Traumatic Brain Injury Laboratory, Kessler Foundation , West Orange, NJ , USA ; Department of Physical Medicine and Rehabilitation, Rutgers - New Jersey Medical School , Newark, NJ , USA.
Department of Physical Medicine and Rehabilitation, Rutgers - New Jersey Medical School , Newark, NJ , USA ; Neuropsychology and Neuroscience Laboratory, Kessler Foundation , West Orange, NJ , USA.
Front Neurol. 2015 Mar 12;6:52. doi: 10.3389/fneur.2015.00052. eCollection 2015.
Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research.
疲劳是多发性硬化症（MS）最普遍的症状之一，针对这一主题已经进行了数百项研究。虽然有越来越多的文献使用各种方法来研究疲劳，但尚未出现一种统一的 MS 疲劳理论。在当前的综述中，我们综合了来自 MS 疲劳的神经影像学、药理学、神经心理学和免疫学研究的发现，提出了 MS 疲劳的一个特定假设：多巴胺失衡假说。纹状体和前额叶皮层之间的通讯依赖于多巴胺，一种调节性神经递质。神经影像学研究表明，疲劳是由于这些区域之间的通讯中断引起的。支持多巴胺失衡假说，结构和功能神经影像学研究显示，多巴胺神经元大量支配的额叶和纹状体区域存在异常。此外，多巴胺能精神兴奋剂药物已被证明可减轻创伤性脑损伤、慢性疲劳综合征和癌症患者的疲劳，这也表明多巴胺可能在疲劳感知中发挥重要作用。本文综述了结构和功能神经影像学证据以及药理学研究，这些研究表明多巴胺在疲劳现象中起着关键作用。我们最后总结了如何在未来的研究中检验多巴胺失衡假说的具体方面。
