Effects of rTMS on Cognitive Functions and Behavior in Individuals With Autism Spectrum Disorder

October 18, 2025 updated by: Hayfa Ali Alghabban, King Saud University

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cognitive Functions and Behavior in Individuals With Autism Spectrum Disorder ( ASD)

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with core symptoms that include impairments in social communication and restricted and repetitive behaviors, interests, and activities. Social cognition is a broad term used to understand, perceive, and interpret information about others and ourselves in a social context. Impairments in social cognition are often highlighted as a potential mechanism underlying social disability in autism spectrum disorder. Repetitive transcranial magnetic stimulation is a noninvasive technique that modulates brain activity through targeted electromagnetic pulses. It's one of the methods used to deliver electrical stimuli through the scalp in conscious humans. Recently, rTMS has not only been used for the treatment of major depressive disorders, but it has also been advanced as a potential therapeutic technique to treat neurologic disorders such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, and many other neuropsychiatric disorders. High-order cognitive functions, such as Executive function (EF) and social cognition, rely on neural network oscillations in the gamma frequency (30-80 Hz) band. It has been proposed that GABA-inhibitory interneurons in the dorsolateral prefrontal cortex (DLPFC) contribute to the synchronization of pyramidal neurons, which is necessary for EF performance. Additionally, given the theory of abnormal synaptic plasticity and excitation/inhibition ratio in ASD, as well as the ability of TMS to modify cortical excitability and plasticity, it leads to exploring the therapeutic potential of rTMS in ASD. This study examines the effectiveness of low-frequency rTMS in improving social, cognitive, and sensory function in individuals with ASD. Further understanding of the effect of low-frequency rTMS in altering the cognitive function in ASD individuals with ASD may help to achieve some answers related to the mechanism behind ASD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Statement of the Problem:

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Core ASD symptoms include impairments in social communication and restricted and repetitive behaviors, interests, and activities. ASD may also present with secondary signs, including hyperactivity, self-injury, and co-occurrence of some psychiatric conditions, e.g., anxiety and major depression. The symptoms of ASD are persistent and typically appear during the first three years of life. It can be recognized and clinically evident in early childhood.

In most cases, but not all, ASD symptoms might follow a steady course without remission. However, deficits and impairment in social skills and behavioral patterns may not be noticed and diagnosed as symptoms of ASD until the child faces significant life demands such as social, educational, and occupational tasks. Moreover, this functional limitation may vary among persons with ASD and could develop over time.

In the past 50 years, ASD's description has changed from a rare disease of childhood-onset to a well-publicized, advocated, and researched lifelong condition, recognized as relatively common and very heterogeneous. Since the 1970s, several studies have reported increased ASD cases. The report documented that the male/female ratio is approximately 4 per 1. According to the Centers for Disease Control, the prevalence of ASD increased from 1 in 80 (1.25%) in 2011-2013 to 1 in 31 children (3.2%) aged 8 years, and the corresponding figure for the whole of the United States in 2022 was 8 and 9. In the Gulf countries, systematic review studies of the epidemiology of autism revealed a prevalence ranging from 1.4 to 29/10,000 persons. In a study in Taif, Saudi Arabia, the estimated prevalence of autism in primary school children aged 7-12 years was 0.035%. Reviews of the literature have revealed no recent prevalence statistics for children with autism/ASD in Saudi Arabia. The Saudi Ministry of Health has indicated that one in every 160 children has an ASD.

ASDs are a financial, emotional, and social burden. An autistic child's care causes more emotional burden to the parents than that of parents, compared to that of parents taking care of terminally ill children.

Social cognition is a broad term that describes cognitive processes related to perceiving, understanding, and implementing linguistic, auditory, visual, and physical cues that communicate emotional and interpersonal information. It is also defined as the perception of others, the perception of self, and interpersonal knowledge. It's the ability to understand, perceive, and interpret information about others and ourselves in a social context. It includes a wide range of processes that allow people to perceive and interpret rapidly changing social information and respond appropriately to social stimuli quickly, effortlessly, and flexibly. Also, social cognition ability gives meaning to the actions of others.

