Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, CH-8032 Zurich, Switzerland; Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Neuropsychopharmacology and Brain Imaging Research Unit, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Lenggstrasse 31, 8032 Zurich, Switzerland.
Eur Neuropsychopharmacol. 2019 Apr;29(4):539-548. doi: 10.1016/j.euroneuro.2019.02.004. Epub 2019 Feb 26.
Performance and conflict monitoring (PM and CM) represent two essential cognitive abilities, required to respond appropriately to demanding tasks. PM and CM can be investigated using event-related brain potentials (ERP) and associated neural oscillations. Namely, the error-related negativity (ERN) represents a correlate of PM, whereas the N2 component reflects the process of CM. Both ERPs originate in the anterior cingulate cortex (ACC) and PM specifically has been shown to be susceptible to gamma-aminobutyric acid (GABA) A receptor activation. Contrarily, the specific effects of GABA receptor (GABAR) stimulation on PM and CM are unknown. Thus, the effects of gamma-hydroxybutyrate (GHB; 20 and 35 mg/kg), a predominant GABAR agonist, on behavioral and electrophysiological correlates of PM and CM were here assessed in 15 healthy male volunteers, using the Eriksen-Flanker paradigm in a randomized, double-blind, placebo-controlled, cross-over study. Electroencephalographic (EEG) data were analyzed in the time and time-frequency domains. GHB prolonged reaction times, without affecting error rates or post-error slowing. Moreover, GHB decreased ERN amplitudes and associated neural oscillations in the theta/alpha1 range. Similarly, neural oscillations associated with the N2 were reduced in the theta/alpha1 range, while N2 amplitude was conversely increased. Hence, GHB shows a dissociating effect on electrophysiological correlates of PM and CM. Reduced ERN likely derives from a GABAR-mediated increase in dopaminergic signaling, disrupting the generation of prediction errors, whereas an enhanced N2 suggests an increased susceptibility towards external stimuli. Conclusively, GHB is the first drug reported, thus far, to have opposite effects on PM and CM, underlined by its unique electrophysiological signature.
表现和冲突监测（PM 和 CM）代表两种基本的认知能力，需要对要求苛刻的任务做出适当的反应。PM 和 CM 可以使用事件相关脑电位（ERP）和相关的神经振荡来研究。即，错误相关负波（ERN）代表 PM 的相关物，而 N2 成分反映了 CM 的过程。这两种 ERP 都起源于前扣带皮层（ACC），PM 特别容易受到γ-氨基丁酸（GABA）A 受体激活的影响。相反，GABA 受体（GABAR）刺激对 PM 和 CM 的具体影响尚不清楚。因此，在一项随机、双盲、安慰剂对照、交叉研究中，使用 Eriksen-Flanker 范式，在 15 名健康男性志愿者中评估了主要的 GABAR 激动剂γ-羟基丁酸（GHB；20 和 35mg/kg）对 PM 和 CM 的行为和电生理相关性的影响。对脑电图（EEG）数据进行了时频域分析。GHB 延长了反应时间，而不影响错误率或错误后减速。此外，GHB 降低了 ERN 幅度和θ/α1 范围内的相关神经振荡。同样，与 N2 相关的神经振荡在θ/α1 范围内减少，而 N2 幅度相反增加。因此，GHB 对 PM 和 CM 的电生理相关性表现出分离效应。ERN 的减少可能源自 GABAR 介导的多巴胺能信号增加，破坏了预测误差的产生，而增强的 N2 表明对外部刺激的敏感性增加。总之，GHB 是迄今为止报道的第一种对 PM 和 CM 具有相反作用的药物，其独特的电生理特征强调了这一点。
