Chen Rong, Dadario Nicholas B, Cook Brennan, Sun Lichun, Wang Xiaolong, Li Yujie, Hu Xiaorong, Zhang Xia, Sughrue Michael E
The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States.
Front Neurol. 2023 Jul 6;14:1063408. doi: 10.3389/fneur.2023.1063408. eCollection 2023.
An improved understanding of the neuroplastic potential of the brain has allowed advancements in neuromodulatory treatments for acute stroke patients. However, there remains a poor understanding of individual differences in treatment-induced recovery. Individualized information on connectivity disturbances may help predict differences in treatment response and recovery phenotypes. We studied the medical data of 22 ischemic stroke patients who received MRI scans and started repetitive transcranial magnetic stimulation (rTMS) treatment on the same day. The functional and motor outcomes were assessed at admission day, 1 day after treatment, 30 days after treatment, and 90 days after treatment using four validated standardized stroke outcome scales. Each patient underwent detailed baseline connectivity analyses to identify structural and functional connectivity disturbances. An unsupervised machine learning (ML) agglomerative hierarchical clustering method was utilized to group patients according to outcomes at four-time points to identify individual phenotypes in recovery trajectory. Differences in connectivity features were examined between individual clusters. Patients were a median age of 64, 50% female, and had a median hospital length of stay of 9.5 days. A significant improvement between all time points was demonstrated post treatment in three of four validated stroke scales utilized. ML-based analyses identified distinct clusters representing unique patient trajectories for each scale. Quantitative differences were found to exist in structural and functional connectivity analyses of the motor network and subcortical structures between individual clusters which could explain these unique trajectories on the Barthel Index (BI) scale but not on other stroke scales. This study demonstrates for the first time the feasibility of using individualized connectivity analyses in differentiating unique phenotypes in rTMS treatment responses and recovery. This personalized connectomic approach may be utilized in the future to better understand patient recovery trajectories with neuromodulatory treatment.
对大脑神经可塑性潜力的深入理解推动了急性中风患者神经调节治疗的进展。然而,对于治疗诱导恢复中的个体差异仍了解不足。关于连接性障碍的个性化信息可能有助于预测治疗反应和恢复表型的差异。我们研究了22名缺血性中风患者的医学数据,这些患者在同一天接受了MRI扫描并开始重复经颅磁刺激(rTMS)治疗。在入院当天、治疗后1天、治疗后30天和治疗后90天,使用四种经过验证的标准化中风结局量表评估功能和运动结局。每位患者都进行了详细的基线连接性分析,以识别结构和功能连接性障碍。采用无监督机器学习(ML)凝聚层次聚类方法,根据四个时间点的结局对患者进行分组,以识别恢复轨迹中的个体表型。检查各个聚类之间连接性特征的差异。患者的中位年龄为64岁,50%为女性,中位住院时间为9.5天。在使用的四种经过验证的中风量表中,有三种在治疗后所有时间点之间均显示出显著改善。基于ML的分析确定了代表每个量表独特患者轨迹的不同聚类。发现在各个聚类之间,运动网络和皮质下结构的结构和功能连接性分析存在定量差异,这可以解释Barthel指数(BI)量表上的这些独特轨迹,但不能解释其他中风量表上的轨迹。本研究首次证明了使用个性化连接性分析来区分rTMS治疗反应和恢复中独特表型的可行性。这种个性化的连接组学方法未来可能会被用于更好地理解神经调节治疗下患者的恢复轨迹。