Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Department of Neurosciences, Cleveland Clinic, Cleveland, OH, USA.
Department of Neurosciences, Cleveland Clinic, Cleveland, OH, USA.
Neuromodulation. 2022 Aug;25(6):804-816. doi: 10.1111/ner.13508. Epub 2022 Jun 14.
To characterize and compare the stability of cortical potentials evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) across the naïve, parkinsonian, and pharmacologically treated parkinsonian states. To advance cortical potentials as possible biomarkers for DBS programming.
Serial electrocorticographic (ECoG) recordings were made more than nine months from a single non-human primate instrumented with bilateral ECoG grids spanning anterior parietal to prefrontal cortex. Cortical evoked potentials (CEPs) were generated through time-lock averaging of the ECoG recordings to DBS pulses delivered unilaterally in the STN region using a chronically implanted, six-contact, scaled DBS lead. Recordings were made across the naïve followed by mild and moderate parkinsonian conditions achieved by staged injections of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin. In addition to characterizing the spatial distribution and stability of the response within each state, changes in the amplitude and latency of CEP components as well as in the frequency content were examined in relation to parkinsonian severity and dopamine replacement.
In the naïve state, the STN DBS CEP presented as a multiphase response maximal over M1 cortex, with components attributable to physiological activity distinguishable from stimulus artifact as early as 0.45-0.75 msec poststimulation. When delivered using therapeutically effective parameters in the parkinsonian state, the CEP was highly stable across multiple recording sessions within each behavioral state. Across states, significant differences were present with respect to both the latency and amplitude of individual response components, with greater differences present for longer-latency components (all p < 0.05). Power spectral density analysis revealed a high-beta peak within the evoked response, with significant changes in power between disease states across multiple frequency bands.
Our findings underscore the spatiotemporal specificity and relative stability of the DBS-CEP associated with different disease states and with therapeutic benefit. DBS-CEP may be a viable biomarker for therapeutic programming.
描述和比较深脑刺激（DBS）刺激丘脑底核（STN）诱发的皮质电位在未受刺激、帕金森病和药物治疗帕金森病状态下的稳定性。将皮质电位作为 DBS 编程的潜在生物标志物进行推进。
对一只经过双侧皮质电图（ECoG）网格覆盖前顶叶至前额叶的非人类灵长类动物进行了超过九个月的连续电生理记录。通过时间锁定平均化 ECoG 记录，生成皮质诱发电位（CEPs），使用慢性植入的六触点、比例 DBS 引线单侧传递 DBS 脉冲到 STN 区域。在未受刺激的情况下进行记录，然后通过分期注射 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）神经毒素来实现轻度和中度帕金森病状态。除了描述每个状态下的反应的空间分布和稳定性外，还检查了 CEP 成分的幅度和潜伏期以及频率内容的变化与帕金森病严重程度和多巴胺替代的关系。
在未受刺激的状态下，STN DBS CEP 呈现出多相反应，最大峰值在 M1 皮层，可归因于生理活动的成分可与刺激伪影区分开来，早在刺激后 0.45-0.75 毫秒。在帕金森病状态下使用治疗有效的参数进行传递时，在每个行为状态的多个记录会话中，CEP 非常稳定。在多个状态下，个体反应成分的潜伏期和幅度都存在显著差异，较长潜伏期成分的差异更大（所有 p<0.05）。功率谱密度分析显示诱发反应内存在高β峰，多个频带的疾病状态之间存在显著的功率变化。
我们的研究结果强调了与不同疾病状态和治疗益处相关的 DBS-CEP 的时空特异性和相对稳定性。DBS-CEP 可能是一种可行的治疗编程生物标志物。
