Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
Neuroimage Clin. 2021;29:102552. doi: 10.1016/j.nicl.2020.102552. Epub 2020 Dec 29.
To determine the extent of metabotropic glutamate receptor type 5 (mGluR5) network abnormalities associated with focal cortical dysplasia (FCD), we performed graph theoretical analysis of [C]ABP688 PET binding potentials (BP), which allows for quantification of mGluR5 availability. Undirected graphs were constructed for the entire cortex in 17 FCD patients and 33 healthy controls using inter-regional similarity of [C]ABP688 BP. We assessed group differences in network integration between healthy controls and the ipsilateral and contralateral hemispheres of FCD patients. Compared to healthy controls, FCD patients showed reduced network efficiency and reduced small-world connectivity. The mGluR5 network of FCD patients was also less resilient to targeted removal of high centrality nodes, suggesting a less integrated network organization. In highly efficient hub nodes of FCD patients, we observed a significant negative correlation between local efficiency and duration of epilepsy only in the contralateral hemisphere, suggesting that some nodes may be more vulnerable to persistent epileptic activity. Our study provides the first in vivo evidence for a widespread reduction in cortical mGluR5 network integration in FCD patients. In addition, we find that ongoing epileptic activity may alter chemoarchitectural brain organization resulting in reduced efficiency in distant regions that are essential for network integration.
为了确定与局灶性皮质发育不良（FCD）相关的代谢型谷氨酸受体 5（mGluR5）网络异常的程度，我们对[C]ABP688 PET 结合势（BP）进行了图论分析，这允许定量测定 mGluR5 的可用性。使用[C]ABP688 BP 的区域间相似性，我们在 17 名 FCD 患者和 33 名健康对照者的整个皮质中构建了无向图。我们评估了健康对照者与 FCD 患者同侧和对侧半球之间的网络整合的组间差异。与健康对照组相比，FCD 患者的网络效率降低，小世界连通性降低。FCD 患者的 mGluR5 网络对靶向去除高中心性节点的弹性也较低，表明网络组织的整合度较低。在 FCD 患者的高有效枢纽节点中，我们仅在对侧半球观察到局部效率与癫痫持续时间之间存在显著的负相关，这表明一些节点可能更容易受到持续癫痫活动的影响。我们的研究首次提供了 FCD 患者皮质 mGluR5 网络整合广泛降低的体内证据。此外，我们发现持续的癫痫活动可能改变化学建筑组织的大脑组织，导致对网络整合至关重要的远距离区域的效率降低。
