4Brain, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
Swammerdam Institute of Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
Epilepsia. 2020 May;61(5):903-913. doi: 10.1111/epi.16498. Epub 2020 Apr 16.
Deep brain stimulation (DBS) is an increasingly applied treatment for various neuropsychiatric disorders including drug-resistant epilepsy, and it may be optimized by rationalizing the stimulation protocol based on increased knowledge of its mechanism of action. We evaluated the effects of minutes to hours of hippocampal DBS on hippocampal evoked potentials (EPs) and local field potentials (LFPs) in freely moving male rats to further investigate some of the previously proposed mechanisms of action.
Hippocampal high-frequency (130 Hz) DBS was administered for 0, 1, or 6 min every 10 min for 160 min. Stimulation parameter settings were similar to those that had previously been shown to reduce seizures in epileptic rats. EPs and LFPs were recorded in the stimulation-free intervals. We investigated both the immediate temporary effects of 1 or 6 min of DBS and the effects of 160 min of intermittent DBS. Input specificity was investigated by using two different stimulation electrodes.
Relatively low DBS intensities corresponding to only 1.8% of the intensity evoking a maximum EP were required to prevent unintended seizure occurrence in healthy rats. Both 1 and 6 min of DBS caused input-specific short-lasting (<60 s) reductions (5%-7%) of the field excitatory postsynaptic potential (fEPSP) slope (P = .005). We observed longer-lasting, input-specific EP reductions during the 160 min intermittent DBS, with statistically significant reductions (3%-4%) of the fEPSP slope (P = .009-.018). The LFP spectrogram remained unaltered.
Deep brain stimulation induced both acute temporary effects compatible with axonal block and/or synaptic depression, and longer-lasting potentially cumulative EP reductions, suggesting the involvement of homeostatic plasticity or long-term depression. This dual time course may parallel the different temporal patterns of improvement observed in clinical trials. The longer-lasting reductions provide a potential neurophysiological basis for the use of intermittent DBS-as typically used in epilepsy patients-as an alternative to continuous DBS.
深部脑刺激（DBS）是一种越来越广泛应用于治疗各种神经精神疾病的方法，包括耐药性癫痫，并且可以通过基于对其作用机制的深入了解来优化刺激方案。我们评估了海马体 DBS 数分钟至数小时对自由活动雄性大鼠海马体诱发电位（EP）和局部场电位（LFP）的影响，以进一步研究一些先前提出的作用机制。
海马体高频（130 Hz）DBS 以每 10 分钟 1 分钟、6 分钟的频率施加 160 分钟。刺激参数设置与先前已显示可减少癫痫大鼠癫痫发作的参数相似。在无刺激间隔记录 EP 和 LFP。我们研究了 1 分钟或 6 分钟 DBS 的即时临时影响以及 160 分钟间歇性 DBS 的影响。通过使用两个不同的刺激电极研究了输入特异性。
仅需达到诱发最大 EP 强度的 1.8%的相对较低的 DBS 强度即可防止健康大鼠发生意外癫痫发作。1 分钟和 6 分钟的 DBS 均导致输入特异性的短暂（<60 s）减少（5%-7%）场兴奋性突触后电位（fEPSP）斜率（P=0.005）。我们观察到在 160 分钟的间歇性 DBS 期间，EP 存在更长时间的输入特异性减少，fEPSP 斜率的统计学显著降低（3%-4%）（P=0.009-0.018）。LFP 频谱图保持不变。
DBS 诱导了急性暂时效应，与轴突阻断和/或突触抑制兼容，以及更长时间的潜在累积 EP 减少，表明涉及到稳态可塑性或长时程抑郁。这种双重时程可能与临床试验中观察到的不同改善时间模式相平行。较长时间的减少为间歇性 DBS 的使用提供了潜在的神经生理学基础，这是作为替代连续 DBS 的一种选择，通常用于癫痫患者。
