title: Levetiracetam reduces abnormal network activations in temporal lobe epilepsy.
abstract: OBJECTIVE
  We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE).
  
  
  METHODS
  In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose.
  
  
  RESULTS
  We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left.
  
  
  CONCLUSIONS
  Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response.
  
  
  METHODS
  This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures.
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: Britta
authors.initials: B
authors.lastname: Wandschneider
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: Jason
authors.initials: J
authors.lastname: Stretton
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: Meneka
authors.initials: M
authors.lastname: Sidhu
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: Maria
authors.initials: M
authors.lastname: Centeno
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: Lajos R
authors.initials: LR
authors.lastname: Kozák
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: Mark
authors.initials: M
authors.lastname: Symms
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Thompson
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary.
authors.forename: John S
authors.initials: JS
authors.lastname: Duncan
authors.affiliation: From the Department of Clinical and Experimental Epilepsy (B.W., J.S., M.S., M.C., M.S., P.J.T., J.S.D., M.J.K.), UCL Institute of Neurology, London; the MRC Cognition and Brain Science Unit (J.S.), University of Cambridge; the Imaging and Biophysics Department (M.C.), UCL Institute of Child Health, Great Ormond Street Hospital, London, UK; and the MR Research Center (L.R.K.), Semmelweis University, Budapest, Hungary. m.koepp@ucl.ac.uk.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Koepp
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D016009:Chi-Square Distribution; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000077287:Levetiracetam; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010100:Oxygen; D010889:Piracetam