Neurocomputational mechanisms of impaired social decision-making in borderline personality

边缘人格社会决策受损的神经计算机制

• 批准号: 10407975
• 负责人: Michael Nelson Hallquist
• 金额: $ 48.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10407975
• 关键词: Adolescence; Adult; Affect; Affective; Age; Aggressive behavior; Amygdaloid structure; Anger; Bayesian Method; Behavior; Behavioral; Biological Markers; Biological Response Modifier Therapy; Borderline Personality Disorder; Case-Control Studies; Cell Nucleus; Clinical; Cognitive; Complex; Computer Models; Control Groups; Corpus striatum structure; Cues; Data; Decision Making; Decision Theory; Development; Diagnosis; Emotional; Emotions; Enrollment; Event; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Goals; Hypersensitivity; Impairment; Impulsivity; Individual; Informal Social Control; Learning; Light; Link; Mental disorders; Modeling; Motivation; National Institute of Mental Health; Neurosciences; Neurosciences Research; Nucleus Accumbens; Outcome; Participant; Pathway interactions; Personality; Phylogenetic Analysis; Prefrontal Cortex; Prevalence; Process; Psychiatry; Psychological reinforcement; Reaction; Regulation; Research; Resistance; Resolution; Rest; Role; Self-Injurious Behavior; Severities; Signal Transduction; Social Anxiety Disorder; Specificity; Stimulus; Strategic Planning; Suicide attempt; Symptoms; System; Testing; Treatment Cost; Work; adaptive learning; age related; base; cognitive neuroscience; emerging adult; follow-up; intimate behavior; maladaptive behavior; neural circuit; neurodevelopment; neuroimaging; psychosocial; recruit; relating to nervous system; response; sex; social; social influence; suicidal; young adult

Borderline Personality Disorder (BPD) is a debilitating condition characterized by affective instability, interpersonal dysfunction, and impulsive and self-harming behaviors. Individuals with BPD often make disadvantageous decisions in response to negative interpersonal events, yet little is known about decision processes that precipitate maladaptive behaviors. The past two decades of neuroscience research has provided overwhelming evidence that decision-making can be understood in terms of Pavlovian and goal- directed computational systems that are implemented in specific cortical-striatal-limbic circuits. Supported by our preliminary data, we propose that in BPD, the cingulo-opercular network’s role in goal-directed learning is vulnerable to disruptions by social-emotional cues that exert Pavlovian influences on decision-making. Although BPD has historically been diagnosed in adults, symptoms often emerge in adolescence and their severity may peak in early adulthood. The maturation of the cingulo-opercular network from adolescence to early adulthood underlies developmental improvements in the integration of motivationally salient cues with goal-directed behavior. We will test the hypothesis that in BPD, both approach- and avoidance-related Pavlovian computations dominate the cingulo-opercular network via the phylogenetically old pathway from the central nucleus of the amygdala to the nucleus accumbens core, which underpins emotion-driven Pavlovian responses. The proposed case-control study will characterize abnormalities in Pavlovian and goal-directed decision-making in 49 young adults with BPD symptoms compared to 49 matched individuals with social anxiety disorder and 49 healthy controls. Studying these processes in early adulthood is essential because BPD symptoms change rapidly during this period, which may reflect neurodevelopmental maturation of emotion- and decision-related circuits. At the behavioral level, we will characterize participants using a decision battery and corresponding hierarchical Bayesian reinforcement learning (RL) models that span social and nonsocial contexts (Aim 1). We will link decision signals, particularly the effects of social cues on goal-directed learning, with their neurocomputational correlates using Bayesian RL models and model-based fMRI analyses (Aim 2). Finally, to characterize separable circuits involved in maladaptive Pavlovian computations in BPD, we will conduct a high-resolution resting-state fMRI study of the integration of the cingulo-opercular network with specific limbic and striatal regions (Aim 3). Altogether, our computational psychiatry approach builds on the unique strengths of our investigative team in BPD and neurodevelopment (Hallquist), Bayesian methodology (Oravecz), and decision neuroscience (Hallquist, Dombrovski). This work aligns well with the NIMH Strategic Plan for Research objectives to describe the neural circuits underlying mental illness (Strategy 1.1) and to identify biomarkers and behavioral indicators that predict change in illness (Strategy 2.2).

边缘型人格障碍（BPD）是一种以情感不稳定为特征的衰弱性疾病， 人际关系障碍，冲动和自我伤害行为。患有BPD的人通常会 不利的决定，以应对负面的人际事件，但很少有人知道决策 导致适应不良行为的过程。过去二十年的神经科学研究 提供了压倒性的证据，证明决策可以用巴甫洛夫和目标来理解， 在特定的皮质-纹状体-边缘回路中实现的定向计算系统。支持 根据我们的初步数据，我们认为在BPD中，扣带-鳃盖网络在目标导向学习中的作用是 容易受到社会情感线索的干扰，这些线索对决策产生了巴甫洛夫式的影响。 虽然BPD在历史上被诊断为成人，但症状通常出现在青春期， 严重程度可能在成年早期达到高峰。扣带-鳃盖网络的成熟从青春期到 成年早期的基础发展的改善，在整合的动机显着线索， 目标导向行为我们将检验这一假设，即在BPD中，接近和回避相关 巴甫洛夫计算通过从大脑皮层到大脑皮层的遗传学上古老的途径控制扣带-鳃盖网络。 杏仁核的中央核到杏仁核的核心，这是情绪驱动的巴甫洛夫神经元的基础。 应答拟议的病例对照研究将描述巴甫洛夫和目标导向的异常 49名BPD症状的年轻人与49名具有社交障碍的匹配个体相比， 焦虑症和49名健康对照。在成年早期研究这些过程至关重要，因为 BPD症状在此期间迅速变化，这可能反映了神经发育成熟， 情绪和决策相关的回路在行为层面，我们将使用决策来描述参与者的特征 电池和相应的分层贝叶斯强化学习（RL）模型， 非社会背景（目标1）。我们将把决策信号联系起来，特别是社会线索对目标导向的影响。 使用贝叶斯RL模型和基于模型的fMRI分析， (Aim 2）的情况。最后，为了表征BPD中的非适应巴甫洛夫计算中涉及的可分离电路，我们 将进行一项高分辨率的静息态功能磁共振成像研究，研究扣带回-鳃盖神经网络与 特定的边缘和纹状体区域（Aim 3）。总而言之，我们的计算精神病学方法建立在 我们的研究团队在BPD和神经发育（Hallquist），贝叶斯方法学的独特优势 （Oravecz）和决策神经科学（Hallquist，Dombrovski）。这项工作符合NIMH战略 研究目标计划：描述精神疾病的神经回路（策略1.1）， 确定预测疾病变化的生物标志物和行为指标（策略2.2）。