Autism spectrum disorder (ASD) is a developmental disorder that affects how people communicate, interact, and behave. ASD is characterized by persistent deficits in social communication and social interaction, as well as restricted, repetitive, and stereotyped patterns of behavior, interests, or activities. ASD affects about 1 in 54 children in the United States and has a significant impact on their quality of life, as well as their families and society.¹

Currently, there is no cure for ASD, and the treatment options are limited and often ineffective. The main goals of treatment are to improve the core symptoms of ASD, such as social communication and interaction, and to reduce the associated symptoms and behaviors, such as anxiety, aggression, irritability, and self-injury. The most common treatment approaches include behavioral interventions and pharmacological interventions. However, these treatments have several limitations, such as high cost, low availability, variable efficacy, adverse effects, and lack of long-term benefits.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that uses magnetic pulses to modulate the activity of specific brain regions. Recently, TMS has also been explored as a potential treatment for ASD. The rationale for using TMS in ASD is based on the theory that ASD is associated with abnormal brain connectivity and excitability, which can be normalized by TMS. This explores the evidence and clinical implications surrounding TMS in the context of ASD. This article will provide an overview of ASD and TMS, then summarize the results of the studies that have investigated the effects of TMS on ASD outcomes. The strengths and limitations of the current research, the potential mechanisms of TMS effects in ASD, and the clinical implications of integrating TMS into the treatment approach for ASD will also be explored. Additionally, future directions and research needs in this area will be highlighted, paving the way for a deeper understanding of the therapeutic potential of TMS for ASD.

Understanding Autism Spectrum Disorder (ASD)

ASD is a complex and disorder that affects how people perceive, process, and respond to social and environmental stimuli. ASD is diagnosed based on the presence of two core symptom domains: social communication and interaction impairments (SCI), and restricted and repetitive behaviors (RRB). SCI include difficulties in verbal and non-verbal communication, such as eye contact, facial expressions, gestures, joint attention, turn-taking, and understanding social cues. RRB include stereotyped or repetitive motor movements, such as hand flapping or rocking; insistence on sameness or routines; restricted or fixated interests; and sensory abnormalities.

The causes of ASD are not fully understood, but they are likely to involve a combination of genetic and environmental factors. ASD is more common in males than females (about 4:1 ratio), and it affects people of all racial, ethnic, and socioeconomic backgrounds.

ASD has a significant impact on the individuals who have it, as well as their families and society. People with ASD often face challenges in various aspects of life, such as education, employment, health care, social relationships, and independent living. They also have higher rates of comorbid conditions, such as intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, depression, epilepsy, sleep disorders, gastrointestinal disorders, and immune system disorders. The economic burden of ASD is estimated to be about $268 billion per year in the United States.

Research on TMS for ASD

Given the success of TMS in treating other neurological and psychiatric disorders, it is reasonable to explore its potential as a treatment for ASD. The rationale for using TMS in ASD stems from the idea that ASD is associated with abnormal brain connectivity and excitability. Brain connectivity refers to the functional or structural links between different brain regions. Brain excitability refers to the responsiveness of neurons to stimulation. Several studies have suggested that people with ASD have reduced connectivity between distant brain regions (long-range connectivity), especially in the social brain network; and increased connectivity between nearby brain regions (short-range connectivity), especially in the sensory-motor network. These connectivity patterns may result in impaired social cognition and communication in ASD.² Moreover, people with ASD have altered excitability of neurons, which may affect their learning, memory, and plasticity. These excitability changes may be related to the imbalance between excitatory and inhibitory neurotransmission in ASD, which is influenced by genetic factors, environmental factors, and neurodevelopmental processes.

TMS can potentially normalize the connectivity and excitability abnormalities in ASD by modulating the activity of specific brain regions that are involved in ASD symptoms. For example, TMS can target different regions such as the prefrontal cortex (PFC), which is implicated in executive functions, social cognition, and emotion regulation; the temporoparietal junction (TPJ), which is involved in theory of mind, perspective taking, and empathy; the fusiform gyrus (FG), which is responsible for face processing; the posterior superior temporal sulcus (pSTS), which is related to biological motion perception; the anterior cingulate cortex (ACC), which is associated with social motivation; and the cerebellum, which is linked to motor coordination, cognition, and emotion. Researchers suggest that many of these processes enable individuals to effectively address the demands of their environment through behavior that is contextually relevant and goal-driven, encompassing elements of planning, self-regulation, and self-monitoring. However, in the case of ASD, it appears that several of these higher-order cognitive processes may not function optimally, resulting in affected individuals exhibiting behaviors that are more reactive and less adaptive to their surroundings.³