Assessment of social cognition, primarily focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. Cognitive impairment is defined as when a person has trouble remembering, learning new things, concentrating, or making decisions that affect their everyday life. The common signs of cognitive impairment may include loss of memory. Asking the same question frequently or repeating the same story over and over, unable to recognize familiar people or places, having trouble exercising judgment, such as knowing what to do in an emergency, changes in mood or behavior, difficulty in vision, difficulty planning or carrying out tasks, such as following a recipe or keeping track of monthly bills.

Studies showed that alterations in social cognition ability were associated with autism, autism severity, and autistic traits. Impairments in social cognition are often highlighted as a potential mechanism underlying social disability in autism spectrum disorder. Different social skills programs have been developed for autistic adults based on the assumption that improving social understanding and ability will improve functional outcomes.

Transcranial magnetic stimulation (TMS) is one method used to deliver electrical stimuli through the scalp in conscious humans. Generally, single-pulse TMS (including paired-pulse TMS) is used to explore brain functioning. In contrast, repetitive TMS (rTMS) is used to induce changes in brain activity that can last beyond the stimulation period. Therefore, TMS and rTMS are indirect and non-invasive methods to induce excitability changes in the motor cortex via a wire coil, generating a magnetic field that passes through the scalp. TMS Non-invasive TMS of the motor cortex leads to a twitch in the target muscle, evoking motor-evoked potential (MEP) on electromyography. As per the literature, TMS might help regulate gamma oscillations, reduce behavioral symptoms, and normalize executive and autonomic dysfunction signs. TMS is a valuable technique for assessing the underlying neurophysiology associated with several neuropathologies. It is a unique tool for establishing potential neural mechanisms responsible for disease progression. Recently, rTMS has been advanced as a potential therapeutic technique to treat selected neurologic disorders. Such neurological disorders include Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis.

Moreover, worldwide, multiple studies have repeatedly demonstrated that TMS has antidepressant effects more significantly than sham treatment and that these effects are clinically meaningful. For diagnostic uses, TMS is a potential diagnostic tool in movement disorders. TMS is used worldwide and represents a novel technique with both diagnostic and therapeutic potential. TMS is used to study cortical excitability and intracortical inhibition and investigate cortical and cortico-spinal plasticity mechanisms implicated in ASD pathophysiology. Published studies showing promising results concluded that specific rTMS protocols targeting particular regions of the cortex might lead to improvement in specific behavioral deficits in some individuals with ASD; both the investigative and therapeutic results have been mixed. rTMS and other electrical stimulation devices can modulate the brain's functioning in either a facilitatory or suppressive manner and, when applied over several sessions, can have an additive effect lasting several months. If theories are correct that cortical mechanisms of excitability, connectivity, and plasticity are abnormal in ASD, then rTMS can modulate these mechanisms. Overall, in the hands of trained technicians, rTMS might have great potential as both a diagnostic and therapeutic tool for ASD.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Saudi Arabia
    • Riyadh Region
      • Riyadh, Riyadh Region, Saudi Arabia, 12372
        • Department of Physiology, Autism Research and Treatment Center (ARTC), King Saud University Medical City (KSUMC)/Collage of Medicine, King Saud University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Target population:

  • Autistic individuals
  • previously Diagnosed with ASD using the American Psychiatric Association's DSM-V criteria
  • previously Diagnosed using the Autism Diagnostic Observation Schedule (ADOS).

Inclusion Criteria:

  • Male and female ASD individuals
  • age between 5 and 11 years old
  • diagnosed with ASD on prior clinical assessment using the American Psychiatric Association's DSM-V criteria and corroborated by assessment using the Autism Diagnostic Observation Schedule (ADOS).
  • Normal hearing ability based on past hearing screens.
  • Participation will be limited to higher functioning (intelligence quotient [IQ] >70) to maximize successful completion of tested paradigms, maintain alertness/attention, furthermore, the ability to follow instructions.

