Interictal high frequency oscillations in an animal model of infantile spasms
While infantile spasms is the most common catastrophic epilepsy of infancy and early-childhood, very little is known about the basic mechanisms responsible for this devastating disorder. In experiments reported here, spasms were induced in rats by the chronic infusion of TTX into the neocortex begin...
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doaj-aa22a67e737c49d5b768630481e106112021-03-22T12:38:15ZengElsevierNeurobiology of Disease1095-953X2012-05-01462377388Interictal high frequency oscillations in an animal model of infantile spasmsJames D. Frost, Jr.0Chong L. Lee1John T. Le2Richard A. Hrachovy3John W. Swann4Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USAThe Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USAThe Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Neurology, Baylor College of Medicine, Houston, TX 77030, USA; The Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USAThe Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author at: The Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, 1250 Moursund St Suite 1225, Houston TX 77030, USA. Fax: +1 832 825 1248.While infantile spasms is the most common catastrophic epilepsy of infancy and early-childhood, very little is known about the basic mechanisms responsible for this devastating disorder. In experiments reported here, spasms were induced in rats by the chronic infusion of TTX into the neocortex beginning on postnatal days 10–12. Studies of focal epilepsy suggest that high frequency EEG oscillations (HFOs) occur interictally at sites that are most likely responsible for seizure generation. Thus, our goal was to determine if HFOs occurred and where they occurred in cortex in the TTX model. We also undertook multiunit recordings to begin to analyze the basic mechanisms responsible for HFOs. Our results show that HFOs occur most frequently during hypsarrhythmia and NREM sleep and are most prominent contralateral to the TTX infusion site in the homotopic cortex and anterior to this region in frontal cortex. While HFOs were largest and most frequent in these contralateral regions, they were also commonly recorded synchronously across multiple and widely-spaced recordings sites. The amplitude and spatial distribution of interictal HFOs were found to be very similar to the high frequency bursts seen at seizure onset. However, the latter differed from the interictal events in that the high frequency activity was more intense at seizure onset. Microwire recordings showed that neuronal unit firing increased abruptly with the generation of HFOs. A similar increase in neuronal firing occurred at the onset of the ictal events. Taken together, results suggest that neocortical networks are abnormally excitable, particularly contralateral to TTX infusion, and that these abnormalities are not restricted to small areas of cortex. Multiunit firing coincident with HFOs is fully consistent with a neocortical hyperexcitability hypothesis particularly since they both occur at seizure onset.http://www.sciencedirect.com/science/article/pii/S0969996112000435EpilepsySeizuresInfantile spasmsTTXHigh frequency oscillationsEEG |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
James D. Frost, Jr. Chong L. Lee John T. Le Richard A. Hrachovy John W. Swann |
spellingShingle |
James D. Frost, Jr. Chong L. Lee John T. Le Richard A. Hrachovy John W. Swann Interictal high frequency oscillations in an animal model of infantile spasms Neurobiology of Disease Epilepsy Seizures Infantile spasms TTX High frequency oscillations EEG |
author_facet |
James D. Frost, Jr. Chong L. Lee John T. Le Richard A. Hrachovy John W. Swann |
author_sort |
James D. Frost, Jr. |
title |
Interictal high frequency oscillations in an animal model of infantile spasms |
title_short |
Interictal high frequency oscillations in an animal model of infantile spasms |
title_full |
Interictal high frequency oscillations in an animal model of infantile spasms |
title_fullStr |
Interictal high frequency oscillations in an animal model of infantile spasms |
title_full_unstemmed |
Interictal high frequency oscillations in an animal model of infantile spasms |
title_sort |
interictal high frequency oscillations in an animal model of infantile spasms |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2012-05-01 |
description |
While infantile spasms is the most common catastrophic epilepsy of infancy and early-childhood, very little is known about the basic mechanisms responsible for this devastating disorder. In experiments reported here, spasms were induced in rats by the chronic infusion of TTX into the neocortex beginning on postnatal days 10–12. Studies of focal epilepsy suggest that high frequency EEG oscillations (HFOs) occur interictally at sites that are most likely responsible for seizure generation. Thus, our goal was to determine if HFOs occurred and where they occurred in cortex in the TTX model. We also undertook multiunit recordings to begin to analyze the basic mechanisms responsible for HFOs. Our results show that HFOs occur most frequently during hypsarrhythmia and NREM sleep and are most prominent contralateral to the TTX infusion site in the homotopic cortex and anterior to this region in frontal cortex. While HFOs were largest and most frequent in these contralateral regions, they were also commonly recorded synchronously across multiple and widely-spaced recordings sites. The amplitude and spatial distribution of interictal HFOs were found to be very similar to the high frequency bursts seen at seizure onset. However, the latter differed from the interictal events in that the high frequency activity was more intense at seizure onset. Microwire recordings showed that neuronal unit firing increased abruptly with the generation of HFOs. A similar increase in neuronal firing occurred at the onset of the ictal events. Taken together, results suggest that neocortical networks are abnormally excitable, particularly contralateral to TTX infusion, and that these abnormalities are not restricted to small areas of cortex. Multiunit firing coincident with HFOs is fully consistent with a neocortical hyperexcitability hypothesis particularly since they both occur at seizure onset. |
topic |
Epilepsy Seizures Infantile spasms TTX High frequency oscillations EEG |
url |
http://www.sciencedirect.com/science/article/pii/S0969996112000435 |
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