Malherbe Caroline, Cheng Bastian, Königsberg Alina, Cho Tae-Hee, Ebinger Martin, Endres Matthias, Fiebach Jochen B, Fiehler Jens, Galinovic Ivana, Puig Josep, Thijs Vincent, Lemmens Robin, Muir Keith W, Nighoghossian Norbert, Pedraza Salvador, Simonsen Claus Z, Wouters Anke, Gerloff Christian, Hilgetag Claus C, Thomalla Götz
University Medical Center Hamburg-Eppendorf, Institute of Computational Neuroscience, Hamburg, Germany.
Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Brain Commun. 2021 Sep 2;3(3):fcab204. doi: 10.1093/braincomms/fcab204. eCollection 2021.
Lesion analysis is a fundamental and classical approach for inferring the causal contributions of brain regions to brain function. However, many studies have been limited by the shortcomings of methodology or clinical data. Aiming to overcome these limitations, we here use an objective multivariate approach based on game theory, Multi-perturbation Shapley value Analysis, in conjunction with data from a large cohort of 394 acute stroke patients, to derive causal contributions of brain regions to four principal functional components of the widely used National Institutes of Health Stroke Score measure. The analysis was based on a high-resolution parcellation of the brain into 294 grey and white matter regions. Through initial lesion symptom mapping for identifying all potential candidate regions and repeated iterations of the game-theoretical approach to remove non-significant contributions, the analysis derived the smallest sets of regions contributing to each of the four principal functional components as well as functional interactions among the regions. Specifically, the factor 'language and consciousness' was related to contributions of cortical regions in the left hemisphere, including the prefrontal gyrus, the middle frontal gyrus, the ventromedial putamen and the inferior frontal gyrus. Right and left motor functions were associated with contributions of the left and right dorsolateral putamen and the posterior limb of the internal capsule, correspondingly. Moreover, the superior corona radiata and the paracentral lobe of the right hemisphere as well as the right caudal area 23 of the cingulate gyrus were mainly related to left motor function, while the prefrontal gyrus, the external capsule and the sagittal stratum fasciculi of the left hemisphere contributed to right motor function. Our approach demonstrates a practically feasible strategy for applying an objective lesion inference method to a high-resolution map of the human brain and distilling a small, characteristic set of grey and white matter structures contributing to fundamental brain functions. In addition, we present novel findings of synergistic interactions between brain regions that provide insight into the functional organization of brain networks.
病灶分析是推断脑区对脑功能因果贡献的一种基本且经典的方法。然而，许多研究受到方法学或临床数据缺点的限制。为克服这些限制，我们在此使用一种基于博弈论的客观多变量方法，即多扰动夏普利值分析，并结合来自394例急性中风患者的大样本队列数据，以得出脑区对广泛使用的美国国立卫生研究院卒中量表测量的四个主要功能成分的因果贡献。该分析基于将大脑高分辨率分割为294个灰质和白质区域。通过初始病灶症状映射以识别所有潜在候选区域，并对博弈论方法进行反复迭代以去除无显著贡献的区域，该分析得出了对四个主要功能成分中每一个都有贡献的最小区域集以及这些区域之间的功能相互作用。具体而言，“语言和意识”因素与左半球皮质区域的贡献有关，包括前额回、额中回、腹内侧壳核和额下回。左右运动功能分别与左右背外侧壳核和内囊后肢的贡献相关。此外，右半球的放射冠上部和中央旁小叶以及扣带回的右尾状区域23主要与左运动功能相关，而左半球的前额回、外囊和矢状层束对右运动功能有贡献。我们的方法展示了一种切实可行的策略，即将客观的病灶推断方法应用于人类大脑的高分辨率图谱，并提炼出一组对基本脑功能有贡献的小型、特征性灰质和白质结构集。此外，我们还展示了脑区之间协同相互作用的新发现，这为脑网络的功能组织提供了见解。
