Neocortical Slow Oscillations Implicated in the Generation of Epileptic Spasms
| Autor: | Chih-Hong Lee, Carlos J. Ballester-Rosado, John T. Le, Anne E. Anderson, John W. Swann |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Spasm Neocortex Tetrodotoxin 03 medical and health sciences 0302 clinical medicine Thalamus Seizures otorhinolaryngologic diseases medicine Premovement neuronal activity Animals Humans Ictal cardiovascular diseases Rats Wistar Electrocorticography Slow-wave sleep medicine.diagnostic_test business.industry Pyramidal Cells Infant Infantile Spasm medicine.disease Brain Waves nervous system diseases Rats body regions stomatognathic diseases Electrophysiology Epileptic spasms Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neurology Female Neurology (clinical) business Neuroscience Spasms Infantile 030217 neurology & neurosurgery Sodium Channel Blockers |
| Zdroj: | Annals of neurology. 89(2) |
| ISSN: | 1531-8249 |
| Popis: | Objective Epileptic spasms are a hallmark of severe seizure disorders. The neurophysiological mechanisms and the neuronal circuit(s) that generate these seizures are unresolved and are the focus of studies reported here. Methods In the tetrodotoxin model, we used 16-channel microarrays and microwires to record electrophysiological activity in neocortex and thalamus during spasms. Chemogenetic activation was used to examine the role of neocortical pyramidal cells in generating spasms. Comparisons were made to recordings from infantile spasm patients. Results Current source density and simultaneous multiunit activity analyses indicate that the ictal events of spasms are initiated in infragranular cortical layers. A dramatic pause of neuronal activity was recorded immediately prior to the onset of spasms. This preictal pause is shown to share many features with the down states of slow wave sleep. In addition, the ensuing interictal up states of slow wave rhythms are more intense in epileptic than control animals and occasionally appear sufficient to initiate spasms. Chemogenetic activation of neocortical pyramidal cells supported these observations, as it increased slow oscillations and spasm numbers and clustering. Recordings also revealed a ramp-up in the number of neocortical slow oscillations preceding spasms, which was also observed in infantile spasm patients. Interpretation Our findings provide evidence that epileptic spasms can arise from the neocortex and reveal a previously unappreciated interplay between brain state physiology and spasm generation. The identification of neocortical up states as a mechanism capable of initiating epileptic spasms will likely provide new targets for interventional therapies. ANN NEUROL 2021;89:226-241. |
| Databáze: | OpenAIRE |
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