Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model
Abstract Objective Neurostimulation is an emerging treatment for patients with drug‐resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even af...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Epilepsia Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/epi4.12861 |
| _version_ | 1797324247179198464 |
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| author | Thomas J. Foutz Nicholas Rensing Lirong Han Dominique M. Durand Michael Wong |
| author_facet | Thomas J. Foutz Nicholas Rensing Lirong Han Dominique M. Durand Michael Wong |
| author_sort | Thomas J. Foutz |
| collection | DOAJ |
| description | Abstract Objective Neurostimulation is an emerging treatment for patients with drug‐resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. Methods We performed high‐throughput testing of high‐frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes. Results We found that the spike‐suppressive effects of high‐frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 μA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. Significance These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti‐seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. Plain Language Summary In this study, we tested how electrical pulses in the brain can help control seizures in mice. We found that the electrode's placement and the stimulation amplitude had a large effect on outcomes. Some brain regions, notably nearby CA1 and CA3, responded positively with reduced seizure‐like activities, while others showed increased activity. These findings emphasize that choosing the right spot for the electrode and adjusting the strength of electrical pulses are both crucial when considering neurostimulation treatments for epilepsy. |
| first_indexed | 2024-03-08T05:53:20Z |
| format | Article |
| id | doaj.art-17f690cffae2486c9a0d49c2be92107b |
| institution | Directory Open Access Journal |
| issn | 2470-9239 |
| language | English |
| last_indexed | 2024-03-08T05:53:20Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj.art-17f690cffae2486c9a0d49c2be92107b2024-02-05T06:37:58ZengWileyEpilepsia Open2470-92392024-02-019121022210.1002/epi4.12861Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse modelThomas J. Foutz0Nicholas Rensing1Lirong Han2Dominique M. Durand3Michael Wong4Department of Neurology Washington University School of Medicine St. Louis Missouri USADepartment of Neurology Washington University School of Medicine St. Louis Missouri USADepartment of Neurology Washington University School of Medicine St. Louis Missouri USADepartment of Biomedical Engineering Case Western Reserve University Cleveland Ohio USADepartment of Neurology Washington University School of Medicine St. Louis Missouri USAAbstract Objective Neurostimulation is an emerging treatment for patients with drug‐resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. Methods We performed high‐throughput testing of high‐frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes. Results We found that the spike‐suppressive effects of high‐frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 μA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. Significance These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti‐seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. Plain Language Summary In this study, we tested how electrical pulses in the brain can help control seizures in mice. We found that the electrode's placement and the stimulation amplitude had a large effect on outcomes. Some brain regions, notably nearby CA1 and CA3, responded positively with reduced seizure‐like activities, while others showed increased activity. These findings emphasize that choosing the right spot for the electrode and adjusting the strength of electrical pulses are both crucial when considering neurostimulation treatments for epilepsy.https://doi.org/10.1002/epi4.12861brain stimulationepilepsyneuromodulationseizuresstatus epilepticus |
| spellingShingle | Thomas J. Foutz Nicholas Rensing Lirong Han Dominique M. Durand Michael Wong Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model Epilepsia Open brain stimulation epilepsy neuromodulation seizures status epilepticus |
| title | Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model |
| title_full | Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model |
| title_fullStr | Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model |
| title_full_unstemmed | Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model |
| title_short | Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model |
| title_sort | spatial and amplitude dynamics of neurostimulation insights from the acute intrahippocampal kainate seizure mouse model |
| topic | brain stimulation epilepsy neuromodulation seizures status epilepticus |
| url | https://doi.org/10.1002/epi4.12861 |
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