ORCID Profile
0000-0002-5039-7793
Current Organisations
University of Cambridge
,
National Taiwan University
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Publisher: Wiley
Date: 23-05-2023
DOI: 10.1002/AUR.2954
Abstract: Although previous open‐label trials suggest the therapeutic potential of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), methodological caveats exist. We conducted an 8‐week randomized, double‐blind sham‐controlled trial to investigate the efficacy of inhibitory continuous theta burst stimulation (cTBS, a variant of rTMS) over the left DLPFC in in iduals with ASD. Sixty children, adolescents and young adults (aged 8–30 years) with ASD without co‐occurring intellectual disabilities were randomized to a 16‐session 8‐week cTBS versus sham stimulation course, with a follow‐up 4 weeks after the trial. The Active group was not superior to the Sham group in any clinical or neuropsychological metrics at Week 8 or Week 12. Time effects of 8‐week cTBS on symptoms and executive function were remarkable in both Active and Sham groups, with comparable response rates and effect sizes of changes in symptoms/cognition between groups. Our results from a sufficiently powered s le do not endorse the superior efficacy of cTBS over the left DLPFC to the shamed stimulation for children, adolescents and adults with ASD. These findings suggest that earlier positive open‐label trial findings may be generalized by generalized lacebo effects. This highlights the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD.
Publisher: Cold Spring Harbor Laboratory
Date: 13-10-2021
DOI: 10.1101/2021.10.11.464005
Abstract: Neuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of in iduals with II (ASD-II-Only) or MV expression (ASD-MV). Sixty-five participants with ASD (ASD-Whole 16.6±5.9 years comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC 17.3±5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross-section (FC), and a combined index (FDC), and brain-symptom/cognition associations. ASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-II, relative to TDC, showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus-splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Non-verbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction. We could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small s le size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms. ASD-associated white matter alterations appear driven by in iduals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied sub-populations on the spectrum in research.
Publisher: SAGE Publications
Date: 25-02-2021
Abstract: The posterior superior temporal sulcus is a potential therapeutic target of brain stimulation for autism spectrum disorder. We conducted a 4-week randomized, single-blind parallel sham-controlled trial, followed by additional 4-week open-label intervention to evaluate the feasibility and efficacy regarding intermittent theta burst stimulation over the bilateral posterior superior temporal sulcus in autism spectrum disorder. In total, 78 intellectually able children and adolescents were randomized to the active ( n = 40) and sham groups ( n = 38). During the first 4 weeks, the active group received two-session/week intermittent theta burst stimulation, whereas the sham group received the same number of sham stimulation. After unblinding, both groups received eight-session real stimulation over the additional 4 weeks. In total, 91% participants completed the protocol with mild and transitory side-effects. There was no significant group-by-time interaction for active versus sham group on clinical symptoms and social cognitive performances in the first 4 weeks. The within-group analysis revealed 8 weeks (including a 4-week blind trial and a 4-week open-label intervention) of intermittent theta burst stimulation achieved greater efficacy than 4-week interventions. Participants with higher intelligence, better social cognitive performances, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. Our study demonstrated the feasibility of long-term intermittent theta burst stimulation over the posterior superior temporal sulcus in children and adolescents with autism spectrum disorder. However, the findings from the first 4-week blind trial do not support the therapeutic efficacy of intermittent theta burst stimulation over the posterior superior temporal sulcus on the clinical symptoms and cognitive performance of social impairment, given the current stimulation protocol. The exploratory analyses suggest that the therapeutic efficacy might be moderated by several in idual characteristics and more intermittent theta burst stimulation sessions. Intermittent theta burst stimulation is a varied form of repetitive transcranial magnetic non-invasive brain stimulation technique used to treat several neurological and psychiatric disorders. Its feasibility and therapeutic effects on the bilateral posterior superior temporal sulcus in children with autism are unknown. We conducted a single-blind, sham-controlled parallel randomized clinical trial in a hitherto largest s le of intellectually able children with autism ( N = 78). Participants randomized to the active group received two-session/week intermittent theta burst stimulation for continuous 8 weeks. Those in the sham group received two-session/week sham stimulations in the first 4 weeks and then active intervention for the following 4 weeks after unblinding. First, we found that continuous 8-week intermittent theta burst stimulation on the bilateral posterior superior temporal sulcus in children with autism is safe and tolerable. Second, we found that 8-week intermittent theta burst stimulation produced greater therapeutic efficacy, although we did not find any significant effects of 4-week intermittent theta burst stimulation on core symptoms and social cognitive performances in autism. Further analysis revealed that participants with higher intelligence and better social cognitive performance, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. This study identified that the factors contribute to responders and the results suggest that longer courses of non-invasive brain stimulation may be needed to produce therapeutic benefits in autism, with consideration of heterogeneous responses.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Tai-Li Chou.