title: Hippocampal-DMN disconnectivity in MS is related to WM lesions and depression.
abstract: The hippocampus is part of the default-mode network (DMN) and is functionally hit early in multiple sclerosis (MS). Hippocampal and DMN dysfunctions have been associated with depression, both in patients with MS and in major depressive disorders. We hypothesized that white matter lesions may contribute, through a disconnection mechanism, to hippocampal dysfunction. To test this, we assessed the relationship between hippocampal resting-state (RS) functional connectivity (FC) abnormalities with brain T2 lesion volumes and the presence and severity of depression. Structural and RS fMRI images were acquired from 69 patients with cognitively intact MS and 42 matched healthy controls (HC). Depression was quantified using the Montgomery-Asberg Depression Rating Scale. Seed-voxel hippocampal RS FC was assessed. SPM8 was used for between-group comparisons and correlation analysis between RS FC abnormalities with clinical and structural MRI variables. Compared to HC, patients with MS showed a significant atrophy of the whole brain and left hippocampus (P < 0.001), and a distributed pattern of decreased RS FC between the hippocampi and several cortical-subcortical regions, which were mostly located within the DMN. Reduced hippocampal RS FC with regions of the DMN was strongly correlated with higher T2 lesion volume, longer disease duration, and the severity of depression and disability. In patients with cognitively preserved MS, brain focal WM lesions are related to the functional integration of the hippocampus to other brain regions of the DMN, suggesting a disconnection syndrome. Such a disruption of hippocampal RS FC is likely to contribute to the occurrence of depression and to clinical disability.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neuroradiology, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Pravatà
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Valsasina
authors.affiliation: Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Radaelli
authors.affiliation: Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Colombo
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Vacchi
authors.affiliation: Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gobbi
authors.affiliation: Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Neuroradiology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D001931:Brain Mapping; D016022:Case-Control Studies; D003863:Depression / Q000150:complications*; D004185:Disability Evaluation; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology; D010100:Oxygen / Q000097:blood; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D010100:Oxygen
keywords: WM lesions; default-mode network; depression; hippocampus; multiple sclerosis; resting-state fMRI