Enhancement of Behavioral and Cognitive Outcomes in Autism Spectrum Disorder Via Neurostimulation

Autism spectrum disorder (ASD) encompasses a range of limitations in reciprocal social and communicative milestones, as well as restrictive and/or repetitive patterns of behavior which lead to significant functional challenges impacting individuals throughout their lifespan. There are major shortcomings in the existing pharmacological interventions; they are of limited efficacy, target a subset of problematic behaviors, and fail to improve social cognition. To overcome these limitations and improve outcomes, the investigators study the use of neurostimulation to mitigate the social and cognitive manifestations of ASD.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Device: Trans Cranial Magnetic Stimulation

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique that alters cortical excitability by repeated induction of electromagnetic activity. FDA approved for depression, rTMS is a promising tool in the field of neuropsychiatry with an excellent safety profile. A prevailing hypothesis in ASD proposes that mirror neuron dysfunction in the inferior parietal lobule (IPL) contributes to the core deficits. The left and right IPL regions support different social and cognitive functions and moreover, are differentially impacted in ASD. Therefore, it can be expected that enhancing function of the IPL may produce positive but hemispheric-dependent effects on social cognition. The investigators long-term goal in this pilot proposal is to understand whether stimulating IPL with rTMS improves social and cognitive outcomes in ASD.

This research, which builds upon our proof-of-concept testing of 4 patients, proposes 10 sessions of rTMS stimulation of the IPL. Participants will be randomized to receive active stimulation to either the left or right-IPL (with sham stimulation to the contralateral side) in a prospective, double-blind protocol during which neither the subject nor the neuropsychologist obtaining and interpreting the outcome measures will have awareness of the rTMS group. For targeting the IPL, which correlates with the Brodmann areas 40/7 on the cortex, the investigators use disposable mapping caps, and for the purpose of blinding, the investigators use a standard shamming technique. Outcome measures include neuropsychological testing administered at baseline, after completion of TMS regime, and three months later. Within this design, the investigators have three aims:

Aim 1: Assess the differential effects of rTMS of the left versus right IPL on linguistic abilities and executive function in ASD. Hypothesis: rTMS stimulation of the IPL leads to long term potentiation and hence enhances cognitive performance in a hemispheric dependent manner with left-IPL stimulation enhancing linguistic ability and right-IPL stimulation enhancing executive function. To measure the effects, the investigators will use the Delis-Kaplan Executive Function System Verbal Fluency task (D-KEFS) and two elements of the NIH toolbox: Flanker: a test to measure the inhibitory and attentional facets of Executive Functioning. Dimensional Change Card Sort (DCCS): a task designed to assess cognitive flexibility. The investigators expect improvement in the Flanker and DCCS scores with right IPL stimulation and D-KEFS score improvement with left IPL stimulation.

Aim 2: Determine the effects of unilateral rTMS of the IPL on social/behavioral deficits in children and young adults with ASD. Hypothesis: rTMS simulation of the mirror neuron system potentiates similar improvements in social cognition despite hemispheric laterality via separate but related mechanisms. To measure the outcomes of right v/s left unilateral IPL stimulation, the investigators will use two standard scales and compare the numerical values before and after the intervention. The Social Responsiveness Scale - 2nd Edition (SRS2) and the Repetitive Behavior Scale-Revised (RRBs) are validated parent/caregiver-rated scale of social/communication deficits and restricted/repetitive behaviors respectively.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Mitra Assadi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Fulfilling the Diagnostic and Statistical Manual for Mental Disorders 5th edition (DSM-V) criteria for ASD and confirmed by Gilliam Asperger Disorder Scale (GADS)
• The patient exhibiting adequate understanding and cooperation for the procedure

Exclusion criteria

• Patients with ASD exhibiting significant anxiety or contact avoidance, precluding them from cooperating with the procedure
• Children with a known diagnosis of seizures
• Presence of any metallic implants or devices in the head or neck area
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: left IPL stimulation; half of the subjects will receive TMS on the left inferior parietal lobule.	Device: Trans Cranial Magnetic Stimulation; Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique that alters cortical excitability by repeated induction of electromagnetic activity. FDA approved for depression, rTMS is a promising tool in the field of neuropsychiatry with an excellent safety profile.
Active Comparator: right IPL stimulation; half of the subjects will receive TMS on the right inferior parietal lobule.	Device: Trans Cranial Magnetic Stimulation; Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique that alters cortical excitability by repeated induction of electromagnetic activity. FDA approved for depression, rTMS is a promising tool in the field of neuropsychiatry with an excellent safety profile.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effects of rTMS on Reciprocal Social Awareness	Social Responsiveness Scale, Second Edition (SRS-2), Parent/Caregiver form; 65 items scored 0-3; total raw score range 0-195. Higher scores = greater social impairment. This study reports raw totals (not T-scores). Instrument: SRS-2	at baseline and 5 weeks of rTMS
The Effects of rTMS on Reciprocal Rigid Patterns of Behavior	Repetitive Behavior Scale-Revised (RBS-R); 43 items scored 0-3; total raw score range 0-129. Higher scores = more severe restricted/repetitive behaviors. We report total raw scores.	at baseline and 5 weeks of rTMS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effect of rTMS on Verbal Fluency	Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency; scores converted to age-normed scaled scores (mean 10, SD 3). Higher scores = better verbal fluency/executive function. We report the Total Correct scaled score per the manual.	at baseline and 5 weeks of rTMS
The Effects of rTMS on Executive Function Using Flanker Task	NIH Toolbox Flanker Inhibitory Control and Attention; Age-Adjusted Standard Scores (mean 100, SD 15) reported. Higher scores = better inhibitory control/attention.	at baseline and 5 weeks of rTMS
The Effects of rTMS on Executive Function	NIH Toolbox Dimensional Change Card Sort (DCCS); Age-Adjusted Standard Scores (mean 100, SD 15) reported. Higher scores = better cognitive flexibility.	at baseline and 5 weeks of rTMS

Collaborators and Investigators

• Sponsor: Christiana Care Health Services
• Collaborators: Dupont Applied Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: May 1, 2022
• First Submitted That Met QC Criteria: May 10, 2022
• First Posted (Actual): May 12, 2022

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 15, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: DDD 604994

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