title: Correlates of Executive Functions in Multiple Sclerosis Based on Structural and Functional MR Imaging: Insights from a Multicenter Study.
abstract: Purpose To study the concomitant use of structural and functional magnetic resonance (MR) imaging correlates to explain information processing speed (IPS) and executive function (EF) in multiple sclerosis (MS). Materials and Methods Local ethics committee approval was obtained at all sites for this prospective, multicenter study. All subjects provided written informed consent. Twenty-six patients with relapsing-remitting MS and 32 healthy control subjects from four centers underwent structural and functional MR imaging, including a go/no-go task and neuropsychological assessment. Subtests of the Brief Repeatable Battery of Neuropsychological Tests, the Wisconsin Card Sorting Test, and the performance with the functional MR imaging paradigm were used as estimates of IPS and EF. Activation of the thalamus and the inferior frontal gyrus (pars triangularis), thalamic volume, T2 lesion load, and age were used to explain IPS and EF in regression models. Results Compared with control subjects, patients showed increased activation in a frontoparietal network, including both thalami, during the execution of the go/no-go task. Patients had decreased thalamic volume (P < .001). Among tested variables, thalamic volume (β = 0.606, P = .001), together with thalamic activation (β = -0.410, P = .022), were the best predictors of IPS and EF and helped explain 52.7% of the variance in IPS and EF. Conclusion This study highlights the potential of the combined use of functional and morphologic parameters to explain IPS and EF in patients with relapsing-remitting MS and confirms the central role of the thalamus as a relay station in executive functioning. (©) RSNA, 2016.
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Marisa
authors.initials: M
authors.lastname: Koini
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Tarek
authors.initials: T
authors.lastname: Yousry
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Tedeschi
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Antonio
authors.initials: A
authors.lastname: Gallo
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Paola
authors.initials: P
authors.lastname: Valsasina
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Gianna
authors.initials: G
authors.lastname: Riccitelli
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Dusan
authors.initials: D
authors.lastname: Damjanovic
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Nils
authors.initials: N
authors.lastname: Muhlert
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Laura
authors.initials: L
authors.lastname: Mancini
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: From the Department of Neurology (M.K., S.R., F.F., C.E.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Auenbruggerplatz 22, A-8036 Graz, Austria; Neuroimaging Research Unit (M.F., M.A.R., P.V., G.R., D.D.) and Department of Neurology (M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; NMR Research Unit, Queen Square MS Centre, UCL Institute of Neurology, London, England (T.Y., O.C., N.M.); SUN-FISM MRI Center, Second University of Naples and Hermitage-Capodimonte Institute of Diagnosis and Care, Naples, Italy (G.T., A.G.); Division of Neurology, Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy (G.T., A.G.); School of Psychological Sciences, University of Manchester, Manchester, England (N.M.); and National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, England (L.M.).
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D056344:Executive Function; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000523:psychology*; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011930:Reaction Time; D013788:Thalamus / Q000000981:diagnostic imaging