Carotenuto Antonio, Valsasina Paola, Hidalgo de la Cruz Milagros, Cacciaguerra Laura, Preziosa Paolo, Marchesi Olga, Filippi Massimo, Rocca Maria A
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Mol Psychiatry. 2022 Mar;27(3):1765-1773. doi: 10.1038/s41380-021-01401-w. Epub 2022 Jan 7.
We aimed to investigate abnormal time-varying functional connectivity (FC) for thalamic sub-regions in multiple sclerosis (MS) and their clinical, cognitive and MRI correlates. Eighty-nine MS patients (49 relapsing-remitting [RR] MS; 40 progressive [P] MS) and 53 matched healthy controls underwent neurological, neuropsychological and resting state fMRI assessment. Time-varying connectivity (TVC) was quantified using sliding-window seed-voxel correlation analysis. Standard deviation of FC across windows was taken as measure of TVC, while mean connectivity across windows expressed static FC. MS patients showed reduced TVC vs controls between most of thalamic sub-regions and fronto-temporo-occipital regions. At the same time, they showed increased static FC between all thalamic sub-regions and structurally connected cortico-subcortical regions. TVC reduction was mainly driven by RRMS; while PMS exhibited a variable pattern of TVC abnormalities, characterized by reduced TVC between frontal/motor thalamic seeds and default-mode network areas and increased TVC vs controls/RRMS between posterior thalamic sub-regions and occipito-temporo-insular cortices, associated with severity of clinical disability. Compared with controls, both cognitively preserved and impaired patients showed reduced TVC between anterior thalamic sub-regions and frontal cortex. Cognitively impaired patients also showed increased TVC of the right postcentral thalamic sub-region with the cingulate cortex and postcentral gyrus vs both controls and cognitively preserved patients. Divergent patterns of TVC thalamic abnormalities were found between RRMS and PMS patients. TVC reduction in RRMS may represent the attempt of thalamic network to keep with stable connections. Conversely, increased TVC of posterior thalamic sub-regions characterized PMS and cognitively impaired MS, possibly reflecting maladaptive mechanisms.
我们旨在研究多发性硬化症（MS）患者丘脑亚区域的异常时变功能连接（FC）及其与临床、认知和MRI的相关性。89例MS患者（49例复发缓解型[RR]MS；40例进展型[P]MS）和53名匹配的健康对照者接受了神经学、神经心理学和静息态功能磁共振成像评估。使用滑动窗口种子体素相关分析对时变连接性（TVC）进行量化。将各窗口间FC的标准差作为TVC的指标，而各窗口间的平均连接性表示静态FC。与对照组相比，MS患者大多数丘脑亚区域与额颞枕叶区域之间的TVC降低。同时，他们所有丘脑亚区域与结构相连的皮质-皮质下区域之间的静态FC增加。TVC降低主要由RRMS驱动；而PMS表现出TVC异常的可变模式，其特征是额叶/运动丘脑种子与默认模式网络区域之间的TVC降低，而后丘脑亚区域与枕颞岛叶皮质之间的TVC相对于对照组/RRMS增加，这与临床残疾的严重程度相关。与对照组相比，认知功能保留和受损的患者丘脑前亚区域与额叶皮质之间的TVC均降低。认知受损的患者还表现出右侧中央后丘脑亚区域与扣带回皮质和中央后回之间的TVC相对于对照组和认知功能保留的患者增加。RRMS和PMS患者之间发现了不同的丘脑TVC异常模式。RRMS中TVC降低可能代表丘脑网络维持稳定连接的尝试。相反，后丘脑亚区域TVC增加是PMS和认知受损MS的特征，可能反映了适应不良机制。
