title: Thalamus structure and function determine severity of cognitive impairment in multiple sclerosis.
abstract: OBJECTIVE
  This study investigates whether changes in functional connectivity, diffusivity, and volume of the thalamus can explain different severities of cognitive impairment in multiple sclerosis (MS).
  
  
  METHODS
  An inception cohort of 157 patients with MS (104 women, mean age 41 years), 6 years postdiagnosis, was divided into 3 groups: cognitively preserved (CP, n = 108), mildly cognitively impaired (MCI, n = 22), and more severely cognitively impaired (SCI, n = 27). These groups were matched to 47 healthy controls (HC, 28 women, mean age 41 years). Thalamic volume, thalamic skeleton diffusivity (fractional anisotropy [FA] and mean diffusivity [MD]), and thalamic resting-state functional connectivity (FC) were compared between groups.
  
  
  RESULTS
  Thalamic volume was significantly lower in all patient groups compared to controls, with lowest volumes in patients with SCI, and no difference between CP and MCI. Thalamic skeleton FA was decreased in SCI compared to HC only; MD was increased in SCI compared to all other groups. Thalamic FC was increased in SCI with a total of 15 regions, mainly sensorimotor, frontal, and occipital parts of the brain. Thalamic volume, FC, and MD remained independent predictors in a linear regression model (R(2) = 0.46), together with male sex and a lower level of education. Lesion and whole-brain volumes were not significant predictors.
  
  
  CONCLUSIONS
  These findings indicate that thalamic changes in structure and function are highly informative regarding overall cognitive performance in MS. Increased thalamic FC only became apparent in SCI, possibly as a sign of maladaption.
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands. m.schoonheim@vumc.nl.
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands.
authors.forename: Hanneke E
authors.initials: HE
authors.lastname: Hulst
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands.
authors.forename: Roemer B
authors.initials: RB
authors.lastname: Brandt
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands.
authors.forename: Myrte
authors.initials: M
authors.lastname: Strik
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands.
authors.forename: Alle Meije
authors.initials: AM
authors.lastname: Wink
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands.
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: From the Department of Anatomy & Neurosciences (M.M.S., H.E.H., J.J.G.G.), Radiology and Nuclear Medicine (R.B.B., M.S., A.M.W., F.B.), and Neurology (B.M.J.U.), Neuroscience Campus Amsterdam, VU University Medical Center, the Netherlands.
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000175:diagnosis* / Q000523:psychology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000523:psychology*; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D013788:Thalamus / Q000473:pathology* / Q000502:physiology