title: Changes in MEG resting-state networks are related to cognitive decline in type 1 diabetes mellitus patients.
abstract: OBJECTIVE
  Integrity of resting-state functional brain networks (RSNs) is important for proper cognitive functioning. In type 1 diabetes mellitus (T1DM) cognitive decrements are commonly observed, possibly due to alterations in RSNs, which may vary according to microvascular complication status. Thus, we tested the hypothesis that functional connectivity in RSNs differs according to clinical status and correlates with cognition in T1DM patients, using an unbiased approach with high spatio-temporal resolution functional network.
  
  
  METHODS
  Resting-state magnetoencephalographic (MEG) data for T1DM patients with (n = 42) and without (n = 41) microvascular complications and 33 healthy participants were recorded. MEG time-series at source level were reconstructed using a recently developed atlas-based beamformer. Functional connectivity within classical frequency bands, estimated by the phase lag index (PLI), was calculated within eight commonly found RSNs. Neuropsychological tests were used to assess cognitive performance, and the relation with RSNs was evaluated.
  
  
  RESULTS
  Significant differences in terms of RSN functional connectivity between the three groups were observed in the lower alpha band, in the default-mode (DMN), executive control (ECN) and sensorimotor (SMN) RSNs. T1DM patients with microvascular complications showed the weakest functional connectivity in these networks relative to the other groups. For DMN, functional connectivity was higher in patients without microangiopathy relative to controls (all p < 0.05). General cognitive performance for both patient groups was worse compared with healthy controls. Lower DMN alpha band functional connectivity correlated with poorer general cognitive ability in patients with microvascular complications.
  
  
  CONCLUSIONS
  Altered RSN functional connectivity was found in T1DM patients depending on clinical status. Lower DMN functional connectivity was related to poorer cognitive functioning. These results indicate that functional connectivity may play a key role in T1DM-related cognitive dysfunction.
authors.affiliation: Department of Electrical and Electronic Engineering, University of Cagliari, Italy ; Department of Public Health, Clinic and Molecular Medicine, University of Cagliari, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Demuru
authors.affiliation: Department of Medical Psychology, VU University Medical Centre, Amsterdam, The Netherlands ; Diabetes Centre/Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Eelco
authors.initials: E
authors.lastname: van Duinkerken
authors.affiliation: Department of Electrical and Electronic Engineering, University of Cagliari, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fraschini
authors.affiliation: Department of Public Health, Clinic and Molecular Medicine, University of Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.affiliation: Department of Medical Psychology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Snoek
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Medical Psychology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.affiliation: Diabetes Centre/Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Department of Clinical Neurophysiology and MEG Centre, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Hillebrand
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests
keywords: Functional connectivity; Magnetoencephalography; Oscillations; Phase Lag Index (PLI); Resting-state networks; Type 1 diabetes mellitus