基于相位幅度耦合的酒精依赖患者ERP脑网络分析

Investigating ERP Brain Network for Alcohol-Dependent Patients Based on Phase-Amplitude Coupling

探索相位幅度耦合和复杂网络方法在酒精依赖患者事件相关电位的脑网络机制研究中的应用。以开源的76例酒精依赖患者和45例健康对照在延迟匹配样本范式中的事件相关电位为研究对象。首先对数据进行预处理,然后使用调制指数方法,计算所有导联对间theta-gamma、alpha-gamma相位幅度耦合(TGC、AGC)强度,构建因果脑网络,并计算网络密度为0.3时的脑网络图论参数。此外,还计算导联内theta、alpha、beta、gamma节律小波包能量,以及疲劳因子,数据以四分位数表示50%(25%, 75%)。结果表明,只有非靶刺激时两组之间的耦合强度有显著差异。酒精依赖患者多个导联对间的TGC、AGC均显著降低(分别占比15.29%、1.29%,均P<0.05),平均耦合强度显著降低,以TGC尤为明显[TGC:0.014(0.011, 0.018) vs 0.012(0.010, 0.014),P=0.002;AGC:0.012(0.010, 0.014) vs 0.011(0.010, 0.012),P=0.005]。在TGC网络中,酒精依赖患者的特征路径长度[84.13(60.96, 110.33) vs 104.24(86.93, 118.98),P=0.005]、直径[222.40(154.78, 254.39) vs 253.39(207.82, 307.99),P=0.003]显著增加,平均聚类系数[0.013(0.010, 0.019) vs 0.009(0.008, 0.012),P<0.001]、全局效率[0.014(0.011, 0.016) vs 0.011(0.010, 0.013),P<0.001]、平均局部效率[0.017(0.013, 0.022) vs 0.013(0.011, 0.017),P<0.001]、传递性[0.011(0.008, 0.016) vs 0.008(0.007, 0.010),P<0.001]均显著降低。AGC网络的结果与TGC网络的结果相似,但是其直径无统计学差异。酒精依赖患者多个导联的theta、alpha、beta节律小波包能量显著降低(分别占比95.08%、100%、50.82%,均P<0.05),部分导联的疲劳因子显著降低(占比45.90%,均P<0.05)。在非靶刺激试验时,酒精依赖患者的皮层兴奋性增强,大脑抑制控制能力减弱,TGC和AGC脑网络的功能分离和整合能力降低,脑网络拓扑组织紊乱。

In this study, we explored the application of complex network methods based on the phase-amplitude coupling of event-related potential brain network mechanisms for alcohol-dependent patients. The open-sourced event-related potentials generated by the delayed matching sample paradigm in 76 alcohol-dependent patients and 45 healthy controls were studied. After pre-processing the data, modulation index method was used to calculate the intensity of theta-gamma and alpha-gamma phase-amplitude coupling(TGC, AGC) among all paired channels to construct causal brain network, and then we measured the parameters of brain network graph theory when the network density was 0.3. In addition, the wavelet packet energy of theta, alpha, beta, gamma rhythms and fatigue factors were also calculated. The data was expressed in quartiles of 50%(25%, 75%). The results showed that there was a significant difference in the coupling intensity between the two groups with only non-target stimulation trials. The TGC and AGC between some paired channels of alcohol-dependent patients were significantly decreased(respectively 15.29%, 1.29%, all P<0.05), and the average coupling intensity was significantly decreased, especially for TGC [TGC: 0.014(0.011, 0.018) vs 0.012(0.010, 0.014), P=0.002;AGC: 0.012(0.010, 0.014) vs 0.011(0.010, 0.012), P=0.005]. In the TGC network, the characteristic path length [84.16(60.96, 110.33) vs 104.24(86.93, 118.98), P=0.005] and diameter [222.40(154.78, 254.39) vs 253.39(207.82, 307.99), P=0.003] of alcohol-dependent patients were significantly increased, and the average clustering coefficient [0.013(0.010, 0.019) vs 0.009(0.008, 0.012), P<0.001], global efficiency [0.014(0.011, 0.016) vs 0.011(0.010, 0.013), P<0.001], average local efficiency [0.017(0.013, 0.022) vs 0.013(0.011, 0.017), P<0.001] and transitivity [0.011(0.008, 0.016) vs 0.008(0.007, 0.010), P<0.001] were significantly decreased. The results of AGC network were like that of the TGC network, but the diameter difference was not statistically significant. The wavelet packet energy of theta, alpha, beta rhythms in most electrodes of alcohol-dependent patients were significantly decreased(respectively 95.08%、100%、50.82%, all P<0.05), also the fatigue factors in some electrodes were significantly decreased(45.90%, all P<0.05). When making judgement in non-target stimulation for alcohol-dependent patients, the cortical excitability increased, the inhibition control ability of brain decreased, the function separation and integration ability of TGC and AGC brain network decreased, and the topological organization of brain network was disordered.