title: Atypical language laterality is associated with large-scale disruption of network integration in children with intractable focal epilepsy.
abstract: Epilepsy is associated with disruption of integration in distributed networks, together with altered localization for functions such as expressive language. The relation between atypical network connectivity and altered localization is unknown. In the current study we tested whether atypical expressive language laterality was associated with the alteration of large-scale network integration in children with medically-intractable localization-related epilepsy (LRE). Twenty-three right-handed children (age range 8-17) with medically-intractable LRE performed a verb generation task in fMRI. Language network activation was identified and the Laterality index (LI) was calculated within the pars triangularis and pars opercularis. Resting-state data from the same cohort were subjected to independent component analysis. Dual regression was used to identify associations between resting-state integration and LI values. Higher positive values of the LI, indicating typical language localization were associated with stronger functional integration of various networks including the default mode network (DMN). The normally symmetric resting-state networks showed a pattern of lateralized connectivity mirroring that of language function. The association between atypical language localization and network integration implies a widespread disruption of neural network development. These findings may inform the interpretation of localization studies by providing novel insights into reorganization of neural networks in epilepsy.
authors: Division of Neurosurgery, Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: georgem.ibrahim@utoronto.ca.
authors: George M
authors: GM
authors: Ibrahim
authors: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Benjamin R
authors: BR
authors: Morgan
authors: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors: Sam M
authors: SM
authors: Doesburg
authors: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors: Margot J
authors: MJ
authors: Taylor
authors: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Elizabeth W
authors: EW
authors: Pang
authors: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Elizabeth
authors: E
authors: Donner
authors: Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Cristina Y
authors: CY
authors: Go
authors: Division of Neurosurgery, Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors: James T
authors: JT
authors: Rutka
authors: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Neuroscience and Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: O Carter
authors: OC
authors: Snead
mesh_terms: D000293:Adolescent; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D000069279:Drug Resistant Epilepsy / Q000503:physiopathology*; D004828:Epilepsies, Partial / Q000503:physiopathology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007802:Language; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*
keywords: Functional connectivity; Laterality index; Resting-state fMRI