The Biology of Human Thalamo-Cortical Pain Related Activity

描述（由申请人提供）：二十年的功能成像研究已经证明了初级躯体感觉皮层（S1）、侧裂旁皮层结构（PS）和内侧额叶皮层结构（MF）的疼痛相关激活，这些结构通常被描述为“疼痛网络”中的模块。丘脑模块在这个网络中的参与很可能是基于丘脑-皮质组件的连接性。然而，方向性和时间动态的动态相互作用之间和内部的皮质模块是不确定的，丘脑模块在这个网络中的作用是知之甚少。 在癫痫手术治疗期间，在植入和取出颅内电极之间的一周内，在约翰霍普金斯癫痫监测中心进行拟议的皮质研究。丘脑神经元，局部场电位（LFPs）和脑电图的研究将在清醒微电极映射，植入脑深部刺激（DBS）电极治疗原发性震颤之前进行。我们还建议使用注意力和分心作为行为探针来研究“疼痛网络”的心理物理学和神经科学。标准临床记录程序期间的这些记录具有前所未有的清晰度和分辨率，并将通过最先进的神经生物学信号分析技术进行检查，以建立模块之间的动态定向功能相互作用（格兰杰因果关系- GRC）。 我们最近的研究已经证明了动态功能连接的变化，无论是皮质模块之间，皮质和丘脑模块之间的注意力与分心的功能，从一个痛苦的皮肤激光刺激。因此，这个建议有可能描述动态的“疼痛网络”在人类的基础上，任务特定的，动态的功能相互作用内和之间的皮层和丘脑模块。这些在人类身上的结果可能对设计和优化基于解剖学的疼痛治疗非常有用，例如通过经皮磁场或植入电极刺激大脑。 公共卫生相关性：二十年的成像研究已经证明了广泛的皮质结构，这被描述为一个“疼痛网络”的疼痛相关的激活，虽然在这个网络的连接的性质和动力学是不确定的。我们现在建议研究非定向和定向功能的相互作用，在注意到疼痛的皮肤激光刺激的证据，本地和分布式组件的“疼痛网络”。这些研究将检查直接从“疼痛网络”中的大脑结构记录的动态功能连接，因此可能对驱动该领域的概念产生重大影响。

DESCRIPTION (provided by applicant): Two decades of functional imaging studies have demonstrated pain-related activations of primary somatic sensory cortex (S1), parasylvian cortical structures (PS) and medial frontal cortical structures (MF), which are often described as modules in a 'pain network'. The participation of thalamic modules in this network is very likely based upon the connectivity of thalamo-cortical assemblies. However, the directionality and temporal dynamics of dynamic interactions between and within the cortical modules is uncertain, and the role of the thalamic modules in this network is poorly understood. The proposed cortical studies would be carried out in the Johns Hopkins Epilepsy Monitoring Unit over the one week period between the implantation and removal of intracranial electrodes during the surgical treatment of epilepsy. Studies of thalamic neurons, local field potentials (LFPs) and EEG would be carried out during the awake microelectrode mapping which precedes the implantation of deep brain stimulating (DBS) electrodes for the treatment of essential tremor. We also propose to use attention and distraction as behavioral probes to study the psychophysics and neuroscience of the 'pain network'. These recordings during standard clinical recording procedures have unprecedented clarity and resolution, and will be examined by state-of-the-art techniques for neurobiological signal analysis to establish the dynamic directional functional interactions between modules (Granger Causality - GRC). Our recent studies have demonstrated changes in dynamic functional connectivity both between cortical modules, and between cortical and thalamic modules as a function of attention to versus distraction from a painful cutaneous laser stimulus. Therefore, this proposal has the potential to describe dynamic 'pain networks' in humans based upon task-specific, dynamic functional interactions within and between cortical and thalamic modules. These results in humans may be uniquely useful to design and optimize anatomically-based pain therapies, such as stimulation of the brain through transcutaneous magnetic fields or implanted electrodes. PUBLIC HEALTH RELEVANCE: Two decades of imaging studies have demonstrated pain-related activations of widespread cortical structures, which are described as a 'pain network', although the nature and dynamics of connectivity in this network are uncertain. We now propose to study non-directional and directional functional interactions during attention to a painful cutaneous laser stimulus for evidence of both local and distributed components to the 'pain network'. These studies will examine dynamic functional connectivity recorded directly from brain structures in the 'pain network', and so may have a substantial effect on the concepts that drive this field.