Investigating the electrophysiological and pharmacological basis of neuronal network function in sensorimotor cortex

感觉运动皮质在控制运动和感觉方面起着重要的功能作用。现在可以使用脑磁图(MEG)技术来研究感觉运动皮质的电生理学，这种技术测量了头部外部由大脑中的电活动产生的微小磁场。它与参与者没有接触，是一种理想的非侵入性方法，可以监测人类的大脑活动。在我们的实验室中，我们对大脑节律的特性特别感兴趣，例如，在休息和不同任务期间，感觉运动皮质中都存在β频率(15-30赫兹)和单位(8-14赫兹)频率的节律。这是一个重要的研究领域，因为这些大脑节律的异常与许多运动障碍(如帕金森氏症)和躯体感觉障碍(如慢性疼痛)有关。作用于人脑中GABA受体的药物已被发现可以改变感觉运动的大脑节律。我们特别感兴趣的是一种名为唑吡坦的药物的效果，因为最近从我们实验室的一名中风患者那里获得的脑磁图记录表明，它可能通过减少病理性大脑节律的力量来改善运动功能障碍。我们将通过使用脑磁图方法记录正常受试者服用唑吡坦前后的大脑活动来进一步研究这一点。除了测量静息的大脑活动外，我们还将测量手指的短暂感觉刺激引起的活动，以及在执行自我和外部节奏的手指运动时产生的活动。这将使我们能够确定唑吡坦改变静息和功能性感觉运动节律的方式。经颅磁刺激(TMS)是一种利用磁场在人脑中产生电流的非侵入性技术。TMS的一种特殊形式，称为爆发性刺激(TBS)，可在时间上降低人类运动皮质的兴奋性，并可产生一过性运动功能障碍。TBS产生这些显著效应的方式尚未完全了解，然而，在动物身上的类似研究表明，TBS可能会扰乱内在的感觉-运动节奏。因此，我们的目标是确定TBS是否以与动物模型中发现的相似的方式影响正常人类参与者的静息和脑功能节律。为了检验这一点，我们将使用脑磁图记录来测量短暂的TBS前后的静息和功能性感觉运动节律的轮廓。这项研究的结果将有助于我们理解TBS功能效应背后的神经机制，并可能导致建立正常人类病理性脑节律的非侵入性模型。我们实验室最近使用动物模型进行的工作也表明，在唑吡坦存在的情况下，大脑电刺激对感觉运动节律的干扰效应可以被阻断。我们想要测试在正常的人脑中是否也是如此。为了检验这一点，我们将使用脑磁图来获得静息和功能性感觉运动节律的基线测量。然后，我们将给参与者服用小剂量的唑吡坦。一旦药物开始起作用，我们将进行一段短暂的TBS，然后我们将使用脑磁图记录来确定静息和功能性感觉运动节律的轮廓。然后，我们将把这些特征与TBS之后记录的大脑活动进行比较，在这些试验中，参与者没有服用药物，以确定唑吡坦是否可以改变大脑刺激的效果。这项研究的潜在应用是广泛的，因为结果将提供关于大脑刺激和药物对感觉运动皮质发挥作用的方式的重要信息。

The sensorimotor cortex plays a significant functional role in the control of movement and sensation. It is now possible to study the electrophysiology of the sensorimotor cortex using the technique of magnetoencephalography (MEG), which measures tiny magnetic fields outside the head that are produced by electrical activity in the brain. There is no contact with the participant making it an ideal non-invasive method to monitor human brain activity. In our laboratory we are particularly interested in properties of the brain rhythms, such as those in the beta (15-30Hz) and mu (8-14Hz) frequencies, which are present in the sensorimotor cortex both at rest and during different tasks. This is an important area of research as abnormalities in these brain rhythms have been implicated in a number of movement disorders such as Parkinson's disease and somatosensory disorders such as chronic pain. Drugs which act upon GABA receptors in the human brain have been found to modify sensorimotor brain rhythms. We are particularly interested in the effects of one such drug called zolpidem as recent MEG recordings taken from a stroke patient in our laboratory have indicated that it may act to improve motor dysfunction by reducing the power of pathological brain rhythms. We will examine this further by using the MEG method to record the brain activity of normal human subjects before and after the ingestion of zolpidem. In addition to measuring resting brain activity we will also measure the activity elicited by a brief sensory stimulation of the finger and the activity generated during the performance of self and externally paced finger movements. This will allow us to determine the way in which zolpidem modifies the profile of resting and functional sensorimotor rhythms. Transcranial magnetic stimulation (TMS) is a non-invasive technique which uses magnetic fields to generate electrical currents in the human brain. A specific form of TMS, termed theta burst stimulation (TBS) temporally reduces the excitability of the human motor cortex and can produce a transient impairment of motor function. The way in which TBS produces these remarkable effects is not yet fully understood, however, similar work in animals suggests that TBS may disrupt the intrinsic sensorimotor rhythms. We, therefore, aim to establish whether TBS affects the resting and functional brain rhythms of normal human participants in similar manner to those found in the animal models. To examine this we will use MEG recordings to measure the profile of the resting and functional sensorimotor rhythms before and after a brief period of TBS. The results of this study will aid our understanding of the neuronal mechanisms behind the functional effects of TBS and may lead to the development of a non-invasive model of pathological brain rhythms in normal humans. Recent work conducted in our laboratory using animal models has also shown that the disruptive effects of electrical brain stimulation on sensorimotor rhythms can be blocked in the presence of zolpidem. We would like to test whether this is also the case in the normal human brain. To examine this we will use MEG to obtain a baseline measure of the resting and functional sensorimotor rhythms. We will then give our participants a small dose of zolpidem. Once the drug begins to act we will apply a brief period of TBS and then we will use MEG recordings to determine the profile of the resting and functional sensorimotor rhythms. We will then compare these profiles to the brain activity recorded following TBS in trials in which the participants did not take the drug to establish whether zolpidem can modified the effects of the brain stimulation. The potential applications of this study are widespread as the results will provide important information both about the way in which the brain stimulation and the drug exert their effects on the sensorimotor cortex.