Multiple sclerosis: altered thalamic resting-state functional connectivity and its effect on cognitive function.
OBJECTIVE
To investigate, by using resting-state (RS) functional magnetic resonance (MR) imaging, thalamocortical functional connectivity (FC) and its correlations with cognitive impairment in multiple sclerosis (MS).


METHODS
All subjects provided written informed consent; the study protocol was approved by the university institutional review board for this HIPAA-compliant study. Forty-eight patients with relapsing-remitting MS and 24 control subjects underwent multimodal MR imaging, including diffusion-tensor imaging, three-dimensional (3D) T1-weighted imaging, and functional MR imaging at rest and a neuropsychological examination with the Paced Auditory Serial Addition Test (PASAT). Functional MR imaging data were analyzed with tools from FMRIB Software Library, by using the seed-based method to identify the thalamic RS network (RSN).


RESULTS
When compared with control subjects, patients showed gray matter and white matter atrophy, as well as diffusion-tensor imaging abnormalities (P < .01). Patients displayed significantly greater synchronization than control subjects in the cerebellum; basal ganglia; hippocampus; cingulum; and temporo-occipital, insular, frontal, and parietal cortices. They also exhibited significantly lower synchronization in the thalamus; cerebellum; cingulum; and insular, prefrontal, and parieto-occipital cortices (cluster level, P < .05, corrected for familywise error [FWE]). In patients, the PASAT score at 3 seconds significantly inversely correlated with the thalamus, cerebellum, and some cortical areas in all cerebral lobes; the PASAT score at 2 seconds significantly correlated, even more strongly, with all the aforementioned regions and, in addition, with the cingulum and the left hippocampus (cluster level, P < .05, corrected for FWE).


CONCLUSIONS
Thalamic RSN is disrupted in MS, and decreased performance in cognitive testing is associated with increased thalamocortical FC, thus suggesting that neuroplasticity changes are unable to compensate for tissue damage and to prevent cognitive dysfunction.
From the Department of Neurology and Psychiatry, Sapienza University of Rome, Viale dell'Università 30, 00185 Rome, Italy; and IRCCS Neuromed, Pozzilli, Italy (P.P.).
Francesca
F
Tona
Nikolaos
N
Petsas
Emilia
E
Sbardella
Luca
L
Prosperini
Maurizio
M
Carmellini
Carlo
C
Pozzilli
Patrizia
P
Pantano
D000328:Adult; D016880:Anisotropy; D001931:Brain Mapping / Q000379:methods*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D003287:Contrast Media; D056324:Diffusion Tensor Imaging; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000503:physiopathology; D011446:Prospective Studies; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology
D003287:Contrast Media; C064925:gadodiamide; D019786:Gadolinium DTPA