Leone Riccardo, Geysen Steven, Deco Gustavo, Kobeleva Xenia
Computational Neurology Group, Ruhr University Bochum, Bochum, Germany.
Faculty of Medicine, University of Bonn, Bonn, Germany.
Hum Brain Mapp. 2024 Dec 1;45(17):e70081. doi: 10.1002/hbm.70081.
White matter (WM) tracts shape the brain's dynamical activity and their damage (e.g., white matter hyperintensities, WMH) yields relevant functional alterations, ultimately leading to cognitive symptoms. The mechanisms linking the structural damage caused by WMH to the arising alterations of brain dynamics is currently unknown. To estimate the impact of WMH on brain dynamics, we combine neural-mass whole-brain modeling with a virtual-lesioning (disconnectome) approach informed by empirical data. We account for the heterogeneous effects of WMH either on inter-regional communication (i.e., edges) or on dynamics (i.e., nodes) and create models of their local versus global, and edge versus nodal effects using a large fMRI dataset comprising 188 non-demented individuals (120 cognitively normal, 68 with mild cognitive impairment) with varying degrees of WMH. We show that, although WMH mainly determine local damage to specific WM tracts, these lesions yield relevant global dynamical effects by reducing the overall synchronization of the brain through a reduction of global coupling. Alterations of local nodal dynamics through disconnections are less relevant and present only at later stages of WMH damage. Exploratory analyses suggest that education might play a beneficial role in counteracting the reduction in global coupling associated with WMH. This study provides generative models linking the structural damage caused by WMH to alterations in brain dynamics. These models might be used to evaluate the detrimental effects of WMH on brain dynamics in a subject-specific manner. Furthermore, it validates the use of whole-brain modeling for hypothesis-testing of structure-function relationships in diseased states characterized by empirical disconnections.
白质（WM）束塑造了大脑的动态活动，其损伤（例如，白质高信号，WMH）会产生相关的功能改变，最终导致认知症状。目前尚不清楚将WMH导致的结构损伤与大脑动力学改变联系起来的机制。为了估计WMH对大脑动力学的影响，我们将神经团全脑建模与基于经验数据的虚拟损伤（断开连接组）方法相结合。我们考虑了WMH对区域间通信（即边）或动力学（即节点）的异质性影响，并使用包含188名非痴呆个体（120名认知正常，68名轻度认知障碍）且具有不同程度WMH的大型功能磁共振成像数据集，创建了其局部与全局、边与节点效应的模型。我们表明，尽管WMH主要决定对特定白质束的局部损伤，但这些损伤通过降低全局耦合来减少大脑的整体同步性，从而产生相关的全局动态效应。通过断开连接导致的局部节点动力学改变不太相关，仅在WMH损伤的后期出现。探索性分析表明，教育可能在抵消与WMH相关的全局耦合减少方面发挥有益作用。这项研究提供了将WMH导致的结构损伤与大脑动力学改变联系起来的生成模型。这些模型可用于以个体特异性方式评估WMH对大脑动力学的有害影响。此外，它验证了全脑建模在以经验性断开连接为特征的疾病状态下用于结构 - 功能关系假设检验的用途。
