Data from: The cortical evoked potential corresponds with deep brain stimulation efficacy in rats

Objective. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease, although its mechanism of action is uncertain. Previous work has demonstrated that a critical component to its mechanism may be the activation of the primary motor cortex (M1) via the antidromic firing of neurons within the hyperdirect pathway from STN to M1. This antidromic firing exhibits high rates of spike failure when stimulated at high frequencies, and the spike failure rate appears to correlate with DBS efficacy. This synchronous antidromic spiking takes the form of a short-latency evoked potential in electrocorticography (ECoG) recordings of M1, with the magnitude of the cortical evoked potential (cEP) similarly declining at high stimulation frequencies. In this study, we aimed to characterize the cEP in response to various stimulation conditions and to determine whether changes in the cEP correlate with symptom reduction from DBS. Approach. We used the unilateral 6-hydroxydopamine lesioned rat model in female, Sprague Dawley rats, with stimulating electrodes implanted in the STN and the ECoG recorded above M1. We then recorded the cEP during various stimulation conditions and while performing behavioral assessments of hypokinetic symptoms. Main results. We found that the cEP is strongly affected by stimulation conditions, with the cEP magnitude declining and cEP latency increasing with higher stimulation frequencies. These effects occur over multiple minutes, and likely with multiple time-scales. Additionally, the cEP magnitude and latency each correlate strongly with symptom reduction from DBS, with superior correlations to conventional spectral-based biomarkers from ECoG. Significance. This study demonstrates the potential clinical utility of the cEP as a biomarker for symptom reduction from DBS, which may be used in determining proper lead location, stimulation parameter selection, or closed-loop control. Additionally, it provides further insight into the cortical mechanism by which DBS relieves symptoms, suggesting that it may be related to a potential desynchronizing effect caused by high rates of sporadic antidromic spike failure during high frequency DBS.

### 研究目的
脑深部电刺激（Deep Brain Stimulation, DBS）丘脑底核（subthalamic nucleus, STN）是治疗帕金森病运动症状的有效手段，但其具体作用机制尚未明确。既往研究表明，其作用机制的关键环节可能是通过丘脑底核至初级运动皮层（primary motor cortex, M1）的超直接通路内神经元的逆向放电，激活初级运动皮层。当以高频率进行刺激时，该逆向放电会出现较高的锋电位失败率，且锋电位失败率似乎与DBS的治疗效果相关。这种同步化逆向锋电位放电在初级运动皮层的皮层脑电描记法（electrocorticography, ECoG）记录中表现为短潜伏期诱发电位，且皮层诱发电位（cortical evoked potential, cEP）的幅度在高刺激频率下同样会下降。本研究旨在对不同刺激条件下的皮层诱发电位进行特征表征，并明确皮层诱发电位的变化是否与DBS治疗后的症状改善相关。

### 研究方法
本研究选用雌性斯普拉格-道利（Sprague Dawley）大鼠，采用单侧6-羟基多巴胺（6-hydroxydopamine）损毁的大鼠模型，于丘脑底核植入刺激电极，并在初级运动皮层上方记录皮层脑电信号。随后，在不同刺激条件下以及开展运动减退症状的行为学评估过程中，记录皮层诱发电位。

### 主要结果
本研究发现，皮层诱发电位受刺激条件的影响显著：随着刺激频率升高，皮层诱发电位的幅度下降、潜伏期延长。上述效应可持续数分钟，且可能存在多个时间尺度。此外，皮层诱发电位的幅度与潜伏期均与DBS治疗后的症状改善呈强相关性，其相关性优于传统的基于皮层脑电频谱的生物标志物。

### 研究意义
本研究证实了皮层诱发电位作为DBS治疗症状改善的生物标志物的潜在临床应用价值，可用于确定合适的电极植入位置、刺激参数选择或实施闭环控制。此外，本研究进一步揭示了DBS缓解症状的皮层机制，提示其可能与高频DBS期间频繁出现的散发性逆向锋电位失败所引发的潜在去同步化效应相关。