Fatigue and cognitive effort in multiple sclerosis: an fMRI study

Despite recent advances in therapy and diagnosis, fatigue remains a mayor challenge in multiple sclerosis (MS). To further the understanding of the neural underpinnings of fatigue, we undertook a study using functional magnetic resonance imaging (fMRI) to investigate neural networks that may be affected by MS-related fatigue. Twelve MS patients and 12 age- and sex matched controls were administered the Fatigue Impact Scale (FIS) to assess clinically significant fatigue, and underwent a neuropsychological examination. The participants performed a working memory task (Daneman’s ‘Reading Span’ task) while being monitored by means of a 1.5 T Philips Achieva MR scanner. We have previously shown that this task triggers an executive network comprising frontal and parietal areas typically involved in working memory. In addition, the task engages a core network involving the anterior insula and the anterior cingulate cortex. This latter network may be implicated in allocation of mental resources and monitoring of the present state of the individual. There were two main findings. MS participants evidenced less activation than controls in the anterior cingulate and the left parietal cortex (Brodmann area 7) and more activation in left hemisphere language areas as well as the anterior insula. The second main finding was that clinical ratings of fatigue were strongly correlated with activity in wide areas of the core network, as well as posterior language areas. We take this finding to indicate that fatigue is related to compensatory involvement of the core network, and that excess activity in the core network possibly could be used as an objective marker of fatigue in MS.