Association between abnormal functional connectivity of thalamic sub-regions and clinical disability in CIS patients: a longitudinal study

Objective: To investigate sub-regional thalamic resting-state (RS) functional connectivity (FC) abnormalities in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) and their correlations with disability. Background: Several studies have characterized thalamic structural damage in patients at the early stages of MS, while no study has explored thalamic RS FC abnormalities. Design/Methods: Structural and RS fMRI data were acquired from 59 CIS patients and 13 healthy controls (HC) at baseline (within 3 months from first attack), year 1 and year 2. Five thalamic sub-regions (frontal, motor, postcentral, occipital, temporal) were parcellated according with their cortico-thalamic structural connectivity, and used for a seed-based RS FC analysis. Thalamic RS FC abnormalities were assessed and correlated with Expanded Disability Status Scale (EDSS) at follow-up. Results: Forty-nine (83%) patients developed clinically definite MS at year 2. At baseline, compared to HC, CIS patients had a reduced thalamic RS FC with frontal cortices and cerebellum, for the frontal and motor sub-regions. During the follow-up, there was a progressive reduction of thalamic RS FC with: 1) the cerebellum, for the whole thalamus, motor, postcentral, occipital, and temporal sub-regions; 2) some areas of the default-mode network, for the occipital and postcentral sub-regions; and 3) the temporal cortices, for the whole-thalamus, frontal and temporal sub-regions. Significant correlations were found between thalamic RS FC abnormalities and higher EDSS at follow-up. Conclusions: Significant and dynamic alterations of thalamic sub-regional RS FC abnormalities with frontal, temporal, default-mode and cerebellar regions occur in CIS patients. Regional thalamic RS FC abnormalities with the frontal cortex and cerebellum at baseline contribute to explain more severe disability after two years, highlighting the relevant role of thalamic involvement in the first stages of the disease for subsequent clinical outcome. Study Supported by: Partially supported by a grant from the Ministry of Science, Republic of Serbia (# 175031). Disclosure: Dr. Hidalgo de la Cruz has nothing to disclose. Dr. Rocca has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Novartis, Teva Neurosciences and Genzyme. Dr. Meani has nothing to disclose. Dr. Mesaros has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with scientific advisory board for Merck Serono. Dr. Mesaros has received research support from research grant support from the Ministry of Education and Science, Republic of Serbia (project no. 175031). Dr. Dackovic has nothing to disclose. Dr. Dujmovic Basuroski has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with advisory board for Bayer Schering Pharma; received honoraria for speaking from Merck Serono, Roche and Medis. Dr. Dujmovic Basuroski has received research support from research grant support from the Ministry of Education and Science, Republic of Serbia (project no. 175031). Dr. Drulovic has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with advisory boards: Bayer Schering Pharma, merck Serono, Teva, Genzyme, a Sanofi Company, Roche; speaking honoraria: merck Serono, teva, Bayer Schering, genzyme, a Sanofi Company, Medis, Roche. Dr. Drulovic has received research support from research grant support: Ministry of Education and Science, Republic of Serbia (project no. 175031). Dr. Filippi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Merk-Serono, Novartis, Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in an editorial capacity for Journal of Neurology. Dr. Filippi has received research support from Biogen Idec, Novartis, Teva Pharmaceutical Industries.