title: Hippocampal-thalamic wiring in medial temporal lobe epilepsy: Enhanced connectivity per hippocampal voxel.
abstract: OBJECTIVE
  Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis is often accompanied by widespread changes in ipsilateral and contralateral white matter connectivity. Recent studies have proposed that patients may show pathologically enhanced wiring of the limbic circuits. To better address this issue, we specifically probed connection patterns between hippocampus and thalamus and examined their impact on cognitive function.
  
  
  METHODS
  A group of 44 patients with TLE (22 with right and 22 with left hippocampal sclerosis) and 24 healthy control participants were examined with high-resolution T1 imaging, memory functional magnetic resonance imaging (fMRI) and probabilistic diffusion tractography. Thirty-four patients had further extensive neuropsychological testing. After whole brain segmentation with FreeSurfer, tractography streamline samples were drawn with hippocampus as the seed and thalamus as the target region. Two tractography strategies were applied: The first targeted the anatomic thalamic volume segmented in FreeSurfer and the second a functional region of interest in the mediodorsal thalamus derived from the activation during delayed recognition memory.
  
  
  RESULTS
  We found a pronounced enhancement of connectivity between the sclerotic hippocampus and the ipsilateral thalamus both in the right and left TLE as compared to healthy control participants. This finding held for both the anatomically and the functionally defined thalamic target. Although differences were apparent in the number of absolute fibers, they were most pronounced when correcting for hippocampal volume. In terms of cognitive function, the number of hippocampal-thalamic connections was negatively correlated with performance in a variety of executive tasks, notably in the Trail Making Test, thus suggesting that the pathologic wiring did not compensate cognitive curtailing.
  
  
  CONCLUSIONS
  We suggest that TLE is accompanied by an abnormal and dysfunctional enhancement of connectivity between the hippocampus and the thalamus, which is maximal on the side of the sclerosis. This pathologic pattern of limbic wiring might reflect structural remodeling along common pathways of seizure propagation.
authors.affiliation: Epilepsy Unit, Pitié-Salpêtrière Hospital, APHP, Paris, France.|ICM - Brain and Spine Institute, Sorbonne Universities, UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, Paris, France.
authors.forename: Vera
authors.identifier: http://orcid.org/0000-0002-8965-6502
authors.initials: V
authors.lastname: Dinkelacker
authors.affiliation: ICM - Brain and Spine Institute, Sorbonne Universities, UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, Paris, France.|Neuroimaging Center (CENIR), Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Valabregue
authors.affiliation: Epilepsy Unit, Pitié-Salpêtrière Hospital, APHP, Paris, France.|ICM - Brain and Spine Institute, Sorbonne Universities, UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Thivard
authors.affiliation: ICM - Brain and Spine Institute, Sorbonne Universities, UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, Paris, France.|Neuroimaging Center (CENIR), Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehéricy
authors.affiliation: Epilepsy Unit, Pitié-Salpêtrière Hospital, APHP, Paris, France.|ICM - Brain and Spine Institute, Sorbonne Universities, UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Baulac
authors.affiliation: Epilepsy Unit, Pitié-Salpêtrière Hospital, APHP, Paris, France.|Functional Neuroscience Laboratory (EA 4559), Lille University, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Samson
authors.affiliation: Epilepsy Unit, Pitié-Salpêtrière Hospital, APHP, Paris, France.|ICM - Brain and Spine Institute, Sorbonne Universities, UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dupont
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology* / Q000523:psychology; D056324:Diffusion Tensor Imaging; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology* / Q000523:psychology; D056344:Executive Function; D005260:Female; D007839:Functional Laterality; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D009929:Organ Size; D021641:Recognition, Psychology / Q000502:physiology; D012598:Sclerosis; D013788:Thalamus / Q000503:physiopathology*; D055815:Young Adult
keywords: Connectivity; Diffusion-weighted imaging; Executive function; Hippocampal sclerosis; Neuropsychology; Probabilistic tractography