Decreased functional dynamics of thalamo-cortical states in cognitively impaired multiple sclerosis

Poster No:


Submission Type:

Late Breaking Abstract Submission 


Stefanos Prouskas1, Tommy Broeders1, Linda Douw1, Jeroen Geurts1, Hanneke Hulst1, Menno Schoonheim1


1Amsterdam UMC, location VUmc, Amsterdam, Noord-Holland

First Author:

Stefanos Prouskas  
Amsterdam UMC, location VUmc
Amsterdam, Noord-Holland


Tommy Broeders  
Amsterdam UMC, location VUmc
Amsterdam, Noord-Holland
Linda Douw  
Amsterdam UMC, location VUmc
Amsterdam, Noord-Holland
Jeroen Geurts  
Amsterdam UMC, location VUmc
Amsterdam, Noord-Holland
Hanneke Hulst  
Amsterdam UMC, location VUmc
Amsterdam, Noord-Holland
Menno Schoonheim  
Amsterdam UMC, location VUmc
Amsterdam, Noord-Holland


Thalamic atrophy in MS has been consistently associated with disability and cognitive impairment (CI). The thalamus is a major brain network hub, widely functionally connected with the cortex. It remains unclear, however, whether the highly dynamic thalamus exhibits altered thalamo-cortical dynamics in MS patients with CI. This study investigated the dynamics of thalamic connectivity states in MS patients with different levels of cognitive impairment.


332 MS patients (age=48.1±11.1 years, disease duration=16.7±5.7 years) and 96 healthy controls (HC; age=45.9±10.5 years) underwent structural and functional MRI, and neuropsychological testing. Patients were classified as cognitively preserved (CP; n=180), cognitively impaired (CI; n=87, z≤−2 on ≥2 domains), or mildly cognitively impaired (MCI; n=65, z≤−1.5 on ≥2 cognitive domains). A sliding window approach was used to determine meta-states, i.e. the thalamo-cortical FC pattern for each window. Five states were determined using k-means clustering. To describe thalamo-cortical dynamics across states, the total number and switches between meta-states, the maximum state-span, and total distance travelled were calculated. Occupancy and dwell time were quantified to investigate state-specific dynamics. General linear models assessed differences between cognitive groups.


Compared to HC, CI patients showed fewer meta-states (39.8 vs 36.2; p=0.034) and a smaller state span (11.2 vs 10.5; p=0.05). Compared to CP, CI patients showed fewer meta-states (39.5 vs 36.2; p=0.022) and a shorter distance travelled (122.5 vs 113.3; p=0.03). Looking at individual states, MS patients occupied a state of generalized low thalamo-cortical connectivity significantly more than HC (HC=21%, CP=28%, MCI=29%, CI=34%; p<0.001), with slightly higher default-mode and visual connectivity. More dwell time in this thalamo-cortical state correlated with cortical grey matter volume (r=−0.18, p=0.007) and worse average cognition (r=−0.23, p<0.001): most strongly with information processing speed (r=−0.22, p<0.001) and attention (r=−0.20, p<0.001).
Supporting Image: FR4HCMS1.png
   ·Fractional occupancy of the low-connectivity thalamo-cortical state in healthy controls and MS patients
Supporting Image: NoMeSt.png
   ·Number of meta-states across groups


The thalamus shows reduced state dynamics in MS in the form of fewer switches between states and an increased time spent in a state of generalized low thalamo-cortical connectivity. These thalamic changes were most prominent in patients with cognitive impairment, underlining the dysfunction of this important hub structure in MS.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural)
fMRI Connectivity and Network Modeling 1

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Subcortical Structures


Other - Meta-states

1|2Indicates the priority used for review

My abstract is being submitted as a Software Demonstration.


Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):


Was any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.


Was any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI
Structural MRI
Neuropsychological testing

For human MRI, what field strength scanner do you use?


Which processing packages did you use for your study?


Provide references using author date format

Eshaghi A. (2018), 'Deep gray matter volume loss drives disability worsening in multiple sclerosis', Annals of Neurology,vol. 83, no. 2, pp. 210–222.
Houtchens M.K. (2007), 'Thalamic atrophy and cognition in multiple sclerosis', Neurology, vol. 69, pp. 1213–1223.
Minagar A. (2013), 'The thalamus and multiple sclerosis: Modern views on pathologic, imaging, and clinical aspects', Neurology vol. 80, pp. 210–219.