The Psychophysiology of Fear and Anxiety

恐惧和焦虑的心理生理学

• 批准号: 10703917
• 负责人: Christian Grillon
• 金额: $ 157.3万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703917
• 关键词: Adult; Affect; American; Amygdaloid structure; Anatomy; Animal Experimentation; Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Arousal; Attention; Attenuated; Basic Science; Brain; Brain imaging; Brain region; COVID-19 pandemic; COVID-19 pandemic effects; Child; Chronic; Classification; Cognition; Cognitive; Computer Analysis; Computer Models; Congenital adrenal hyperplasia; Conscious; Data; Data Analyses; Decision Making; Development; Diagnosis; Diffusion; Disease; Economics; Emotional; Enrollment; Experimental Models; Fingers; Fostering; Fright; Functional Magnetic Resonance Imaging; General Population; Goals; Habenula; Hippocampus (Brain); Human; Individual; Intervention; Knowledge; Learning; Light; Link; Maps; Mediating; Mediation; Mental Health; Methods; Mind; Modality; Motivation; Nature; Neurobiology; Neurocognitive; Nootropic Agents; Outcome; Pathologic; Pathological anxiety; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Play; Prefrontal Cortex; Process; Psychopharmacology; Psychophysiology; Public Health; Recording of previous events; Reporting; Research; Resources; Rest; Risk Factors; Ritalin; Role; Safety; Sampling; Short-Term Memory; Signal Transduction; Stimulus; Structure; Structure of terminal stria nuclei of preoptic region; Task Performances; Techniques; Teenagers; Telephone; Testosterone; Time; United States National Institutes of Health; affective neuroscience; anxiety symptoms; anxious; attentional bias; base; biological adaptation to stress; blood oxygenation level dependent response; brain based; cingulate cortex; clinical anxiety; clinical efficacy; cognitive enhancement; cognitive process; comorbidity; conditioned fear; conditioning; cost estimate; dorsal raphe nucleus; drug discovery; endophenotype; experience; healthy volunteer; improved; in utero; insight; midbrain central gray substance; mindfulness-based stress reduction; neural; neural circuit; neuroimaging; novel; pandemic disease; physical symptom; programs; protective factors; psychologic; psychological distress; psychological symptom; response; sexual dimorphism; side effect; statistics; tool; uptake

The lab focuses on understanding several aspects of normal and pathological anxiety. Our research includes neuroimaging to understand brain mechanisms; psychophysiology to explore emotional reactivity; affective neuroscience to investigate cognitive processes; and psychopharmacology to screen new treatments. In addition, the COVID-19 pandemic gave us the opportunity to examine risk factors of anxiety in response to a chronic environmental threat. To study attentional problems caused by anxiety, we have developed a research program that explores the interaction between anxiety and working memory (WM). WM refers to the temporary storage and manipulation of information (e.g., remembering a phone number when dialing the number). WM not only helps keep in mind our current goals, but it also gives rise to the conscious experience of anxiety. In past studies, we have identified brain structures of a frontoparietal control network that play important roles in the interaction between anxiety and WM. More recently, we implemented a pharmacological manipulation using a cognitive enhancer, methylphenidate (MPH), to investigate the impact of improving cognition on anxiety. We showed that MPH increases overall WM performance and strengthened the engagement of the frontoparietal control network while also reducing the default mode network deactivation. The facilitation of neural activation can be interpreted as an expansion of cognitive resources, which could foster both the representation and integration of anxiety-provoking stimuli as well as the top-down regulatory processes to protect against the detrimental effect of anxiety. This year, we expanded our knowledge of the anxiety-related effects of MPH during WM on brain function, using a computational analysis. This analysis, Topological Data Analysis (TDA)-based Mapper. . Findings showed that MPH facilitated greater differential engagement of neural resources (brain activity) across low and high working memory load conditions. Furthermore, load-based differential management of neural resources reflected enhanced efficiency. These results provide novel insights regarding brain mechanisms that facilitate cognitive enhancement under MPH and, in future research, may be used to help mitigate anxiety-related cognitive underperformance. We have pursued the fear conditioning thematic. We reframe components of fear conditioning as prediction errors and report how neural circuits reflect prediction errors during aversive Pavlovian learning. We queried the periaqueductal gray matter (PAG), a structure exquisitely linked to fear responses. Results of this study suggest that the PAG and mid-cingulate cortex play a role in processing salient information related to safety during differential conditioning and may function to attenuate and regulate defensive responses to conditioned threat stimuli. Expanding research on the interaction of anxiety with inhibitory/attentional processes, we reanalyzed past data using the drift-diffusion computational model (DDM). The DDM analysis showed that induced anxiety was associated with an amplified drift rate process, which reflects increased informational uptake. Moreover, these changes in drift rate during the anxiety condition were associated with enhanced BOLD responses within the posterior cingulate cortex during Go trials. Collectively, these results shed light on the mechanisms underlying facilitated task performance and suggest that anxiety can improve cognitive processing by enhancing information uptake and increasing activity within the posterior cingulate cortex. The DDM approach is currently applied to a larger sample of both healthy volunteers and individuals with an anxiety disorder. Another direction of the lab has focused on decision-making in anxiety. Two projects have been dedicated to this theme. The first project examined loss aversion, an economic concept that has been extensively studied in the general population. Our goal was to examine how loss aversion was affected by the presence of anxiety, both clinical anxiety and experimentally induced anxiety. We found that high ratings of symptoms of anxiety arousal, but not of symptoms of psychological distress, were associated with worsened loss aversion. This was found only in individuals with anxiety, independently of the threat or safe context. These findings underscore the importance of the subjective experience of physical symptoms of anxiety in decision-making for patients with clinical anxiety. In the past year, the lab has increased research in the neuroimaging analysis of intrinsic functional connectivity. Analysis of resting state fMRI data has gained prominence as a tool to infer functional connectivity (fc) in brain networks. Functional connectivity is defined as the level of coherence in neural activity of anatomically distinct brain regions. Surprisingly, one underlying assumption of most fc analyses is temporal stationarity, i.e., no phase difference between the signals considered. However, there is increasing evidence that challenges this assumption. There are several methods that capture the dynamic nature of the fc. Our lab has implemented a new technique based on dynamic time warping (DTW). This technique was found to be more efficient in assessing the separability of the SNc-cortical and VTA-cortical network compared to traditional methods. We expanded this study by enrolling individuals with anxiety. Finally, we have initiated a project that examines the effects of the COVID-19 pandemic on mental health, particularly risk factors and protective factors, in three different samples, general population (sample of convenience), individuals who had been participated in an NIH resting state neuroimaging study prior to the pandemic, and a sample of patients with a diagnosis of Congenital Adrenal Hyperplasia. Specifically, this project examines the effects of a severe chronic environmental threat (pandemic) on mental health and cognitive processes of attention bias and motivation. A number of studies have been planned: (1) The examination of sexual dimorphism in mental health responses, with an emphasis on a comparison of individuals with a history of excess testosterone in utero (CAH), which is expected to affect responses of stress; (2) The examination of neural predictors of mental health outcomes using data from the NIH sample; (3) Longitudinal data analysis of changes in stress responses to the pandemic, at an average of 6 months intervals; and (4) Relationships between attention bias to threat (on-line dot-probe task) and motivation to approach or avoid outcomes (online finger-tapping task) with stress responses to the pandemic.

