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

人类和动物的行为是由一系列因素决定的，包括环境影响和脑功能的生物学差异。大脑机制的个体特征差异导致心理处理的差异，最终产生行为的差异。例如，以前（可能仍然）预测环境中奖励的线索的能力，要么吸引和指挥注意力（例如通过一种被称为“符号跟踪”的特征），要么控制行为（如习惯性或强迫行为）。习惯可以是适应性的，它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，如果习惯变成强迫性的，“必须做”的重复冲动而不受个人控制，习惯就会变得不适应。这发生在许多精神健康障碍中，包括强迫症（OCD）和毒瘾，但并非所有的强迫行为都会导致精神健康障碍的诊断。强迫症，像许多心理表型特征一样，是一个连续体。我们假设，从正常/适应到在精神健康状况下观察到的不适应行为，在整个范围内，类似的机制都是强迫行为的基础。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中是保守的。从理解基本学习过程的角度来看，了解影响曾经适应的习惯变得不适应和强迫性的可能性的因素是很重要的。这个项目的目的是在人类和大鼠身上验证这些假设，使用我们的完全翻译，大鼠对人观察反应任务（ORT）来利用每个物种研究的优势。我们已经知道，在人类中，将高水平的注意力和价值归因于与奖励相关的线索（“符号跟踪”）与调查问卷中强迫行为的自我报告相关，我们之前在老鼠身上的研究表明，符号跟踪与ORT上的强迫检查行为有关。然而，对人类自我报告测量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手势跟踪、习惯形成和强迫性有关，那么我们需要从经验上测试人类的手势跟踪是否与重复行为的客观行为测量有关，比如人类版的ORT。此外，我们需要知道由ORT测量的重复行为是否具有不适应性和强迫性，以及将高激励价值归因于奖励相关线索的倾向是否会导致习惯形成和强迫性。这些实验将跨物种阐明食欲动机系统的个体差异与习惯（有时是不适应）行为发展之间的关系。除了自我报告（人类）、特定的实验室转化行为任务（人类和大鼠）和精神药理学研究（大鼠）之外，我们还使用多种行为测量方法，确定个体差异如何影响适应到不适应行为的连续体中的习惯和强迫行为，以及这些特征差异是否直接驱动习惯形成和强迫行为。这将使我们能够弥合强迫行为研究的翻译差距，强迫行为研究通常依赖于人类的自我报告和啮齿动物的行为学测量。

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.