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

研究感觉运动皮层神经元网络功能的电生理学和药理学基础

• 批准号: BB/H003894/1
• 负责人: Stephen Hall
• 金额: $ 41.11万
• 依托单位: Aston University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH003894%2F1
• 关键词: Investigating; electrophysiological; pharmacological; basis; neuronal

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.

感觉运动皮层在运动和感觉的控制中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层的电生理学，该技术测量由大脑中的电活动产生的头部外部的微小磁场。与参与者没有接触，使其成为监测人类大脑活动的理想非侵入性方法。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β（15- 30 Hz）和μ（8- 14 Hz）频率，这些频率在休息和不同任务期间都存在于感觉运动皮层中。这是一个重要的研究领域，因为这些脑节律的异常与许多运动障碍（例如帕金森病）和躯体感觉障碍（例如慢性疼痛）有关。已经发现作用于人脑中GABA受体的药物可以改变感觉运动脑节律。我们特别感兴趣的是一种名为唑吡坦的药物的作用，因为最近在我们实验室中从中风患者中采集的MEG记录表明，它可能通过降低病理性脑节律的功率来改善运动功能障碍。我们将通过使用MEG方法记录正常人受试者摄入唑吡坦前后的脑活动来进一步研究这一点。除了测量静息时的大脑活动，我们还将测量由手指的短暂感觉刺激引起的活动，以及在自我和外部节奏手指运动的表现期间产生的活动。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）是一种非侵入性技术，它使用磁场在人脑中产生电流。TMS的一种特殊形式，称为θ爆发刺激（TBS），暂时降低了人类运动皮层的兴奋性，并可产生运动功能的短暂损伤。TBS产生这些显着效果的方式尚未完全了解，然而，在动物中的类似工作表明TBS可能会破坏内在的感觉运动节律。因此，我们的目标是确定TBS是否以与动物模型中发现的类似方式影响正常人类参与者的静息和功能性脑节律。为了检验这一点，我们将使用MEG记录来测量短暂TBS之前和之后的静息和功能性感觉运动节律的概况。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，并可能导致正常人病理性脑节律的非侵入性模型的发展。最近在我们实验室使用动物模型进行的工作也表明，脑电刺激对感觉运动节律的破坏性影响可以在唑吡坦存在下被阻断。我们想测试一下正常人脑是否也是如此。为了检验这一点，我们将使用MEG来获得静息和功能感觉运动节律的基线测量。然后，我们将给受试者服用小剂量的唑吡坦。一旦药物开始起作用，我们将应用短暂的TBS，然后我们将使用MEG记录来确定静息和功能性感觉运动节律的概况。然后，我们将这些曲线与试验中TBS后记录的大脑活动进行比较，在这些试验中，参与者没有服用唑吡坦，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，因为结果将提供有关大脑刺激和药物对感觉运动皮层产生影响的方式的重要信息。

项目成果

A multimodal perspective on the composition of cortical oscillations.

• DOI: 10.3389/fnhum.2013.00132
• 发表时间: 2013
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9
• 作者: Ronnqvist KC;McAllister CJ;Woodhall GL;Stanford IM;Hall SD
• 通讯作者: Hall SD

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco-magnetoencephalography.

使用药物脑磁图确定人类皮质中 GABA 能调节的神经网络药效学。

• DOI: 10.1002/hbm.20889
• 发表时间: 2010-04
• 期刊: HUMAN BRAIN MAPPING
• 影响因子: 4.8
• 作者: Hall, Stephen D.;Barnes, Gareth R.;Furlong, Paul L.;Seri, Stefano;Hillebrand, Arjan
• 通讯作者: Hillebrand, Arjan

Bradykinesia Is Driven by Cumulative Beta Power During Continuous Movement and Alleviated by Gabaergic Modulation in Parkinson's Disease.

帕金森病患者的运动迟缓是由连续运动过程中累积的 Beta 功率驱动的，并通过 Gabaergic 调节来缓解。

• DOI: 10.3389/fneur.2019.01298
• 发表时间: 2019
• 期刊: Frontiers in neurology
• 影响因子: 3.4
• 作者: Prokic EJ

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans.

• DOI: 10.1523/jneurosci.5624-12.2013
• 发表时间: 2013-05-01
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: McAllister CJ;Rönnqvist KC;Stanford IM;Woodhall GL;Furlong PL;Hall SD
• 通讯作者: Hall SD

Gamma oscillatory amplitude encodes stimulus intensity in primary somatosensory cortex.

• DOI: 10.3389/fnhum.2013.00362
• 发表时间: 2013
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9
• 作者: Rossiter HE;Worthen SF;Witton C;Hall SD;Furlong PL
• 通讯作者: Furlong PL