Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Wayne State University, Detroit, MI 48201, USA.
Department of Neurosurgery, Yokohama City University, Yokohama, Kanagawa 2360004, Japan.
Brain. 2021 Dec 16;144(11):3340-3354. doi: 10.1093/brain/awab225.
During a verbal conversation, our brain moves through a series of complex linguistic processing stages: sound decoding, semantic comprehension, retrieval of semantically coherent words, and overt production of speech outputs. Each process is thought to be supported by a network consisting of local and long-range connections bridging between major cortical areas. Both temporal and extratemporal lobe regions have functional compartments responsible for distinct language domains, including the perception and production of phonological and semantic components. This study provides quantitative evidence of how directly connected inter-lobar neocortical networks support distinct stages of linguistic processing across brain development. Novel six-dimensional tractography was used to intuitively visualize the strength and temporal dynamics of direct inter-lobar effective connectivity between cortical areas activated during each linguistic processing stage. We analysed 3401 non-epileptic intracranial electrode sites from 37 children with focal epilepsy (aged 5-20 years) who underwent extra-operative electrocorticography recording. Principal component analysis of auditory naming-related high-gamma modulations determined the relative involvement of each cortical area during each linguistic processing stage. To quantify direct effective connectivity, we delivered single-pulse electrical stimulation to 488 temporal and 1581 extratemporal lobe sites and measured the early cortico-cortical spectral responses at distant electrodes. Mixed model analyses determined the effects of naming-related high-gamma co-augmentation between connecting regions, age, and cerebral hemisphere on the strength of effective connectivity independent of epilepsy-related factors. Direct effective connectivity was strongest between extratemporal and temporal lobe site pairs, which were simultaneously activated between sentence offset and verbal response onset (i.e. response preparation period); this connectivity was approximately twice more robust than that with temporal lobe sites activated during stimulus listening or overt response. Conversely, extratemporal lobe sites activated during overt response were equally connected with temporal lobe language sites. Older age was associated with increased strength of inter-lobar effective connectivity especially between those activated during response preparation. The arcuate fasciculus supported approximately two-thirds of the direct effective connectivity pathways from temporal to extratemporal auditory language-related areas but only up to half of those in the opposite direction. The uncinate fasciculus consisted of <2% of those in the temporal-to-extratemporal direction and up to 6% of those in the opposite direction. We, for the first time, provided an atlas which quantifies and animates the strength, dynamics, and direction specificity of inter-lobar neural communications between language areas via the white matter pathways. Language-related effective connectivity may be strengthened in an age-dependent manner even after the age of 5.
在口头交流中，我们的大脑会经历一系列复杂的语言处理阶段：声音解码、语义理解、检索语义连贯的单词，以及言语输出的显性产生。每个过程都被认为是由一个网络支持的，该网络由连接大脑主要皮质区域的局部和远程连接组成。颞叶和颞外叶区域都有负责不同语言领域的功能隔室，包括语音和语义成分的感知和产生。这项研究提供了定量证据，证明了直接连接的脑叶间新皮质网络如何在大脑发育过程中支持语言处理的不同阶段。使用新颖的六维束流追踪直观地可视化了在每个语言处理阶段激活的皮质区域之间直接脑叶间有效连接的强度和时间动态。我们分析了 37 名患有局灶性癫痫（年龄 5-20 岁）的儿童的 3401 个非癫痫性颅内电极部位，这些儿童接受了手术外脑电描记术记录。听觉命名相关高伽马调制的主成分分析确定了每个皮质区域在每个语言处理阶段的相对参与度。为了量化直接有效连接，我们向 488 个颞叶和 1581 个颞外叶部位发送单脉冲电刺激，并测量了远距离电极处的早期皮质-皮质光谱响应。混合模型分析确定了与命名相关的高伽马共增强、年龄和大脑半球对有效连接强度的影响，这些影响独立于癫痫相关因素。颞叶和颞外叶部位之间的直接有效连接最强，这些部位在句子结束和言语反应开始之间同时激活（即反应准备期）；这种连接的强度大约是刺激聆听或显性反应期间激活的颞叶部位的两倍。相反，显性反应期间激活的颞外叶部位与颞叶语言部位同样连接。年龄较大与脑叶间有效连接强度的增加有关，尤其是在反应准备期间激活的部位。弓状束支持大约三分之二来自颞叶听觉语言相关区域到颞外叶的直接有效连接通路，但仅支持相反方向的一半。钩束由颞叶到颞外叶方向的通路的<2%组成，最多可达相反方向的 6%。我们首次提供了一个图谱，通过白质通路定量和动画化了语言区域之间脑叶间神经通讯的强度、动态和方向特异性。即使在 5 岁以后，语言相关的有效连接也可能以年龄依赖的方式增强。
