Macroscale and microcircuit dissociation of focal and generalized human epilepsies.

Journal: Communications biology
PMID: 32424317

Abstract

Thalamo-cortical pathology plays key roles in both generalized and focal epilepsies, but there is little work directly comparing these syndromes at the level of whole-brain mechanisms. Using multimodal imaging, connectomics, and computational simulations, we examined thalamo-cortical and cortico-cortical signatures and underlying microcircuits in 96 genetic generalized (GE) and 107 temporal lobe epilepsy (TLE) patients, along with 65 healthy controls. Structural and functional network profiling highlighted extensive atrophy, microstructural disruptions and decreased thalamo-cortical connectivity in TLE, while GE showed only subtle structural anomalies paralleled by enhanced thalamo-cortical connectivity. Connectome-informed biophysical simulations indicated modest increases in subcortical drive contributing to cortical dynamics in GE, while TLE presented with reduced subcortical drive and imbalanced excitation-inhibition within limbic and somatomotor microcircuits. Multiple sensitivity analyses supported robustness. Our multiscale analyses differentiate human focal and generalized epilepsy at the systems-level, showing paradoxically more severe microcircuit and macroscale imbalances in the former.

Authors

  • Yifei Weng
    Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
  • Sara Lariviere
    McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
  • Lorenzo Caciagli
    University College London Queen Square Institute of Neurology, London, United Kingdom.
  • Reinder Vos de Wael
    McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
  • Raúl Rodríguez-Cruces
    McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, 3801 University Street, Montreal, QC, H3A2B4, Canada.
  • Jessica Royer
    McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
  • Qiang Xu
    University of Huddersfield, Queensgate, Huddersfield, United Kingdom . Electronic address: Q.Xu2@hud.ac.uk.
  • Neda Bernasconi
    McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, 3801 University Street, Montreal, QC, H3A2B4, Canada.
  • Andrea Bernasconi
    Evidence-based Public Health, Centre for International Health Protection, Robert Koch Institute, Berlin, Germany.
  • B T Thomas Yeo
    Department of Electrical and Computer Engineering, Centre for Sleep and Cognition, Clinical Imaging Research Centre and N.1 Institute for Health, National University of Singapore, Singapore, Singapore.
  • Guangming Lu
    Department of Computer Science and Technology, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, China.
  • Zhiqiang Zhang
    Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
  • Boris C Bernhardt
    McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada. boris.bernhardt@mcgill.ca.

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