Cognitive Fatigue in Patients with MS

Although fatigue is one of the most common symptoms among patients with multiple sclerosis (MS), it remains poorly understood, and its underlying neural mechanisms still pose many questions, leaving patients with limited, inadequate treatment options. A study evaluated cognitive fatigue-related functional connectivity in patients with MS.

The study compared 26 patients with MS to 14 demographically matched healthy controls. All participants underwent functional MRI scanning while performing a working memory task (n-back). Two conditions were implemented—a higher cognitive load one (2-back) and a lower cognitive load one (0-back). The researchers evaluated task-independent residual functional connectivity with seeds in brain regions known to be connected with cognitive fatigue: dorsolateral prefrontal cortex, ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), insula, and striatum. The visual analog scale (VAS) for fatigue was used to determine cognitive fatigue.

In the healthy controls, increasing VAS fatigue scores were correlated with increased residual functional connectivity between the striatum and the vmPFC—which plays a significant role in reward processing—during the 2-back condition versus the 0-back condition. When evaluating the patients with MS, residual functional connectivity increased from the insula and dACC to the striatum.

“The current study identified altered cognitive fatigue-related functional connectivity in the interoceptive and reward pathways among [patients with MS]. Specifically, [patients with MS] showed a hyperconnectivity within the interoceptive network and disconnection within the reward circuitry. Such alterations may be the result of inefficient brain connectivity when meeting increased task demands,” the study authors concluded.