Addressing the generalization problem in neural models of fear

解决恐惧神经模型中的泛化问题

• 批准号: 2241938
• 负责人: Ajay Satpute
• 金额: $ 73万
• 依托单位: Northeastern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2241938&HistoricalAwards=false
• 关键词: Addressing; generalization; problem; neural; models

Emotions are one of the most important aspects of human cognition. Whether it’s the thrill of sky diving, the amusement of a comedy show, or the serene tranquility of meditation, emotions are often intrinsically desirable states. In the extreme, they can also be undesirable or even debilitating, such as in cases of uncontrollable fear or anxiety. Emotions also play a role in perhaps every aspect of human psychology by influencing people’s memories, perceptions, thoughts, behaviors, and decisions. The search for an understanding of emotions has stimulated research on the representation of emotions in the brain. This research has lead to considerable insight into emotions, but also has lead to some apparently conflicting results: different brain regions were activated for the same emotional state depending on the context, and how scientists studied it. Take fear, for example. Since fear is an ancient emotion, common to animals as well as humans, it was originally studied in animal models. Thus, at first, most of what was understood about the neuroscience of fear was based on studies in non-human animals, particularly rodents, who were placed in threatening circumstances while scientists recorded autonomic responses (e.g. heart rate, sweating) and defensive behaviors (e.g. freezing or escape). This work uncovered a network of activated brain regions centered on a part of the brain (the amygdala), and was initially called a “fear circuit”. Based on these results from animal research, this circuit was also proposed to underlie human subjective experiences or feelings of fear. To discover if this was the case, non-invasive neuroimaging studies using fMRI (functional magnetic resonance imaging) were used to examine brain activity during fear in humans. Of great advantage to this research was that the human subjects could simply tell scientists whether they in fact felt fear in response to certain stimuli. However, the results from these human neuroimaging studies were quite different than the results from animal research. In humans, the brain regions predicting and experiencing fear were widespread and highly distributed throughout the brain. Strikingly, the amygdala and other areas in the “fear circuit” were not activated in these studies. These apparently conflicting results stimulated many new questions. If the brain regions underlying fear are different in humans and animals, and depend on the tasks, measurements, and methods that are used, how can a unified scientific account of fear be developed that generalizes across the particularities of any specific study to the diverse variety of fears in everyday life? One possible explanation of the divergent results could be that the early neuroimaging studies in humans were not precise enough in delineating activation of key brain areas that are important in mediating fear. Components of the “fear circuit” including the amygdala, hypothalamus, and periaqueductal gray are small brain nuclei and each are composed of several subregions. It is at the level of these small brain nuclei that circuits for fear and defensive behaviors are organized. In this project, researchers use a more powerful fMRI scanner, with greater spatial resolution that previous neuroimaging studies in order to examine these brain regions and the pattern of fear-related brain activation in greater detail. Participants are induced to feel fear in many distinct situations using both videos and threat of pain (but no actual pain). High resolution recordings of brain activity, subjective self-reported fear, and autonomic activity are all obtained simultaneously. This rich dataset provides a basis for studying how subjective fear and autonomic activity both relate to activity in all parts of the brain, including the subregions of key subcortical structures in the “fear circuit”. This project also includes analyses to identify brain states where subjective fear and measures of autonomic activity (such as heart rate, galvanic skin response) coincide. These correlations reveal whether autonomic measures can be used as indices for human feelings of fear, and thus provide information about whether functionally homologous findings from studies in non-human animals may generalize to subjective experiences of fear in humans. This may reconcile the results from animal and human research and lead to a deeper understanding of the neural mechanisms of fear, with implications for treatments to alleviate fear and anxiety disorders. Complementing the research project, this project also includes an extensive set of broader impacts including a summer workshop for local high school students from underserved communities on the neuroscience of fear and emotion, and ways of overcoming fear and anxiety.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

情绪是人类认知的重要方面之一。无论是跳伞的刺激，喜剧表演的娱乐，还是冥想的宁静，情感往往是内在的理想状态。在极端的情况下，它们也可能是不受欢迎的，甚至使人衰弱，例如在无法控制的恐惧或焦虑的情况下。情绪通过影响人们的记忆、感知、思想、行为和决定，在人类心理的各个方面都发挥着作用。对情感理解的探索刺激了对大脑中情感表征的研究。这项研究让我们对情绪有了相当深入的了解，但也导致了一些明显相互矛盾的结果：根据环境和科学家的研究方式，相同的情绪状态会激活不同的大脑区域，比如恐惧。由于恐惧是一种古老的情感，对动物和人类都很常见，因此最初是在动物模型中进行研究的。因此，起初，人们对恐惧的神经科学的理解大多是基于对非人类动物的研究，特别是啮齿动物，当科学家们记录自主反应（例如心率，出汗）和防御行为（例如冻结或逃跑）时，这些动物被置于威胁环境中。这项工作揭示了一个以大脑的一部分（杏仁核）为中心的激活的大脑区域网络，最初被称为“恐惧回路”。基于这些动物研究的结果，这个回路也被认为是人类主观体验或恐惧感的基础。为了发现这是否是事实，使用功能性磁共振成像（fMRI）的非侵入性神经成像研究被用来检查人类在恐惧时的大脑活动。这项研究的一大优势是，人类受试者可以简单地告诉科学家，他们是否真的对某些刺激感到恐惧。然而，这些人类神经成像研究的结果与动物研究的结果截然不同。在人类中，预测和体验恐惧的大脑区域广泛分布在整个大脑中。引人注目的是，在这些研究中，杏仁核和“恐惧回路”中的其他区域并没有被激活。这些明显相互矛盾的结果引发了许多新的问题。如果人类和动物产生恐惧的大脑区域是不同的，并且取决于所使用的任务、测量方法和方法，那么如何才能建立一个统一的恐惧科学解释，将任何特定研究的特殊性概括为日常生活中各种各样的恐惧呢？对这些不同结果的一种可能解释是，早期的人类神经成像研究在描绘对调节恐惧很重要的关键大脑区域的激活方面不够精确。“恐惧回路”的组成部分包括杏仁核、下丘脑和导水管周围灰质，这些都是小的脑核团，每个都由几个亚区组成。正是在这些小的脑核团的水平上，恐惧和防御行为的回路被组织起来。在这个项目中，研究人员使用更强大的功能磁共振成像扫描仪，具有比以前的神经成像研究更高的空间分辨率，以便更详细地检查这些大脑区域和与恐惧相关的大脑激活模式。参与者在许多不同的情况下使用视频和疼痛威胁（但没有实际的疼痛）诱导感到恐惧。大脑活动的高分辨率记录，主观自我报告的恐惧和自主活动都是同时获得的。这个丰富的数据集为研究主观恐惧和自主活动如何与大脑所有部分的活动相关提供了基础，包括“恐惧回路”中关键皮层下结构的子区域。该项目还包括分析，以确定主观恐惧和自主活动（如心率，皮肤电反应）的措施相吻合的大脑状态。这些相关性揭示了自主措施是否可以作为人类恐惧感的指标，从而提供信息，是否功能同源的研究结果在非人类动物可能会推广到人类的主观经验的恐惧。这可能会调和动物和人类研究的结果，并导致对恐惧的神经机制有更深入的了解，并对缓解恐惧和焦虑症的治疗产生影响。作为对该研究项目的补充，该项目还包括一系列广泛的影响，包括为来自服务不足社区的当地高中学生举办的关于恐惧和情绪的神经科学以及克服恐惧和焦虑的方法的夏季研讨会。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。