Nguyen Duc, Konofagou Elisa, Dmochowski Jacek P
Department of Biomedical Engineering, City College of New York, New York NY 10031.
Department of Biomedical Engineering, Columbia University, New York NY 10027.
bioRxiv. 2025 May 1:2025.04.30.650712. doi: 10.1101/2025.04.30.650712.
Low-intensity transcranial focused ultrasound stimulation (tFUS) has emerged as a promising technique for non-invasive neuromodulation, offering deep brain penetration and high spatial precision. However, the electrophysiological effects of tFUS remain poorly understood, in part due to challenges distinguishing genuine neural responses from mechanical artifacts. Here we investigated the electrophysiological signatures captured during tFUS of the anesthetized rat hippocampus using silicon microelectrodes. We observed a strong, stereotyped local field potential (LFP) response that was time-locked to the onset and offset of sonication and resembled sensory-evoked potentials. Critically, the same waveform was observed in euthanized animals, confirming a non-biological, artifact-driven origin. The artifact scaled with acoustic intensity and was most pronounced under continuous-wave sonication. These findings suggest that electrode movement induced by ultrasound can generate artifactual LFP signals that closely mimic authentic neural responses. Our results underscore the need for caution when interpreting in situ electrophysiological recordings during tFUS and advocate for alternative, artifact-resistant readouts such as fiber photometry to unambiguously detect neuromodulatory effects.
低强度经颅聚焦超声刺激（tFUS）已成为一种有前景的非侵入性神经调节技术，具有深部脑穿透能力和高空间精度。然而，tFUS的电生理效应仍知之甚少，部分原因是难以将真正的神经反应与机械伪迹区分开来。在此，我们使用硅微电极研究了麻醉大鼠海马体在tFUS过程中捕获的电生理特征。我们观察到一种强烈的、刻板的局部场电位（LFP）反应，该反应与超声处理的开始和结束时间锁定，类似于感觉诱发电位。关键的是，在安乐死的动物中也观察到了相同的波形，证实了其非生物、伪迹驱动的起源。该伪迹与声强成比例，在连续波超声处理下最为明显。这些发现表明，超声引起的电极移动可产生紧密模拟真实神经反应的伪迹LFP信号。我们的结果强调了在解释tFUS过程中的原位电生理记录时需要谨慎，并提倡使用诸如光纤光度法等抗伪迹的替代读数来明确检测神经调节效应。
