title: Using network dynamic fMRI for detection of epileptogenic foci.
abstract: BACKGROUND
  Epilepsy is one of the most prevalent neurological disorders. It remains medically intractable for about one-third of patients with focal epilepsy, for whom precise localization of the epileptogenic zone responsible for seizure initiation may be critical for successful surgery. Existing fMRI literature points to widespread network disturbances in functional connectivity. Per previous scalp and intracranial EEG studies and consistent with excessive local synchronization during interictal discharges, we hypothesized that, relative to same regions in healthy controls, epileptogenic foci would exhibit less chaotic dynamics, identifiable via entropic analyses of resting state fMRI time series.
  
  
  METHODS
  In order to first validate this hypothesis on a cohort of patients with known ground truth, here we test individuals with well-defined epileptogenic foci (left mesial temporal lobe epilepsy). We analyzed voxel-wise resting-state fMRI time-series using the autocorrelation function (ACF), an entropic measure of regulation and feedback, and performed follow-up seed-to-voxel functional connectivity analysis. Disruptions in connectivity of the region exhibiting abnormal dynamics were examined in relation to duration of epilepsy and patients' cognitive performance using a delayed verbal memory recall task.
  
  
  RESULTS
  ACF analysis revealed constrained (less chaotic) functional dynamics in left temporal lobe epilepsy patients, primarily localized to ipsilateral temporal pole, proximal to presumed focal points. Autocorrelation decay rates differentiated, with 100 % accuracy, between patients and healthy controls on a subject-by-subject basis within a leave-one-subject out classification framework. Regions identified via ACF analysis formed a less efficient network in patients, as compared to controls. Constrained dynamics were linked with locally increased and long-range decreased connectivity that, in turn, correlated significantly with impaired memory (local left temporal connectivity) and epilepsy duration (left temporal - posterior cingulate cortex connectivity).
  
  
  CONCLUSIONS
  Our current results suggest that data driven functional MRI methods that target network dynamics hold promise in providing clinically valuable tools for identification of epileptic regions.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University School of Medicine, Stony Brook, NY, 11794, USA. Sanja.Nedic@stonybrook.edu.|Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA. Sanja.Nedic@stonybrook.edu.
authors.forename: Sanja
authors.initials: S
authors.lastname: Nedic
authors.affiliation: Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA. sms@nmr.mgh.harvard.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Stufflebeam
authors.affiliation: Department of Neurosciences and Behavior, University of Sao Paulo (USP), Ribeirao Preto, SP, 14049, Brazil. crondi2001@yahoo.com.br.
authors.forename: Carlo
authors.initials: C
authors.lastname: Rondinoni
authors.affiliation: Department of Neurosciences and Behavior, University of Sao Paulo (USP), Ribeirao Preto, SP, 14049, Brazil. tvelasco@fmrp.usp.br.
authors.forename: Tonicarlo R
authors.initials: TR
authors.lastname: Velasco
authors.affiliation: Department of Neurosciences and Behavior, University of Sao Paulo (USP), Ribeirao Preto, SP, 14049, Brazil. acsantos@fmrp.usp.br.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: dos Santos
authors.affiliation: Department of Neurosciences and Behavior, University of Sao Paulo (USP), Ribeirao Preto, SP, 14049, Brazil. jpleite@fmrp.usp.br.
authors.forename: Joao P
authors.initials: JP
authors.lastname: Leite
authors.affiliation: Department of Neurosciences and Behavior, University of Sao Paulo (USP), Ribeirao Preto, SP, 14049, Brazil. acgargaro@usp.br.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Gargaro
authors.affiliation: Department of Biomedical Engineering, Stony Brook University School of Medicine, Stony Brook, NY, 11794, USA. Lilianne.Strey@stonybrook.edu.|Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA. Lilianne.Strey@stonybrook.edu.
authors.forename: Lilianne R
authors.initials: LR
authors.lastname: Mujica-Parodi
authors.affiliation: Department of Biomedical Engineering, Stony Brook University School of Medicine, Stony Brook, NY, 11794, USA. Jaime.Ide@stonybrook.edu.|Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA. Jaime.Ide@stonybrook.edu.|Department of Science and Technology, Federal University of Sao Paulo, Sao Jose dos Campos, SP, 12231, Brazil. Jaime.Ide@stonybrook.edu.
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Ide
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged