Yang Yuping, Woollams Anna, Lipp Ilona, Zhuo Zhizheng, Litwińczuk Marta Czime, Tomassini Valentina, Liu Yaou, Trujillo-Barreto Nelson J, Muhlert Nils
Division of Psychology, Communication and Human Neurosciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Hum Brain Mapp. 2025 Jul;46(10):e70284. doi: 10.1002/hbm.70284.
Recent research suggests that individuals with multiple sclerosis (MS) and cognitive impairment exhibit more effortful and less efficient transitions in brain network activity. Previous studies further highlight the increased vulnerability of specific regions, particularly the thalamus, to disease-related damage. This study investigates whether MS affects the controllability of specific brain regions in driving network activity transitions across the brain and examines the relationship between these changes and cognitive impairment in patients. Resting-state functional MRI and neuropsychological data were collected from 102 MS and 27 healthy controls. Functional network controllability analysis was performed to quantify how specific regions influence transitions between brain activity patterns or states. Disease alterations in controllability were assessed in the main dataset and then replicated in an independent dataset of 95 MS and 45 healthy controls. Controllability metrics were then used to distinguish MS from healthy controls and predict cognitive status. MS-specific controllability changes were observed in the subcortical network, particularly the thalamus, which were further confirmed in the replication dataset. Cognitively impaired patients showed significantly greater difficulty in the thalamus steering brain transitions towards difficult-to-reach states, which are typically associated with high-energy-cost cognitive functions. Thalamic network controllability proved more effective than thalamic volume in distinguishing MS from healthy controls (AUC = 88.3%), and in predicting cognitive status in MS (AUC = 80.7%). This study builds on previous research highlighting early thalamic damage in MS, aiming to demonstrate how this damage disrupts activity transitions across the cerebrum and may predict cognitive deficits. Our findings suggest that the thalamus in MS becomes less capable of facilitating broader brain activity transitions essential for high-energy-cost cognitive functions, implying a potential pathological mechanism that links thalamic functional changes to cognitive impairment in MS.
最近的研究表明，患有多发性硬化症（MS）和认知障碍的个体在脑网络活动中表现出更费力且效率更低的转换。先前的研究进一步强调了特定区域，尤其是丘脑，对疾病相关损伤的易损性增加。本研究调查MS是否会影响驱动全脑网络活动转换的特定脑区的可控性，并检查这些变化与患者认知障碍之间的关系。从102名MS患者和27名健康对照者中收集了静息态功能磁共振成像和神经心理学数据。进行功能网络可控性分析以量化特定区域如何影响脑活动模式或状态之间的转换。在主要数据集中评估可控性的疾病改变，然后在一个包含9名MS患者和45名健康对照者的独立数据集中进行重复验证。然后使用可控性指标区分MS患者和健康对照者，并预测认知状态。在皮层下网络，尤其是丘脑中观察到了MS特异性的可控性变化，这在重复数据集中得到了进一步证实。认知受损的患者在丘脑引导脑转换至难以达到的状态时表现出明显更大的困难，这些状态通常与高能量消耗的认知功能相关。丘脑网络可控性在区分MS患者和健康对照者方面（曲线下面积[AUC]=88.3%）以及在预测MS患者的认知状态方面（AUC=80.7%）比丘脑体积更有效。本研究基于先前强调MS早期丘脑损伤的研究，旨在证明这种损伤如何破坏大脑活动的转换，并可能预测认知缺陷。我们的研究结果表明，MS患者的丘脑促进对高能量消耗认知功能至关重要的更广泛脑活动转换的能力下降，这意味着一种将丘脑功能变化与MS认知障碍联系起来的潜在病理机制。
