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，我们不断地与其他人互动或思考其他人：社会认知。社会关系对身心健康很重要。孤独对健康的影响与吸烟和饮酒的危害不相上下。精神障碍对我们的社交行为和我们对社会世界的看法有着巨大的影响。无法区分自己的想法与他人的想法是精神病中的一个极端例子，说明完整的社会认知如何失败。因此，了解大脑在社会环境中通常如何产生和控制我们的思维和行为，对于长期改善健康可能很重要。在这里，我开发了新的方法来研究大脑如何导航社会情境。位于大脑深处的脑细胞和连接的集合对社会认知很重要。这个回路包括前额叶皮层和一个叫做杏仁核的小结构，我称之为深层前额叶-杏仁核回路（DPA回路）。这种回路的异常被认为会产生几种精神障碍。虽然我们知道DPA回路对社会认知很重要，但我们并不确切地知道（1）它以何种方式（2）在多大程度上控制着人们的社会行为。这是我将要回答的两个问题。(1)使用大脑成像，可以识别大脑中何时何地发生了心理过程。我将使用大脑成像来验证我的理论，即DPA回路对理解社会关系很重要。我们知道这个电路对于理解空间关系很重要，比如我的车相对于我的房子的位置，以及它是如何工作的。我将扩展这个想法，并测试DPA回路是否对理解社会关系很重要，比如我们自己的信仰如何与其他人的信仰相关，或者理解社会群体中存在哪些联盟。这种过程可能会在精神病等情况下出错。最近，来自人工智能的新理论模型和分析技术已经可用，这将使我能够以全新的方式测试这个想法。(2)当一个人执行一项任务时，观察大脑中发生了什么是一回事，但当我们操纵大脑并导致新事物发生时，这就更有启发性了。我们可以暂时和安全地使用脑刺激技术。如果我们操纵活动，同时测量人们参与社会行为的后果，我们就可以得出关于被操纵的大脑回路的因果结论。到目前为止，还不可能在人类中安全地操纵DPA回路中的活动，因为它位于大脑深处，正常的脑刺激方法无法到达它。然而，我们已经能够通过使用一种新的非侵入性和安全的脑刺激技术来克服猕猴的这一障碍。在这里，我将在人类身上使用这种技术来测试DPA回路在实验条件下是否对控制社会行为具有因果重要性，以及它做什么和不做什么。总之，我的项目将（1）提出一个关于DPA回路支持自然社会行为的新观点。它将通过精确测量大脑活动并使用新的正式数学模型来实现这一目标。这将为理解导致社交焦虑和精神病等情况的社会认知问题奠定基础。(2)我将介绍一种新的、非侵入性的、安全的脑深部电刺激方法。通过瞄准DPA回路，我将因果地操纵大脑网络中最常与精神疾病相关的活动。这为有一天建立一套使用神经调节技术的新干预措施迈出了第一步，这些技术可用于评估甚至治疗患有精神健康状况的患者。