Spontaneous Gamma Activity in Schizophrenia.
Spontaneous Gamma Activity in Schizophrenia.
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DOI：
10.1001/jamapsychiatry.2014.2642
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发表时间：
2015-08
期刊：
影响因子：
25.8
通讯作者：
Spencer KM
中科院分区：
文献类型：
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作者：
Hirano Y;Oribe N;Kanba S;Onitsuka T;Nestor PG;Spencer KM
转化神经科学的一个主要目标是识别神经精神疾病中的神经回路异常，可以在动物模型中进行研究，以促进新疗法的开发。脑电图伽玛波段（30-100 Hz）的振荡引起了人们极大的兴趣，因为这些振荡的基本机制已被了解，并且在精神分裂症（SZ）中发现了伽玛异常。基于 N-甲基-d-天冬氨酸受体 (NMDAR) 功能减退的 SZ 动物模型显示自发宽带伽马功率增加，但这种现象在 SZ 患者中尚未明确识别。检查自发性伽马功率及其与精神分裂症患者听觉皮层诱发伽马振荡的关系。我们进行了一项横断面研究，包括 2009 年 1 月 1 日至 2012 年 12 月 31 日期间波士顿退伍军人事务医疗保健系统的 24 名慢性精神分裂症患者和 24 名匹配的健康对照参与者。每组 18 名参与者在多个频率（20、30 和 40 Hz）的听觉稳态刺激期间以及在静息状态下获得脑电图。使用偶极源定位来估计听觉皮层的脑电图活动。听觉稳态反应（ASSR）测量包括锁相因子和诱发功率。自发伽马功率在 ASSR 数据中测量为感应（非锁相）伽马功率，在静息态数据中测量为总伽马功率。与 40 Hz 刺激的对照组相比，SZ 患者的 ASSR 锁相因子显着降低（平均值 [SD]，0.075 [0.028] vs 0.113 [0.065]；F1,46 = 6.79[P = .012]），但 20 Hz 或 30 Hz 刺激则没有显着降低（0.042 [0.038] vs 0.043） [0.034]；F1，46 = 0.006 [P = .938] 和 0.084 [0.040] vs 0.098 [0.050]； F1,46 = 1.605 [P = .212]，分别），重复了之前的发现。与对照组相比，在稳态刺激期间，SZ 患者的平均 [SD] 宽带诱导 (30–100 Hz) 伽马功率有所增加（6.579 [3.783] vs 3.984 [1.843]；F1,46 = 9.128 [P = .004]；d = 0.87），但在休息期间则没有增加（0.006 [0.003] vs 0.005） [0.002]；F1，34 = 1.067 [P = .309]； d = 0.35）。在 40 Hz 刺激期间，SZ 患者左半球的感应伽马功率与幻听症状呈正相关（切向，ρ = 0.587 [P = .031]；径向，ρ = 0.593 [P = .024]），与 ASSR 锁相因子负相关（基线：ρ = -0.572 [P = .024]； ASSR：ρ = -0.568 [P = .032]）。在 SZ 的听觉稳态刺激期间，自发伽马活性增加，反映了兴奋和抑制的正常平衡被破坏。这种现象与诱发振荡相互作用，可能导致 SZ 中发现的伽马 ASSR 缺陷。 SZ 中自发伽马功率增加与 NMDAR 功能减退动物模型中自发伽马功率增加的相似性表明，自发伽马功率可以作为人类和神经精神疾病动物模型中表达小白蛋白的抑制性中间神经元上 NMDAR 完整性的生物标志物。
A major goal of translational neuroscience is to identify neural circuit abnormalities in neuropsychiatric disorders that can be studied in animal models to facilitate the development of new treatments. Oscillations in the gamma band (30–100 Hz) of the electroencephalogram have received considerable interest as the basic mechanisms underlying these oscillations are understood, and gamma abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased spontaneous broadband gamma power, but this phenomenon has not been identified clearly in patients with SZ. To examine spontaneous gamma power and its relationship to evoked gamma oscillations in the auditory cortex of patients with SZ. We performed a cross-sectional study including 24 patients with chronic SZ and 24 matched healthy control participants at the Veterans Affairs Boston Healthcare System from January 1, 2009, through December 31, 2012. Electroencephalograms were obtained during auditory steady-state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a resting state in 18 participants in each group. Electroencephalographic activity in the auditory cortex was estimated using dipole source localization. Auditory steady-state response (ASSR) measures included the phase-locking factor and evoked power. Spontaneous gamma power was measured as induced (non–phase-locked) gamma power in the ASSR data and as total gamma power in the resting-state data. The ASSR phase-locking factor was reduced significantly in patients with SZ compared with controls for the 40-Hz stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46 = 6.79[P = .012]) but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46 = 0.006 [P = .938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46 = 1.605 [P = .212], respectively), repeating previous findings. The mean [SD] broadband-induced (30–100 Hz) gamma power was increased in patients with SZ compared with controls during steady-state stimulation (6.579 [3.783] vs 3.984 [1.843]; F1,46 = 9.128 [P = .004]; d = 0.87) but not during rest (0.006 [0.003] vs 0.005 [0.002]; F1,34 = 1.067 [P = .309]; d = 0.35). Induced gamma power in the left hemisphere of the patients with SZ during the 40-Hz stimulation was positively correlated with auditory hallucination symptoms (tangential, ρ = 0.587 [P = .031]; radial, ρ = 0.593 [P = .024]) and negatively correlated with the ASSR phase-locking factor (baseline: ρ = −0.572 [P = .024]; ASSR: ρ = −0.568 [P = .032]). Spontaneous gamma activity is increased during auditory steady-state stimulation in SZ, reflecting a disruption in the normal balance of excitation and inhibition. This phenomenon interacts with evoked oscillations, possibly contributing to the gamma ASSR deficit found in SZ. The similarity of increased spontaneous gamma power in SZ to the findings of increased spontaneous gamma power in animal models of NMDAR hypofunction suggests that spontaneous gamma power could serve as a biomarker for the integrity of NMDARs on parvalbumin-expressing inhibitory interneurons in humans and in animal models of neuropsychiatric disorders.