Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation.

Florian Missey, Emma Acerbo, Adam Dickey, Jan Trajlinek, Ondrej Studnicka, Claudia Lubrano, Mariane De Araujo E Silva, Evan Brady, Vit Vsiansky, Johanna Petra Szabo, Irena Dolezalova, Daniel Fabo, Martin Pail, Claire-Anne Gutekunst, Rosanna Migliore, Michele Migliore, Stanislas Lagarde, Romain Carron, Fariba Karimi, Raul Astorga, Antonino Cassara, Niels Kuster, Esra Neufeld, Fabrice Bartolomei, Nigel Paul Pedersen, Robert Gross, Viktor Jirsa, Daniel Drane, Milan Brazdil, Adam Williamson
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Abstract

Medication refractory focal epilepsy creates a significant challenge, with approximately 30% of patients ineligible for surgery due to the involvement of eloquent cortex in the epileptogenic network. For such patients with limited surgical options, electrical neuromodulation represents a promising alternative therapy. In this study, we investigate the potential of non-invasive temporal interference (TI) electrical stimulation to reduce epileptic biomarkers in patients with epilepsy by comparing intracerebral recordings obtained before, during, and after TI stimulation, to recordings during low and high kHz frequency (HF) sham stimulation. Thirteen patients with symptoms of mesiotemporal epilepsy (MTLE) and implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130Hz (df), where the AM was delivered with lower frequency kHz carriers (1kHz + 1.13kHz), or higher frequency carriers (9kHz + 9.13kHz), targeting the hippocampus, a common epileptic focus and consequently stimulation target in MTLE. Our results show that TI stimulation yields a statistically significant decrease in interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs) specifically fast ripples (FR), where the suppression is apparent in the hippocampal focus and propagation from the focus is reduced brain-wide. HF sham stimulation at 1kHz frequency also impacted the IED rate in the cortex, but without reaching the hippocampal focus. The HF sham effect diminished with increasing frequencies (2, 5, and 9kHz, respectively), specifically as a function of depth into the cortex. This depth dependence was not observed with the TI, independent of the employed carrier frequency (low or high kHz). Furthermore, a strong carry-over effect, i.e., suppression of epileptic biomarkers for a period of time after the end of stimulation, was observed for TI but not for kHz. Our findings underscore the possible application of TI in epilepsy, as an additional non-invasive brain stimulation tool, potentially offering opportunities to assess brain region response to electrical neuromodulation before committing to a deep brain stimulation (DBS) or responsive neurostimulation (RNS) implants. Our results further demonstrate distinct biophysical differences between kHz and focal AM stimulation.

海马非侵入性颞干扰刺激抑制癫痫患者的癫痫生物标志物:千赫兹和调幅刺激之间的生物物理差异。
药物难治性局灶性癫痫是一项重大挑战,大约30%的患者不适合手术治疗,因为在致痫网络中涉及到大脑皮层。对于这些手术选择有限的患者,电神经调节是一种有前途的替代疗法。在这项研究中,我们通过比较非侵入性时间干扰(TI)电刺激之前、期间和之后的脑内记录,以及在低和高kHz (HF)假刺激期间记录的脑内记录,研究了非侵入性时间干扰(TI)电刺激在癫痫患者中减少癫痫生物标志物的潜力。13例中颞叶癫痫(MTLE)症状患者植入立体脑电图(sEEG)深度电极,接受频率为130Hz的调幅(AM)的TI刺激(Δf),其中AM以低频kHz载波(1kHz + 1.13kHz)或高频载波(9kHz + 9.13kHz)传递,目标是海马-一个常见的癫痫病灶,因此是MTLE的刺激目标。我们的研究结果表明,TI刺激可显著降低间歇癫痫样放电(IEDs)和病理性高频振荡(hfo),特别是快速波纹(FR),其中海马灶的抑制很明显,病灶的传播在全脑范围内减少。频率为1kHz的高频假刺激也影响了皮层的IED率,但没有到达海马灶。高频虚假效应随着频率的增加(分别为2、5和9kHz)而减弱,特别是作为进入皮层深度的函数。这种深度依赖关系没有观察到的TI,独立于所采用的载波频率(低或高kHz)。我们的研究结果强调了TI在癫痫中的潜在应用,作为一种额外的非侵入性脑刺激工具,在进行深部脑刺激(DBS)或反应性神经刺激(RNS)植入之前,有可能提供评估脑区域对电神经调节反应的机会。我们的研究结果进一步证明了千赫和焦点调幅刺激之间存在明显的生物物理差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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