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，我们不断地与他人互动或思考：社会认知。社会联系对于身心健康非常重要。孤独对健康的影响与吸烟和饮酒的危害相当。精神疾病对我们的社交行为以及我们如何看待社会世界有着巨大的影响。无法区分自己的想法和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可能会失败。因此，从长远来看，了解大脑如何正常产生和控制我们在社交场合的思维和行为对于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驾驭社交情境。位于大脑深处的脑细胞和连接的集合对于社交认知非常重要。该回路由前额叶皮层和一个称为杏仁核的小结构组成，我将其称为深层前额叶-杏仁核回路（DPA 回路）。该回路的异常被认为会产生多种精神障碍。尽管我们知道 DPA 回路对于社会认知很重要，但我们并不确切知道 (1) 以什么方式以及 (2) 它在多大程度上实际控制人们的社交行为。这是我要解决的两个问题。 (1) 利用脑成像，可以识别大脑中何时何地发生心理过程。我将使用大脑成像来检验我的理论，即 DPA 回路对于理解社会关系非常重要。我们知道这条电路对于理解空间关系非常重要，例如我的车相对于我的房子的位置以及它的工作原理。我将扩展这个想法并测试 DPA 电路对于理解社会关系是否重要，例如我们自己的信仰如何与他人的信仰相关，或者理解社会群体中存在哪些联盟。在精神病等情况下，这样的过程可能会出错。最近，来自人工智能的新理论模型和分析技术已经出现，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，观察大脑中发生的事情是一回事，但当我们操纵大脑并导致新事物发生时，这就更具启发性。我们可以使用大脑刺激技术暂时安全地做到这一点。如果我们操纵活动，同时测量人们参与社会行为的后果，我们就可以得出有关被操纵的大脑回路的因果结论。到目前为止，还不可能安全地操纵人类 DPA 回路的活动，因为它位于大脑深处，普通的大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且安全的声波脑刺激技术来克服猕猴身上的这一障碍。在这里，我将在人类身上使用这种技术来测试 DPA 电路对于在实验条件下控制社会行为是否具有因果关系，以及它还能做什么和不做什么。总而言之，我的项目将 (1) 建议关于 DPA 电路支持自然社会行为方式的新视角。它将通过精确测量大脑活动并使用新的、形式化的数学模型来实现这一点。这将为理解导致社交焦虑和精神病等状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、安全的脑深部刺激方法。通过瞄准 DPA 回路，我将因果性地操纵大脑网络中最常与精神疾病相关的活动。这为有一天使用神经调节技术建立一套新的干预措施迈出了第一步，该技术可用于评估甚至治疗患有精神健康问题的患者。