Cortical state and attention: How cognitive variables and neuromodulators shape neural communication and conscious perception

意识是什么？我们是如何意识到自己和周围环境的呢？几个世纪以来，这些问题一直困扰着人文科学(如哲学、法学)和生命科学(如心理学、生物学、医学)的各个学科，并一直存在激烈的争论。生物学方法试图将大脑活动的特定模式与报告的意识活动联系起来。这可能是一件复杂的事情，像向朋友解释为什么新的工作机会是一个绝佳的机会，或者像检测(感知)屏幕上有没有刺激，并报告看到的东西一样简单。这个更简单的例子提供了一种方法，不仅可以在人类中捕捉和研究意识及其报告，还可以在其他动物中进行研究。最大的问题是：大脑活动是如何组织起来的，以便意识产生，当意识失效时，有什么不同？关于意识的神经关联，已经提出了许多相互竞争的理论，但它们在很大程度上仍未得到证实。一个突出的观点是，如果刺激同时激活许多大脑皮层区域的神经元，就会产生对刺激的有意识感知。换句话说，如果一种刺激可以“点燃”大脑许多区域正在进行的活动模式，它更有可能被感知到。据信，只有当某些大脑区域与其他区域有效沟通，以及这些区域之间相反的沟通方向同样有效时，才会发生这种情况。这几乎就像一场鼓舞人心的讨论，两个沟通伙伴将彼此推向新的高度。然而，这是否真的是这样，或者这是如何发生的，目前尚不清楚。我们的项目将通过记录猕猴的多个大脑区域来探索和测试这一想法，这些区域被训练成注意屏幕上的刺激(而不是直接看着它)，并报告它是否发生了微小的变化。我们将使用新的大脑记录技术，使我们能够在动物执行这项任务时同时监测重要脑区数百个神经元的活动。这将使我们能够通过观察猴子无法感知刺激变化时大脑活动受到的影响，来测试“点火”是否确实是支撑有意识报告的关键过程。我们将了解大脑活动差异发生在哪里，我们将了解这些差异的本质。我们还将调查某些大脑化学物质的具体作用，这些化学物质被认为是通过操纵它们在大脑中的水平来参与的。我们还将使用新的技术，通过基因改变神经元，这样我们就可以通过向它们照射短暂的光脉冲来局部激活它们。这将使我们能够探索当刺激被有意识地感知和没有被感知时，大脑区域内和大脑区域之间的交流有何不同，并了解哪些大脑化学物质参与其中。这项研究将揭示我们大脑的不同部分如何相互作用来实现有意识的感知，以及当它失败时会出现什么问题。我们的数据将批判性地检验意识的神经关联的有影响力的理论，并为完善(或驳斥)这些理论提供基石。我们的研究对我们理解健康人的认知有重要意义，但对患病的大脑同样如此，并将为目前注意力和知觉功能障碍(如注意缺陷多动障碍、精神分裂症)的治疗策略提供参考。

What is consciousness? How do we become aware of our surroundings and of ourselves? These questions have troubled disciplines across the humanities (e.g. philosophy, law) and the life sciences (e.g. psychology, biology, medicine) for centuries, and remain intensely debated. Biological approaches try to relate specific patterns of brain activity to reported conscious activities. This can be something as complex as explaining to a friend why a new job offer is a fantastic opportunity, or as simple as detecting (perceiving) the presence or absence of a stimulus on a screen, and reporting what is seen. This simpler example offers a way by which consciousness and its reporting can be captured and studied not only in humans, but also in other animals. The big question is: how is brain activity organised for consciousness to come about, and what differs when it fails? Many competing theories have been proposed regarding neural correlates of consciousness, but they remain largely unproven. One prominent idea is that conscious perception of a stimulus occurs if it simultaneously activates neurons across many cortical areas. Put another way, if a stimulus can "ignite" a pattern of ongoing activity across many brain areas, it is more likely to be perceived. It is believed that this only happens when certain brain areas communicate effectively with others, and when the opposite communication direction between these areas is equally effective. It is almost like an inspired discussion, where two communication partners drive one another to new heights. However, whether this is indeed the case, or how this happens, is currently unknown. Our project will explore and test this idea by recording from multiple brain areas in macaque monkeys trained to pay attention to a stimulus on a screen (without directly looking at it), and report whether (or not) it changes just ever so slightly. We will use new brain recording techniques, which allow us to simultaneously monitor the activity of hundreds of neurons across important brain areas while animals perform this task. This will allow us to test if 'ignition' is indeed the key process that underpins conscious reporting, by looking at how brain activity is affected when monkeys fail to perceive stimulus changes. We will understand where in the brain activity differences occur, and we will understand the nature of these differences. We will also investigate the specific roles of certain brain chemicals proposed to be involved by manipulating their levels in the brain. We will additionally employ novel techniques where we genetically alter neurons, so we can activate them locally by shining brief pulses of light on them. This will allow us to probe how communication within and between brain areas differs when stimuli are consciously perceived and when they are not perceived, and understand which brain chemicals are involved. The study will reveal how different parts of our brain interact to allow for conscious perception, and what goes wrong when it fails. Our data will critically test influential theories of the neural correlates of consciousness, and provide a cornerstone to refine (or refute) these. Our study has important implications for our understanding of cognition in healthy, but equally in diseased brains, and will inform current treatment strategies for attention and perceptual dysfunctions (e.g. attention deficit hyperactivity disorders, schizophrenia).