Connectivity-Based Parcellation of the Thalamus in Multiple Sclerosis and Its Implications for Cognitive Impairment: A Multicenter Study (P6.136)

OBJECTIVE: To investigate the relationship between thalamic connectivity abnormalities and cognitive impairment in multiple sclerosis (MS). BACKGROUND: Several studies have consistently detected a high vulnerability to damage of the thalamus in patients with MS from the earliest stages of the disease. The study of the whole thalamus could be inadequate to explain deficits of specific cognitive functions. DESIGN/METHODS: Dual-echo, morphological and diffusion tensor (DT) MRI scans were collected from 52 relapsing-remitting MS patients and 57 healthy controls from six European centers. Patients underwent an extensive neuropsychological assessment. Thalamic connectivity defined regions (CDRs) were segmented based on their cortical connectivity using Diffusion Tractography-Based Parcellation. Between-group differences of CDRs and cortico-thalamic tracts DT MRI indices were assessed. A vertex analysis of thalamic shape was also performed. A random forest analysis was run to identify the best imaging predictor of global cognitive impairment and deficits of specific cognitive domains. RESULTS: Twenty-two (43[percnt]) MS patients were cognitively impaired (CI). Compared to cognitively preserved (CP), CI MS patients had: 1) increased fractional anisotropy (FA) of motor, post-central and occipital connected CDRs (0.003<p<0.05) and 2) decreased FA of temporal connected CDRs (0.01<p<0.02). They also experienced more pronounced atrophy in anterior thalamic regions and abnormal DT MRI indices of all cortico-thalamic tracts. Damage of specific cortico-thalamic tracts explained global cognitive dysfunction and impairment of selected cognitive domains better than all other MRI variables. Thalamic CDR DT MRI abnormalities were correlated with abnormalities of the corresponding cortico-thalamic tracts. CONCLUSIONS: Cortico-thalamic disconnection is, at various levels, implicated in cognitive dysfunction in MS. Study Supported by: Supported by the ECTRIMS-MAGNIMS Fellowship in Magnetic Resonance Imaging.