Disruption of Hippocampal Resting State Functional Connectivity in MS: Relation With WM Lesions and Clinical Measures (P6.127)

OBJECTIVE: To assess the relationship between abnormalities of hippocampal resting state (RS) functional connectivity (FC) and an hippocampal-related deficit (depression) as well as global clinical impairment in multiple sclerosis (MS). To explore the correlation between hippocampal RS FC abnormalities and T2 lesion volumes and atrophy. BACKGROUND: The hippocampi are part of the default-mode network and are precociously hit in MS. DESIGN/METHODS: Structural and RS fMRI images were acquired from 69 MS patients without cognitive impairment and 42 matched healthy controls (HC). In patients, depression was assessed using the Mongomery-Asberg Depression Rating Scale (MADRS). Hippocampal RS FC was assessed using a seed-voxel approach. SPM8 was used for between-group comparisons and analysis of correlation between RS FC abnormalities and clinical and structural MRI variables. RESULTS: Compared to HC, MS patients had significant atrophy of the whole brain and left hippocampus (p<0.001). They also showed a distributed pattern of decreased RS FC between the hippocampi and several regions located in the frontal, temporal and parietal lobes, the cingulate cortex, insulae, thalami, caudate nuclei and cerebellum. Such a pattern of reduced hippocampal RS FC was significantly correlated to longer disease duration, and the severity of depression and global clinical disability. Reduced hippocampal RS FC was strongly influenced by the volume of focal white matter (WM) lesions. CONCLUSIONS: In cognitively preserved MS patients, the progressive accumulation of focal WM lesions profoundly influences the functional integration of the hippocampus, which is part of the DMN, with the majority of other brain regions, leading a global disconnection. Neurological disability and depressive symptoms are related to such a disruption of hippocampal RS FC. Study Supported by: Partially supported by grants from Italian Ministry of Health (GR-2009-1529671) and FISM 2011/R/19