title: Connectivity-based parcellation of the thalamus in multiple sclerosis and its implications for cognitive impairment: A multicenter study.
abstract: In this multicenter study, we performed a tractography-based parcellation of the thalamus and its white matter connections to investigate the relationship between thalamic connectivity abnormalities and cognitive impairment in multiple sclerosis (MS). Dual-echo, morphological and diffusion tensor (DT) magnetic resonance imaging (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. Twenty-two (43%) MS patients were cognitively impaired (CI). Compared to cognitively preserved, CI MS patients had increased fractional anisotropy of frontal, motor, postcentral and occipital connected CDRs (0.002<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. Cortico-thalamic disconnection is, at various levels, implicated in cognitive dysfunction in MS. Thalamic involvement in CI MS patients is likely related to gray matter rather than white matter damage of thalamic subregions.
authors: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.|MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte,", Naples, Italy.
authors: Alvino
authors: A
authors: Bisecco
authors: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: Maria A
authors: MA
authors: Rocca
authors: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: Elisabetta
authors: E
authors: Pagani
authors: National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, UK.
authors: Laura
authors: L
authors: Mancini
authors: Department of Neurology, Medical University of Graz, Austria.
authors: Christian
authors: C
authors: Enzinger
authors: I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.|MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte,", Naples, Italy.
authors: Antonio
authors: A
authors: Gallo
authors: Department of Radiology and Nuclear Medicine, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors: Hugo
authors: H
authors: Vrenken
authors: Department of Neurological and Behavioral Sciences, University of Siena, Italy.
authors: Maria Laura
authors: ML
authors: Stromillo
authors: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: Massimiliano
authors: M
authors: Copetti
authors: Neuroradiological Academic Unit, UCL Institute of Neurology, Queen Square, London, United Kingdom.
authors: David L
authors: DL
authors: Thomas
authors: Department of Neurology, Medical University of Graz, Austria.
authors: Franz
authors: F
authors: Fazekas
authors: I Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.|MRI Center "SUN-FISM," Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte,", Naples, Italy.
authors: Gioacchino
authors: G
authors: Tedeschi
authors: Department of Radiology and Nuclear Medicine, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors: Frederik
authors: F
authors: Barkhof
authors: Department of Neurological and Behavioral Sciences, University of Siena, Italy.
authors: Nicola De
authors: ND
authors: Stefano
authors: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors: Massimo
authors: M
authors: Filippi
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology; D013788:Thalamus / Q000473:pathology*; D055815:Young Adult
keywords: DT MRI; cognitive impairment; gray matter; multiple sclerosis; thalamus; white matter