CoreMind Ltd, NW1 8NP London, UK.
Department of Clinical and Movement Neuroscience, Institute of Neurology, University College London, WC1N 3BG London, UK.
Brain. 2022 Mar 29;145(1):285-294. doi: 10.1093/brain/awab287.
Persistent fatigue is a major debilitating symptom in many psychiatric and neurological conditions, including stroke. Post-stroke fatigue has been linked to low corticomotor excitability. Yet, it remains elusive as to what the neuronal mechanisms are that underlie motor cortex excitability and chronic persistence of fatigue. In this cross-sectional observational study, in two experiments we examined a total of 59 non-depressed stroke survivors with minimal motoric and cognitive impairments using 'resting-state' MRI and single- and paired-pulse transcranial magnetic stimulation. In the first session of Experiment 1, we assessed resting motor thresholds-a typical measure of cortical excitability-by applying transcranial magnetic stimulation to the primary motor cortex (M1) and measuring motor-evoked potentials in the hand affected by stroke. In the second session, we measured their brain activity with resting-state MRI to assess effective connectivity interactions at rest. In Experiment 2 we examined effective inter-hemispheric connectivity in an independent sample of patients using paired-pulse transcranial magnetic stimulation. We also assessed the levels of non-exercise induced, persistent fatigue using Fatigue Severity Scale (FSS-7), a self-report questionnaire that has been widely applied and validated across different conditions. We used spectral dynamic causal modelling in Experiment 1 and paired-pulse transcranial magnetic stimulation in Experiment 2 to characterize how neuronal effective connectivity relates to self-reported post-stroke fatigue. In a multiple regression analysis, we used the balance in inhibitory connectivity between homologue regions in M1 as the main predictor, and have included lesioned hemisphere, resting motor threshold and levels of depression as additional predictors. Our novel index of inter-hemispheric inhibition balance was a significant predictor of post-stroke fatigue in Experiment 1 (β = 1.524, P = 7.56 × 10-5, confidence interval: 0.921 to 2.127) and in Experiment 2 (β = 0.541, P = 0.049, confidence interval: 0.002 to 1.080). In Experiment 2, depression scores and corticospinal excitability, a measure associated with subjective fatigue, also significantly accounted for variability in fatigue. We suggest that the balance in inter-hemispheric inhibitory effects between primary motor regions can explain subjective post-stroke fatigue. Findings provide novel insights into neural mechanisms that underlie persistent fatigue.
持续性疲劳是许多精神和神经疾病的主要致残症状，包括中风。中风后疲劳与皮质运动兴奋性降低有关。然而，运动皮层兴奋性和慢性疲劳持续存在的神经机制仍不清楚。在这项横断面观察性研究中，我们在两个实验中总共检查了 59 名非抑郁中风幸存者，他们的运动和认知障碍最小，使用“静息状态”MRI 和单脉冲和双脉冲经颅磁刺激。在实验 1 的第一次会议中，我们通过应用经颅磁刺激到初级运动皮层（M1）并测量受中风影响的手部的运动诱发电位来评估静息运动阈值 - 皮质兴奋性的典型测量值。在第二次会议中，我们使用静息状态 MRI 测量他们的大脑活动，以评估静息时的有效连接相互作用。在实验 2 中，我们使用双脉冲经颅磁刺激检查了患者的独立样本中的有效半球间连接。我们还使用广泛应用于不同条件的自我报告问卷疲劳严重程度量表（FSS-7）评估非运动引起的持续性疲劳水平。我们在实验 1 中使用频谱动态因果建模，在实验 2 中使用双脉冲经颅磁刺激来描述神经元有效连接如何与自我报告的中风后疲劳相关。在多元回归分析中，我们使用 M1 同源区域之间抑制性连接的平衡作为主要预测因子，并包括损伤半球、静息运动阈值和抑郁水平作为附加预测因子。我们的半球间抑制平衡新指数是实验 1 中中风后疲劳的重要预测因子（β=1.524，P=7.56×10-5，置信区间：0.921 至 2.127）和实验 2（β=0.541，P=0.049，置信区间：0.002 至 1.080）。在实验 2 中，抑郁评分和皮质脊髓兴奋性，与主观疲劳相关的测量，也显著解释了疲劳的可变性。我们认为，初级运动区域之间的半球间抑制效应平衡可以解释中风后主观疲劳。研究结果为持续性疲劳的神经机制提供了新的见解。