Several studies have investigated the effects of TMS on ASD outcomes. A few studies have reported positive effects of TMS social communication and interaction impairments (SCI), and restricted and repetitive behaviors (RRB) in ASD. A meta-analysis including over 800 participants across 22 studies showed that non-invasive brain stimulation such as TMS can be used to improve core symptoms of ASD, stereotyped behavior, executive function, irritability, language function, hand-eye coordination, social interaction ability, and emotional state depending on the brain region.⁴

Clinical Implications of TMS for ASD

The evidence and clinical implications of using TMS for ASD are still emerging and evolving, but they suggest that TMS may have some potential as a novel and promising treatment option for ASD.

It is important to consider that ASD is a heterogeneous disorder that affects people differently depending on their age, gender, IQ, symptom severity, comorbidity, genotype, phenotype, and other factors. Therefore, TMS should not be applied in a one-size-fits-all manner, but rather in a personalized and tailored way. The selection of the appropriate patient population, stimulation protocol, target region, outcome measure, and follow-up assessment should be based on the individual characteristics, needs, preferences, and goals of each patient. Moreover, the response to TMS may vary from person to person depending on their baseline brain state, plasticity potential, stimulation history, and other factors. Therefore, the efficacy and safety of TMS should be monitored and adjusted accordingly for each patient.

TMS is generally considered to be a safe and well-tolerated technique in people with ASD, with minimal and transient side effects, such as headache, scalp discomfort, facial twitching, and hearing impairment. The most serious risk associated with TMS is the induction of seizures,⁵ which is very rare and can be prevented by following the safety guidelines and screening procedures.

Ethical considerations and patient consent: The use of TMS for ASD raises some ethical issues that need to be considered carefully. One of these issues is the informed consent of the patients or their legal guardians. Since ASD affects the cognitive and social abilities of the patients, they may have difficulties in understanding the nature, purpose, risks, and benefits of TMS. They may also have difficulties in expressing their preferences, wishes, and concerns. Therefore, the informed consent process should be conducted in a clear, simple, and respectful manner; and should involve the patients as much as possible. Another ethical issue is the respect for the dignity, autonomy, and identity of the patients. Since ASD is not a disease or a disorder per se, but rather a spectrum of neurodiversity; some patients may not view their condition as a problem or a deficit that needs to be fixed or changed. They may value their unique traits and abilities as part of their selfhood and identity. Therefore, the use of TMS for ASD should not aim to normalize or conform the patients to a certain standard or norm; but rather to enhance their well-being and quality of life.

The use of TMS in these populations should also involve the participation and collaboration of the patients, their families, their caregivers, and their health care providers.

TMS holds promise as a potential treatment for ASD, offering hope for improving symptoms and enhancing the lives of those affected. TMS for ASD represents a step forward in our commitment to understanding and addressing this complex condition. Continued research, personalized approaches, and collaboration within the ASD community will play pivotal roles in shaping the future of treatment and enhancing the well-being of individuals with ASD.

References

1. National Institute on Deafness and Other Communication Disorders. (2018, June 18). Autism spectrum disorder: Communication problems in children [Webpage]. U.S. Department of Health and Human Services, National Institutes of Health
2. Darwish, M. E., El-Beshlawy, H. W., Ramadan, E. S., & Serag, S. M. (2021). Study of the role of the transcranial magnetic stimulation on language progress in autism spectrum disorder. The Egyptian Journal of Otolaryngology, 37(1), 1-7.https://doi.org/10.1186/s43163-021-00116-7
3. Casanova MF, Sokhadze EM, Casanova EL, Li X. Transcranial Magnetic Stimulation in Autism Spectrum Disorders: Neuropathological Underpinnings and Clinical Correlations. Semin Pediatr Neurol. 2020 Oct;35:100832. doi: 10.1016/j.spen.2020.100832. Epub 2020 Jun 24. PMID: 32892959; PMCID: PMC7477302.
4. Liu, A., Gong, C., Wang, B., Sun, J., & Jiang, Z. (2023). Non-invasive brain stimulation for patient with autism: a systematic review and meta-analysis. Frontiers in psychiatry, 14, 1147327. https://doi.org/10.3389/fpsyt.2023.1147327
5. Huashuang, Z., Yang, L., Chensheng, H., Jing, X., Bo, C., Dongming, Z., … & Shi-Bin, W. (2022). Prevalence of adverse effects associated with transcranial magnetic stimulation for autism spectrum disorder: a systematic review and meta-analysis. Frontiers in Psychiatry, 13, 875591.