Mult Scler. 2017 Jun 1:1352458517717807. doi: 10.1177/1352458517717807. [Epub ahead of print]
Abnormal functional connectivity of thalamic sub-regions contributes to fatigue in multiple sclerosis.
Hidalgo de la Cruz M, d’Ambrosio A, Valsasina P, Pagani E, Colombo B, Rodegher M, Falini A, Comi G, Filippi M, Rocca MA.
To investigate sub-regional thalamic resting-state (RS) functional connectivity (FC) abnormalities in multiple sclerosis (MS) and their correlation with fatigue and its subcomponents (physical, cognitive, and psychosocial).
From 122 MS patients and 94 healthy controls, 5 thalamic sub-regions (frontal, motor, postcentral, occipital, temporal) were parcellated based on their cortico-thalamic structural connectivity and used for a seed-based RS FC analysis. Abnormalities of thalamic RS FC in MS patients and their correlation with Modified Fatigue Impact Scale (MFIS) were assessed.
Compared to controls and non-fatigued MS ( n = 86), fatigued MS patients ( n = 36) showed thalamic RS FC abnormalities with middle frontal gyrus, sensorimotor network, precuneus, insula, and cerebellum, which correlated with global MFIS. Higher thalamic RS FC with precuneus and lower RS FC with posterior cerebellum correlated with cognitive MFIS. Higher thalamic RS FC with sensorimotor network in frontal-, motor-, and temporal thalamic sub-regions correlated with physical and psychosocial MFIS. Reduced thalamic RS FC with right insula in motor-, postcentral-, and occipital thalamic sub-regions correlated with psychosocial fatigue.
Regional thalamic RS FC abnormalities with different cortical regions, including the frontal lobe, sensorimotor network, precuneus, insular cortices, and cerebellum contribute to fatigue in MS. Abnormal RS FC of selected thalamo-cortical connections explains different components of fatigue.
I’m on the Rhyd Ddu path (or commonly known as the South Ridge, 8.5 miles) of m.Snowdon in Wales. As a vegetarian for my whole life, I’ve struggled with fatigue under the strains of my busy working life. But, over the years the old me has gradually metamorphosed into a person of greater endurance, as a rock climbing, mountain climbing chick. Change was key, and for me at least tiredness seems to be a thing of the past.
“I am old, Gandalf. I don’t look it, but I am beginning to feel it in my heart of hearts. Well-preserved indeed! Why, I feel all thin, sort of stretched, if you know what I mean: like butter that has been scraped over too much bread. That can’t be right. I need a change, or something.”
― J.R.R. Tolkien, The Lord of the Rings
MS like all illness afflicting the body consumes energy, resulting in debilitating tiredness, but is there more to this than that? Can changes in the brain itself be an explanation for this?
Previously. brain volume assessments by MRI have hinted at loss of volume in the forebrain (frontal, sensorimotor, temporal cortices, and precuneus
) to be associated with fatigue in MS. Here, the authors have looked at a specific region deep in the brain, called the thalamus, which is the relay centre for integrating communication between the different brain regions. They’ve based their thinking around previous work, which has demonstrated that both functional and structural abnormalities in this area of the brain can contribute to fatigue in neurological disorders. In MS, in particular, cognitive (ability to think and process) fatigue has been linked to microstructural abnormalities in the white matter tracts of the thalamus.
The authors included 187 PwMS with the following characteristics: 1) relapse free and having not received steroids for at least 3 months before the scan, 2) having no significant medical illness or substance abuse that can interfere with fatigue assessment, 3) not on treatments for fatigue, 4) no psychiatric or mood/sleep disorders, 5) right-handed (to give a left-sided dominant brain and to subsequently match to controls). They were then compared to 94 age and sex-matched, right-handed individuals without MS.
On the day of the scan, participants had a battery of assessments, including cognition assessments and fatigue impact scale. They found that compared to controls and non-fatigued PwMS, fatigued PwMS showed lowered connectivity between the thalamus and the different cortical regions: superior frontal gyrus, middle frontal gyrus (deals with preparation and execution of movements, decision making and social behaviour), sensorimotor network, precuneus, insula, and posterior lobes of the cerebellum. Pretty much everywhere! Interestingly, there were associations with different components of fatigue; involvement of the precuneus (a critical node of the default-mode network linking to the dorso-lateral pre-frontal cortex, and therefore modulates the awake state) and posterior region of the cerebellum in cognitive fatigue, whilst sensorimotor regions contributed to physical and psychosocial fatigue, with the addition of abnormalities in the anterior insula (deals with emotion) contributing to psychosocial fatigue.
What this means is that a multi-modality approach to tackling fatigue is needed in MS, in order to modulate these different network regions: cognitive rehabilitation, physical exercise, behavioural, and problem-solving techniques being some of them. As a next step, it would be good to see if behavioural modifications can in fact lead to changes in the thalamic connections over time.