Autism Spectrum Disorder
Conditions
Keywords
Autism spectrum, transcranial magnetic stimulation, neuronal connectivity
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.
Interventions
DEVICEtranscranial magnetic stimulation
The investigators will deliver a type of high frequency rTMS known as intermittent theta burst stimulation (iTBS), 2400 stimulations per session, equally divided between the bilateral IPL and IFG.
Sponsors
Christiana Care Health Services
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
The investigators will recruit ASD cases 13-18 years of age and implementing 18 sessions (3 times/week for 6 weeks) of rTMS or sham stimulation of the bilateral IPL/IFG in a prospective, single blind study design. During phase I (3 weeks), half of the subjects will receive rTMS, while the other half will receive sham stimulation. During phase II (3 weeks) all subjects will receive active stimulation. The investigators will deliver a type of high frequency rTMS known as intermittent theta burst stimulation (iTBS), 2400 stimulations per session, equally divided between the bilateral IPL and IFG.
Eligibility
Sex/Gender
ALL
Age
13 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1\. Fulfilling the DSM-V criteria for ASD and confirmed by CARS2, HF
Exclusion criteria
1. Patients with ASD exhibiting significant anxiety or contact avoidance, precluding them from cooperating with the procedure 2. Patients with a known diagnosis of seizures 3. Presence of any metallic implants or devices in the head or neck area 4. Pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
Primary ContactMitra Assadi, MD
Backup ContactRyan Ally, MD
Outcome results
None listed