Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Melbourne, Australia.
J Neurol. 2023 May;270(5):2360-2369. doi: 10.1007/s00415-023-11637-x. Epub 2023 Mar 1.
Friedreich ataxia (FRDA) is a rare, inherited neurodegenerative disease characterised in most cases by progressive and debilitating motor dysfunction. Degeneration of cerebellar white matter pathways have been previously reported, alongside indications of cerebello-cerebral functional alterations. In this work, we examine resting-state functional connectivity changes within cerebello-cerebral circuits, and their associations with disease severity (Scale for the Assessment and Rating of Ataxia [SARA]), psychomotor function (speeded and paced finger tapping), and white matter integrity (diffusion tensor imaging) in 35 adults with FRDA and 45 age and sex-matched controls. Voxel-wise seed-based functional connectivity was assessed for three cerebellar cortical regions (anterior lobe, lobules I-V; superior posterior lobe, lobules VI-VIIB; inferior posterior lobe, lobules VIIIA-IX) and two dentate nucleus seeds (dorsal and ventral). Compared to controls, people with FRDA showed significantly reduced connectivity between the anterior cerebellum and bilateral pre/postcentral gyri, and between the superior posterior cerebellum and left dorsolateral PFC. Greater disease severity correlated with lower connectivity in these circuits. Lower anterior cerebellum-motor cortex functional connectivity also correlated with slower speeded finger tapping and less fractional anisotropy in the superior cerebellar peduncles, internal capsule, and precentral white matter in the FRDA cohort. There were no significant between-group differences in inferior posterior cerebellar or dentate nucleus connectivity. This study indicates that altered cerebello-cerebral functional connectivity is associated with functional status and white matter damage in cerebellar efferent pathways in people with FRDA, particularly in motor circuits.
弗里德赖希共济失调（FRDA）是一种罕见的遗传性神经退行性疾病，在大多数情况下表现为进行性和使人虚弱的运动功能障碍。以前曾报道过小脑白质通路的变性，以及小脑-大脑功能改变的迹象。在这项工作中，我们研究了小脑-大脑回路中的静息状态功能连接变化，及其与疾病严重程度（共济失调严重程度评定量表[SARA]）、运动功能（快速和节奏手指敲击）和白质完整性（弥散张量成像）的关联在 35 名 FRDA 成年人和 45 名年龄和性别匹配的对照组中。评估了三个小脑皮质区域（前叶，I-V 叶；上后叶，VI-VIIB 叶；下后叶，VIIIA-IX 叶）和两个齿状核种子（背侧和腹侧）的基于体素种子的功能连接。与对照组相比，FRDA 患者在前小脑与双侧额/顶叶回之间以及在上后小脑与左背外侧前额叶皮质之间的连接明显减少。疾病严重程度较高与这些回路中的连接性降低相关。较低的前小脑-运动皮层功能连接也与 FRDA 队列中更快的手指敲击速度和上小脑脚、内囊和中央前白质的各向异性分数降低相关。在后下小脑或齿状核连接中，两组间无显著差异。这项研究表明，小脑-大脑功能连接的改变与 FRDA 患者的功能状态和小脑传出通路的白质损伤有关，尤其是在运动回路中。
