反映内源性节律的深部脑刺激方案在终止癫痫发作方面显示出更高的功效

Tiwalade Sobayo, D. Mogul
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摘要

深部脑刺激(DBS)是一种潜在的有效手段,可以扰乱癫痫发作期间出现的异常节律。然而,目前通常采用的DBS策略是先验制定的,不能反映脑内的动态,这可能严重限制刺激效果。本研究探讨了如何利用内源性动力学来改善DBS刺激方案。在慢性大鼠边缘癫痫模型中计算了Papez回路内的多位点脑动力学。刺激/记录电极被放置在海马的CA3区和丘脑的前内侧核。使用经验模式分解和相干分析的信号反卷积用于识别癫痫发作进展的关键动力学。当自发性和诱发性癫痫发作自然终止时,各部位的场电位同步发生。同步性的位置和频率在受试者之间有所不同,这表明人类在癫痫自然终止时的内源性节律也可能不同。当多位点同步刺激的频率反映每个受试者观察到的内源性同步动力学时,DBS的疗效明显更有效。因此,根据可能代表大脑如何自然解决癫痫发作的个体内源性节律调整DBS方案,可能在提高这种潜在重要疗法的整体疗效方面发挥关键作用。
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Deep brain stimulation protocols that mirror endogenous rhythms show increased efficacy at terminating seizures
Deep brain stimulation (DBS) is a potentially potent means for disrupting the aberrant rhythms that arise during a seizure. However, current DBS strategies typically employed are formulated a priori and do not reflect dynamics within the brain during ictogenesis which may severely limit stimulation efficacy. This study investigated how DBS could be improved using endogenous dynamics to inform stimulation protocols. Multi-site brain dynamics within the circuit of Papez was calculated in a chronic rat limbic epilepsy model. Stimulation/recording electrodes were placed in the CA3 region of both hippocampi and in the anteromedial nucleus of the thalamus. Deconvolution of signals using empirical mode decomposition and coherence analysis were used to identify key dynamics as seizures progressed. Synchronization of field potentials across sites occurred as both spontaneous and evoked seizures naturally terminated. The location and frequency of synchrony varied between subjects suggesting that endogenous rhythms during natural seizure termination may vary in humans as well. DBS efficacy was significantly more effective at stopping seizures when the frequency of multisite synchronized stimulation reflected endogenous synchrony dynamics observed in each subject. Thus, tailoring DBS protocols to individual endogenous rhythms that may represent how brains naturally resolve epileptic seizures could play a critical role in improving overall efficacy of this potentially important therapy.
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