该实验室的重点是了解正常和病理性焦虑的几个方面。我们的研究包括通过神经影像学来了解大脑机制；心理生理学探索情绪反应；情感神经科学研究认知过程；和精神药理学来筛选新的治疗方法。此外，COVID-19 大流行让我们有机会研究因长期环境威胁而产生焦虑的危险因素。 为了研究焦虑引起的注意力问题，我们制定了一项研究计划，探索焦虑与工作记忆 (WM) 之间的相互作用。 WM 是指信息的临时存储和操作（例如，拨打号码时记住电话号码）。 WM 不仅有助于记住我们当前的目标，而且还会引起有意识的焦虑体验。在过去的研究中，我们已经确定了额顶叶控制网络的大脑结构在焦虑和 WM 之间的相互作用中发挥着重要作用。最近，我们使用认知增强剂哌醋甲酯（MPH）实施了药物操作，以研究改善认知对焦虑的影响。我们表明 MPH 提高了整体 WM 性能并加强了额顶控制网络的参与，同时还减少了默认模式网络停用。神经激活的促进可以解释为认知资源的扩展，这可以促进引起焦虑的刺激的表征和整合，以及自上而下的调节过程，以防止焦虑的有害影响。今年，我们通过计算分析扩展了对 WM 期间 MPH 对大脑功能的焦虑相关影响的认识。此分析基于拓扑数据分析 (TDA) 的映射器。 。研究结果表明，MPH 促进了在低工作记忆负载和高工作记忆负载条件下神经资源（大脑活动）的更大差异性参与。此外，基于负载的神经资源差异化管理体现了效率的提高。这些结果提供了关于促进 MPH 下认知增强的大脑机制的新颖见解，并且在未来的研究中，可能用于帮助减轻与焦虑相关的认知表现不佳。 我们追求的是恐惧条件反射的主题。我们将恐惧条件反射的组成部分重新定义为预测错误，并报告神经回路如何在厌恶性巴甫洛夫学习过程中反映预测错误。我们询问了导水管周围灰质（PAG），这是一种与恐惧反应密切相关的结构。这项研究的结果表明，PAG 和中扣带皮层在处理差异调节过程中与安全相关的显着信息方面发挥着作用，并且可能起到减弱和调节对条件威胁刺激的防御反应的作用。 为了扩展对焦虑与抑制/注意力过程相互作用的研究，我们使用漂移扩散计算模型（DDM）重新分析了过去的数据。 DDM 分析表明，诱发的焦虑与放大的漂移率过程相关，这反映了信息吸收的增加。此外，焦虑状态下漂移率的这些变化与 Go 试验期间后扣带皮层内 BOLD 反应的增强有关。总的来说，这些结果揭示了促进任务表现的潜在机制，并表明焦虑可以通过增强信息吸收和增加后扣带皮层内的活动来改善认知处理。 DDM 方法目前适用于健康志愿者和患有焦虑症的个体的更大样本。 实验室的另一个方向集中在焦虑时的决策。有两个项目致力于这个主题。第一个项目研究了损失厌恶，这是一个已在普通人群中广泛研究的经济概念。我们的目标是研究焦虑（临床焦虑和实验诱发的焦虑）的存在如何影响损失厌恶。我们发现，焦虑唤起症状的高评分与损失厌恶的恶化相关，但心理困扰症状的评分不高。这种情况只出现在焦虑的个体中，与威胁或安全环境无关。这些发现强调了焦虑身体症状的主观体验在临床焦虑患者决策中的重要性。 在过去的一年里，该实验室加大了对内在功能连接的神经影像分析的研究力度。静息态功能磁共振成像数据的分析作为推断大脑网络功能连接 (fc) 的工具已受到重视。功能连接被定义为解剖学上不同的大脑区域的神经活动的一致性水平。令人惊讶的是，大多数 FC 分析的一个基本假设是时间平稳性，即所考虑的信号之间没有相位差。然而，越来越多的证据挑战了这一假设。有几种方法可以捕捉 fc 的动态特性。我们的实验室实施了一种基于动态时间规整（DTW）的新技术。与传统方法相比，该技术在评估 SNc 皮质和 VTA 皮质网络的可分离性方面更有效。我们通过招募患有焦虑症的个体来扩大这项研究。 最后，我们启动了一个项目，在三个不同的样本中检查 COVID-19 大流行对心理健康的影响，特别是危险因素和保护因素，即普通人群（方便样本）、大流行前参加过 NIH 静息态神经影像研究的个体，以及诊断为先天性肾上腺增生症的患者样本。具体来说，该项目研究了严重的慢性环境威胁（流行病）对心理健康以及注意力偏差和动机的认知过程的影响。已计划开展多项研究：（1）检查心理健康反应中的性别二态性，重点是对有子宫内睾酮过多（CAH）史的个体进行比较，预计这会影响压力反应； (2) 使用 NIH 样本数据检查心理健康结果的神经预测因子； （3）对疫情应激反应变化的纵向数据分析，平均间隔6个月； (4) 对威胁的注意偏差（在线点探测任务）和接近或避免结果的动机（在线手指敲击任务）与对流行病的压力反应之间的关系。

