Human mechanosensation: From 1st-order neurone to somatosensory cortex

关于外部和内部世界的信息通过一个广泛的感觉神经系统传递到大脑。皮肤包含多种类型的感官受体/神经，它们向大脑通报发生在身体表面的事件。关于人类触觉加工背后的神经科学，有许多非常基本的问题仍然没有答案。我们的目标是利用超高场功能磁共振成像(UHF-fMRI)和脑磁图(MEG)等神经成像技术的最新进展，结合神经记录(显微神经成像)和刺激技术(神经内微刺激(INMS))，为人类操作触觉的大脑机制提供新的见解。使用功能磁共振成像，我们可以测量随着神经活动增加而发生的局部血流量的变化。这些变化导致大脑活跃部分的MR图像信号强度增加。这意味着，例如，当受试者感觉到物体触摸他们的手指时，我们可以测量大脑的哪些部分更活跃。在研究触觉的机制时，我们面临的一个问题是，发生的信号强度变化相对较小。我们已经克服了这个问题，使用了一种非常高场磁共振扫描仪，它允许我们非侵入性地测量对触摸的强大神经反应，空间分辨率比以前可能的高得多，我们现在可以获得单个参与者大脑的强大激活图。这使得UHF-fMRI成为一种非常有吸引力的临床应用工具。脑磁图是另一种非侵入性神经成像技术，它提供了一种探索体感加工的时间方面的方法。显微神经学技术可以史无前例地进入信息传输到大脑的最早阶段，它涉及将一根非常细的针穿过皮肤插入潜在的神经，这样你就可以听到和看到(神经记录)向大脑发送信息。更进一步的是，使用INMS技术，用非常小的电流电刺激单个神经纤维，这样一个人就可以在没有实际皮肤刺激的情况下感觉到触摸。将INMS与神经成像UHF-fMRI和MEG相结合，将使我们能够揭示单个感觉神经在大脑中的表现。在这个项目中，我们将使用这些尖端技术，并采取多学科的方法，结合MRI、神经科学、神经生理学和神经学的专业知识，以提高我们对感觉通路的理解。具体地说，我们将使用UHF-fMRI来仔细绘制体感皮质的详细解剖和功能图，并将使用脑磁图来表征大脑对皮肤触觉刺激的反应的时间动力学。我们将开发一种新的MR和MEG兼容的设备，用于在UHF-fMRI扫描仪和MEG扫描仪上进行INMS。在INMS期间使用功能磁共振成像将使我们能够映射大脑对单一感觉传入的反应(与刺激各种类型的多个感觉感受器的振动相反)。我们还将应用这些方法来测量患有神经病理的患者组的躯体感觉通路的变化。具体地说，我们将研究局灶性手部肌张力障碍和腕管综合征，并评估治疗干预如何改变躯体感觉处理。总体而言，这项研究将极大地促进我们对人类躯体感觉和感知的理解，并将与与神经创伤损伤、神经学、神经发育、神经退行性变、神经病理学、药物干预和疼痛相关的一系列临床疾病相关。

Information about the external and internal world is conveyed to the brain by an extensive system of sensory nerves. The skin contains multiple types of sensory receptors/nerves which inform the brain about events occurring on the body surface. There are many very basic questions about the neuroscience underlying human tactile processing that remain unanswered. We aim to use recent advances in the neuroimaging techniques of ultra-high field functional magnetic resonance imaging (UHF-fMRI) and magnetoencephalography (MEG), coupled in conjunction with nerve recording (microneurography) and stimulating techniques (intraneural microstimulation (INMS)), to provide novel insight into the brain mechanisms involved in operating the sense of touch in humans. Using fMRI, we can measure changes in the local blood flow that occur with increased neural activity. These changes cause an increase in the signal intensity in the MR image in the part of brain that is active. This means that we can measure, for example, which parts of the brain are more active while subjects feel an object touch their finger. One of the problems we face when studying the mechanism underlying our sense of touch is that the changes in signal intensity that occur are relatively small. We have overcome this problem by using a very high field magnetic resonance scanner which allows us to measure robust neural responses to touch, non-invasively, with much higher spatial resolution than has previously been possible, and we can now obtain robust activation maps of individual participants brains. This makes UHF- fMRI a very attractive tool for clinical applications. MEG is another non-invasive neuroimaging technique that offers a way to probe the temporal aspects of somatosensory processing. The technique of microneurography allows unprecedented access to the earliest stages of information transfer to the brain, it involves inserting a very fine needle through the skin into an underlying nerve, so you can hear and see (the nerve recording) sending messages to the brain. A step further is to electrically stimulate a single nerve fibre with a very small current, using the technique of INMS, so that a person can feel touch when there is no actual skin stimulus. Combining INMS with neuroimaging UHF-fMRI and MEG, will allow us to reveal the representation of single sensory nerves in the brain.In this project, we will use these cutting-edge techniques and take a multidisciplinary approach, combining expertise in MRI, neuroscience, neurophysiology and neurology, to improve our understanding of sensory pathways. Specifically, we will use UHF-fMRI to map carefully the detailed anatomy and function of the somatosensory cortex, and will use MEG to characterize the temporal dynamics of brain responses to tactile stimulation of the skin. We will develop a new MR- and MEG-compatible device to perform INMS in the UHF-fMRIscanner and MEG scanner. The use of fMRI during INMS will allow us to map the brain's response to single sensory afferents (in contrast to vibration, which stimulates multiple sensory receptors of various types). We will also apply these methods to measure alterations in the somatosensory pathways in patient groups with neuropathologies. Specifically we will study Focal Hand Dystonia and Carpal Tunnel Syndrome, and assess how somatosensory processing is altered by therapeutic interventions. Overall, this research will considerably advance our understanding of human somatosensation and perception and will be relevant to a wide range of clinical disorders related to neurotraumatic injury, neurology, neurodevelopment, neurodegeneration, neuropathology, pharmaceutical interventions and pain.