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Investigating the neural basis for checking, selective attention and working memory in obsessive compulsive disorder, through MEG and TMS

通过 MEG 和 TMS 研究强迫症中检查、选择性注意和工作记忆的神经基础

基本信息

批准号：
MR/J001953/1
负责人：
Klaus Kessler
金额：
$ 35.5万
依托单位：
Aston University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FJ001953%2F1
关键词：
Investigating neural basis checking selective

项目摘要

We all seem to know someone who tends to check repeatedly whether the door is locked, the oven is off, the alarm is set, etc. Thorough checking may even be regarded as part of being conscientious and we accept the fact that some people 'slightly overdo it', which, however, in the extreme can take on the form of compulsive checking, clinically diagnosed as part of Obsessive Compulsive Disorder (OCD). Despite consistent reporting in the literature of the maladaptive nature of checking and the high rate of subclinical compulsive checking tendencies in the typical population (~15%), the involved cognitive and brain systems have not been thoroughly investigated so far. Our recent research led us to believe that individuals with compulsive checking tendencies are less able to suppress external distractions that are perceived as threatening and are less efficient at controlling internal thoughts that are distracting and evoke further fear, thus, promoting a vicious circle of anxiety and deficient control. Such a circle of perceived threat and control deficits affects the contents of the individual's short-term memory. We further suggest that deficits in the control and suppression of distractions might underlie in a similar neuropathological form other clinical syndromes, while the strongly debilitating influences and the observed knock-on effects of deficient control on memory functions in OCD emphasise this syndrome as an optimal starting point for research. Adopting a symptom-specific approach focused on compulsive checking will further help clarifying the inconsistent results with OCD patients so far that have been related to the heterogeneity in OCD phenotypes. By means of our well-developed experimental paradigms the primary goal of this project will therefore be to characterise the neural signatures of deficient suppression and control in attention and short-term memory tasks by comparing clinical OCD checkers to subclinical high checkers and to non-checkers. A substantial body of research by others and by our team suggests that brain waves (i.e. "rhythms" or "oscillations") are key to understanding how communication within large-scale brain networks is established. To this end, we will employ cutting-edge neuroimaging in form of Magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS) with Electroencephalography (EEG) co-recordings. Besides characterising in detail the oscillatory biomarkers of deficient suppression and control beyond our particular paradigms and patient group (OCD) we will use the emerging new application of frequency-tuned TMS to mimic brain oscillations with the following two aims. First, by controlled entrainment of brain oscillations, frequency-tuned TMS-EEG will allow us to test which oscillatory signatures play a causal role in behaviour, providing biomarkers of control deficits and increased risk of OCD as well as new candidate endophenotypes. Second, if TMS-induced oscillations directly improve performance in high checkers then a proof of concept will be achieved for future therapeutic applications.

我们似乎都知道有人倾向于反复检查门是否锁上，烤箱是否关闭，闹钟是否设置等彻底检查甚至可能被视为尽责的一部分，我们接受这样一个事实，即有些人“稍微过度”，然而，在极端情况下，可以采取强迫性检查的形式，临床诊断为强迫症（OCD）的一部分。尽管文献中一致报道了检查的适应不良性质和典型人群中亚临床强迫检查倾向的高发生率（约15%），但迄今为止尚未对所涉及的认知和大脑系统进行彻底研究。我们最近的研究使我们相信，有强迫性检查倾向的人抑制被认为具有威胁性的外部干扰的能力较低，并且在控制分散注意力并引起进一步恐惧的内部思想方面效率较低，因此，促进了焦虑和控制不足的恶性循环。这种感知威胁和控制缺陷的循环会影响个人短期记忆的内容。我们进一步表明，在控制和抑制分心的赤字可能是在一个类似的神经病理学形式的其他临床综合征的基础，而强烈衰弱的影响和观察到的连锁效应控制不足的记忆功能强迫症强调这种综合征作为一个最佳的研究起点。采用针对强迫性检查的神经元特异性方法，将进一步有助于澄清迄今为止与强迫症表型异质性相关的与强迫症患者不一致的结果。通过我们完善的实验范例，本项目的主要目标将是通过比较临床强迫症检查者与亚临床高检查者和非检查者，来验证注意力和短期记忆任务中抑制和控制缺陷的神经特征。其他人和我们团队的大量研究表明，脑电波（即“节奏”或“振荡”）是理解大规模大脑网络内如何建立通信的关键。为此，我们将采用脑磁图（MEG）和经颅磁刺激（TMS）与脑电图（EEG）共同记录的尖端神经成像。除了详细描述我们特定范例和患者组（OCD）之外的抑制和控制不足的振荡生物标志物之外，我们将使用频率调谐TMS的新兴新应用来模拟脑振荡，具有以下两个目标。首先，通过控制脑振荡的夹带，频率调谐的TMS-EEG将使我们能够测试哪些振荡特征在行为中起因果作用，提供控制缺陷和增加强迫症风险的生物标志物以及新的候选内在表型。其次，如果TMS诱导的振荡直接改善高跳棋的性能，那么将实现未来治疗应用的概念验证。