GABA+ in the literature ( Ip et al, 2021 , Bernardino et al, 2022 , Heise et al, 2022 , Stoby et al, 2022 , Trujillo et al, 2022 ). Relative GM vs WM levels of other metabolites, such as GSH and Glu are not defined ( Srinivasan et al, 2010 , An et al, 2015 , Chan et al, 2019 ).…”