项目成果

Impaired discriminative fear-conditioning resulting from elevated fear responding to learned safety cues among individuals with panic disorder.

• DOI: 10.1016/j.brat.2008.10.017
• 发表时间: 2009-02
• 期刊: Behaviour research and therapy
• 影响因子: 4.1
• 作者: Lissek S;Rabin SJ;McDowell DJ;Dvir S;Bradford DE;Geraci M;Pine DS;Grillon C
• 通讯作者: Grillon C

Two-week treatment with the selective serotonin reuptake inhibitor citalopram reduces contextual anxiety but not cued fear in healthy volunteers: a fear-potentiated startle study.

• DOI: 10.1038/npp.2008.141
• 发表时间: 2009-03
• 期刊: NEUROPSYCHOPHARMACOLOGY
• 影响因子: 7.6
• 作者: Grillon, Christian;Chavis, Chanen;Covington, Matthew F.;Pine, Daniel S.
• 通讯作者: Pine, Daniel S.

The Unpredictive Brain Under Threat: A Neurocomputational Account of Anxious Hypervigilance.

• DOI: 10.1016/j.biopsych.2017.06.031
• 发表时间: 2017-09-15
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: Cornwell BR;Garrido MI;Overstreet C;Pine DS;Grillon C
• 通讯作者: Grillon C

Evidence of MAOA genotype involvement in spatial ability in males.

MAOA 基因型参与男性空间能力的证据。

• DOI: 10.1016/j.bbr.2014.03.025
• 发表时间: 2014
• 期刊: Behavioural brain research
• 影响因子: 2.7
• 作者: Mueller,SvenC;Cornwell,BrianR;Grillon,Christian;Macintyre,Jessica;Gorodetsky,Elena;Goldman,David;Pine,DanielS;Ernst,Monique
• 通讯作者: Ernst,Monique

Age and Social Context Modulate the Effect of Anxiety on Risk-taking in Pediatric Samples.

年龄和社会背景调节焦虑对儿科样本中冒险行为的影响。

• DOI: 10.1007/s10802-015-0098-4
• 发表时间: 2016
• 期刊: Journal of abnormal child psychology
• 影响因子: 3.6
• 作者: Rosen,Dana;Patel,Nilam;Pavletic,Nevia;Grillon,Christian;Pine,DanielS;Ernst,Monique
• 通讯作者: Ernst,Monique