Personalized theta-burst stimulation enhances social skills in young minimally verbal children with autism: a double-blind randomized controlled trial.
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Abstract
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 functional connectivity.
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 hyper-connectivity. 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.
背景：语言能力低下的自闭症儿童研究不足，缺乏有效的治疗方案。针对杏仁核及其回路的个性化连续脉冲刺激（cTBS）可能是一种潜在的治疗方法。方法：在一项双盲随机对照试验中，语言能力最低的自闭症儿童（2-8岁）接受4周的cTBS治疗。杏仁核优化功能连接（AOFC）组（N=23）接受针对与杏仁核功能连接的左背外侧前额皮质部位的个性化刺激。非优化对照组（N=21）在标准前额叶部位接受刺激。我们评估了自闭症诊断观察计划评分、杏仁核体积、自发神经活动和功能连通性的变化。结果：个性化aofc引导的cTBS改善了社交和沟通技能，效果值是NO组的两倍（Cohen’s d = 0.55 vs. 0.24）。AOFC组表现出杏仁核体积、自发神经活动和超连通性的更大减少。杏仁核与默认模式、额顶叶和背侧注意网络的网络水平连接变化与临床改善相关。电场映射分析显示，标准靶点和优化靶点之间电场重叠越大，治疗效果越好。结论：个性化的aofc引导下的cTBS通过调节杏仁核结构和连通性来提高自闭症儿童的社交技能和沟通能力。杏仁核网络连通性的变化预测了临床改善，表明神经回路可塑性和行为结果之间存在机制联系。这些发现证明了精确靶向神经调节在解决自闭症治疗中对这一未充分研究人群的关键空白方面的潜力。
期刊介绍：
Biological Psychiatry is an official journal of the Society of Biological Psychiatry and was established in 1969. It is the first journal in the Biological Psychiatry family, which also includes Biological Psychiatry: Cognitive Neuroscience and Neuroimaging and Biological Psychiatry: Global Open Science. The Society's main goal is to promote excellence in scientific research and education in the fields related to the nature, causes, mechanisms, and treatments of disorders pertaining to thought, emotion, and behavior. To fulfill this mission, Biological Psychiatry publishes peer-reviewed, rapid-publication articles that present new findings from original basic, translational, and clinical mechanistic research, ultimately advancing our understanding of psychiatric disorders and their treatment. The journal also encourages the submission of reviews and commentaries on current research and topics of interest.
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