目的:脑深部电刺激(DBS)是治疗运动障碍的有效方法,包括帕金森病和特发性震颤。然而,DBS的潜在机制仍然难以捉摸。尽管现有模型有定性解释实验数据的能力,很少有统一的计算模型可以定量地捕获不同受激核的神经元活动的动力学,包括丘脑底核(STN),黑质网状结构(SNr),和腹侧中间核(Vim)-跨越不同的DBS频率。
方法:模型拟合中使用了合成和实验数据;合成数据是由我们先前工作中报道的已建立的尖峰神经元模型生成的,并且在DBS(微电极刺激)期间使用单单元微电极记录(MERs)提供实验数据。基于这些数据,我们开发了一个新的数学模型来表示接收DBS的神经元的放电率,包括STN中的神经元,SNr,和Vim-跨不同的DBS频率。在我们的模型中,通过突触模型和非线性传递函数对DBS脉冲进行过滤,以制定激发率变异性。对于每个DBS靶向细胞核,我们拟合了一组在不同DBS频率下一致的最优模型参数。
结果:我们的模型准确地再现了从合成和实验数据中观察到和计算的燃烧速率。最佳模型参数在不同的DBS频率上是一致的。
结论:我们的模型拟合结果与DBS期间的实验单单位MER数据一致。在DBS过程中,基底神经节和丘脑不同核的神经元放电率的恢复可能有助于进一步了解DBS的机制,并可能根据刺激参数对神经元活动的实际影响来优化刺激参数。
OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for movement disorders, including Parkinson disease and essential tremor. However, the underlying mechanisms of DBS remain elusive. Despite the capability of existing models in interpreting experimental data qualitatively, there are very few unified computational models that quantitatively capture the dynamics of the neuronal activity of varying stimulated nuclei-including subthalamic nucleus (STN), substantia nigra pars reticulata (SNr), and ventral intermediate nucleus (Vim)-across different DBS frequencies.
METHODS: Both synthetic and experimental data were used in the model fitting; the synthetic data were generated by an established spiking neuron model that was reported in our previous work, and the experimental data were provided using single-unit microelectrode recordings (MERs) during DBS (microelectrode stimulation). Based on these data, we developed a novel mathematical model to represent the firing rate of neurons receiving DBS, including neurons in STN, SNr, and Vim-across different DBS frequencies. In our model, the DBS pulses were filtered through a synapse model and a nonlinear transfer function to formulate the firing rate variability. For each DBS-targeted nucleus, we fitted a single set of optimal model parameters consistent across varying DBS frequencies.
RESULTS: Our model accurately reproduced the firing rates observed and calculated from both synthetic and experimental data. The optimal model parameters were consistent across different DBS frequencies.
CONCLUSIONS: The result of our model fitting was in agreement with experimental single-unit MER data during DBS. Reproducing neuronal firing rates of different nuclei of the basal ganglia and thalamus during DBS can be helpful to further understand the mechanisms of DBS and to potentially optimize stimulation parameters based on their actual effects on neuronal activity.