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能力——我们感知、思考、记忆、推理、想象和感觉的能力——是如何从我们的大脑生理学中产生的。像功能性磁共振成像（fMRI）这样的非侵入性脑成像技术使我们能够观察大脑的活动，检查参与者在执行任务时大脑不同部位的血液流动是如何变化的。这对于理解哪些大脑区域参与不同的任务是很重要的，现在先进的分析方法也允许我们检查这些大脑区域的活动编码的刺激类型和任务区别。然而，功能磁共振成像的推断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（例如，没有它任务就无法完成），或者它可能只是反映了多余的激活（例如，信息的副本），而这对感知并不重要。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，或者是否任何大脑区域的活动实际上是行为所必需的。本研究采用经颅磁刺激（TMS）和功能磁共振成像（fMRI）来克服这一限制。经颅磁刺激是一种成熟的技术，它可以暂时扰乱目标大脑区域的活动。如果经颅磁刺激某一大脑区域改变了认知任务的表现，我们知道这一大脑区域必然与之有因果关系。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对局部和远端大脑区域的隐藏影响，这意味着我们无法解开影响表现的机制。我们建议投资新的尖端经颅磁刺激机制，可以与fMRI同时使用，这样我们就可以用经颅磁刺激干扰目标大脑区域的活动，同时读取整个大脑的扰动效果，同时记录任何行为变化。这将使我们能够追踪TMS刺激的局部和远距离、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。这是之前大多数脑成像研究中缺失的关键见解。该提案汇集了来自剑桥大学心理学系、精神学系和MRC认知和脑科学部门的神经成像和认知专家，在一个新的跨部门合作中，将剑桥大学转变为这一领域的卓越中心，并将英国带到了研究认知因果生物学机制的前沿。我们将使用该技术来发现支持广泛认知过程的偶然生物机制，包括我们如何集中注意力，感知视觉世界，理解语言，获得概念的意义，学习和记忆。这将极大地增强英国在认知生理学方面的研究基础，为博士生和早期职业研究人员提供出色的培训机会，并促进我们对人类健康和福祉（包括健康老龄化）的大脑功能的理解。

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.