BACKGROUND Transcranial electrical stimulation at an appropriate dose may demonstrate intracranial effects, including neuronal stimulation and cerebral blood flow responses. OBJECTIVE We performed in vivo experiments on mouse cortex using transcranial alternating current [AC] stimulation to assess whether cerebral blood flow can be reliably altered by extracranial stimulation. METHODS We performed transcranial AC electrical stimulation transversely across the closed skull in anesthetized mice, measuring transcranial cerebral blood flow with a laser Doppler probe and intracranial electrical responses as endpoint biomarkers. We calculated a stimulation dose-response function between intracranial electric field and cerebral blood flow. RESULTS Stimulation at electric field amplitudes of 5-20 mV/mm at 10-20 Hz rapidly increased cerebral blood flow (within 100 ms), which then quickly decreased with no residual effects. The time to peak and blood flow shape varied with stimulation intensity and duration, showing a linear correlation between stimulation dose and peak blood flow increase. Neither afterdischarges nor spreading depression occurred from this level of stimulation. CONCLUSIONS Extracranial stimulation amplitudes sufficient to evoke reliable blood flow changes requires electric field strengths higher than what is tolerable in unanesthetized humans (<1 mV/mm), but less than electroconvulsive therapy levels (>40 mV/mm). However, anesthesia effects, spontaneous blood flow fluctuations, and sampling error may accentuate the apparent field strength needed for enhanced blood flow. The translation to a human dose-response function to augment cerebral blood flow (i.e., in stroke recovery) will require significant modification, potentially to pericranial, focused, multi-electrode application or intracranial stimulation.

中文翻译：

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通过经颅交流电刺激小鼠脑血流的快速、剂量依赖性增强

背景技术适当剂量的经颅电刺激可表现出颅内效应，包括神经元刺激和脑血流反应。目的我们使用经颅交流电 [AC] 刺激对小鼠皮层进行了体内实验，以评估颅外刺激是否可以可靠地改变脑血流。方法我们对麻醉小鼠的闭合颅骨进行横向经颅交流电刺激，用激光多普勒探头测量经颅脑血流量，并将颅内电反应作为终点生物标志物。我们计算了颅内电场和脑血流量之间的刺激剂量反应函数。结果 在 5-20 mV/mm 的电场幅度和 10-20 Hz 的刺激下，脑血流量迅速增加（在 100 毫秒内），然后迅速减少而没有残留影响。达到峰值的时间和血流形状随刺激强度和持续时间而变化，显示刺激剂量和峰值血流增加之间呈线性相关。这种水平的刺激既没有发生后放电，也没有蔓延的抑郁症。结论 颅外刺激幅度足以引起可靠的血流变化，需要的电场强度高于未麻醉人的耐受水平 (<1 mV/mm)，但低于电惊厥治疗水平 (>40 mV/mm)。然而，麻醉作用、自发血流波动、和采样误差可能会突出增强血流所需的表观场强。转换为人类剂量反应函数以增加脑血流量（即在中风恢复中）将需要显着修改，可能用于颅骨周围、聚焦、多电极应用或颅内刺激。