Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model
Background: Deep brain stimulation (DBS) targeting globus pallidus internus (GPi) is a recognised therapy for drug-refractory dystonia. However, the mechanisms underlying this effect are not fully understood. This study explores how pallidal DBS alters spatiotemporal pattern formation of neuronal dy...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003814 |
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| author | Fabiana Santana Kragelund Konstantinos Spiliotis Marco Heerdegen Tina Sellmann Henning Bathel Anika Lüttig Angelika Richter Jens Starke Rüdiger Köhling Denise Franz |
| author_facet | Fabiana Santana Kragelund Konstantinos Spiliotis Marco Heerdegen Tina Sellmann Henning Bathel Anika Lüttig Angelika Richter Jens Starke Rüdiger Köhling Denise Franz |
| author_sort | Fabiana Santana Kragelund |
| collection | DOAJ |
| description | Background: Deep brain stimulation (DBS) targeting globus pallidus internus (GPi) is a recognised therapy for drug-refractory dystonia. However, the mechanisms underlying this effect are not fully understood. This study explores how pallidal DBS alters spatiotemporal pattern formation of neuronal dynamics within the cerebellar cortex in a dystonic animal model, the dtsz hamster. Methods: We conducted in vitro analysis using a high-density microelectrode array (HD-MEA) in the cerebellar cortex. For investigating the spatiotemporal pattern, mean firing rates (MFR), interspike intervals (ISI), spike amplitudes, and cerebellar connectivity among healthy control hamsters, dystonic dtsz hamsters, DBS- and sham-DBS-treated dtsz hamsters were analysed. A nonlinear data-driven method characterised the low-dimensional representation of the patterns in MEA data. Results: Our HD-MEA recordings revealed reduced MFR and spike amplitudes in the dtsz hamsters compared to healthy controls. Pallidal DBS induced network-wide effects, normalising MFR, spike amplitudes, and connectivity measures in hamsters, thereby countervailing these electrophysiological abnormalities. Additionally, network analysis showed neural activity patterns organised into communities, with higher connectivity in both healthy and DBS groups compared to dtsz. Conclusions: These findings suggest that pallidal DBS exerts some of its therapeutic effects on dystonia by normalising neuronal activity within the cerebellar cortex. Our findings of reduced MFR and spike amplitudes in the dtsz hamsters could be a hint of a decrease in neuronal fibres and synaptic plasticity. Treatment with pallidal DBS led to cerebellar cortical activity similar to healthy controls, displaying the network-wide impact of local stimulation. |
| format | Article |
| id | doaj-art-3c84ecbca585411893576e6e397bb80b |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-3c84ecbca585411893576e6e397bb80b2025-01-24T04:44:38ZengElsevierNeurobiology of Disease1095-953X2025-02-01205106779Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal modelFabiana Santana Kragelund0Konstantinos Spiliotis1Marco Heerdegen2Tina Sellmann3Henning Bathel4Anika Lüttig5Angelika Richter6Jens Starke7Rüdiger Köhling8Denise Franz9Oscar Langendorff Institute of Physiology, University Medical Centre Rostock, Rostock, GermanyInstitute of Mathematics, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University Medical Centre Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University Medical Centre Rostock, Rostock, GermanyInstitute of General Electrical Engineering, University of Rostock, Rostock, Germanynstitute for Pharmacology, Pharmacy and Toxicology, University of Leipzig, Leipzig, Germanynstitute for Pharmacology, Pharmacy and Toxicology, University of Leipzig, Leipzig, GermanyInstitute of Mathematics, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University Medical Centre Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University Medical Centre Rostock, Rostock, Germany; Corresponding author at: Oscar Langendorff Institute of Physiology, University Medical Centre Rostock, Gertrudenstr. 9, 18057 Rostock, Germany.Background: Deep brain stimulation (DBS) targeting globus pallidus internus (GPi) is a recognised therapy for drug-refractory dystonia. However, the mechanisms underlying this effect are not fully understood. This study explores how pallidal DBS alters spatiotemporal pattern formation of neuronal dynamics within the cerebellar cortex in a dystonic animal model, the dtsz hamster. Methods: We conducted in vitro analysis using a high-density microelectrode array (HD-MEA) in the cerebellar cortex. For investigating the spatiotemporal pattern, mean firing rates (MFR), interspike intervals (ISI), spike amplitudes, and cerebellar connectivity among healthy control hamsters, dystonic dtsz hamsters, DBS- and sham-DBS-treated dtsz hamsters were analysed. A nonlinear data-driven method characterised the low-dimensional representation of the patterns in MEA data. Results: Our HD-MEA recordings revealed reduced MFR and spike amplitudes in the dtsz hamsters compared to healthy controls. Pallidal DBS induced network-wide effects, normalising MFR, spike amplitudes, and connectivity measures in hamsters, thereby countervailing these electrophysiological abnormalities. Additionally, network analysis showed neural activity patterns organised into communities, with higher connectivity in both healthy and DBS groups compared to dtsz. Conclusions: These findings suggest that pallidal DBS exerts some of its therapeutic effects on dystonia by normalising neuronal activity within the cerebellar cortex. Our findings of reduced MFR and spike amplitudes in the dtsz hamsters could be a hint of a decrease in neuronal fibres and synaptic plasticity. Treatment with pallidal DBS led to cerebellar cortical activity similar to healthy controls, displaying the network-wide impact of local stimulation.http://www.sciencedirect.com/science/article/pii/S0969996124003814Cerebellar network activitypallidal deep brain stimulationgeneralised dystoniahigh-density microelectrode arraysdtsz mutant hamsterspatiotemporal analysis |
| spellingShingle | Fabiana Santana Kragelund Konstantinos Spiliotis Marco Heerdegen Tina Sellmann Henning Bathel Anika Lüttig Angelika Richter Jens Starke Rüdiger Köhling Denise Franz Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model Neurobiology of Disease Cerebellar network activity pallidal deep brain stimulation generalised dystonia high-density microelectrode arrays dtsz mutant hamster spatiotemporal analysis |
| title | Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model |
| title_full | Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model |
| title_fullStr | Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model |
| title_full_unstemmed | Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model |
| title_short | Network-wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model |
| title_sort | network wide effects of pallidal deep brain stimulation normalised abnormal cerebellar cortical activity in the dystonic animal model |
| topic | Cerebellar network activity pallidal deep brain stimulation generalised dystonia high-density microelectrode arrays dtsz mutant hamster spatiotemporal analysis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003814 |
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