title: Dissociated multimodal hubs and seizures in temporal lobe epilepsy.
abstract: OBJECTIVE
  Brain connectivity at rest is altered in temporal lobe epilepsy (TLE), particularly in "hub" areas such as the posterior default mode network (DMN). Although both functional and anatomical connectivity are disturbed in TLE, the relationships between measures as well as to seizure frequency remain unclear. We aim to clarify these associations using connectivity measures specifically sensitive to hubs.
  
  
  METHODS
  Connectivity between 1000 cortical surface parcels was determined in 49 TLE patients and 23 controls with diffusion and resting-state functional magnetic resonance imaging. Two types of hub connectivity were investigated across multiple brain modules (the DMN, motor system, etcetera): (1) within-module connectivity (a measure of local importance that assesses a parcel's communication level within its own subnetwork) and (2) between-module connectivity (a measure that assesses connections across multiple modules).
  
  
  RESULTS
  In TLE patients, there was lower overall functional integrity of the DMN as well as an increase in posterior hub connections with other modules. Anatomical between-module connectivity was globally decreased. Higher DMN disintegration (DD) coincided with higher anatomical between-module connectivity, whereas both were associated with increased seizure frequency. DD related to seizure frequency through mediating effects of anatomical connectivity, but seizure frequency also correlated with anatomical connectivity through DD, indicating a complex interaction between multimodal networks and symptoms.
  
  
  CONCLUSIONS
  We provide evidence for dissociated anatomical and functional hub connectivity in TLE. Moreover, shifts in functional hub connections from within to outside the DMN, an overall loss of integrative anatomical communication, and the interaction between the two increase seizure frequency.
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Charlestown, Massachusetts ; Department of Radiology, Harvard Medical School Boston, Massachusetts ; Department of Anatomy and Neurosciences, VU University Medical Center Amsterdam, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Douw
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Charlestown, Massachusetts ; Department of Radiology, Harvard Medical School Boston, Massachusetts.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: DeSalvo
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Charlestown, Massachusetts ; Department of Radiology, Harvard Medical School Boston, Massachusetts.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Neurology, Massachusetts General Hospital Boston, Massachusetts.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cole
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Charlestown, Massachusetts ; Department of Radiology, Harvard Medical School Boston, Massachusetts.
authors.forename: Hesheng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Charlestown, Massachusetts ; Department of Neurology, Brigham and Women's Hospital Boston, Massachusetts.
authors.forename: Claus
authors.initials: C
authors.lastname: Reinsberger
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Charlestown, Massachusetts ; Department of Radiology, Harvard Medical School Boston, Massachusetts.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Stufflebeam