fMRI-compatible TMS stimulation equipment for concurrent brain stimulation and measurement

我们这个时代最大的谜团之一是人类的认知--我们感知、思考、记忆、推理、想象和感受的能力--是如何从我们的大脑生理学中产生的。功能性磁共振成像（fMRI）等非侵入性脑成像技术使我们能够观察大脑的活动，检查参与者执行任务时大脑不同部位的血流如何变化。这对于理解哪些大脑区域参与不同的任务非常重要，先进的分析方法现在也允许我们检查这些大脑区域中的活动编码的刺激类型和任务区别。然而，功能性磁共振成像的推论在一个重要方面是有限的：我们无法判断我们观察到的活动是否与产生思想和行为有因果关系。例如，如果一个特定的大脑区域在刺激出现时是活跃的，这个区域可能是感知刺激所必需的（即没有它就不能完成任务），或者它可能只是反映了对感知不重要的多余激活（例如信息的副本）。使用传统技术，我们无法检查一个大脑区域的活动是否与另一个大脑区域的活动有因果关系，或者任何大脑区域的活动是否实际上是行为所必需的。拟议的研究使用经颅磁刺激（TMS）与功能磁共振成像同时克服这一限制。经颅磁刺激（TMS）是一种已建立的技术，可以暂时干扰目标大脑区域的活动。如果对某个大脑区域进行TMS会改变认知任务的表现，我们就知道该大脑区域一定有因果关系。通常，推理到此为止。然而，这又是有限的，因为我们无法观察到TMS对本地和远程大脑区域的隐藏影响，这意味着我们无法解开影响性能的机制。我们建议投资新的尖端TMS机器，可以与功能磁共振成像同时使用，这样我们就可以用TMS干扰目标大脑区域的活动，同时读取整个大脑的干扰效果，同时记录行为的任何变化。这将使我们能够追踪TMS刺激的局部和远程，即时和持续的生理效应，从而将目标大脑区域的神经活动与整个大脑的信息处理和行为联系起来。通过这种方式，我们将最终开始理解不同大脑区域在产生思想和行动中的因果作用。这是一个关键的洞察力，一直在失踪的大多数以前的大脑成像研究。这一建议汇集了神经成像和认知专家从整个剑桥大学的心理学系，精神病学和MRC认知和脑科学单位，在一个新的十字架上-部门合作，将大学转变为这一领域的卓越中心，并将英国带到因果生物学研究的最前沿。认知的基础机制我们将利用这项技术来发现支撑广泛认知过程的偶然生物机制，包括我们如何注意，感知视觉世界，理解语音，推导概念的含义，学习和记忆。有助于全球努力了解人类大脑，这将显着增强英国在认知生理学的研究基础，为博士生和早期职业研究人员提供出色的培训机会，并推进我们对大脑功能的理解，对人类健康和福祉的影响，包括健康老龄化。

One of the great mysteries of our time is how human cognition - our ability to perceive, think, remember, reason, imagine and feel - arises from our brain physiology. Non-invasive brain imaging techniques like functional magnetic resonance imaging (fMRI) allow us to observe the brain in action, examining how blood flow to different parts of the brain changes when participants perform task. This has been important for understanding which brain regions are involved in different tasks, and advanced analysis methods now also allow us to examine the types of stimulus and task distinctions that activity in these brain regions encodes. However, the inference from fMRI is limited in an important way: we cannot tell whether the activity we observe is causally involved in generating thought and behaviour. For example, if a particular brain region is active when a stimulus is shown, this region may be necessary for perception of that stimulus (i.e. the task could not be done without it), or it may just reflect superfluous activation (e.g. a copy of information) that is not critical for perception. Using traditional techniques, we cannot examine whether activity in one brain region is causally linked to activity in another, or whether activity in any brain region is actually necessary for behaviour. The proposed research uses transcranial magnetic stimulation (TMS) concurrent with fMRI to overcome this limitation. TMS is an established technique which temporarily perturbs activity in a targeted brain region. If TMS to a brain region changes performance on a cognitive task, we know that the brain region must be causally involved. Typically, the inference stops there. However, this is again limited because we cannot observe the hidden effects that the TMS is having on local and distant brain regions, meaning that we cannot unpick the mechanisms by which performance was affected. We propose to invest in new cutting-edge TMS machinery that can be used simultaneously with fMRI, so that we can perturb activity in a targeted brain region with TMS and simultaneously read of the effects of the perturbation throughout the brain, while also recording any changes in behaviour. This will allow us to trace the local and distant, immediate and sustained physiological effects of the TMS stimulation, and thus to link neural activity in the targeted brain region with information processing throughout the brain, and behaviour. In this way we will finally begin to understand the causal role of different brain regions in giving rise to thought and action. This is a critical insight that has been missing from the majority of previous brain imaging studies.This proposal brings together experts in neuroimaging and cognition from across the University of Cambridge in the Departments of Psychology, Psychiatry and the MRC Cognition and Brain Sciences unit, in a new cross-departmental collaboration that will transform the University to a centre of excellence in this field and bring the UK to the forefront of research into the causal biological mechanisms underpinning cognition. We will use the technology to discover the casual biological mechanisms underpinning a wide range of cognitive processes, including how we pay attention, perceive the visual world, understand speech, derive meaning of concepts, learn, and remember. Contributing to a global endeavour to understand the human brain, this will significantly enhance the UK research base in the physiology of cognition, provide outstanding training opportunities for PhD students and early career researchers, and advance our understanding of brain function with implications for human health and well-being including healthy ageing.