Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, the Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, the Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Curr Biol. 2014 Dec 15;24(24):2878-87. doi: 10.1016/j.cub.2014.10.017. Epub 2014 Nov 26.
Impressive in vitro research in rodents and computational modeling has uncovered the core mechanisms responsible for generating neuronal oscillations. In particular, GABAergic interneurons play a crucial role for synchronizing neural populations. Do these mechanistic principles apply to human oscillations associated with function? To address this, we recorded ongoing brain activity using magnetoencephalography (MEG) in healthy human subjects participating in a double-blind pharmacological study receiving placebo, 0.5 mg and 1.5 mg of lorazepam (LZP; a benzodiazepine upregulating GABAergic conductance). Participants performed a demanding visuospatial working memory (WM) task.
We found that occipital gamma power associated with WM recognition increased with LZP dosage. Importantly, the frequency of the gamma activity decreased with dosage, as predicted by models derived from the rat hippocampus. A regionally specific gamma increase correlated with the drug-related performance decrease. Despite the system-wide pharmacological intervention, gamma power drug modulations were specific to visual cortex: sensorimotor gamma power and frequency during button presses remained unaffected. In contrast, occipital alpha power modulations during the delay interval decreased parametrically with drug dosage, predicting performance impairment. Consistent with alpha oscillations reflecting functional inhibition, LZP affected alpha power strongly in early visual regions not required for the task demonstrating a regional specific occipital impairment.
GABAergic interneurons are strongly implicated in the generation of gamma and alpha oscillations in human occipital cortex where drug-induced power modulations predicted WM performance. Our findings bring us an important step closer to linking neuronal dynamics to behavior by embracing established animal models.
令人印象深刻的啮齿动物体内研究和计算模型揭示了产生神经元振荡的核心机制。特别是，GABA 能中间神经元对于同步神经群体起着至关重要的作用。这些机械原理是否适用于与功能相关的人类振荡？为了解决这个问题，我们使用健康人类受试者的脑磁图（MEG）记录了正在进行的大脑活动，这些受试者参加了一项双盲药物研究，接受安慰剂、0.5 毫克和 1.5 毫克劳拉西泮（LZP；一种上调 GABA 能传导的苯二氮䓬类药物）。参与者执行了一项具有挑战性的视觉空间工作记忆（WM）任务。
我们发现，与 WM 识别相关的枕部伽马功率随着 LZP 剂量的增加而增加。重要的是，伽马活动的频率随着剂量的增加而降低，这与从大鼠海马体得出的模型预测一致。与药物相关的性能下降相关的区域性特定伽马增加。尽管存在系统范围的药物干预，但伽马功率药物调节是视觉皮层特有的：按钮按下期间的感觉运动伽马功率和频率不受影响。相比之下，在延迟间隔期间，枕部阿尔法功率的调制随药物剂量呈参数性降低，这预示着性能受损。与反映功能抑制的阿尔法振荡一致，LZP 强烈影响早期视觉区域的阿尔法功率，这些区域不需要执行任务，表明存在区域性特定的枕部损伤。
GABA 能中间神经元强烈参与人类枕叶伽马和阿尔法振荡的产生，其中药物诱导的功率调制预测了 WM 性能。我们的发现使我们朝着通过采用既定的动物模型将神经元动力学与行为联系起来迈出了重要的一步。
