Neural dynamics of response inhibition and gambling across the lifespan

反应抑制或“冲动控制”是灵活和智能行为的标志，每当一个想法或行动必须停止或放慢时，都需要这种控制。如果没有抑制，许多日常行为就不可能发生，比如驾驶汽车或参与正常的社交活动。抑制的重要性突出的事实是，患有精神疾病或脑损伤的患者往往表现出改变生活的抑制控制缺陷，包括严重的成瘾。此外，随着我们进入中年及以后，反应抑制是几种认知功能之一，见证了稳步下降。目前的科学共识是，人类的反应抑制是由额叶支持的，但这一大片区域究竟是如何调节我们的认知和行为的，仍然是一个谜。该项目的目的是丰富对大脑如何抑制行为的理解，旨在更深入地了解衰老过程和成瘾的新疗法。为了实现这一目标，该项目将联合收割机结合一系列不同的人类神经科学技术，包括刺激大脑和测量复杂大脑网络的生理和化学的方法。该项目的A部分研究人类额叶中的特定大脑区域如何控制其他大脑区域以支持反应抑制。特别是，抑制控制可能需要额叶脑区对更原始的区域施加“远程控制”，这些区域对情绪或协调运动输出做出反应。为了直接观察这些长距离大脑连接如何支持抑制，我们将使用磁共振成像（MRI）测量大脑活动，同时用经颅磁刺激（TMS）刺激额叶的部分。我们还将测试这些大脑连接是如何随着正常年龄的增长而改变的。B部分侧重于理解反应抑制和冒险行为之间的联系，特别是赌博。我们最近的研究表明，期望停止一个简单的运动反应，或者接受训练停止简单的反应，可以减少赌博时的冒险行为。这些效果可以比作建立一个抑制性的“肌肉”，一旦训练，可以更有效地抵制冲动。在B部分，我们将再次使用TMS和MRI来研究为什么运动反应抑制会影响赌博决策，不同的大脑系统是如何受到影响的，以及这些过程如何随着年龄的增长而演变。我们还将使用一种名为磁共振光谱的技术来测试反应抑制训练如何影响大脑化学。总的来说，这个项目有望揭示对反应抑制的复杂大脑过程的新见解，并对未来的成瘾治疗产生影响。赌博成瘾是一个严重的公共卫生问题，影响全球至少1亿人。一种简单的训练反应抑制的方法可能会为减轻这种负担提供一种补充性的新疗法，但首先我们必须了解反应抑制是如何与监督风险决策的更高级别系统联系在一起的。我们项目中的研究将朝着这个方向迈出关键的一步，为反应抑制的基础神经科学提供新的见解，同时进一步了解这种潜在的新疗法。

Response inhibition or 'impulse control' is a hallmark of flexible and intelligent behavior, required whenever a thought or action must be stopped or slowed. Without inhibition, many everyday behaviors would be impossible, such as driving a motor vehicle or engaging in normal social interactions. The importance of inhibition is highlighted by the fact that patients with psychiatric conditions or brain damage often present with life-changing deficits of inhibitory control, including severe addictions. Furthermore, as we advance into middle-age and beyond, response inhibition is one of several cognitive functions that witnesses a steadily decline.The current scientific consensus is that response inhibition in humans is supported by the frontal lobe, but precisely how this large area mediates our cognition and behaviour is deeply mysterious. The aim of this project is to enrich understanding of how the brain inhibits behaviour, with the goal of working toward a deeper understanding of the ageing process and new therapies for addiction. To achieve this, the project will combine a series of different human neuroscience techniques, including methods for stimulating the brain and for measuring the physiology and chemistry of complex brain networks.Part A of the project investigates how specific brain regions in the human frontal lobe might control other brain regions to support response inhibition. In particular, it is possible that inhibitory control requires frontal brain regions to exert 'remote control' over more primitive areas that respond to emotion or coordinate motor output. To observe directly how these long-range brain connections support inhibition, we will measure brain activity using magnetic resonance imaging (MRI) while simultaneously stimulating parts of the frontal lobe with transcranial magnetic stimulation (TMS). We will also test how these brain connections are altered by normal ageing.Part B focuses on understanding links between response inhibition and risk-taking behavior, specifically gambling. Our recent research shows that expecting to stop a simple motor response, or being trained to stop simple responses, can reduce risk-taking when gambling. These effects may be likened to building an inhibitory "muscle" that, once trained, can more effectively resist urges. In Part B we will again use TMS and MRI to study why motor response inhibition influences gambling decisions, how different brain systems are affected, and how these processes evolve with age. We will also use a technique called magnetic resonance spectroscopy to test how training in response inhibition influences brain chemistry.Overall, this project promises to reveal new insights into the complex brain processes that enable response inhibition, with future implications for addiction therapy. Gambling addiction is a severe public health concern, affecting at least 100 million people worldwide. A simple method for training response inhibition may provide a complementary new therapy for reducing this burden, but first we must understand how response inhibition is linked to higher-level systems that oversee risky decision-making. The studies in our project will provide a crucial step forward in this direction, yielding new insights into the basic neuroscience of response inhibition while furthering understanding of this potential new therapy.