Abnormal Connectivity Involving the Social Reciprocity Network in Autism and the Impact of Neurostimulation in Mitigating the Abnormalities

Not Applicable

Recruiting

• Conditions: Autism Spectrum Disorder

• Registration Number: NCT06807684
• Lead Sponsor: Christiana Care Health Services

Brief Summary

There is no consensus regarding the neurological substrate underpinning ASD. The investigators describe the novel concept of "social reciprocity network" and hypothesize that aberrant connectivity/oscillatory patterns affecting this network contribute to the core deficits in ASD.

The overarching goal of this trial is to explore abnormalities involving the neuronal connectivity and oscillatory patterns within the social reciprocity network and to elucidate the role of modulating this network via rTMS in improving the above measures and social cognition in ASD. Quantitative electroencephalography (QEEG) coherence and spectral power analysis are reliable measures of neuronal connectivity and dynamics. The investigators aim to study the QEEG coherence/spectral power analysis to explore the neuronal dynamics affecting the social reciprocity network in ASD.

Detailed Description

Autism spectrum disorder (ASD) encompasses a range of limitations in reciprocal and communicative milestones, leading to significant functional challenges throughout the lifespan. While there is no consensus regarding the neuroanatomical substrate underpinning ASD, there are two major schools of thought: a group of researchers have focused on abnormalities affecting the mirror neurons and other cortical areas involved in social reciprocity, while others have proposed a more widespread alteration in neuronal organization in this condition resulting in abnormal white matter trajectories leading to cortical over or under connectivity. The investigators describe the social reciprocity network: the mirror neurons populated in the inferior frontal gyrus (IFG) and inferior parietal lobule (IPL), plus cortical areas involved in abstract social cognition including the medial prefrontal cortex, temporal-parietal junction and posterior cingulate gyrus. We hypothesize that aberrant connectivity affecting the above neuronal circuitry, "the social reciprocity network" contributes significantly to the core deficits in this condition.

Quantitative electroencephalography (QEEG) coherence and spectral power analysis are reliable measures of functional connectivity and neuronal dynamics. The investigators aim to study the QEEG coherence/spectral power analysis to explore the abnormal neuronal dynamics affecting the social reciprocity network in ASD. The existing literature suggest that noninvasive brain modulation, via Repetitive transcranial magnetic stimulation (rTMS), could potentially ameliorate the aberrant connectivity and the behaviors in ASD by altering neuronal dynamics. The investigator's overarching goal is to explore the neuronal connectivity in the social reciprocity network and to elucidate the mechanism of modulating these connections in improving social cognition in ASD.

Within this design, there are 3 aims:

Aim 1: Exploring the QEEG measures of connectivity and oscillatory patterns in the social reciprocity network in ASD. Hypothesis: abnormal connectivity affecting the social reciprocity network contributes to the core deficits in ASD.

Aim 2: Assessing the effects of rTMS of the bilateral social reciprocity network on the connectivity/spectral analysis as well as social cognition in ASD. Hypothesis: neurostimulation of the social reciprocity network ameliorates social cognition, power densities and the functional connectivity within the network.

Study Timeline

• Study First Submitted: 2024-08-12
• Study Start: 2024-08-15
• Study First Submitted QC: 2025-01-29
• Status Verified: 2025-02
• Study First Posted: 2025-02-04
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Exploring neuronal connectivity and oscillatory patterns in the social reciprocity network in ASD	9 weeks	Abnormal connectivity affecting the social reciprocity network contributes to the core deficits in ASD. The investigators will record an electroencephalogram (EEG) at baseline and after completing treatments with transcranial magnetic stimulation. The EEG data will be subjected to mathematical analysis in order to calculate measures of EEG coherence, functional connectivity and oscillatory patterns within the social reciprocity network. These numerical values will be used to discern: 1. presence of a consistent pattern across the social reciprocity network at baseline for measurements of neuronal connectivity as well as the oscillatory patterns including alpha, beta, gamma, theta and mu rhythms; 2. improvement of the above neuronal connectivity and oscillatory patterns after the transcranial magnetic intervention

Secondary Outcome Measures

Name	Time	Method
Assessing the effects of iTBS stimulation of the bilateral social reciprocity network on social cognition in ASD	9 weeks	Presence and severity of autism spectrum disorder as assessed using the Childhood Autism Rating Scale, 2nd addition, high functioning.; The investigators hypothesize that iTBS of the social reciprocity network ameliorates social cognition in ASD. To measure the outcomes, the investigators will implement the Childhood Autism Rating Scale, 2nd addition, high functioning (CARS2, HF). This is a validated test that is based on actual measures of patient performance on behavioral tasks (score 30-37). The test is administered by a board-certified neuropsychologist before and after neurostimulation intervention. The test produces numerical values quantifying social cognition, reciprocity and rigid behaviors, comparing the results before and after the treatment to discern any potential efficacy.

Trial Locations

Locations (1)

Christiana Care; 🇺🇸 Newark, Delaware, United States