Abstract：
Gamma oscillations have been frequently observed in levodopa-induced dyskinesia (LID), manifest as broadband (60-120 Hz) and narrowband (80-110 Hz) gamma activity in cortico-striatal projection. We investigated the electrophysiological mechanisms and correlation of gamma oscillations with dyskinesia severity, while assessing the administration of fenobam, a selective metabotropic glutamate receptor 5 (mGluR5) antagonist, in regulating dyskinesia-associated gamma activity. We conducted simultaneous electrophysiological recordings in Striatum (Str) and primary motor cortex (M1), together with Abnormal Involuntary Movement Scale scoring (AIMs). Phase-amplitude coupling (PAC), power, coherence, and Granger causality analyses were conducted for electrophysiological data. The findings demonstrated increased beta oscillations with directionality from M1 to Str in parkinsonian state. During on-state dyskinesia, elevated broadband gamma activity was modulated by the phase of theta activity in Str, while M1 → Str gamma causality mediated narrowband gamma oscillations in Str. Striatal gamma power (both periodic and aperiodic power), periodic power, peak frequency, and PAC at 80 min (corresponding to the peak dyskinesia) after repeated levodopa injections across recording days (day 30, 33, 36, 39, and 42) increased progressively, correlating with total AIMs. Additionally, a time-dependent parabolic trend of PAC, peak frequency and gamma power was observed after levodopa injection on day 42 from 20 to 120 min, which also correlated with corresponding AIMs. Fenobam effectively alleviates dyskinesia, suppresses enhanced gamma oscillations in the M1-Str directionality, and reduces PAC in Str. The temporal characteristics of gamma oscillations provide parameters for classifying LID severity. Antagonizing striatal mGluR5, a promising therapeutic target for dyskinesia, exerts its effects by modulating gamma activity.
摘要：
在左旋多巴引起的运动障碍（LID）中经常观察到伽马振荡，表现为皮质纹状体投射中的宽带（60-120Hz）和窄带（80-110Hz）伽马活性。我们研究了伽玛振荡与运动障碍严重程度的电生理机制和相关性，在评估非诺班的管理时，选择性代谢型谷氨酸受体5（mGluR5）拮抗剂，在调节运动障碍相关的γ活性。我们在纹状体（Str）和初级运动皮层（M1）中同时进行了电生理记录，连同异常非自愿运动量表评分(AIM)。相位-振幅耦合(PAC),电源,连贯性,对电生理数据进行了格兰杰因果关系分析。研究结果表明，在帕金森状态下，从M1到Str的方向性增加了β振荡。在状态运动障碍期间，升高的宽带γ活性受Str中θ活性的相位调节，而M1→Str伽马因果关系介导Str中的窄带伽马振荡。纹状体伽马功率（周期性和非周期性功率），周期性功率,峰值频率,在记录天数(第30、33、36、39和42天)重复左旋多巴注射后80分钟(对应于运动障碍高峰)的PAC逐渐增加，与总AIM相关。此外，PAC的时间依赖性抛物线趋势，在第42天注射左旋多巴后，从20到120分钟观察到峰值频率和伽马功率，这也与相应的AIM相关。Fenobam有效缓解运动障碍，抑制M1-Str方向性增强的伽马振荡，并减少Str中的PAC。伽马振荡的时间特性提供了用于对LID严重性进行分类的参数。拮抗纹状体mGluR5，一个有希望的运动障碍治疗靶点，通过调节伽马活性发挥其作用。
