Effects of rTMS on Cognitive Functions and Behavior in Individuals With Autism Spectrum Disorder
NCT Number: NCT06524310
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Autism Spectrum Disorder
Interventions: DEVICE: Stimulation with low frequency rTMS at 1 Hz
Sponsor: King Saud University
Sex: ALL
Age: CHILD
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: HEALTH_SERVICES_RESEARCH
Start Date: 2023-12-21
Completion Date: 2025-01-31
Locations: Department of Physiology, Autism Research and Treatment Center (ARTC), King Saud University Medical City (KSUMC)/Collage of Medicine, King Saud University, Riyadh, 12372, Saudi Arabia

Summary:
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. 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. Impaired GABAergic neurotransmission within the DLPFC has been linked with altered gamma oscillatory activity and working memory deficits. Transcranial magnetic stimulation (TMS) is one method used to deliver electrical stimuli through the scalp in conscious humans. Recently, rTMS is not only 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. It is still undetermined whether it is possible to improve the symptoms of ASD individuals through noninvasive neural modulation. Previous studies in ASD indicate that rTMS applied to DLPFC can modulate gamma oscillatory activity.

In this study, the investigators aim to examine the effectiveness of low-frequency rTMS in improving social cognitive function and emotion recognition in ASD individuals.

Further understanding of the effect of low-frequency rTMS in altering the cognitive function in ASD individuals may help to achieve some answers related to the mechanism behind ASD. This stimulation protocol could be a vital therapeutic strategy for the treatment of ASD in future clinical practice.

Primary Outcome Measures: Cognitive function, 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), 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, 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) )., 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) )., 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: Psychology and behaviours, 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, 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), 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, 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