title: Diminished default mode network recruitment of the hippocampus and parahippocampus in temporal lobe epilepsy.
abstract: OBJECTIVE
  Functional neuroimaging has shown that the brain organizes into several independent networks of spontaneously coactivated regions during wakeful rest (resting state). Previous research has suggested that 1 such network, the default mode network (DMN), shows diminished recruitment of the hippocampus with temporal lobe epilepsy (TLE). This work seeks to elucidate how hippocampal recruitment into the DMN varies by hemisphere of epileptogenic focus.
  
  
  METHODS
  The authors addressed this issue using functional MRI to assess resting-state DMN connectivity in 38 participants (23 control participants, 7 patients with TLE and left-sided epileptogenic foci, and 8 patients with TLE and right-sided foci). Independent component analysis was conducted to identify resting-state brain networks from control participants' data. The DMN was identified and deconstructed into its individual regions of interest (ROIs). The functional connectivity of these ROIs was analyzed both by hemisphere (left vs right) and by laterality to the epileptogenic focus (ipsilateral vs contralateral).
  
  
  RESULTS
  This attempt to replicate previously published methods with this data set showed that patients with left-sided TLE had reduced connectivity between the posterior cingulate (PCC) and both the left (p = 0.012) and right (p < 0.002) hippocampus, while patients with right-sided TLE showed reduced connectivity between the PCC and right hippocampus (p < 0.004). After recoding ROIs by laterality, significantly diminished functional connectivity was observed between the PCC and hippocampus of both hemispheres (ipsilateral hippocampus, p < 0.001; contralateral hippocampus, p = 0.017) in patients with TLE compared with control participants. Regression analyses showed the reduced DMN recruitment of the ipsilateral hippocampus and parahippocampal gyrus (PHG) to be independent of clinical variables including hippocampal sclerosis, seizure frequency, and duration of illness. The graph theory metric of strength (or mean absolute correlation) showed significantly reduced connectivity of the ipsilateral hippocampus and ipsilateral PHG in patients with TLE compared with controls (hippocampus: p = 0.028; PHG: p = 0.021, after correction for false discovery rate). Finally, these hemispheric asymmetries in strength were observed in patients with TLE that corresponded to hemisphere of epileptogenic focus; 87% of patients with TLE had weaker ipsilateral hippocampus strength (compared with the contralateral hippocampus), and 80% of patients had weaker ipsilateral PHG strength.
  
  
  CONCLUSIONS
  This study demonstrated that recoding brain regions by the laterality to their epileptogenic focus increases the power of statistical approaches for finding interhemispheric differences in brain function. Using this approach, the authors showed TLE to selectively diminish connectivity of the hippocampus and parahippocampus in the hemisphere of the epileptogenic focus. This approach may prove to be a useful method for determining the seizure onset zone with TLE, and could be broadly applied to other neurological disorders with a lateralized onset.
authors.affiliation: Psychiatric Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA. gajames@uams.edu
authors.forename: G Andrew
authors.initials: GA
authors.lastname: James
authors.forename: Shanti Prakash
authors.initials: SP
authors.lastname: Tripathi
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Ojemann
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gross
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Drane
mesh_terms: D000328:Adult; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D020534:Parahippocampal Gyrus / Q000503:physiopathology*