Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Department of Physiology, Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA.
Brain Stimul. 2022 Jan-Feb;15(1):141-151. doi: 10.1016/j.brs.2021.11.015. Epub 2021 Nov 30.
Intracortical microstimulation (ICMS) is used to map neural circuits and restore lost sensory modalities such as vision, hearing, and somatosensation. The spatial effects of ICMS remain controversial: Stoney and colleagues proposed that the volume of somatic activation increased with stimulation intensity, while Histed et al., suggested activation density, but not somatic activation volume, increases with stimulation intensity.
We used computational modeling to quantify the spatial effects of ICMS intensity and unify the apparently paradoxical findings of Histed and Stoney.
We implemented a biophysically-based computational model of a cortical column comprising neurons with realistic morphology and representative synapses. We quantified the spatial effects of single pulses and short trains of ICMS, including the volume of activated neurons and the density of activated neurons as a function of stimulation intensity.
At all amplitudes, the dominant mode of somatic activation was by antidromic propagation to the soma following axonal activation, rather than via transsynaptic activation. There were no occurrences of direct activation of somata or dendrites. The volume over which antidromic action potentials were initiated grew with stimulation amplitude, while the volume of somatic activation increased marginally. However, the density of somatic activation within the activated volume increased with stimulation amplitude.
The results resolve the apparent paradox between Stoney and Histed's results by demonstrating that the volume over which action potentials are initiated grows with ICMS amplitude, consistent with Stoney. However, the volume occupied by the activated somata remains approximately constant, while the density of activated neurons within that volume increase, consistent with Histed.
皮层内微刺激(ICMS)用于绘制神经回路并恢复失去的感觉模式,如视觉、听觉和体感。ICMS 的空间效应仍然存在争议:Stoney 等人提出,躯体激活体积随刺激强度增加而增加,而 Histed 等人则提出,激活密度而不是躯体激活体积随刺激强度增加而增加。
我们使用计算建模来量化 ICMS 强度的空间效应,并统一 Histed 和 Stoney 看似矛盾的发现。
我们实现了一个包含具有真实形态和代表性突触的神经元的皮层柱的基于生物物理的计算模型。我们量化了单脉冲和短串 ICMS 的空间效应,包括激活神经元的体积和激活神经元的密度作为刺激强度的函数。
在所有幅度下,躯体激活的主要模式是轴突激活后逆行传播到轴突,而不是通过突触激活。没有发生直接激活胞体或树突的情况。引发动作电位的逆行激活体积随刺激幅度增大而增大,而躯体激活体积仅略有增加。然而,激活体积内的躯体激活密度随刺激幅度增加而增加。
这些结果通过证明动作电位起始的体积随 ICMS 幅度增加而增加,与 Stoney 的结果一致,从而解决了 Stoney 和 Histed 结果之间的明显矛盾。然而,激活胞体占据的体积保持大致恒定,而该体积内激活神经元的密度增加,与 Histed 的结果一致。