Functional brain mapping in pediatric neurosurgery

描述（由申请人提供）：该项目的目标是：（i）生成一个经验模型来预测癫痫手术后的长期语言结果，以及（ii）更好地了解语言系统在语音过程中的工作方式。大约1%的普通人群患有癫痫，而五分之一的癫痫是医学上难以治愈的。难治性局灶性癫痫患者的亚组受益于手术切除癫痫灶，保留重要功能区域。然而，在现实中，准确识别语言区域是困难的，特别是在儿童中，因为电刺激映射缺乏足够的灵敏度，通常需要几个小时才能完成，并且有刺激诱发癫痫发作的风险。在第一次融资中 在此期间，我们证明了皮层电图（ECoG）记录中与命名相关的γ活动（50-120 Hz）增强可以描绘语言回路，并且显示这种γ增强的部位的手术损伤比电刺激映射更好地预测急性术后语言结果。重要的下一步是确定长期语言结果的预测程度，因为一些但不是所有的儿童在切除语言网络后都能很好地恢复语言功能。为了最大限度地提高预测性能，我们将确定语言皮质和皮质下通路，同时将ECoG伽马映射与扩散加权成像（DWI）纤维追踪成像相结合。此外，预测模型将考虑功能恢复的慢性影响，以及受损语言网络对神经心理结局指标的急性影响。该项目意义重大，因为其结果将直接转化为患者管理，我们的创新多模态技术有可能成为定位功能重要的大脑结构的主流方法。 我们还将使用ECoG伽马映射，DWI纤维束成像和皮质-皮质诱发电位（CCEP）确定语言网络内的解剖和功能连接。人类语音的理论模型提出，语音和语义信息是通过弓状神经束在颞叶和额叶语言区之间传递的。然而，语音和语义信息的每个弓形通路的确切位置尚未阐明。此外，虽然现代理论模型表明额叶和颞叶之间存在双向信号传递，但每条通路中信号传递的方向效率尚未阐明。在这个项目中，我们将 明确确定这些涉及语音和语义功能的位点是否通过不同的弓状纤维束有差异地连接。我们还将确定“哪个方向”电信号在语言所涉及的两个脑叶内和跨脑叶传播更有效。本研究所建立的模型将有助于预测局灶性脑损伤后的特定语言症状，并最终可能更好地定位治疗靶点，以改善神经系统疾病中不同类型的语言障碍。

DESCRIPTION (provided by applicant): The goals of this project are: (i) to generate an empirical model to predict the long-term language outcome following epilepsy surgery and (ii) to better understand 'how' the language system works during speech. About 1% of the general population has epilepsy, while one-fifth of epilepsy is medically intractable. Subsets of patients with intractable focal epilepsy benefit from surgical resection of the seizure focus with functionally-important areas preserved. Yet, in reality, accurate identification of language areas is difficult, especially in children, since electrical stimulation mapping lacks sufficient sensitiity, often takes hours to complete, and has a risk of stimulation-induced seizures. In the first funding period, we demonstrated that naming-related augmentation of gamma activity (50-120 Hz) on electrocorticography (ECoG) recording can delineate the language circuitry, and that surgical damage of sites showing such gamma-augmentation predicted the acute postoperative language outcome better than electrical stimulation mapping. An important next step is to determine how well the long-term language outcome can be predicted, since some but not all children recover language function well after the resection of language networks. To maximize the predictive performance, we will determine the language cortex and subcortical pathway, while combining ECoG gamma mapping with diffusion weighted imaging (DWI) fiber tractography. Furthermore, the prediction model will take into account the chronic effect of functional recovery in addition to the acute effect of damaged language networks on neuropsychological outcome measures. This project is significant since the results will be directly translatable into patient management, and our innovative multimodality technique has the potential to become a mainstream method to localize functionally-important brain structures. We will also determine the anatomical and functional connectivity within the language networks, using ECoG gamma mapping, DWI tractography and cortico-cortical evoked potentials (CCEPs). Theoretical models of human speech propose that phonologic and semantic information is transferred, via the arcuate fasciculus, between the temporal and frontal language areas. Yet, the exact location of each arcuate pathway for phonologic and semantic information has not been elucidated. Furthermore, directional efficiency of signal transferring in each pathway has not been clarified, although a modern theoretical model indicates the presence of bi-directional signal transferring between the frontal and temporal lobes. In this project, we will specifically determine if these sites involved in phonological and semantic functions are differentially connected via distinct arcuate fasciculus fibers. We will also determine 'in which direction' electrical signals propagate more efficiently within and across the two lobes involved in language. The model refined or revised by this empirical study will help in prediction of specific language symptoms following focal brain damage, and ultimately may better localize the therapeutic targets for improving different types of language impairments in neurological diseases.