Have we found the brain’s fatigue pathway? #ResearchSpeak #MSBlog #MSResearch
“I have been very interested in the neural substrate that underpins fatigue in people in general and in people with MS. Unlike other symptoms there is not a specific area of the brain where the percept of fatigue lies. What I mean is that unlike other sensory percepts (a conscious awareness of sensations) that have a specific area of the cerebral cortex allocated to them there is no area that has been identified for fatigue. Why? I am not sure and this is why we think fatigue is similar to alertness or wakefulness and is controlled by a distributed network that comes from the brainstem.”
“The study below suggests that in MSers with fatigue there is a disruption of the projections linking the posterior hypothalamus to the brain stem. This is very interesting; if fatigue can be made worse by focal brainstem or hypothalamic pathology it could explain the disconnect between fatigue and physical disability. Not everyone who is physically disabled necessarily has pathology in this pathway. Similarly, people with ‘benign MS’ may have a lesion in this pathway and have profound fatigue and no physical or cognitive disabilities. Clearly this study needs to be repeated and some basic science done in this area. Who knows it may lead to a new treatment for MS-related fatigue.”
“Did you know fatigue comes out on top of the list of symptoms that MSers would like to get rid of?”
“Please note that the negative affect, or low mood, associated with chronic fatigue is controlled by an area of the brain located the frontal lobe called the anterior cingulate gyrus. This area controls mood and not fatigue. If you lesion this area you potentially remove, or neutralise, the negative emotions that are associated with several unpleasant percepts, for example chronic intractable pain.”
“I hope you are beginning to realise that although the central nervous system is modular, it is a highly connected network, which makes decoding its function at a molecular, cellular or network level so interesting. You can’t say neuroscience and neurology are boring.”
Hanken et al. On the relation between self-reported cognitive fatigue and the posterior hypothalamic-brainstem network. Eur J Neurol. 2015 Aug. doi: 10.1111/ene.12815.
BACKGROUND AND PURPOSE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.