Department of Neurology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
J Neurol. 2018 Mar;265(3):607-617. doi: 10.1007/s00415-018-8754-6. Epub 2018 Jan 22.
Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.
疲劳是影响多发性硬化症（MS）患者的最常见和最具致残性的症状之一。持续的认知努力会引起认知疲劳，表现为随着时间推移而出现的主观疲惫和与疲劳相关的客观警觉性下降。在长时间的认知测试中，MS 患者表现出简单反应时间（RT）的增加，同时伴随着 P300 事件相关电位的幅度降低和潜伏期延长。先前的研究表明，额叶皮层的结构和功能异常在疲劳发病机制中起着重要作用，包括额叶皮层的低激活。在本研究中，我们研究了经颅直流电刺激（tDCS）对左侧背外侧前额叶皮层（DLPFC）对 MS 患者认知表现与疲劳相关的客观测量的神经调节作用。在基线、刺激期间和刺激后记录听觉Oddball 任务中的 P300 和警觉性测试中的简单反应时间。与假刺激相比，阳极 tDCS 引起 P300 幅度增加，并且在刺激结束后仍然持续，并消除了 RT 在测试过程中与疲劳相关的增加。我们的发现表明，左侧 DLPFC 的阳极 tDCS 可以抵消与疲劳相关的表现下降，从而提高患者应对持续认知需求的能力。这为左侧 DLPFC 在疲劳病理生理学中的功能相关性提供了因果证据。结果表明，tDCS 诱导的额叶活动调节可能是治疗 MS 患者与疲劳相关的认知表现下降的有效治疗选择。
