Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA.
J Neurophysiol. 2013 Aug;110(4):826-43. doi: 10.1152/jn.00074.2013. Epub 2013 May 29.
Closed-loop deep brain stimulation (DBS) systems could provide automatic adjustment of stimulation parameters and improve outcomes in the treatment of Parkinson's disease and essential tremor. The evoked compound action potential (ECAP), generated by activated neurons near the DBS electrode, may provide a suitable feedback control signal for closed-loop DBS. The objectives of this work were to characterize the ECAP across stimulation parameters and determine the neural elements contributing to the signal. We recorded ECAPs during thalamic DBS in anesthetized cats and conducted computer simulations to calculate the ECAP of a population of thalamic neurons. The experimental and computational ECAPs were similar in shape and had characteristics that were correlated across stimulation parameters (R(2) = 0.80-0.95, P < 0.002). The ECAP signal energy increased with larger DBS amplitudes (P < 0.0001) and pulse widths (P < 0.002), and the signal energy of secondary ECAP phases was larger at 10-Hz than at 100-Hz DBS (P < 0.002). The computational model indicated that these changes resulted from a greater extent of neural activation and an increased synchronization of postsynaptic thalamocortical activity, respectively. Administration of tetrodotoxin, lidocaine, or isoflurane abolished or reduced the magnitude of the experimental and computational ECAPs, glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D(-)-2-amino-5-phosphonopentanoic acid (APV) reduced secondary ECAP phases by decreasing postsynaptic excitation, and the GABAA receptor agonist muscimol increased the latency of the secondary phases by augmenting postsynaptic hyperpolarization. This study demonstrates that the ECAP provides information about the type and extent of neural activation generated during DBS, and the ECAP may serve as a feedback control signal for closed-loop DBS.
闭环深部脑刺激 (DBS) 系统可以提供刺激参数的自动调节，从而改善帕金森病和原发性震颤的治疗效果。由 DBS 电极附近激活的神经元产生的诱发复合动作电位 (ECAP)，可能为闭环 DBS 提供合适的反馈控制信号。本研究的目的是描述刺激参数下的 ECAP，并确定产生信号的神经元件。我们在麻醉猫的丘脑 DBS 期间记录了 ECAP，并进行了计算机模拟以计算丘脑神经元群体的 ECAP。实验和计算的 ECAP 在形状上相似，并且在刺激参数之间具有相关性（R²=0.80-0.95，P<0.002）。ECAP 信号能量随较大的 DBS 幅度（P<0.0001）和脉冲宽度（P<0.002）增加，10-Hz 比 100-Hz DBS 的二次 ECAP 相位的信号能量更大（P<0.002）。计算模型表明，这些变化分别源于更大程度的神经激活和突触后丘脑皮质活动的同步增加。肉毒毒素、利多卡因或异氟醚的给药消除或降低了实验和计算 ECAP 的幅度，谷氨酸受体拮抗剂 6-氰基-7-硝基喹喔啉-2,3-二酮 (CNQX) 和 D(-)-2-氨基-5-磷戊酸 (APV) 通过减少突触后兴奋降低了二次 ECAP 相位，GABAA 受体激动剂 muscimol 通过增强突触后超极化增加了二次相位的潜伏期。本研究表明，ECAP 提供了关于 DBS 期间产生的神经激活类型和程度的信息，并且 ECAP 可能作为闭环 DBS 的反馈控制信号。
