Using FMRI and TMS to probe the functional connectivity of prefrontal cortex and amygdala in top-down regulation of emotion

根据世界卫生组织的数据，在英国和其他西方国家，抑郁和焦虑等情绪障碍已成为导致残疾的主要原因，预计到2020年将成为全球第二大残疾原因。因此，努力了解这些疾病的原因和潜在的治疗途径对普通民众具有极其重要的意义。然而，事实证明，这项任务很困难。与抑郁症密切相关的一个话题是允许我们调节情绪的大脑机制。虽然在某些情况下，人们有负面情绪是正常的，也是健康的，但情绪障碍的一个特征是患者无法摆脱这些负面情绪。情绪障碍患者的大脑与健康人的大脑有何不同？这种差异能解释他们无法调节情绪吗？最近对健康人的脑成像研究发现，大脑额叶的特定部分似乎参与调节情绪。然而，尽管大脑成像可以表明当我们调节情绪时，大脑的哪些部分是活跃的，但它不能告诉我们，大脑的这些部分是否真的负责情绪调节。例如，它们可能只是我们情绪受到调节的指标，而不是在调节本身中发挥积极作用。大脑成像也不能告诉我们大脑的不同部分如何控制我们的情绪。对动物的研究提供了一些证据，但人类的情感可能在许多方面是不同的。这项拟议的研究将结合大脑刺激和脑成像方面的新颖和尖端技术，为大脑额叶部分在调节我们情绪方面的作用提供新的见解。经颅磁刺激(TMS)是一种允许大脑部分区域暂时受到干扰的方法，将被用来直接测试额叶在调节人类情绪方面所起的作用。TMS对大脑中在人类情绪中起作用的其他部分的活动的影响将被测量，比如杏仁核。此外，还将评估下游对情绪反应的影响。另一项最先进的技术，磁共振波谱(MRS)，将被用来测量杏仁核中一种名为GABA的神经递质的浓度，这种神经递质被认为是让额叶对情绪反应施加控制的重要因素。这项拟议研究的长期目标是更好地了解基本的情绪过程，并将其应用于抑郁症和焦虑症临床人群的研究。通过这种方式，我们的目标是开发新的方法来诊断和治疗这种令人衰弱的疾病，或者从一开始就防止它们的发生。

According to the World Health Organization, emotional disorders such as depression and anxiety have become the leading causes of disability in the UK and other western countries, and are estimated to become the second greatest cause of disability worldwide by 2020. Efforts to understand the causes of these conditions and potential avenues for treatment are therefore of enormous importance to the general population. This task, however, has proved difficult. One topic of great relevance to depression is the brain mechanisms that allow us to regulate our emotions. Although it's normal and healthy for people to have negative emotions in certain circumstances, one of the features of emotional disorders is that sufferers can't pull themselves out of those negative emotional moods. How do the brains of people with emotional disorders differ from those of healthy individuals, and can such differences explain their inability to regulate emotions? Recent brain imaging studies in healthy individuals have identified specific parts of the frontal lobe of the brain that appear to be involved in regulating emotions. However, although brain imaging can indicate what parts of the brain are active when we regulate our emotions, it cannot tell us whether those parts of the brain are actually responsible for emotion regulation. They could, for example, merely be indicators that our emotions are being regulated, and not play an active role in the regulation itself. Nor can brain imaging tell us how different parts of the brain exert control over our emotions. Research with animals provides some evidence, but human emotions are likely distinct in many ways. The proposed research will combine novel and cutting edge techniques in brain stimulation and brain imaging to provide new insights into the role of parts of the brain's frontal lobes in regulating our emotions. Transcranial magnetic stimulation (TMS), a method that allows parts of the brain to be temporarily perturbed, will be used to directly test the role the frontal lobes play in regulating human emotions. The effects of TMS on activity in other parts of the brain that play a role in human emotions, such as the amygdala, will be measured. In addition, the downstream effects on emotional responses will also be assessed. Another state of the art technique, magnetic resonance spectroscopy (MRS), will be used to measure concentrations of a neurotransmitter called GABA in the amygdala, which is thought to be important in allowing the frontal lobes to exert control over emotional responses. The long term goal of the proposed research is to develop a better understanding of basic emotion processes that can be applied to the study of clinical populations with depression and anxiety disorders. In this way, we aim to develop new ways of diagnosing and treating such debilitating conditions, or preventing them from occurring in the first place.