The impact of attention on the neuronal mechanisms of adaptation in humans and animals

大脑神经元在重复环境事件（如个人的声音或面孔）后适应或改变其反应。神经元适应/重复效应被认为是重要的，因为减少的反应可能表明我们对刚刚遇到的个体的熟悉程度，并帮助认知过程识别和记住个体。人类功能性磁共振成像（fMRI）是一种非侵入性的技术，越来越多地被利用来推断神经元在适应过程中的反应。需要在动物模型中进行神经元水平的研究以阐明神经元机制。然而，尽管许多动物神经元适应性研究表明，神经元通常会降低对所有刺激的放电率（所谓的“反应疲劳”适应模型），但最新的人类fMRI适应性研究表明，这种观点是不完整的。人类的研究结果表明，某些大脑区域可能含有神经元，这些神经元在适应后对特定刺激或其特征更具选择性（所谓的“锐化选择性”模型）。无论如何，几个科学问题似乎使对功能性磁共振成像适应反应的解释变得复杂。也就是说，注意力的影响在两个物种中没有以相同的方式进行研究，不一致的实验范式被用来获得人类和动物的适应结果，并且不清楚适应机制（主要在视觉系统中进行研究）是否可以与另一种感觉系统（如听觉）中的机制相比较。因此，尽管流行的fMRI适应现象的重要性，支持它的神经元机制仍然存在很大争议。本项目旨在通过实施基于相同的注意力控制实验的人类和动物fMRI项目，结合精确的靶向神经元记录在动物中来解决这一争议。具体而言，我们的目标是：1）通过对人类和动物进行相同的注意实验，评估fMRI适应反应在人类和动物中是否具有可比性; 2）将最新的人类fMRI适应范式扩展到动物的工作中，特别是能够揭示神经元选择性区域变化的新范式;和3）精确靶向显示选择性变化和/或与动物中的反应-疲劳模型一致的那些变化的神经元记录区域。此外，我们的目标是进行实验中的视觉和听觉方式（分别使用，面孔或声音作为刺激），以解决跨不同的感觉方式的fMRI适应反应的对应关系。这是一个重要的次要目标，因为电生理学研究已经在各种动物中获得了听觉适应结果，这些结果可能与动物视觉模式的适应相当，也可能不相当。最后，虽然这对项目的成功并不重要，但我们有机会将fMRI和动物电生理学结合起来，能够更直接地将fMRI信号和神经元反应联系起来。如果成功的话，我们英国的机构将成为世界上第二个在有意识行为的动物身上实现这一目标的机构。总之，通过使用基于注意力控制任务的相同实验（和刺激）来测试人类和动物适应结果之间的联系已经变得至关重要。我们的项目有可能极大地推进我们对fMRI适应的神经元机制的理解，以及它们如何受到认知过程（如注意力）的影响或相互作用。这一结果可能会指导未来利用功能磁共振成像适应来影响心理过程的努力，包括记忆和预期。

Brain neurons adapt or change their responsiveness following the repetition of an environmental event, such as the voice or face of an individual. Neuronal adaptation/repetition effects are thought to be important because a reduced response could indicate familiarity with an individual that we have just met and help cognitive processes to recognize and remember the individual. The neuronal mechanisms of adaptation are of great interest but remain controversial.Human functional magnetic resonance imaging (fMRI) is a non-invasive technique that is increasingly being harnessed to make inferences about neuronal responses during adaptation. Neuronal level study in animal models is required to clarify the neuronal mechanisms. However, although a number of animal neuronal studies of adaptation have shown that neurons generally reduce their firing rates to all stimuli (what is called the ‘response-fatigue’ model of adaptation), the latest human fMRI adaptation studies suggest that this perspective is incomplete. The human results indicate that certain brain regions might contain neurons that can become more selective to specific stimuli or their features after adaptation (what is called the ‘sharpened selectivity’ model). In any case, several scientific issues appear to have complicated the interpretation of the fMRI adaptation response. Namely, the impact of attention has not been studied in the same way in both species, inconsistent experimental paradigms have been used to obtain the human and animal adaptation results, and it is not clear whether the mechanisms of adaptation (which have primarily been studied in the visual system) would be comparable to those in another sensory system, such as the auditory. Therefore, despite the importance of the popular fMRI adaptation phenomenon, the neuronal mechanisms that support it remain highly controversial.This project is designed to address this controversy by implementing a human and animal fMRI project based on the same attentionally-controlled experiment, combined with precisely targeted neuronal recordings in the animals. Specifically, we aim to: 1) evaluate whether fMRI adaptation responses are comparable in humans and animals by conducting the same attentional experiment with both species; 2) extend the latest human fMRI adaptation paradigms to the work with animals, especially the new paradigms that appear to be able to reveal regional changes in neuronal selectivity; and 3) precisely target for neuronal recordings regions showing changes in selectivity and/or those consistent with the response-fatigue model in the animals. Moreover, we aim to conduct the experiment in the visual and auditory modalities (using, respectively, faces or voices as stimuli) to address the correspondence of fMRI adaptation responses across different sensory modalities. This is an important secondary objective because electrophysiological studies have obtained auditory adaptation results in various animals that may or may not be comparable to adaptation in the visual modality of animals. Lastly, although it is not critical for the success of the project, we have the opportunity here to combine fMRI and electrophysiology in animals to be able to more directly associate the fMRI signal and neuronal responses. If successful, our UK institution would be only the second institution in the world to achieve this in conscious behaving animals.In summary, it has become crucial to test the link between human and animal adaptation results by using the same experiment (and stimuli) based on an attentionally controlled task. Our project has the potential to greatly advance our understanding of the neuronal mechanisms of fMRI adaptation and how they might be influenced by or interact with cognitive processes such as those of attention. The results are likely to guide future efforts that employ fMRI adaptation to influence mental processes, including memory and expectancy.