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Understanding Phenotypic Trait Differences and their Impact on Habitual Behaviour: A Fully Translational Approach

了解表型性状差异及其对习惯行为的影响：一种完全转化的方法

基本信息

批准号：
BB/W001195/1
负责人：
Amy Milton
金额：
$ 57.57万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW001195%2F1
关键词：
Understanding Phenotypic Trait Differences their

项目摘要

Human and animal behaviour is determined by a range of factors, including environmental influences and biological differences in brain function. Individual trait differences in brain mechanisms lead to differences in psychological processing, ultimately producing differences in behaviour. Examples include the ability of cues that have previously (and may still) predict rewards in the environment to either attract and command attention (e.g. through a trait known as 'sign-tracking') or to control behaviour (as is the case with habitual or compulsive behaviour).Habits can be adaptive, allowing behaviour to proceed automatically with minimal cognitive effort and producing often-appropriate behaviour in the absence of conscious awareness. However, habits can become maladaptive if they become compulsive, 'must do' repetitive urges out of the individual's control. This occurs in many mental health disorders, including Obsessive-Compulsive Disorder (OCD) and drug addiction, but not all compulsive behaviours lead to a mental health disorder diagnosis. Compulsivity, like many psychological phenotypic traits, is on a continuum. We hypothesise that similar mechanisms underlie compulsivity across the spectrum, ranging from normal/adaptive to the maladaptive behaviour observed in mental health conditions. Furthermore, we hypothesise that these mechanisms, and the phenotypic traits that associate with habit formation and compulsivity, are conserved across species. Understanding the factors that influence the likelihood of once-adaptive habits becoming maladaptive and compulsive is important from the perspective of understanding fundamental learning processes.This project aims to test these hypotheses empirically in humans and rats, using our fully translational, rat-to-human Observing Response Task (ORT) to exploit the strengths of studies in each species. It is already known that in humans, attributing high levels of attention and value to reward-related cues ('sign-tracking') correlates with self-report of compulsive behaviours on questionnaires, and our previous work in rats has shown that sign-tracking is associated with compulsive-like checking behaviour on the ORT. However, the reliance on self-report measures in humans limits comparability to the rodent behavioural data. If we are to test whether the same mechanisms relate sign-tracking, habit formation and compulsivity in humans and animals, then we need to test empirically whether sign-tracking in humans is associated with objective behavioural measurements of repetitive behaviour, such as in the human version of the ORT. Furthermore, we need to know whether repetitive behaviours measured by the ORT are maladaptive and compulsive, and if the propensity to attribute high incentive value to reward-related cues leads to habit formation and compulsivity. These experiments will clarify, across species, the relationship between individual differences in the appetitive motivational system and the development of habitual (and sometimes maladaptive) behaviour. Using multiple behavioural measures, in addition to self-report (humans), specific lab-based translational behavioural tasks (humans and rats) and psychopharmacological studies (rats), we can determine how individual differences influence habitual and compulsive behaviour along the continuum of adaptive to maladaptive behaviour, and whether these trait differences directly drive habit formation and compulsivity. This will allow us to bridge the translational gap in studies of compulsive behaviour, which often rely upon self-report in humans and ethological measures in rodents.

人类和动物的行为是由一系列因素决定的，包括环境影响和大脑功能的生物差异。大脑机制中的个体特质差异导致心理处理的差异，最终产生行为的差异。例子包括线索的能力，（并且仍然可能）预测环境中的奖励，以吸引和命令注意力（例如，通过一种被称为“信号跟踪”的特征）或控制行为（如习惯性或强迫性行为）。习惯可以是适应性的，允许行为以最小的认知努力自动进行，并在没有意识的情况下产生通常适当的行为。然而，如果习惯变得强迫性，“必须做”的重复冲动超出了个人的控制，那么习惯就会变得适应不良。这发生在许多精神健康障碍中，包括强迫症（OCD）和药物成瘾，但并非所有的强迫行为都会导致精神健康障碍的诊断。像许多心理表型特征一样，nasivity是一个连续体。我们假设，类似的机制在整个范围内的强迫性的基础，从正常/适应性的适应不良行为中观察到的心理健康状况。此外，我们假设这些机制，以及与习惯形成和强迫性相关的表型特征，在物种间是保守的。从理解基本学习过程的角度来看，理解影响曾经适应的习惯变得适应不良和强迫的可能性的因素是很重要的。本项目旨在使用我们完全翻译的大鼠到人类的观察反应任务（ORT），在人类和大鼠中实证检验这些假设，以利用每个物种的研究优势。我们已经知道，在人类中，将高水平的注意力和价值归因于奖励相关的线索（“符号追踪”）与问卷上强迫行为的自我报告相关，我们以前在大鼠中的工作表明，符号追踪与ORT上的强迫性检查行为相关。然而，对人类自我报告措施的依赖限制了与啮齿动物行为数据的可比性。如果我们要测试相同的机制是否与人类和动物的符号跟踪，习惯形成和强迫性有关，那么我们需要经验性地测试人类的符号跟踪是否与重复行为的客观行为测量有关，例如在人类版本的ORT中。此外，我们需要知道ORT测量的重复行为是否是适应不良和强迫性的，以及是否倾向于将高激励价值归因于奖励相关线索导致习惯形成和强迫性。这些实验将澄清，跨物种，个体差异之间的关系，在食欲动机系统和习惯性（有时是适应不良）行为的发展。除了自我报告（人类），特定的基于实验室的翻译行为任务（人类和大鼠）和精神药理学研究（大鼠）之外，使用多种行为测量，我们可以确定个体差异如何影响习惯和强迫行为沿着适应不良行为的连续体，以及这些特质差异是否直接驱动习惯形成和强迫性。这将使我们能够弥合强迫行为研究中的翻译差距，这些研究通常依赖于人类的自我报告和啮齿动物的行为学措施。