title: Loss of network efficiency associated with cognitive decline in chronic epilepsy.
abstract: OBJECTIVE
  To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed.
  
  
  METHODS
  Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis.
  
  
  RESULTS
  Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering.
  
  
  CONCLUSIONS
  These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.
authors.affiliation: Department of Radiology, Maastricht University Medical Center, 6202 AZ Maastricht, the Netherlands.
authors.forename: M C G
authors.initials: MC
authors.lastname: Vlooswijk
authors.forename: M J
authors.initials: MJ
authors.lastname: Vaessen
authors.forename: J F A
authors.initials: JF
authors.lastname: Jansen
authors.forename: M C F T M
authors.initials: MC
authors.lastname: de Krom
authors.forename: H J M
authors.initials: HJ
authors.lastname: Majoie
authors.forename: P A M
authors.initials: PA
authors.lastname: Hofman
authors.forename: A P
authors.initials: AP
authors.lastname: Aldenkamp
authors.forename: W H
authors.initials: WH
authors.lastname: Backes
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D002908:Chronic Disease; D003072:Cognition Disorders / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology*; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants