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

人类和动物的行为由一系列因素决定，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征差异会导致心理处理的差异，最终导致行为上的差异。例如，以前(现在仍然可能)预测环境中奖赏的线索能够吸引和吸引注意力(例如，通过一种被称为“手势跟踪”的特征)，或者控制行为(习惯性或强迫性行为就是这种情况)。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经常适当的行为。然而，如果习惯变成了强迫性的、不受个人控制的“必须做”的重复冲动，那么它们可能会变得不适应。这发生在许多精神健康障碍中，包括强迫症(OCD)和药物成瘾，但并不是所有的强迫行为都会导致精神健康障碍的诊断。强迫性，就像许多心理表型特征一样，是一个连续体。我们假设，从正常/适应到在心理健康状况下观察到的不适应行为，类似的机制是整个范围内强迫症的基础。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之间是保守的。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不适应和强迫的可能性的因素是重要的。这个项目旨在通过在人类和大鼠身上经验地测试这些假说，使用我们的完全翻译的、大鼠到人类的观察反应任务(ORT)来开发每个物种中研究的优势。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(“手势跟踪”)与问卷上对强迫行为的自我报告相关，我们之前在大鼠身上的研究表明，手势跟踪与ORT上的强迫性检查行为有关。然而，人类对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、习惯形成和强迫症有关，那么我们需要实证地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，比如在人类版本的ORT中。此外，我们需要知道ORT衡量的重复行为是否是不适应和强迫的，以及将高激励价值归因于与奖励相关的线索的倾向是否会导致习惯形成和强迫。这些实验将在不同物种之间阐明欲望动机系统中的个体差异与习惯性(有时是不适应的)行为发展之间的关系。除了自我报告(人类)、特定的基于实验室的翻译行为任务(人和大鼠)和精神药理学研究(大鼠)之外，我们还可以使用多种行为测量方法，确定个体差异如何影响适应不良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中的翻译鸿沟，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.