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Modeling the motor striatum under Deep Brain Stimulation in normal and MPTP conditions

机译:在正常和MPTP条件下在深部脑刺激下模拟运动纹状体

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Striatum (STR) is the major input stage of the basal ganglia (BG). It combines information from cortex, subthalamic nucleus (STN) and external globus pallidus (GPe), and projects to the output stages of the BG, where selection between concurrent motor programs is performed. Parkinson's disease (PD) reduces the concentration of dopamine (DA, a neurotransmitter) in STR and changes in the level of DA correlate with the onset of PD motor disorders. Though STR plays a pivotal role in BG, its behavior under PD and Deep Brain Stimulation (DBS) is still unclear. We develop point-process models of the STR neurons as a function of the activity in GPe, cortex, and DBS. We use single unit recordings from a monkey under STN DBS at different frequencies before and after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) to develop PD motor symptoms. The models suggest that STR neurons have prominent bursting activity in normal conditions, positive correlation with cortex (3–10 ms delay), and mild negative correlation with GPe (1–5 ms lag). DA depletion evokes 30–60 Hz oscillations, and increases the propensity of each neuron to be inhibited by surrounding neurons. DBS elicits antidromical activation, masks existent dynamics, reinforces dependencies between nuclei, and entrains at the stimulation frequency in both conditions.
机译:纹状体(STR)是基底神经节(BG)的主要输入阶段。它结合了来自皮层,丘脑下核(STN)和外部苍白球(GPe)的信息,并投影到BG的输出级,在其中执行并发运动程序之间的选择。帕金森氏病(PD)会降低STR中的多巴胺(DA,一种神经递质)的浓度,并且DA水平的变化与PD运动障碍的发作有关。尽管STR在BG中起着举足轻重的作用,但其在PD和深度脑刺激(DBS)下的行为仍不清楚。我们开发了STR神经元的点过程模型,作为GPe,皮质和DBS中活性的函数。我们使用猴子在STN DBS下以1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)治疗之前和之后以不同频率的单单位录音来发展出PD运动症状。这些模型表明,STR神经元在正常情况下具有突出的爆发活动,与皮质呈正相关(延迟3-10 ms),与GPe呈轻度负相关(延迟1-5 ms)。 DA耗竭引起30–60 Hz振荡,并增加了每个神经元被周围神经元抑制的倾向。 DBS引发抗自由基激活,掩盖存在的动力学,增强核之间的依赖性,并在两种情况下都以刺激频率夹带。

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