Kragelund Fabiana Santana, Spiliotis Konstantinos, Heerdegen Marco, Sellmann Tina, Bathel Henning, Lüttig Anika, Richter Angelika, Starke Jens, Köhling Rüdiger, Franz Denise
Oscar Langendorff Institute of Physiology, University Medical Centre Rostock, Rostock, Germany.
Institute of Mathematics, University of Rostock, Rostock, Germany.
Neurobiol Dis. 2025 Feb;205:106779. doi: 10.1016/j.nbd.2024.106779. Epub 2024 Dec 24.
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 dt hamster.
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 dt hamsters, DBS- and sham-DBS-treated dt hamsters were analysed. A nonlinear data-driven method characterised the low-dimensional representation of the patterns in MEA data.
Our HD-MEA recordings revealed reduced MFR and spike amplitudes in the dt 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 dt.
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 dt 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.
靶向苍白球内侧部（GPi）的脑深部电刺激（DBS）是一种公认的治疗药物难治性肌张力障碍的方法。然而，这种效应的潜在机制尚未完全明确。本研究探讨苍白球DBS如何改变肌张力障碍动物模型dt仓鼠小脑皮质内神经元动力学的时空模式形成。
我们在小脑皮质中使用高密度微电极阵列（HD-MEA）进行体外分析。为了研究时空模式，分析了健康对照仓鼠、肌张力障碍dt仓鼠、接受DBS治疗和假DBS治疗的dt仓鼠的平均放电率（MFR）、峰间期（ISI）、动作电位幅度和小脑连通性。一种非线性数据驱动方法表征了MEA数据中模式的低维表示。
我们的HD-MEA记录显示，与健康对照相比，dt仓鼠的MFR和动作电位幅度降低。苍白球DBS诱导全网络效应，使仓鼠的MFR、动作电位幅度和连通性测量值正常化，从而抵消这些电生理异常。此外，网络分析表明神经活动模式组织成群落，与dt组相比，健康组和DBS组的连通性更高。
这些发现表明，苍白球DBS通过使小脑皮质内的神经元活动正常化，对肌张力障碍发挥了部分治疗作用。我们发现dt仓鼠的MFR和动作电位幅度降低，这可能暗示神经元纤维和突触可塑性降低。苍白球DBS治疗导致小脑皮质活动类似于健康对照，显示了局部刺激的全网络影响。
