Amrit Misra1, Xianda Long1, Michael R Sperling2, Ashwini D Sharan3, Karen A Moxon1,4. 1. School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA. 2. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA. 3. Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA. 4. Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA.
Abstract
OBJECTIVE: To gain understanding of the neuronal mechanisms underlying regional seizure spread, the impact of regional synchrony between seizure focus and downstream networks on neuronal activity during the transition to seizure in those downstream networks was assessed. METHODS: Seven patients undergoing diagnostic intracranial electroencephalographic studies for surgical resection of epileptogenic regions were implanted with subdural clinical electrodes into the cortex (site of seizure initiation) and mesial temporal lobe (MTL) structures (downstream) as well as microwires into MTL. Neural activity was recorded (24/7) in parallel with the clinical intracranial electroencephalogram recordings for the duration of the patient's diagnostic stay. Changes in (1) regional synchrony (ie, coherence) between the presumptive neocortical seizure focus and MTL, (2) local synchrony between MTL neurons and their local field potential, and (3) neuronal firing rates within MTL in the time leading up to seizure were examined to study the mechanisms underlying seizure spread. RESULTS: In seizures of neocortical origin, an increase in regional synchrony preceded the spread of seizures into MTL (predominantly hippocampal). Within frequencies similar to those of regional synchrony, MTL networks showed an increase in unit-field coherence and a decrease in neuronal firing rate, specifically for inhibitory interneuron populations but not pyramidal cell populations. SIGNIFICANCE: These results suggest a mechanism of spreading seizures whereby the seizure focus first synchronizes local field potentials in downstream networks to the seizure activity. This change in local field coherence modifies the activity of interneuron populations in these downstream networks, which leads to the attenuation of interneuronal firing rate, effectively shutting down local interneuron populations prior to the spread of seizure. Therefore, regional synchrony may influence the failure of downstream interneurons to prevent the spread of the seizures during generalization. Wiley Periodicals, Inc.
OBJECTIVE: To gain understanding of the neuronal mechanisms underlying regional seizure spread, the impact of regional synchrony between seizure focus and downstream networks on neuronal activity during the transition to seizure in those downstream networks was assessed. METHODS: Seven patients undergoing diagnostic intracranial electroencephalographic studies for surgical resection of epileptogenic regions were implanted with subdural clinical electrodes into the cortex (site of seizure initiation) and mesial temporal lobe (MTL) structures (downstream) as well as microwires into MTL. Neural activity was recorded (24/7) in parallel with the clinical intracranial electroencephalogram recordings for the duration of the patient's diagnostic stay. Changes in (1) regional synchrony (ie, coherence) between the presumptive neocortical seizure focus and MTL, (2) local synchrony between MTL neurons and their local field potential, and (3) neuronal firing rates within MTL in the time leading up to seizure were examined to study the mechanisms underlying seizure spread. RESULTS: In seizures of neocortical origin, an increase in regional synchrony preceded the spread of seizures into MTL (predominantly hippocampal). Within frequencies similar to those of regional synchrony, MTL networks showed an increase in unit-field coherence and a decrease in neuronal firing rate, specifically for inhibitory interneuron populations but not pyramidal cell populations. SIGNIFICANCE: These results suggest a mechanism of spreading seizures whereby the seizure focus first synchronizes local field potentials in downstream networks to the seizure activity. This change in local field coherence modifies the activity of interneuron populations in these downstream networks, which leads to the attenuation of interneuronal firing rate, effectively shutting down local interneuron populations prior to the spread of seizure. Therefore, regional synchrony may influence the failure of downstream interneurons to prevent the spread of the seizures during generalization. Wiley Periodicals, Inc.
Authors: Catherine A Schevon; Steven Tobochnik; Tahra Eissa; Edward Merricks; Brian Gill; R Ryley Parrish; Lisa M Bateman; Guy M McKhann; Ronald G Emerson; Andrew J Trevelyan Journal: Neurobiol Dis Date: 2019-03-18 Impact factor: 5.996
Authors: Edward M Merricks; Elliot H Smith; Ronald G Emerson; Lisa M Bateman; Guy M McKhann; Robert R Goodman; Sameer A Sheth; Bradley Greger; Paul A House; Andrew J Trevelyan; Catherine A Schevon Journal: J Neurosci Date: 2020-11-23 Impact factor: 6.167