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.

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.

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

3 month

We had to adverse events, adverse events were monitored

Although we were budgeted for 20 patients, we only recruited 16 patients and 5 dropped out and did not complete behavioral measures. Fortunately, all 16 subjects completed the 10 sessions of TMS and there were no adverse effects. One of the impediments was persuading families to attend 10 sessions of TMS as well as the neuropsychic assessments.

The TMS coil will be placed on the scalp at a 90 degree angle and will be turned on to create the perception of delivering the stimulation to the brain.