Exclusion Criteria:

  • Individuals that are known to have epilepsy ( including Hx. of febrile convulsion) or have a family history of epilepsy.
  • Any individual with a previous Hx. Of head injuries
  • Any individual has been diagnosed with psychiatric illness, including ADHD, depression, psychosis, bipolar disorder, anxiety disorders, or OCD.
  • Individuals using a combination of Psychotropic Medications known for their significant seizure threshold lowering potential, for example, and not as a limitation: Bupropion, Citalopram, Duloxetine, Fluoxetine, Fluvoxamine, Mirtazapine, Paroxetine, Sertraline, Venlafaxine, Tricyclics, Olanzapine, Quetiapine, Aripiprazole, Ziprasidone, and Risperidone.
  • The presence of metallic objects, e.g., cranium clips or implanted biomedical devices.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: active rTMS group
Male and female ASD individuals aged between 5 and 11 years old who have been diagnosed with ASD. They should have a confirmed clinical diagnosis according to the DSM-5. This will be verified by a diagnostic report or direct communication with the diagnosing clinician. Also, with normal hearing based on past hearing screens. Exclusion criteria to ensure participant safety for the rTMS intervention and included: (1) a history of seizures or epileptiform activity; (2) the presence of any metallic implants within the cranium; (3) a history of significant head trauma or loss of consciousness; and (4) the presence of implanted electronic medical devices (e.g., pacemakers, cochlear implants). All participants in both study groups did not stop their medical or behavioral therapy for ASD. However, participants will be instructed to have a consistent medication regimen or behavioral treatment for at least one month before enrollment and throughout the trial.
Device: Stimulation with low frequency rTMS at 1 Hz
Stimulation with low-frequency rTMS at 1 Hz with 90% MT will be applied with a total of 180 pulses each time, which contains 18 trains with ten pulses and an interval of 20 s between any two adjacent trains. The TMS treatment course will be administered twice per week for 9 weeks; the first six treatments will be over the left DLPFC, the second six sessions will be over the right DLPFC, and the remaining six sessions will be placed on the bilateral DLPFC stimulation.
Other Names:
  • NeuroStar TMS Therapy System (Neuronetics, Inc; Malvern, Pennsylvania). with figure of 8- Coil and a special sensory guard ( SenStarTreatment Link).
No Intervention: wait-list-control group
Male and female ASD individuals aged between 5 and 11 years old who have been diagnosed with ASD. They should have a confirmed clinical diagnosis according to the DSM-5. This will be verified by a diagnostic report or direct communication with the diagnosing clinician. Also, with normal hearing based on past hearing screens. Exclusion criteria to ensure participant safety for the rTMS intervention and included: (1) a history of seizures or epileptiform activity; (2) the presence of any metallic implants within the cranium; (3) a history of significant head trauma or loss of consciousness; and (4) the presence of implanted electronic medical devices (e.g., pacemakers, cochlear implants). All participants in both study groups did not stop their medical or behavioral therapy for ASD. However, participants will be instructed to have a consistent medication regimen or behavioral treatment for at least one month before enrollment and throughout the trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive function
Time Frame: of intervention and 2 week, 3 Months after the last session in intervention for each participant
Measure the cognitive function by using Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task, looking of any Statistical significance changes in this score of cognitive testing by using CANTAB battery in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.
of intervention and 2 week, 3 Months after the last session in intervention for each participant
Severity level of Autism Spectrum disorders (ASD)
Time Frame: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Any Statistical significance change in the severity level of Autism (ASD) , looking for any changes in the score of Childhood Autism Rating Scale,Second Edition (CARS2-ST) in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

