Effects of transcranial pulse stimulation on autism spectrum disorder: a double-blind, randomized, sham-controlled trial

Abstract

Transcranial pulse stimulation (TPS) has been proven effective to improve cognition, memory, and depressive symptoms of Alzheimer’s disease, but supporting evidence on other neurological diseases or neuropsychiatric disorders remains limited. This study aimed to investigate the effects of TPS on the right temporoparietal junction, which is a key node for social cognition for Autism Spectrum Disorder, and to examine the association between TPS and executive and social functions. This double-blinded, randomized, sham-controlled trial included 32 participants (27 males), aged 12–17years with Autism Spectrum Disorder. All eligible participants were randomized into either the verum or sham TPS group, on a 1: 1 ratio, based on the Childhood Autism Rating Scale (CARS) screening score. Sixteen participants received 6 verum TPS sessions (energy level: 0.2–0.25 mJ/mm2, and 2.5–4.0 Hz pulse frequency, 800 pulse/session) in two weeks on alternate days. The remaining 16 participants received sham TPS stimulation. The primary outcome measure included CARS score changes, evaluated by parents, from baseline to 3-month follow-ups. Secondary outcomes included a self-reported questionnaire responded to by parents and cognitive tests responded to by participants. A licensed mental health professional evaluated clinical global impression-severity (CGI-S), improvement (CGI-I), efficacy (CGI-E), and total score (CGI-T). Results revealed significant interactions in CARS and other secondary outcomes. Significant group and time effects were found in most secondary outcomes. Additionally, significant differences were found between the TPS and Sham TPS groups in CARS, CGI-I, and CGI-T immediately after 2 weeks of TPS intervention (all P < 0 .05), and effects were sustainable at 1-and 3-month follow-up, compared with baseline. The effect size of CARS (d= 0.83–0.95) and CGI-I (d =4.12–4.37) were large to medium immediately after intervention and sustained at 1-month post-stimulation; however, the effects were reduced to small at 3-month post-stimulation (d= 2.31). These findings indicated that TPS, over rTPJ, was effective to reduce the core symptoms of autism spectrum disorder, as evidenced by a 24% reduction in the total CARS score in the verum TPS group. Additionally, the CGI total score was reduced by 53.7% in the verum TPS group at a 3-month follow-up, compared with the baseline. Participants in the verum TPS group had shown substantial improvement at 1-and 3-month follow-up, compared with baseline, although some of the neuropsychological test results were deemed statistically insignificant. Future replication of this study should include a larger sample derived from multi-nations to determine TPS as an alternative top-on treatment option in neuropsychiatry.

Current state of clinical ultrasound neuromodulation

“…So far, only one clinical ultrasound neuromodulation study has been published in developmental disorders. Cheung et al (2023b) investigated the effect of TPS in a randomized sham-controlled clinical trial in 32 participants between 12 and 17 years of age with autism spectrum disorder who received sonication directed towards the right temporoparietal junction. Autism symptoms and global clinical impression significantly improved in the verum group compared to sham, and changes sustained for at least 3 months.…”

Efficacy and safety of transcranial pulse stimulation in young adolescents with attention-deficit/hyperactivity disorder: a pilot, randomized, double-blind, sham-controlled trial

“…Placebo effects must be considered when interpreting the results. The third study was a double-blind, randomized, sham-controlled trial evaluating the efficacy of TPS for autism spectrum disorder in 32 young adolescents (27 males) aged between 12 and 17 years in Hong Kong ( 40 , 41 ). This trial used the same stimulation protocol (energy level: 0.2–0.25 mJ/mm2, pulse frequency: 2.5–4.0 Hz, 800 pulses/session) over 2 weeks on alternate days, but the ASD trial targeted the rTPJ.…”

“…We set up the hypothesis of 30% improvement of ADHD symptoms in the TPS group was based on a similar published double blinded RCT using TPS on young adolescents (age 12–18) with Autism Spectrum Disorder ( 41 ) which led to a 24% reduction in the Childhood Autism Rating Scale (CARS), the primary outcome of this trial ( 41 ). We speculated the 5% increase in discomfort for the sham TPS group was based on the following arguments:…”

“…headache/pain is the most common adverse effect reported in three trials: (1) TPS randomized, sham-controlled trial on young adolescents with Autism Spectrum Disorder ( 41 ); (2) TPS randomized controlled trial using waitlist control on patients with Major Depressive Disorder (age 18–65) ( 39 ); and (3) the first open-label study that tested the efficacy of TPS on older adults (age 65+) with Alzheimer’s Disease ( 27 ). These three published trials had a < 4% adverse effect in either the TPS group or the sham group/waitlist control group.…”

“…Prior to this study, we also adopted a similar double-blind, randomized, sham-controlled trial on young adolescents with autism spectrum disorder (aged 12–17 years), but we used 800 TPS pulse (energy level: 0.2–0.3 mJmm −2; pulse frequencies of 2–4 Hz pulse per second) in each session, administered in 6 sessions spanning across 2-week period, as we only targeted on the rTPJ (right temporoparietal junction). Only 1/3 of participants out of 15 in the TPS group reported transient headache on a numerical pain score of 3–5 out of 10 but none of these participants required any pain analgesics after the intervention ( 41 ).…”