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TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism
Published on: December 28, 2010
Personalized Theta Burst Stimulation Enhances Social Skills in Young Minimally Verbal Children With Autism: A
Jinming Xiao1, Yating Ming1, Lei Li1
1Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China; MOE Key Laboratory for Neuro Information, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, China.
Insights
Personalized continuous theta burst stimulation (cTBS) improved social and communication skills in minimally verbal children with autism. This precision neuromodulation approach targeted amygdala connectivity, showing promising results for an understudied population.
Area of Science:
- Neuroscience
- Neuromodulation
- Developmental Psychology
Background:
- Minimally verbal children with autism spectrum disorder (ASD) remain an understudied population with limited therapeutic options.
- The amygdala and its associated circuitry are implicated in core ASD symptoms, suggesting it as a potential therapeutic target.
- Personalized continuous theta burst stimulation (cTBS) offers a novel approach for neuromodulation in this group.
Purpose of the Study:
- To investigate the efficacy of personalized amygdala-optimized functional connectivity (AOFC)-guided cTBS in improving social and communication skills in minimally verbal children with autism.
- To explore the effects of AOFC-guided cTBS on amygdala structure, neural activity, and functional connectivity.
- To establish a mechanistic link between neural circuit modulation and behavioral improvements.
Main Methods:
- A double-blind, randomized controlled trial involving minimally verbal children with autism (ages 2-8 years) over 4 weeks of cTBS.
- Two groups: AOFC group received personalized cTBS targeting a left dorsolateral prefrontal cortex site functionally connected to the amygdala; a non-optimized (NO) control group received stimulation at a standard prefrontal site.
- Outcome measures included Autism Diagnostic Observation Schedule scores, amygdala volume, spontaneous neural activity, and functional connectivity (FC).
Main Results:
- AOFC-guided cTBS demonstrated a clinically significant improvement in social and communication skills, with an effect size twice that of the NO group (Cohen's d = 0.55 vs. 0.24).
- The AOFC group exhibited greater reductions in amygdala volume, spontaneous neural activity, and hyperconnectivity.
- Network-level amygdala connectivity changes with default mode, frontoparietal, and dorsal attention networks correlated with clinical improvements, and greater electric field overlap predicted better outcomes.
Conclusions:
- Personalized AOFC-guided cTBS effectively enhanced social and communication abilities in minimally verbal children with autism by modulating amygdala structure and connectivity.
- Observed changes in amygdala network connectivity provide a mechanistic explanation for the behavioral improvements, highlighting neural circuit plasticity.
- Precision-targeted neuromodulation, specifically AOFC-guided cTBS, shows significant potential for treating this understudied population with autism spectrum disorder.
Background:
Minimally verbal children with autism are understudied and lack effective treatment options. Personalized continuous theta burst stimulation (cTBS) targeting the amygdala and its circuitry may be a potential therapeutic approach for this population.
Methods:
In a double-blind randomized controlled trial, minimally verbal children with autism (ages 2-8 years) received 4 weeks of cTBS. An amygdala-optimized functional connectivity (AOFC) group (n = 23) received personalized stimulation targeting a left dorsolateral prefrontal cortex site functionally connected with the amygdala. A non-optimized (NO) control group (n = 21) received stimulation at a standard prefrontal site. We assessed changes in Autism Diagnostic Observation Schedule scores, amygdala volume, spontaneous neural activity, and FC.
Results:
Personalized AOFC-guided cTBS improved social and communication skills with an effect size twice that of the NO group (Cohen's d = 0.55 vs. 0.24). The AOFC group showed greater reductions in amygdala volume, spontaneous neural activity, and hyperconnectivity. Network-level amygdala connectivity changes with default mode, frontoparietal, and dorsal attention networks were correlated with clinical improvements. Field mapping analysis revealed that greater electric field overlap between standard and optimized targets predicted better treatment outcomes.
Conclusions:
Personalized AOFC-guided cTBS enhanced social skills and communication in minimally verbal children with autism by modulating amygdala structure and connectivity. Changes in amygdala network connectivity predicted clinical improvements, suggesting a mechanistic link between neural circuit plasticity and behavioral outcomes. These findings demonstrate the potential of precision-targeted neuromodulation in addressing a critical gap in autism treatment for this understudied population.
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