Intracortical microstimulation pulse waveform and frequency recruits distinct spatiotemporal patterns of cortical neuron and neuropil activation.

Intracortical microstimulation pulse waveform and frequency recruits distinct spatiotemporal patterns of cortical neuron and neuropil activation.
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DOI:
10.1088/1741-2552/ac5bf5
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发表时间:
2022-03-31
影响因子:
4
通讯作者:
Kozai, Takashi D. Y.
Kozai, Takashi D. Y.
中科院分区:
工程技术2区
文献类型:
--
作者:
Stieger, Kevin C.;Eles, James R.;Ludwig, Kip A.;Kozai, Takashi D. Y.

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神经修复术通常使用皮质内微刺激(ICMS)进行感觉恢复。为了恢复自然和功能反馈,我们必须首先了解刺激参数如何影响神经群体的募集。ICMS波形不对称性调节10 Hz下电极周围神经元的空间激活;然而,目前尚不清楚不对称性如何在临床常用频率(例如100 Hz)下差异调节群体活动。我们假设,刺激波形的不对称性将不同地调节某些神经群体的优先激活,并且不同的群体活动将是频率依赖性的。我们量化了如何在10或100 Hz的非对称刺激波形提供了30秒调制的皮质层II/III锥体神经元的时空活动,在体内双光子和中尺度钙成像麻醉小鼠。不对称性是根据电荷平衡的阴极和阳极优先波形的超前相位的持续时间与返回相位的持续时间的比率来定义的(即,相对于返回的较长超前相位具有较大的不对称性)。电极40-60 μm范围内的神经元显示稳定的刺激诱导活动,表明直接激活,这与波形不对称无关。72%的激活神经元的稳定性和20%~ 90%的优先激活依赖于波形的不对称性。此外,这种不对称依赖激活不同的神经群体与人口活动的差异进展。具体而言,对于某些波形,在10 Hz刺激期间神经活动倾向于随时间增加,而对于其他波形,在整个刺激期间活动保持在相同水平。在100 Hz刺激期间,所有波形的神经活动均随时间推移而降低,但在10 Hz刺激期间导致神经活动增加的波形降低更多。这些数据表明,在通常用于感觉恢复的频率下,刺激波形改变了不同但重叠的兴奋性神经元群体的激活模式。这些波形特异性反应对不同亚型神经元的激活以及感觉知觉的影响值得进一步研究。
Neural prosthetics often use intracortical microstimulation (ICMS) for sensory restoration. To restore natural and functional feedback, we must first understand how stimulation parameters influence the recruitment of neural populations. ICMS waveform asymmetry modulates the spatial activation of neurons around an electrode at 10 Hz; however, it is unclear how asymmetry may differentially modulate population activity at frequencies typically employed in the clinic (e.g. 100 Hz). We hypothesized that stimulation waveform asymmetry would differentially modulate preferential activation of certain neural populations, and the differential population activity would be frequency-dependent. We quantified how asymmetric stimulation waveforms delivered at 10 or 100 Hz for 30 s modulated spatiotemporal activity of cortical layer II/III pyramidal neurons using in vivo two-photon and mesoscale calcium imaging in anesthetized mice. Asymmetry is defined in terms of the ratio of the duration of the leading phase to the duration of the return phase of charge-balanced cathodal- and anodal-first waveforms (i.e. longer leading phase relative to return has larger asymmetry). Neurons within 40–60 μm of the electrode display stable stimulation-induced activity indicative of direct activation, which was independent of waveform asymmetry. The stability of 72% of activated neurons and the preferential activation of 20%–90% of neurons depended on waveform asymmetry. Additionally, this asymmetry-dependent activation of different neural populations was associated with differential progression of population activity. Specifically, neural activity tended to increase over time during 10 Hz stimulation for some waveforms, whereas activity remained at the same level throughout stimulation for other waveforms. During 100 Hz stimulation, neural activity decreased over time for all waveforms, but decreased more for the waveforms that resulted in increasing neural activity during 10 Hz stimulation. These data demonstrate that at frequencies commonly used for sensory restoration, stimulation waveform alters the pattern of activation of different but overlapping populations of excitatory neurons. The impact of these waveform specific responses on the activation of different subtypes of neurons as well as sensory perception merits further investigation.
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