Citation: Kang, J.; Fan, X.; Zhong, Y.; Casanova, M.F.; Sokhadze, E.M.; Li, X.; Niu, Z.; Geng, X. Transcranial Direct Current Stimulation Modulates EEG Microstates in Low-Functioning Autism: A Pilot Study. Bioengineering 2023, 10, 98. https://doi.org/10.3390/ bioengineering10010098 Academic Editor: Larbi Boubchir Received: 4 December 2022 Revised: 28 December 2022 Accepted: 8 January 2023 Published: 11 January 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). bioengineering Article Transcranial Direct Current Stimulation Modulates EEG Microstates in Low-Functioning Autism: A Pilot Study Jiannan Kang 1,† , Xiwang Fan 2,† , Yiwen Zhong 2 , Manuel F. Casanova 3 , Estate M. Sokhadze 3 , Xiaoli Li 4 , Zikang Niu 4, * and Xinling Geng 5, * 1 College of Electronic & Information Engineering, Hebei University, Baoding 071000, China 2 Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China 3 Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville Campus, Greenville Health System, Greenville, SC 29605, USA 4 State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100859, China 5 School of Biomedical Engineering, Capital Medical University, Beijing 100069, China * Correspondence: 201831061058@mail.bnu.edu.cn (Z.N.); gengxl@ccmu.edu.cn (X.G.) † These authors contributed equally to this work. Abstract: Autism spectrum disorder (ASD) is a heterogeneous disorder that affects several behavioral domains of neurodevelopment. Transcranial direct current stimulation (tDCS) is a new method that modulates motor and cognitive function and may have potential applications in ASD treatment. To identify its potential effects on ASD, differences in electroencephalogram (EEG) microstates were compared between children with typical development (n = 26) and those with ASD (n = 26). Furthermore, children with ASD were divided into a tDCS (experimental) and sham stimulation (control) group, and EEG microstates and Autism Behavior Checklist (ABC) scores before and after tDCS were compared. Microstates A, B, and D differed significantly between children with TD and those with ASD. In the experimental group, the scores of microstates A and C and ABC before tDCS differed from those after tDCS. Conversely, in the control group, neither the EEG microstates nor the ABC scores before the treatment period (sham stimulation) differed from those after the treatment period. This study indicates that tDCS may become a viable treatment for ASD. Keywords: autism spectrum disorder (ASD); transcranial direct current stimulation (tDCS); EEG microstate; autism behavior checklist (ABC) scale 1. Introduction Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous neu- rodevelopmental disorder for which no single cause has been identified [1]. Studies have shown that ASD is related to multiple genetic and environmental factors [2,3]. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the core symptoms of ASD are deficits in social communication, as well as restricted and repetitive patterns of behavior, interests, and activities. ASD is highly comorbid with other chronic medical disorders, including attention deficit disorder, sleep disorders, gastrointestinal dis- turbances, and movement disorders [4,5]. The Centers for Disease Control and Prevention (CDC) monitors epidemiological data on ASD to understand its impact on communities in the United States. According to these data, the prevalence of ASD is increasing, and the latest report published on 27 April 2018 indicated that the overall prevalence across 11 locations in the United States was 1 in 59 (approximately 1.68%). The CDC estimates that ASD is four times more likely to occur in males than in females [4,6]. Furthermore, most children with autism need lifelong care, and the lifetime expenditure for an individual with ASD with no intellectual disabilities is about USD 2 million to 2.4 million in the Bioengineering 2023, 10, 98. https://doi.org/10.3390/bioengineering10010098 https://www.mdpi.com/journal/bioengineering