Functional brain mapping in pediatric neurosurgery

描述(由申请人提供)：这个项目的目标是：(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)更好地理解语言系统在语言过程中是如何工作的。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。部分难治性局灶性癫痫患者可从保留重要功能区的癫痫灶切除手术中获益。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敏感性，通常需要几个小时才能完成，并且有刺激诱发癫痫的风险。在第一笔资金中 期间，我们证明了皮层脑电(ECoG)记录上与命名相关的伽马活动(50-120赫兹)的增强可以描绘语言回路，并且手术损伤显示这种伽马活动的部位比电刺激标测更好地预测术后急性语言结果。下一步重要的是确定长期语言结果的预测能力，因为在切除语言网络后，一些但不是所有儿童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，同时结合ECoG伽玛图和扩散加权成像(DWI)纤维束成像。此外，预测模型将考虑到功能恢复的慢性影响，以及语言网络受损对神经心理结果指标的急性影响。这个项目意义重大，因为结果将直接转化为患者管理，我们创新的多模式技术有潜力成为定位重要功能大脑结构的主流方法。我们还将使用皮层脑电伽马图、弥散加权成像和皮质诱发电位(CCEP)来确定语言网络中的解剖和功能连接。人类言语的理论模型认为，语音和语义信息通过弧形神经束在颞叶和额叶语言区之间传递。然而，语音和语义信息的每条弧形通路的确切位置还没有被阐明。此外，尽管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性效率尚不清楚。在这个项目中，我们将 明确地确定这些参与语音和语义功能的位置是否通过不同的弓状束纤维差异地联系在一起。我们还将确定电信号在语言所涉及的两个脑叶内和跨脑叶更有效地传播。通过这项实证研究改进或修订的模型将有助于预测局灶性脑损伤后特定的语言症状，并最终可能更好地定位改善神经疾病不同类型语言障碍的治疗靶点。

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.