Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, the Netherlands.
PLoS Biol. 2018 Feb 8;16(2):e2003453. doi: 10.1371/journal.pbio.2003453. eCollection 2018 Feb.
The ascending modulatory systems of the brain stem are powerful regulators of global brain state. Disturbances of these systems are implicated in several major neuropsychiatric disorders. Yet, how these systems interact with specific neural computations in the cerebral cortex to shape perception, cognition, and behavior remains poorly understood. Here, we probed into the effect of two such systems, the catecholaminergic (dopaminergic and noradrenergic) and cholinergic systems, on an important aspect of cortical computation: its intrinsic variability. To this end, we combined placebo-controlled pharmacological intervention in humans, recordings of cortical population activity using magnetoencephalography (MEG), and psychophysical measurements of the perception of ambiguous visual input. A low-dose catecholaminergic, but not cholinergic, manipulation altered the rate of spontaneous perceptual fluctuations as well as the temporal structure of "scale-free" population activity of large swaths of the visual and parietal cortices. Computational analyses indicate that both effects were consistent with an increase in excitatory relative to inhibitory activity in the cortical areas underlying visual perceptual inference. We propose that catecholamines regulate the variability of perception and cognition through dynamically changing the cortical excitation-inhibition ratio. The combined readout of fluctuations in perception and cortical activity we established here may prove useful as an efficient and easily accessible marker of altered cortical computation in neuropsychiatric disorders.
脑脑干的上行调节系统是大脑状态的强大调节者。这些系统的紊乱与几种主要的神经精神疾病有关。然而，这些系统如何与大脑皮层的特定神经计算相互作用，从而塑造感知、认知和行为，仍然知之甚少。在这里，我们探讨了两种这样的系统，即儿茶酚胺（多巴胺能和去甲肾上腺素能）和胆碱能系统，对皮层计算的一个重要方面的影响：其内在变异性。为此，我们结合了人类的安慰剂对照药物干预、使用脑磁图（MEG）记录皮层群体活动，以及对模糊视觉输入感知的心理物理测量。低剂量的儿茶酚胺（但不是胆碱能）操作改变了自发感知波动的速率，以及视觉和顶叶皮层大片区域的“无标度”群体活动的时间结构。计算分析表明，这两种效应都与视觉感知推断下的皮层区域中兴奋性相对于抑制性活动的增加一致。我们提出，儿茶酚胺通过动态改变皮层兴奋-抑制比来调节感知和认知的变异性。我们在这里建立的感知波动和皮层活动的综合读数，可能被证明是一种有效的、易于获得的神经精神疾病中改变的皮层计算的标记物。
