Stypulkowski Paul H, Stanslaski Scott R, Jensen Randy M, Denison Timothy J, Giftakis Jonathon E
Medtronic Neuromodulation, 7000 Central Avenue NE, Minneapolis, MN 55432, USA.
Medtronic Neuromodulation, 7000 Central Avenue NE, Minneapolis, MN 55432, USA.
Brain Stimul. 2014 May-Jun;7(3):350-8. doi: 10.1016/j.brs.2014.02.002. Epub 2014 Feb 10.
The use of Deep Brain Stimulation (DBS) as a potential therapy for treatment resistant epilepsy remains an area of active clinical investigation. We recently reported the first chronic evaluation of an implantable, clinical-grade system that permits concurrent stimulation and recording, in a large animal (ovine) model developed to study DBS for epilepsy.
In this study we extended this work to compare the effects of remote (anterior thalamic) and direct (hippocampal) stimulation on local field potential (LFP) activity and network excitability, and to assess closed-loop stimulation within this neural network.
Following anesthesia and 1.5T MRI acquisition, unilateral anterior thalamic and hippocampal DBS leads were implanted in three subjects using a frameless stereotactic system. Chronic, awake recordings of evoked potentials (EPs) and LFPs in response to thalamic and hippocampal stimulation were collected with the implanted device and analyzed off-line.
Consistent with earlier reports, thalamic DBS and direct stimulation of the hippocampus produced parameter-dependent effects on hippocampal activity. LFP suppression could be reliably induced with specific stimulation parameters, and was shown to reflect a state of reduced network excitability, as measured by effects on hippocampal EP amplitudes and after-discharge thresholds. Real-time modulation of network excitability via the implanted device was demonstrated using hippocampal theta-band power level as a control signal for closed-loop stimulation.
The results presented provide evidence of network excitability changes induced by stimulation that could underlie the clinical effects that have been reported with both thalamic and direct cortical stimulation.
深部脑刺激（DBS）作为治疗难治性癫痫的一种潜在疗法，仍是一个活跃的临床研究领域。我们最近报道了在一个为研究癫痫的DBS而开发的大型动物（绵羊）模型中，对一种可同时进行刺激和记录的植入式临床级系统的首次长期评估。
在本研究中，我们扩展了这项工作，以比较远程（丘脑前核）和直接（海马体）刺激对局部场电位（LFP）活动和网络兴奋性的影响，并评估该神经网络内的闭环刺激。
在麻醉和1.5T磁共振成像（MRI）采集后，使用无框架立体定向系统将单侧丘脑前核和海马体DBS电极植入三名受试者体内。使用植入装置收集对丘脑和海马体刺激的诱发电位（EPs）和LFP的长期清醒记录，并进行离线分析。
与早期报告一致，丘脑DBS和海马体直接刺激对海马体活动产生了参数依赖性效应。特定刺激参数可可靠地诱导LFP抑制，并且显示其反映了网络兴奋性降低的状态，这通过对海马体EP振幅和后放电阈值的影响来衡量。使用海马体θ波段功率水平作为闭环刺激的控制信号，证明了通过植入装置对网络兴奋性进行实时调制。
所呈现的结果提供了刺激诱导网络兴奋性变化的证据，这可能是丘脑和直接皮层刺激所报道的临床效果的基础。
