On the relation between self-reported cognitive fatigue and the posterior hypothalamic-brainstem network

Various causes have been suggested for multiple sclerosis (MS) related fatigue. Hypothalamus-brainstem fibres play a role in sleep-wake regulation and in hypothalamic deactivation during inflammatory states. Hence, they may play a role for experiencing fatigue by changing bottom-up hypothalamic activation.

Multiple sclerosis patients with and without self-reported cognitive fatigue and healthy controls were analysed with respect to the integrity of hypothalamus-brainstem fibres using diffusion-tensor imaging based tractography, focusing on the anterior, medial and posterior hypothalamic areas, controlling for clinical impairment and excluding participants with depressive mood.

Multiple sclerosis patients without self-reported cognitive fatigue showed increased axial and radial diffusivity levels specifically for fibres connecting the right posterior hypothalamus with the right locus coeruleus, but not for the medial hypothalamus and the corpus callosum. Moreover, there were no differences between MS patients with and without fatigue in brain atrophy and lesion load, which could explain our results.

Multiple sclerosis patients not experiencing fatigue show increased axial and radial diffusivity for fibres connecting the posterior hypothalamus and the brainstem, which might prevent bottom-up activation of the posterior hypothalamus and therefore downregulation of structures responsible for wakefulness and exploratory states of mind.