基于胼胝体量化连接的痫性电活动跨半球传导机制研究

The detailed interrelation between the cerebral cortex and the corpus callosum remain to be defined, making the inter-hemispherical pathway of epileptic discharge inadequately elucidated. Our previous quantitative analysis of white matter connections with a focus on epileptic propagation has already mapped the correspondance between the splenium of corpus callosum and temporal cortices, suggesting comparable relationship might be prevalent among corpus callosum and other major parts of cerebral cortex. In this, we further hypothesized that the inherent interflow based on substantial linkage of cerebral cortices via specific parts of plays a critical role in whole-brained generalization of epileptic activity. Thus, we plan to clarify such relevance. By advanced technology of neuroimaging quantitative analysis, the white matter connections between the corpus callosum and function-defined districts partitioned by the modern atlas of cortex in human population is supposed to be displayed and comprehensively verified by“quantified parcellation of subregions based on fibroarchitechture” and “subcortico-cortical evoked potential” from the point of pathology and electrophysiology. Furthermore, as an ultimate result, the refined connectionism between corpus callosum and bilateral cortical areas will be inspected in epilepsy patients. It will be valuable in answering the theoretical question which is currently unclear as how the pathological activity of epilepsy transmit crossing hemispheres. In consideration of the massive neurological impairment after classic anterior two third or full-length corpus callosotomy, the clinical significance of this study lies in the theoretical support for methods of minimal invasive treatment including selective ablation of corpus callosum or even neuromodulation in generalized epilepsy patients.

胼胝体与大脑皮层之间的连接排列并不确切，导致痫性电活动跨半球传导的机制也不明确。从研究癫痫传导出发，本项目前期通过可定量的白质连接分析，测绘出了胼胝体压部到颞叶各脑区之间的对应关系，有证据表明，其余胼胝体与皮层之间可能也有类似的对应关系，由此本项目提出假说:“胼胝体与大脑皮层是固定对应的，此种对应关系是痫性活动跨半球传导的连接基础”。本次申请将明确这种对应关系，通过最新的可定量化的白质连接分析方法，首先明确皮层脑图谱中的功能亚区与胼胝体的白质连接，再参考病理学“定量化的基于纤维构筑的亚区分割”和电生理的“皮层下-皮层诱发电位”连接测量结果，得出人群中胼胝体与大脑皮层的连接机制，最后在癫痫患者个体中进一步证实，从而回答尚不明确的痫性电活动跨半球传导机制的理论问题。本项目可改进传统的胼胝体2/3离断术或全离断术损伤过大的问题，为微创的胼胝体精准离断和神经调控等新治疗方法提供理论依据。

研究背景与目的.研究发现癫痫发作过程中常出现痫性电活动的双侧半球传导，使发作复杂化，但目前胼胝体各区域与皮层的对应关系并不清楚。本研究旨在从结构连接、纤维构筑及电生理连接等方向，对半球间跨胼胝体脑网络进行定量分析，明确胼胝体各亚区与皮层的对应关系，阐明癫痫电活动跨胼胝体传导的机制。.研究方法.首先，本研究采集100例健康年轻受试者的高分辨弥散加权MRI数据，定量化分析脑图谱中各皮层亚区在胼胝体上的结构连接；其次，作为参考和验证，我们纳入8例人胼胝体标本进行切片、染色及定量化测绘其纤维构筑的特征，以及纳入40例双侧埋置SEEG电极的癫痫患者，以皮层—皮层诱发电位的方式明确胼胝体与皮层的电生理连接机制；最后，构建一个组水平的胼胝体亚区标准化模板，用于癫痫患者的个体化治疗。.研究结果.我们构建了一个包含100例健康受试者的脑网络结构连接组，并基于皮层自动解剖标记图谱和人脑网络组图谱定义胼胝体各亚区与大脑皮层的对应关系，综合对半球间跨胼胝体脑网络的结构连接组学、组织纤维构筑和电生理连接的分析结果，我们发现：连接单模态、初级的皮层功能亚区（如中央区的初级体感运动区、枕叶的初级视觉区等）的胼胝体亚区内，定量各向异性值更高，以较大直径的有髓纤维分布为主，半球间电信号传导速率更高；连接多模态、高级的皮层功能亚区（如前额内侧、前额背外侧及颞叶新皮层等区域）的胼胝体纤维亚区内，定量各向异性值较低，以较小直径的纤维分布为主，半球间电信号传导速率相对较低。基于上述对应关系，我们构建了一个涵盖解剖标记和长程功能连接信息的胼胝体亚区标准化模板。.结论.本研究基于结构连接组学、组织纤维构筑和电生理连接特征等角度，围绕半球间跨胼胝体脑网络进行定量分析，初步阐明癫痫电活动跨胼胝体传导并双侧泛化的机制，基于上述结果创建了一个涵盖解剖标记和长程功能连接信息的胼胝体分区模板，为临床上对难治性癫痫患者进行神经调控或精准离断胼胝体亚区等个体化的治疗方式提供理论依据和指导。