Intracortical neural activity distal to seizure-onset-areas predicts human focal seizures.

Journal: PloS one
Published Date:

Abstract

The apparent unpredictability of epileptic seizures has a major impact in the quality of life of people with pharmacologically resistant seizures. Here, we present initial results and a proof-of-concept of how focal seizures can be predicted early in advance based on intracortical signals recorded from small neocortical patches away from identified seizure onset areas. We show that machine learning algorithms can discriminate between interictal and preictal periods based on multiunit activity (i.e. thresholded action potential counts) and multi-frequency band local field potentials recorded via 4 X 4 mm2 microelectrode arrays. Microelectrode arrays were implanted in 5 patients undergoing neuromonitoring for resective surgery. Post-implant analysis revealed arrays were outside the seizure onset areas. Preictal periods were defined as the 1-hour period leading to a seizure. A 5-minute gap between the preictal period and the putative seizure onset was enforced to account for potential errors in the determination of actual seizure onset times. We used extreme gradient boosting and long short-term memory networks for prediction. Prediction accuracy based on the area under the receiver operating characteristic curves reached 90% for at least one feature type in each patient. Importantly, successful prediction could be achieved based exclusively on multiunit activity. This result indicates that preictal activity in the recorded neocortical patches involved not only subthreshold postsynaptic potentials, perhaps driven by the distal seizure onset areas, but also neuronal spiking in distal recurrent neocortical networks. Beyond the commonly identified seizure onset areas, our findings point to the engagement of large-scale neuronal networks in the neural dynamics building up toward a seizure. Our initial results obtained on currently available human intracortical microelectrode array recordings warrant new studies on larger datasets, and open new perspectives for seizure prediction and control by emphasizing the contribution of multiscale neural signals in large-scale neuronal networks.

Authors

  • Timothée Proix
    Department of Neuroscience, Brown University, Providence, Rhode Island, United States of America.
  • Mehdi Aghagolzadeh
    Department of Neuroscience, Brown University, Providence, Rhode Island, United States of America.
  • Joseph R Madsen
    Neurodynamics Laboratory, Department of Neurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Rees Cosgrove
    Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Emad Eskandar
  • Leigh R Hochberg
    Center for Neurorestoration and Neurotechnology, Rehabilitation R&D Service, Department of Veterans Affairs Medical Center, Providence, RI 02908; Carney Institute for Brain Science and School of Engineering, Brown University, Providence, RI 02912; Center for Neurotechnology and Neurorecovery, Neurology, Massachusetts General Hospital, Boston, MA 02114; and Neurology, Harvard Medical School, Boston, MA 02115, U.S.A. leigh_hochberg@brown.edu.
  • Sydney S Cash
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Wilson Truccolo
    Department of Neuroscience, Brown University, Providence, Rhode Island, United States of America.