Pujol Carolina Fernandez, Blundon Elizabeth G, Dykstra Andrew R
Department of Biomedical Engineering, University of Miami, Coral Gables, FL, United States.
Present address: Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
bioRxiv. 2023 Mar 8:2023.03.06.531459. doi: 10.1101/2023.03.06.531459.
How perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-V pyramidal neurons (PNs). In turn, this leads to increased local field potential activity, increased spiking activity in layer-V PNs, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity.
To date, our understanding of the brain basis of conscious perception has mostly been restricted to large-scale, network-level activity that can be measured non-invasively in human subjects. However, we lack understanding of how such network-level activity is supported by individual neurons and neural circuits. This is at least partially because conscious perception is difficult to study in experimental animals, where such detailed characterization of neural activity is possible. To address this gap, we used biophysical modeling to gain circuit-level insight into an auditory brain response known as the auditory awareness negativity (AAN). This response can be recorded non-invasively in humans and is associated with perceptual awareness of sounds of interest. Our model shows that the AAN likely arises from specific cortical layers and cell types. These data help bridge the gap between circuit- and network-level theories of consciousness, and could lead to new, targeted treatments for perceptual dysfunction and disorders of consciousness.
感觉刺激的感知如何从大脑活动中产生是神经科学的一个基本问题。迄今为止,有两条不同的研究路线探讨了这个问题。一方面,人类神经成像研究帮助我们理解了感知的大规模脑动力学。另一方面,动物模型(通常是小鼠)的研究工作让我们对感知背后的微观神经回路有了基本认识。然而,将这种从动物模型获得的基本认识转化到人类身上一直具有挑战性。在这里,我们使用生物物理建模表明,听觉觉知负波(AAN),一种与噪声中目标声音感知相关的诱发反应,可以由听觉皮层(AC)颗粒上层的突触输入来解释,当听到目标声音时该输入存在,而当错过目标声音时则不存在。这种额外的输入可能源于皮质 - 皮质反馈和/或非lemniscal丘脑投射,并靶向V层锥体神经元(PNs)的顶端树突。反过来,这会导致局部场电位活动增加、V层PNs的放电活动增加以及AAN。这些结果与当前有意识加工的细胞模型一致,并有助于弥合感知相关脑活动的宏观和微观层面之间的差距。
迄今为止,我们对有意识感知的脑基础的理解大多局限于可以在人类受试者中无创测量的大规模、网络水平的活动。然而,我们缺乏对单个神经元和神经回路如何支持这种网络水平活动的理解。这至少部分是因为在实验动物中很难研究有意识感知,而在实验动物中可以对神经活动进行如此详细的表征。为了填补这一空白,我们使用生物物理建模来深入了解一种被称为听觉觉知负波(AAN)的听觉脑反应。这种反应可以在人类中无创记录,并且与对感兴趣声音的感知觉知相关。我们的模型表明,AAN可能源于特定的皮质层和细胞类型。这些数据有助于弥合意识的回路和网络水平理论之间的差距,并可能导致针对感知功能障碍和意识障碍的新的、有针对性的治疗方法。