Causal contributions of deep prefrontal-amygdala circuits to social cognition

深层前额叶杏仁核回路对社会认知的因果贡献

• 批准号: MR/Y010477/1
• 负责人: Marco Wittmann
• 金额: $ 187.7万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY010477%2F1
• 关键词: Causal; contributions; deep; prefrontal; amygdala

As humans, we constantly interact with - or think about - other people: social cognition. Social connections are important for mental and physical wellbeing. The impact of loneliness on health is on par with the dangers of smoking and alcohol consumption. Psychiatric disorders have dramatic effects on how we act socially and how we think about the social world. The inability to distinguish one's own thoughts from those of another person is an extreme example seen in psychosis, of how intact social cognition can fail. Understanding how the brain normally produces and controls our thinking and behaviour in social situations is therefore likely to be important for improving health in the longer term. Here, I develop new ways to study how the brain navigates social situations.A collection of brain cells and connections located deep inside the brain is important for social cognition. The circuit comprises the prefrontal cortex and a small structure called the amygdala which I call the deep prefrontal-amygdala circuit (DPA circuit). Abnormalities in this circuit are thought to produce several mental disorders. Although we know that the DPA circuit is important for social cognition, we don't know exactly (1) in what way and (2) to what degree it actually controls how people act socially. These are the two questions I will address. (1) Using brain imaging, it is possible to identify where and when in the brain a mental process takes place. I will use brain imaging to test my theory that it is the DPA circuit that is important for understanding social relationships. We know that this circuit is important for understanding spatial relationships like where my car is relative to my house and a lot about how it works. I will extend this idea and test whether the DPA circuit is important for understanding social relationships like how our own beliefs are related to someone else's, or understanding what alliances exist in a social group. Such processes might go awry in conditions like psychosis. Very recently, new theoretical models and analysis techniques taken from artificial intelligence have become available that will allow me to test this idea in a brand-new way. (2) It is one thing to observe what is happening in the brain when a person performs a task, but it is much more revealing when we manipulate the brain and cause new things to occur. We can do this temporarily and safely using brain stimulation techniques. If we manipulate activity and, in parallel, measure the consequences on people's engagement in social behaviour we can derive causal conclusions about the manipulated brain circuit. So far, it was not possible to manipulate activity in the DPA circuit safely in humans, because it is so deep in the brain that normal brain stimulation methods cannot reach it. However, we have been able to overcome this obstacle in macaque monkeys by using a new non-invasive and safe brain stimulation technique that uses sound waves. Here, I will use this technique in humans to test whether the DPA circuit is causally important for controlling social behaviour under experimental conditions, as well as what else it does and doesn't do.In summary, my project will (1) suggest a new perspective on the way that the DPA circuit supports natural social behaviour. It will do so with precise measures of brain activity and by using new, formalised mathematical models. This will lay the foundation for understanding problems in social cognition leading to conditions like social anxiety and psychosis. (2) I will introduce a new, non-invasive, and safe deep brain stimulation method. By targeting the DPA circuit, I will causally manipulate activity in the brain network that is most frequently associated with mental illness. This provides the first step towards one day establishing a new suite of interventions using neuromodulation techniques which could be used to evaluate and perhaps even treat patients with mental health conditions.

作为人类，我们不断与其他人互动或思考 - 社会认知。社会联系对于身心健康很重要。孤独对健康的影响与吸烟和饮酒的危险相提并论。精神疾病对我们在社会上的行动以及我们如何看待社会世界产生了巨大影响。无法将自己的思想与另一个人的思想区分开来是精神病中看到的一个极端榜样，即完整的社会认知会如何失败。因此，了解大脑通常如何在社交情况下如何产生和控制我们的思维和行为对于长期改善健康很重要。在这里，我开发了研究大脑如何导航社交状况的新方法。大脑内部深处的脑细胞和连接的收集对于社交认知很重要。该电路包括前额叶皮层和一个称为杏仁核的小结构，我称之为深质 - 杏仁核电路（DPA电路）。该电路中的异常被认为会产生多种精神障碍。尽管我们知道DPA巡回赛对于社会认知很重要，但我们并不确切知道（1）以什么方式和（2）它实际上控制着人们在社会上的行为。这是我将要解决的两个问题。 （1）使用大脑成像，可以识别出在大脑中发生心理过程的何时何地。我将使用脑成像来测试我的理论，即DPA电路对于理解社会关系很重要。我们知道，该电路对于理解空间关系很重要，例如我的汽车相对于我的房屋的位置以及有关其工作原理的很多。我将扩展这个想法，并测试DPA巡回赛对于理解社会关系是否重要，例如我们自己的信念与他人的信念如何相关，或者了解社会群体中存在的联盟。在精神病等条件下，此类过程可能会出现问题。最近，从人工智能中采用的新理论模型和分析技术已获得，这将使我能够以崭新的方式测试这个想法。 （2）当一个人执行任务时，观察大脑中发生的事情是一回事，但是当我们操纵大脑并导致新事物发生时，它会更加揭示。我们可以使用大脑刺激技术暂时，安全地进行此操作。如果我们操纵活动，并同时衡量对人们参与社会行为的后果，我们可以得出有关操纵脑电路的因果结论。到目前为止，无法在人类中安全地操纵DPA电路中的活动，因为它在大脑中如此之深，以至于正常的大脑刺激方法无法达到它。但是，我们已经能够使用使用声波的新的非侵入性和安全的脑刺激技术来克服猕猴中的这一障碍。在这里，我将在人类中使用这种技术来测试DPA电路对于在实验条件下控制社会行为以及它所做的和不做什么非常重要。总而言之，我的项目将（1）提出对DPA电路支持自然社会行为的方式的新观点。它将通过精确的大脑活动度量和使用新的，正式的数学模型来做到这一点。这将奠定理解社会认知问题的基础，从而导致社交焦虑和精神病等状况。 （2）我将引入一种新的，无创和安全的深脑刺激方法。通过针对DPA电路，我将在最常见的精神疾病有关的大脑网络中操纵活动。这提供了一天迈出的第一步，使用神经调节技术建立一套新的干预措施，这些技术可用于评估甚至治疗患有精神健康状况的患者。