Score will be represented as Total row score and will be interpreted based on the following : for the age between 2-12 years old

  • (15-29.5) Minimal to no symptoms of autism spectrum disorder
  • (30 - 36.5) Mild to moderate symptoms of autism spectrum disorder
  • ( 37 and higher) Severe symptoms of autism spectrum disorder. CARS2-ST Score minimum= 15 and maximum= - , high CARS scores mean a worse outcome.
pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
Autism Spectrum disorder (ASD) Severity level
Time Frame: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Any Statistical significance change in the severity level of Autism (ASD) , looking for any changes in the score of The Social Responsiveness Scale (SRS) teste in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

Score will be represented as Total T-score and will be interpreted based on the following:

  • T-score of 59T or less ; the result in the normal range.
  • T-score of 60T through 75T; the result in the mild to moderate range.
  • T-score of 76T or higher; The result in the severe range. high SRS T-scores mean a worse outcome.
pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
Blood Biomarker ( Microtubule associated proteins (MAPs) ).
Time Frame: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Any Statistical significance change in the plasma levels of Blood biomarkers in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

Score will be represented as plasma concentration , Units of Measure: concentration unit pg/ml
pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
Blood Biomarker ( Neuron Specific Enolase (NSE);MYO 16 (myosin XVI); kirre like nephrin family adhesion molecule 3 (KIRREL3) ).
Time Frame: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Any Statistical significance change in the plasma levels of Blood biomarkers in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

Score will be represented as plasma concentration , Units of Measure: concentration unit ng/ml
pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Psychology and behaviours
Time Frame: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Any change in Psychology and behaviours in participants , looking for significant statistical analysis in the score of The Child Behavior Checklist (CBCL) in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

The CBCL uses a normative sample to create standard scores+ Percentile scores. These compare the raw score to what would be typical compared to responses for participants of the same gender and similar age . The standard scores are scaled so that 50 is average for the participants age and gender, with a standard deviation of 10 points. Higher scores indicate greater problems.
pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
Language,Speech and Communication skills
Time Frame: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Any speech and communication skills change in participants , looking for significant statistical analysis in the score of Orion's Pragmatic Language skills in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

Score will be represented as Total row score for each test Item in scale higher scores mean worse outcome.
pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
Sensory Processing using Sensory Processing Measure (SPM)
Time Frame: Before the beginning of intervention and 2 week, 3 Months after the last session in intervention for each participant

Any change in participants Sensory Processing , looking for significant statistical analysis in the score of Sensory Processing Measure (SPM)- (Home Form); in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

Score will be represented as Total row score for scale higher scores mean worse outcome. Scores for each scale fall into one of three interpretive ranges: Typical, Some Problems, or Definite Dysfunction
Before the beginning of intervention and 2 week, 3 Months after the last session in intervention for each participant
Sensory Processing
Time Frame: Before the beginning of intervention and 2 week, 3 Months after the last session in intervention for each participant

Any change in participants Sensory Processing , looking for significant statistical analysis in the score of the Short Sensory Profile in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

Score will be represented as Total row score for scale higher scores mean a better outcome; Total row score will be interpreted based on the following : (38-141) Define difference (142-154) Probable difference (155-190) typical performance
Before the beginning of intervention and 2 week, 3 Months after the last session in intervention for each participant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King Saud University

Investigators

  • Principal Investigator: HAYFA A ALGHABBAN, MD,MSc, Department of physiology, collage of Medicine, King Saud University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 20, 2024

Primary Completion (Actual)

April 30, 2025

Study Completion (Actual)

September 30, 2025

Study Registration Dates

First Submitted

June 30, 2024

First Submitted That Met QC Criteria

July 22, 2024

First Posted (Actual)

July 29, 2024

Study Record Updates

Last Update Posted (Estimated)

October 21, 2025

Last Update Submitted That Met QC Criteria

October 18, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • rTMS_ASD_SA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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