Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
Brain Stimul. 2022 Mar-Apr;15(2):352-359. doi: 10.1016/j.brs.2022.01.015. Epub 2022 Jan 30.
Transcranial focused ultrasound (tFUS) neuromodulation provides a promising emerging non-invasive therapy for the treatment of neurological disorders. Many studies have demonstrated the ability of tFUS to elicit transient changes in neural responses. However, the ability of tFUS to induce sustained changes need to be carefully examined. In this study, we use the long-term potentiation/long term depression (LTP/LTD) model in the rat hippocampus, the medial perforant path (mPP) to dentate gyrus (DG) pathway, to explore whether tFUS is capable of encoding frequency specific information to induce plasticity. Single-element focused transducers were used for tFUS stimulation with ultrasound fundamental frequency of 0.5 MHz and nominal focal distance of 38 mm tFUS stimulation is directed to mPP. Measurement of synaptic connectivity is achieved through the slope of field excitatory post synaptic potentials (fEPSPs), which are elicited using bipolar electrical stimulation electrodes and recorded at DG using extracellular electrodes to quantify degree of plasticity. We applied pulsed tFUS stimulation with total duration of 5 min, with 5 levels of pulse repetition frequencies each administered at 50 Hz sonication frequency at the mPP. Baseline fEPSP is recorded 10 min prior, and 30+ minutes after tFUS administration. In N = 16 adult wildtype rats, we observed sustained depression of fEPSP slope after 5 min of tFUS focused at the presynaptic field mPP. Across all PRFs, no significant difference in maximum fEPSP slope change was observed, average tFUS induced depression level was observed at 19.6%. When compared to low frequency electrical stimulation (LFS) of 1 Hz delivered to the mPP, the sustained changes induced by tFUS stimulation show no statistical difference to LFS for up to 24 min after tFUS stimulation. When both the maximum depression effects and the duration of sustained effects are both taken into account, PRF 3 kHz can induce significantly larger effects than other PRFs tested. tFUS stimulation is measured with a spatial-peak pressure amplitude of 99 kPa, translating to an estimation of 0.43 °C temperature increase when assuming no loss of heat. The results suggest the ability of tFUS to encode sustained changes in synaptic connectivity through mechanism which are unlikely to involve thermal changes.
经颅聚焦超声（tFUS）神经调节为治疗神经疾病提供了一种有前途的新兴非侵入性治疗方法。许多研究已经证明了 tFUS 诱发神经反应瞬时变化的能力。然而，tFUS 诱导持续变化的能力需要仔细检查。在这项研究中，我们使用大鼠海马中的长时程增强/长时程抑制（LTP/LTD）模型，内侧穿通路径（mPP）到齿状回（DG）途径，探讨 tFUS 是否能够编码频率特异性信息以诱导可塑性。使用单元素聚焦换能器进行 tFUS 刺激，超声基频为 0.5 MHz，标称焦点距离为 38 mm，tFUS 刺激直接指向 mPP。通过场兴奋性突触后电位（fEPSP）的斜率来测量突触连接，使用双极电刺激电极诱发 fEPSP，并使用细胞外电极在 DG 记录，以量化可塑性程度。我们施加了持续 5 分钟的脉冲 tFUS 刺激，在 mPP 处以 50 Hz 的声频施加 5 个不同的脉冲重复频率水平。在 tFUS 给药前 10 分钟记录基线 fEPSP，并在给药后 30 分钟以上记录。在 16 只成年野生型大鼠中，我们观察到在 mPP 处聚焦 5 分钟的 tFUS 后，fEPSP 斜率持续下降。在所有 PRF 中，未观察到最大 fEPSP 斜率变化的显著差异，平均 tFUS 诱导的抑制水平为 19.6%。与施加于 mPP 的 1 Hz 低频电刺激（LFS）相比，tFUS 刺激引起的持续变化在 tFUS 刺激后长达 24 分钟与 LFS 无统计学差异。当同时考虑最大抑制效果和持续效果的持续时间时，PRF 3 kHz 可以比测试的其他 PRF 引起更大的效果。tFUS 刺激的空间峰值声压幅度为 99 kPa，当假设没有热量损失时，这转化为估计的 0.43°C 温升。结果表明，tFUS 通过不太可能涉及热变化的机制来编码突触连接的持续变化。
