Ruiu Elisa, Dubbioso Raffaele, Madsen Kristoffer Hougaard, Svolgaard Olivia, Raffin Estelle, Andersen Kasper Winther, Karabanov Anke Ninija, Siebner Hartwig Roman
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Section 714, Hvidovre, Denmark.
Department of Neurology, University Hospital of Sassari, Sassari, Italy.
Front Neurol. 2020 May 5;11:193. doi: 10.3389/fneur.2020.00193. eCollection 2020.
We employed dual-site TMS to test whether ipsilateral functional premotor-motor connectivity is altered in relapsing-remitting Multiple Sclerosis (RR-MS) and is related to central fatigue. Twelve patients with RR-MS and 12 healthy controls performed a visually cued Pinch-NoPinch task with their right hand. During the reaction time (RT) period of Pinch and No-Pinch trials, single-site TMS was applied to the left primary motor cortex (M1) or dual-site TMS was applied to the ipsilateral dorsal premotor cortex (PMd) and to M1. We traced context-dependent changes of corticospinal excitability and premotor-motor connectivity by measuring Motor-Evoked Potentials (MEPs) in the right first dorsal interosseus muscle. Central fatigue was evaluated with the Fatigue Scale for Motor and Cognitive Functions (FSMS). In both groups, single-pulse TMS revealed a consistent increase in mean MEP amplitude during the Reaction Time (RT) period relative to a resting condition. Task-related corticospinal facilitation increased toward the end of the RT period in Pinch trials, while it decreased in No-Pinch trials. Again, this modulation of MEP facilitation by trial type was comparable in patients and controls. Dual-site TMS showed no significant effect of a conditioning PMd pulse on ipsilateral corticospinal excitability during the RT period in either group. However, patients showed a trend toward a relative attenuation in functional PMd-M1 connectivity at the end of the RT period in No-Pinch trials, which correlated positively with the severity of motor fatigue ( = 0.69; = 0.007). Dynamic regulation of corticospinal excitability and ipsilateral PMd-M1 connectivity is preserved in patients with RR-MS. MS-related fatigue scales positively with an attenuation of premotor-to-motor functional connectivity during cued motor inhibition. The temporal, context-dependent modulation of ipsilateral premotor-motor connectivity, as revealed by dual-site TMS of ipsilateral PMd and M1, constitutes a promising neurophysiological marker of fatigue in MS.
我们采用双部位经颅磁刺激（TMS）来测试复发缓解型多发性硬化症（RR-MS）患者同侧功能性运动前区-运动区连接是否改变，以及是否与中枢性疲劳有关。12例RR-MS患者和12名健康对照者用右手执行视觉提示的捏-不捏任务。在捏和不捏试验的反应时间（RT）期间，对左侧初级运动皮层（M1）施加单部位TMS，或对同侧背侧运动前皮层（PMd）和M1施加双部位TMS。我们通过测量右侧第一背侧骨间肌的运动诱发电位（MEP）来追踪皮质脊髓兴奋性和运动前区-运动区连接的情境依赖性变化。用运动和认知功能疲劳量表（FSMS）评估中枢性疲劳。在两组中，单脉冲TMS显示，与静息状态相比，反应时间（RT）期间平均MEP波幅持续增加。在捏试验中，与任务相关的皮质脊髓易化在RT期结束时增加，而在不捏试验中则降低。同样，试验类型对MEP易化的这种调节在患者和对照中是可比的。双部位TMS显示，在RT期，条件性PMd脉冲对两组同侧皮质脊髓兴奋性均无显著影响。然而，在不捏试验中，患者在RT期结束时功能性PMd-M1连接有相对减弱的趋势，这与运动疲劳的严重程度呈正相关（r = 0.69；P = 0.007）。RR-MS患者保留了皮质脊髓兴奋性和同侧PMd-M1连接的动态调节。MS相关疲劳与提示性运动抑制期间运动前区到运动区功能连接的减弱呈正相关。同侧PMd和M1的双部位TMS所揭示的同侧运动前区-运动区连接的时间性、情境依赖性调节，是MS中一种有前景的疲劳神经生理学标志物。
