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

关于外部和内部世界的信息通过广泛的感觉神经系统传递到大脑。皮肤包含多种类型的感觉受体/神经，它们将身体表面发生的事件通知大脑。关于人类触觉处理的神经科学基础，有许多非常基本的问题仍然没有答案。我们的目标是使用最新进展的超高场功能磁共振成像（UHF-fMRI）和脑磁图（MEG），结合神经记录（显微神经造影术）和刺激技术（神经内微刺激（INMS）），提供新的洞察大脑机制参与操作的触觉在人类。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变化。这些变化导致活跃大脑部分的MR图像中的信号强度增加。这意味着我们可以测量，例如，当受试者感觉到物体触摸他们的手指时，大脑的哪些部分更活跃。我们在研究触觉机制时面临的一个问题是，信号强度的变化相对较小。我们已经通过使用非常高的磁场磁共振扫描仪克服了这个问题，该扫描仪使我们能够非侵入性地测量对触摸的强大神经反应，其空间分辨率比以前高得多，我们现在可以获得个体参与者大脑的强大激活图。这使得超高频功能磁共振成像成为一个非常有吸引力的临床应用工具。MEG是另一种非侵入性神经成像技术，提供了一种方法来探测躯体感觉处理的时间方面。显微神经成像技术允许前所未有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底层神经，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，这样一个人在没有实际皮肤刺激的情况下也能感觉到触摸。将INMS与神经影像学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代表性。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，神经生理学和神经病学的专业知识，以提高我们对感觉通路的理解。具体来说，我们将使用UHF-fMRI仔细绘制躯体感觉皮层的详细解剖结构和功能，并将使用MEG来表征皮肤触觉刺激的大脑反应的时间动态。我们将开发一种新的MR和MEG兼容设备，用于在UHF-fMRI扫描仪和MEG扫描仪中执行INMS。在INMS期间使用功能磁共振成像将使我们能够绘制大脑对单一感觉传入的反应（与振动相反，振动刺激各种类型的多个感觉受体）。我们还将应用这些方法来测量神经病理学患者组的躯体感觉通路的改变。具体来说，我们将研究局灶性手肌张力障碍和腕管综合征，并评估如何通过治疗干预改变体感处理。总的来说，这项研究将大大提高我们对人类躯体感觉和感知的理解，并将与神经创伤性损伤，神经病学，神经发育，神经变性，神经病理学，药物干预和疼痛相关的广泛临床疾病相关。

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.