Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Electrical and Computer Engineering, Duke University, Durham, NC, USA; Department of Neurobiology, Duke University, Durham, NC, USA; Department of Neurosurgery, Duke University, Durham, NC, USA.
Brain Stimul. 2024 Mar-Apr;17(2):365-381. doi: 10.1016/j.brs.2024.03.012. Epub 2024 Mar 16.
Intracortical microstimulation (ICMS) is used to map neuronal circuitry in the brain and restore lost sensory function, including vision, hearing, and somatosensation. The temporal response of cortical neurons to single pulse ICMS is remarkably stereotyped and comprises short latency excitation followed by prolonged inhibition and, in some cases, rebound excitation. However, the neural origin of the different response components to ICMS are poorly understood, and the interactions between the three response components during trains of ICMS pulses remains unclear.
We used computational modeling to determine the mechanisms contributing to the temporal response to ICMS in model cortical neurons.
We implemented a biophysically based computational model of a cortical column comprising neurons with realistic morphology and synapses and quantified the temporal response of cortical neurons to different ICMS protocols. We characterized the temporal responses to single pulse ICMS across stimulation intensities and inhibitory (GABA-B/GABA-A) synaptic strengths. To probe interactions between response components, we quantified the response to paired pulse ICMS at different inter-pulse intervals and the response to short trains at different stimulation frequencies. Finally, we evaluated the performance of biomimetic ICMS trains in evoking sustained neural responses.
Single pulse ICMS evoked short latency excitation followed by a period of inhibition, but model neurons did not exhibit post-inhibitory excitation. The strength of short latency excitation increased and the duration of inhibition increased with increased stimulation amplitude. Prolonged inhibition resulted from both after-hyperpolarization currents and GABA-B synaptic transmission. During the paired pulse protocol, the strength of short latency excitation evoked by a test pulse decreased marginally compared to those evoked by a single pulse for interpulse intervals (IPI) < 100 m s. Further, the duration of inhibition evoked by the test pulse was prolonged compared to single pulse for IPIs <50 m s and was not predicted by linear superposition of individual inhibitory responses. For IPIs>50 m s, the duration of inhibition evoked by the test pulse was comparable to those evoked by a single pulse. Short ICMS trains evoked repetitive excitatory responses against a background of inhibition. However, the strength of the repetitive excitatory response declined during ICMS at higher frequencies. Further, the duration of inhibition at the cessation of ICMS at higher frequencies was prolonged compared to the duration following a single pulse. Biomimetic pulse trains evoked comparable neural response between the onset and offset phases despite the presence of stimulation induced inhibition.
The cortical column model replicated the short latency excitation and long-lasting inhibitory components of the stereotyped neural response documented in experimental studies of ICMS. Both cellular and synaptic mechanisms influenced the response components generated by ICMS. The non-linear interactions between response components resulted in dynamic ICMS-evoked neural activity and may play an important role in mediating the ICMS-induced precepts.
皮层内微刺激（ICMS）用于绘制大脑中的神经元回路并恢复丧失的感觉功能，包括视觉、听觉和体感。皮质神经元对单脉冲 ICMS 的时间响应非常刻板，包括潜伏期短的兴奋，随后是长时间的抑制，在某些情况下还会出现反弹兴奋。然而，皮质神经元对 ICMS 不同反应成分的神经起源知之甚少，ICMS 脉冲串中三个反应成分之间的相互作用也不清楚。
我们使用计算建模来确定模型皮质神经元对 ICMS 时间响应的机制。
我们实现了一个包含具有真实形态和突触的神经元的皮层柱的生物物理计算模型，并量化了皮质神经元对不同 ICMS 方案的时间响应。我们描述了在不同刺激强度和抑制性（GABA-B/GABA-A）突触强度下对单脉冲 ICMS 的时间响应。为了探测反应成分之间的相互作用，我们量化了在不同脉冲间隔下对双脉冲 ICMS 的反应和在不同刺激频率下对短脉冲串的反应。最后，我们评估了仿生 ICMS 脉冲串在引发持续神经反应方面的性能。
单脉冲 ICMS 引起潜伏期短的兴奋，随后是一段抑制期，但模型神经元没有表现出抑制后的兴奋。随着刺激幅度的增加，潜伏期短的兴奋增强，抑制期延长。潜伏期短的兴奋增加，抑制期延长。长期抑制既来自超极化后电流，也来自 GABA-B 突触传递。在双脉冲方案中，与单脉冲相比，测试脉冲引起的潜伏期短的兴奋强度在脉冲间隔（IPI）<100 m s 时略有降低。此外，与单脉冲相比，IPI<50 m s 时测试脉冲引起的抑制持续时间延长，且不能通过个体抑制反应的线性叠加来预测。对于 IPI>50 m s，测试脉冲引起的抑制持续时间与单脉冲相当。短的 ICMS 脉冲串在抑制背景下引发重复的兴奋反应。然而，在较高频率的 ICMS 中，重复兴奋反应的强度会下降。此外，与单脉冲相比，较高频率下 ICMS 停止时的抑制持续时间延长。尽管存在刺激诱导的抑制，但仿生脉冲串在起始和结束阶段都能引起类似的神经反应。
皮层柱模型复制了实验研究中记录到的 ICMS 诱导的刻板神经反应的潜伏期短的兴奋和持久的抑制成分。细胞和突触机制都影响了 ICMS 产生的反应成分。反应成分之间的非线性相互作用导致了动态的 ICMS 诱导的神经活动，这可能在介导 ICMS 诱导的感知方面发挥重要作用。
