Schmitt Lauren M, Wang Jun, Pedapati Ernest V, Thurman Angela John, Abbeduto Leonard, Erickson Craig A, Sweeney John A
Division of Developmental and Behavioral Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Brain Commun. 2020;2(1). doi: 10.1093/braincomms/fcz042. Epub 2019 Dec 9.
Fragile X syndrome is the most common inherited intellectual disability and monogenic cause of autism spectrum disorder. Expressive language deficits, especially in speech production, are nearly ubiquitous among individuals with fragile X, but understanding of the neurological bases for these deficits remains limited. Speech production depends on feedforward control and the synchronization of neural oscillations between speech-related areas of frontal cortex and auditory areas of temporal cortex. Interaction in this circuitry allows the corollary discharge of intended speech generated from an efference copy of speech commands to be compared against actual speech sounds, which is critical for making adaptive adjustments to optimize future speech. We aimed to determine whether alterations in coherence between frontal and temporal cortices prior to speech production are present in individuals with fragile X and whether they relate to expressive language dysfunction. Twenty-one participants with full-mutation fragile X syndrome (aged 7-55 years, eight females) and 20 healthy controls (matched on age and sex) completed a talk/listen paradigm during high-density EEG recordings. During the talk task, participants repeated pronounced short vocalizations of 'Ah' every 1-2 s for a total of 180 s. During the listen task, participants passively listened to their recordings from the talk task. We compared pre-speech event-related potential activity, N1 suppression to speech sounds, single trial gamma power and fronto-temporal coherence between groups during these tasks and examined their relation to performance during a naturalistic language task. Prior to speech production, fragile X participants showed reduced pre-speech negativity, reduced fronto-temporal connectivity and greater frontal gamma power compared to controls. N1 suppression during self-generated speech did not differ between groups. Reduced pre-speech activity and increased frontal gamma power prior to speech production were related to less intelligible speech as well as broader social communication deficits in fragile X syndrome. Our findings indicate that coordinated pre-speech activity between frontal and temporal cortices is disrupted in individuals with fragile X in a clinically relevant way and represents a mechanism contributing to prominent speech production problems in the disorder.
脆性X综合征是最常见的遗传性智力残疾以及自闭症谱系障碍的单基因病因。表达性语言缺陷，尤其是在言语产生方面，在脆性X患者中几乎普遍存在，但对这些缺陷的神经学基础的理解仍然有限。言语产生依赖于前馈控制以及额叶皮层言语相关区域与颞叶皮层听觉区域之间神经振荡的同步。该神经回路中的相互作用使得从言语命令的传出副本生成的预期言语的伴随放电能够与实际语音进行比较，这对于进行适应性调整以优化未来言语至关重要。我们旨在确定脆性X患者在言语产生之前额叶和颞叶皮层之间的连贯性是否存在改变，以及它们是否与表达性语言功能障碍有关。21名患有完全突变脆性X综合征的参与者（年龄7 - 55岁，8名女性）和20名健康对照者（年龄和性别匹配）在高密度脑电图记录期间完成了一个说/听范式。在说话任务中，参与者每1 - 2秒重复发出清晰的短音“啊”，共持续180秒。在听任务中，参与者被动聆听他们在说话任务中的录音。我们比较了两组在这些任务期间的言语前事件相关电位活动、对语音的N1抑制、单次试验伽马功率以及额颞连贯性，并检查了它们与自然语言任务表现的关系。与对照组相比，在言语产生之前，脆性X参与者表现出言语前负波减少、额颞连接性降低以及额叶伽马功率增加。两组在自我产生言语期间的N1抑制没有差异。言语产生之前言语前活动减少以及额叶伽马功率增加与脆性X综合征中言语清晰度较低以及更广泛的社会沟通缺陷有关。我们的研究结果表明，额叶和颞叶皮层之间协调的言语前活动在脆性X患者中以临床相关的方式受到破坏，并且代表了导致该疾病中突出言语产生问题的一种机制。
