Tshimanga Louis Fabrice, Zanola Andrea, Facchini Silvia, Bisogno Antonio Luigi, Pini Lorenzo, Atzori Manfredo, Corbetta Maurizio
Department of Neuroscience, University of Padua, Padua, 35128 Italy.
Padova Neuroscience Center, University of Padua, Padua, 35128 Italy.
J Healthc Inform Res. 2025 Mar 26;9(3):401-436. doi: 10.1007/s41666-025-00197-6. eCollection 2025 Sep.
Stroke, a leading cause of mortality and disability, results in diverse dysfunctions linked to brain lesion locations. The intricate relationship between lesions and symptoms often defies linear analysis methods. Unraveling these connections can yield valuable insights to enhance patient care, optimize rehabilitation strategies, and unveil fundamental principles of healthy brain function. This study introduces a novel unsupervised framework to stratify patients into clinically coherent subgroups based on behavioral symptom profiles and identify their distinct neural correlates. NIHSS assessments are modeled as ordinal feature vectors, integrating symptom prevalence, severity, and covariance patterns into a unified measure of behavioral similarity among stroke survivors. The resulting similarity network is partitioned using Repeated Spectral Clustering, which accumulates partition evidence for stable subgroup discovery. Voxel-wise lesion analysis subsequently highlights each subgroup's collective neuroanatomical signatures. Despite being identified in a completely unsupervised manner based solely on NIHSS scores, the emergent clusters correspond to well-documented syndromes, validating the purely data-driven symptom groupings alongside established neurological knowledge. Clusters exhibit critical voxels in group-specific anatomical locations, even when average lesion maps spatially overlap, suggesting that our method disentangles functionally distinct substrates within shared vascular territories. Our workflow represents a significant methodological advancement, providing robust, clinically relevant insights into symptom phenotyping and lesion patterns. The framework's mathematical transparency and validation against canonical knowledge underscore its potential for generalization to multimodal biomarkers and broader biomedical research. To foster reproducibility, we provide open-source code.
中风是导致死亡和残疾的主要原因,会引发与脑损伤部位相关的各种功能障碍。损伤与症状之间的复杂关系常常使线性分析方法失效。解开这些联系可以为改善患者护理、优化康复策略以及揭示健康脑功能的基本原理提供有价值的见解。本研究引入了一种新颖的无监督框架,根据行为症状特征将患者分层为临床相关的亚组,并识别其独特的神经关联。美国国立卫生研究院卒中量表(NIHSS)评估被建模为有序特征向量,将症状患病率、严重程度和协方差模式整合为卒中幸存者行为相似性的统一度量。使用重复谱聚类对所得的相似性网络进行划分,该方法累积划分证据以发现稳定的亚组。随后的体素级损伤分析突出了每个亚组的集体神经解剖学特征。尽管这些亚组完全是基于NIHSS评分以无监督方式识别出来的,但出现的聚类对应于有充分文献记载的综合征,验证了纯粹由数据驱动的症状分组以及已有的神经学知识。即使平均损伤图谱在空间上重叠,聚类在特定组的解剖位置仍显示出关键体素,这表明我们的方法能够在共享血管区域内区分功能不同的基质。我们的工作流程代表了一项重大的方法学进展,为症状表型分析和损伤模式提供了强大的、与临床相关的见解。该框架的数学透明度以及针对经典知识的验证强调了其推广到多模态生物标志物和更广泛生物医学研究的潜力。为促进可重复性,我们提供了开源代码。