Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI
Abstract Focused ultrasound (FUS) has emerged as a promising neuromodulation technique for reducing regional brain excitability, offering a potential therapeutic approach for drug-resistant epilepsy (DRE). However, its underlying mechanisms remain unclear, particularly regarding functional connectiv...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-15305-0 |
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| author | Po-Chun Chu Wei-Hong Ruan Chen-Syuan Huang Yi-Jing Juan Jyh-Horng Chen Hsiang-Yu Yu Robert S. Fisher Hao-Li Liu |
| author_facet | Po-Chun Chu Wei-Hong Ruan Chen-Syuan Huang Yi-Jing Juan Jyh-Horng Chen Hsiang-Yu Yu Robert S. Fisher Hao-Li Liu |
| author_sort | Po-Chun Chu |
| collection | DOAJ |
| description | Abstract Focused ultrasound (FUS) has emerged as a promising neuromodulation technique for reducing regional brain excitability, offering a potential therapeutic approach for drug-resistant epilepsy (DRE). However, its underlying mechanisms remain unclear, particularly regarding functional connectivity alterations in seizure-related brain networks. This study investigates the relationship between FUS-induced seizure suppression and brain functional connectivity using EEG and resting-state fMRI (rs-fMRI). Using a pentylenetetrazol (PTZ)-induced epilepsy rat model (n = 28), we applied burst-mode FUS with 0.25 MI, ISPTA = 0.3 W/cm2 with low (30s-on-90s-off)/high (90s-on-30s-off) doses with 10-minute sonication durations to the anterior nucleus of the thalamus (ANT), resulting in approximately 36% reduction in hippocampal spike activity. Rs-fMRI analysis (36 × 36 connectivity matrix) revealed that the PTZ-induced seizure reduction strongly correlates with significant whole-brain connectivity changes, including a 45.1% decrease in connectivity between the anterior thalamic and hippocampal networks. Histological analysis confirmed that FUS preferentially modulates key brain regions involved in epileptic circuits, particularly the thalamus and hippocampus. These findings provide compelling evidence that FUS selectively alters seizure-related functional networks, highlighting its potential as a noninvasive therapeutic approach for epilepsy. |
| format | Article |
| id | doaj-art-9a25227ebdf440e7abab20cc407dc0bf |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-9a25227ebdf440e7abab20cc407dc0bf2025-08-20T03:04:38ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-15305-0Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRIPo-Chun Chu0Wei-Hong Ruan1Chen-Syuan Huang2Yi-Jing Juan3Jyh-Horng Chen4Hsiang-Yu Yu5Robert S. Fisher6Hao-Li Liu7Department of Electrical Engineering, National Taiwan UniversityGraduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan UniversityDepartment of Electrical Engineering, National Taiwan UniversityGraduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan UniversityDepartment of Electrical Engineering, National Taiwan UniversityDepartment of Neurology, Taipei Veteran General HospitalDepartment of Neurology and Neurological Sciences, Stanford University School of MedicineDepartment of Electrical Engineering, National Taiwan UniversityAbstract Focused ultrasound (FUS) has emerged as a promising neuromodulation technique for reducing regional brain excitability, offering a potential therapeutic approach for drug-resistant epilepsy (DRE). However, its underlying mechanisms remain unclear, particularly regarding functional connectivity alterations in seizure-related brain networks. This study investigates the relationship between FUS-induced seizure suppression and brain functional connectivity using EEG and resting-state fMRI (rs-fMRI). Using a pentylenetetrazol (PTZ)-induced epilepsy rat model (n = 28), we applied burst-mode FUS with 0.25 MI, ISPTA = 0.3 W/cm2 with low (30s-on-90s-off)/high (90s-on-30s-off) doses with 10-minute sonication durations to the anterior nucleus of the thalamus (ANT), resulting in approximately 36% reduction in hippocampal spike activity. Rs-fMRI analysis (36 × 36 connectivity matrix) revealed that the PTZ-induced seizure reduction strongly correlates with significant whole-brain connectivity changes, including a 45.1% decrease in connectivity between the anterior thalamic and hippocampal networks. Histological analysis confirmed that FUS preferentially modulates key brain regions involved in epileptic circuits, particularly the thalamus and hippocampus. These findings provide compelling evidence that FUS selectively alters seizure-related functional networks, highlighting its potential as a noninvasive therapeutic approach for epilepsy.https://doi.org/10.1038/s41598-025-15305-0Focused ultrasoundNeuromodulationGeneralized epilepsyPTZ model |
| spellingShingle | Po-Chun Chu Wei-Hong Ruan Chen-Syuan Huang Yi-Jing Juan Jyh-Horng Chen Hsiang-Yu Yu Robert S. Fisher Hao-Li Liu Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI Scientific Reports Focused ultrasound Neuromodulation Generalized epilepsy PTZ model |
| title | Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI |
| title_full | Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI |
| title_fullStr | Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI |
| title_full_unstemmed | Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI |
| title_short | Focused ultrasound suppresses pentylenetetrazol-induced epileptiform activity in rats and alters connectivity measured by functional MRI |
| title_sort | focused ultrasound suppresses pentylenetetrazol induced epileptiform activity in rats and alters connectivity measured by functional mri |
| topic | Focused ultrasound Neuromodulation Generalized epilepsy PTZ model |
| url | https://doi.org/10.1038/s41598-025-15305-0 |
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