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 individual characteristics and more intermittent theta burst stimulation sessions.

Lay abstract

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 sample 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.

中文翻译：

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自闭症谱系障碍儿童颞上后沟的间歇性 theta 爆发刺激：一项为期 4 周的随机盲法对照试验，随后进行另一项为期 4 周的开放标签干预

后上颞沟是自闭症谱系障碍脑刺激的潜在治疗靶点。我们进行了一项为期 4 周的随机、单盲平行假手术对照试验，随后进行了额外的 4 周开放标签干预，以评估在自闭症谱系障碍中对双侧颞上沟间歇性 theta 脉冲刺激的可行性和有效性。总共有 78 名有智力的儿童和青少年被随机分配到活跃组 ( n  = 40) 和假组 ( n = 38）。在前 4 周内，活跃组接受了两次/周的间歇性 theta 爆发刺激，而假手术组接受了相同数量的假刺激。揭盲后，两组都在额外的 4 周内接受了 8 次真正的刺激。总共有 91% 的参与者完成了该协议，但有轻微和短暂的副作用。在前 4 周，主动组与假组在临床症状和社会认知表现方面没有显着的组间交互作用。组内分析显示 8 周（包括 4 周盲试验和 4 周开放标签干预）间歇性 theta 脉冲刺激比 4 周干预取得了更大的疗效。智力较高、社会认知能力较好的参与者，除了基线时注意力缺陷多动障碍的严重程度较低之外，他们更有可能成为反应者。我们的研究证明了对患有自闭症谱系障碍的儿童和青少年的颞后上沟进行长期间歇性 theta 脉冲刺激的可行性。然而，鉴于当前的刺激方案，第一个 4 周盲试验的结果不支持间歇性 theta 脉冲刺激对后颞上沟的临床症状和社会障碍认知表现的治疗效果。探索性分析表明，治疗效果可能会受到几个个体特征和更多间歇性 theta 脉冲刺激会话的影响。我们的研究证明了对患有自闭症谱系障碍的儿童和青少年的颞后上沟进行长期间歇性 theta 脉冲刺激的可行性。然而，鉴于当前的刺激方案，第一个 4 周盲试验的结果不支持间歇性 theta 脉冲刺激对后颞上沟的临床症状和社会障碍认知表现的治疗效果。探索性分析表明，治疗效果可能会受到几个个体特征和更多间歇性 theta 脉冲刺激会话的影响。我们的研究证明了对患有自闭症谱系障碍的儿童和青少年的颞后上沟进行长期间歇性 theta 脉冲刺激的可行性。然而，鉴于当前的刺激方案，第一个 4 周盲试验的结果不支持间歇性 theta 脉冲刺激对后颞上沟的临床症状和社会障碍认知表现的治疗效果。探索性分析表明，治疗效果可能会受到几个个体特征和更多间歇性 theta 脉冲刺激会话的影响。考虑到当前的刺激方案，第一个 4 周盲试验的结果不支持间歇性 theta 脉冲刺激对后颞上沟的临床症状和社交障碍的认知表现的治疗效果。探索性分析表明，治疗效果可能会受到几个个体特征和更多间歇性 theta 脉冲刺激会话的影响。考虑到当前的刺激方案，第一个 4 周盲试验的结果不支持间歇性 theta 脉冲刺激对后颞上沟的临床症状和社交障碍认知表现的治疗效果。探索性分析表明，治疗效果可能会受到几个个体特征和更多间歇性 theta 脉冲刺激会话的影响。

摘要

间歇性 theta 脉冲刺激是一种不同形式的重复经颅磁非侵入性脑刺激技术，用于治疗多种神经和精神疾病。其对自闭症儿童双侧颞后上沟的可行性和治疗效果尚不清楚。我们在迄今为止最大的智商自闭症儿童样本中进行了一项单盲、假对照平行随机临床试验（N = 78）。随机分配到活动组的参与者连续 8 周接受两次/周的间歇性 theta 脉冲刺激。假手术组在前 4 周接受两次/周假刺激，然后在揭盲后的接下来 4 周内接受积极干预。首先，我们发现对自闭症儿童双侧颞上沟进行连续 8 周间歇性 theta 脉冲刺激是安全且可耐受的。其次，我们发现 8 周间歇性 theta 爆发刺激产生了更大的治疗效果，尽管我们没有发现 4 周间歇性 theta 爆发刺激对自闭症的核心症状和社会认知表现有任何显着影响。进一步的分析显示，具有更高智力和更好社会认知表现的参与者，除了基线时注意力缺陷多动障碍的严重程度较低之外，他们更有可能成为反应者。这项研究确定了这些因素对反应有影响，结果表明可能需要更长的非侵入性脑刺激疗程才能在自闭症中产生治疗益处，同时考虑到异质反应。