Transcranial Temporal Interference Stimulation for Children With Autism Spectrum Disorders

Individualized Targeted Transcranial Temporal Interference Stimulation for Children With Autism Spectrum Disorder: A Single-Blinded, Randomized, Controlled Exploratory Trial

The goal of this single-blinded, randomized controlled trial is to assess the safety, tolerability, and feasibility of tTIS for children with ASD. The main question it aims to answer is:

- Is tTIS safe, tolerable, and feasible for use for children with autism spectrum disorder?

Researchers will compare tTIS group with control group to explore the safety and feasibility of the transcranial electrical stimulation for children with autism.

Participants will:

• tTIS group: undergo 5 days of temporal tTIS.
• Sham group: undergo 5 days of temporal tTIS without low-frequency envelope.

From baseline to 4 weeks after intervention completion, subjects will be followed up regarding clinical symptoms and adverse events:

• Primary Outcome Measures: Safety and feasibility of tTIS, assessed by adverse events, treatment completion rate, adherence to the stimulation protocol and tolerability.
• Secondary/Exploratory Outcome Measures: Changes in SRS-2 total scores and other clinical measures related to language, adaptive functioning, and cognition.

This research is a 5-week single-blinded, randomized controlled trial, planning to enroll 16 ASD children aged 4-10 with a full-scale intelligence quotient (FSIQ) of 50 or above. Children who satisfy all inclusion criteria without meeting any exclusion criteria, may be enrolled after their legal guardians provided the written informed consent.

Eligible subjects will be randomly divided into two groups: tTIS group and sham group. The tTIS group will undergo 5 days of temporal TI stimulation (1.5mA, 2040/2000Hz, 20min/session, 6 sessions/day); the control group will undergo 5 days of temporal TI stimulation (1.5mA, 2000/2000Hz, 20min/session, 6 sessions/day, without 40Hz envelope compared to tTIS group)

At baseline, subjects will undergo physical measurements, demographic and medical history collection, intelligence test and symptom clinical scale assessments, and resting-state EEG collection. From the start of intervention until 4 weeks after completion, subjects will be followed up regarding clinical symptoms, neuroimaging, and adverse events.

Primary Outcome Measures:

- Safety and feasibility of tTIS, assessed by adverse events, treatment completion rate, adherence to the stimulation protocol and tolerability.

Secondary outcomes:

• Change in Social Responsiveness Scale, Second Edition (SRS-2) total score from baseline to immediately after completion of the 5-day intervention.
• Change in SRS-2 total score from baseline to 4 weeks after completion of the 5-day intervention.
• Changes in other clinical measures from baseline to 4 weeks after completion of the 5-day intervention, including the Chinese Communicative Development Inventory (CCDI), Childhood Autism Rating Scale (CARS), Peabody Picture Vocabulary Test (PPVT), selected subtests of A Developmental Neuropsychological Assessment, Second Edition (NEPSY-II; Narrative Memory, Memory for Faces, Theory of Mind, Word Generation, and Affect Recognition), and Clinical Global Impression (CGI) scale scores.

Exploratory Outcomes:

- resting-state and task-state EEG neuroimaging characteristics before intervention, immediately after the 5-day intervention, and 4 weeks after completion of the 5-day intervention

Inclusion Criteria:

• Children aged 4-10 years
• Meeting the diagnostic criteria for ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and confirmed by the Autism Diagnostic Observation Schedule (ADOS) and/or the Autism Diagnostic Interview-Revised (ADI-R)
• Full Scale Intelligence Quotient (FSIQ) ≥50
• Signed informed consent form

Exclusion Criteria:

• Individuals with metal implants in the body
• Individuals with neurological disorders such as epilepsy
• Those requiring surgical treatment due to structural abnormalities indicated by brain MRI examination
• Those diagnosed with genetic or chromosomal abnormalities
• Individuals with mental illness (such as early-onset schizophrenia)
• Those with severe cardiac disease
• Individuals with increased intracranial pressure
• Those currently participating in other clinical trials
• Those who received new intervention protocols within 4 weeks prior to enrollment.