The Biology of Human Thalamo-Cortical Pain Related Activity

描述(申请人提供)：二十年的功能成像研究表明，初级躯体感觉皮质(S1)、副神经皮质结构(PS)和内侧额叶皮质结构(MF)与疼痛相关，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，皮质模块之间和内部动态相互作用的方向性和时间动力学是不确定的，丘脑模块在这个网络中的作用也鲜为人知。拟议的皮质研究将在约翰·霍普金斯癫痫监测股进行，为期一周，在癫痫外科治疗期间植入和移除颅内电极。在植入脑深部刺激(DBS)电极治疗特发性震颤之前，将在清醒微电极标测过程中对丘脑神经元、局部场电位(LFP)和脑电进行研究。我们还建议使用注意力和分心作为行为探测器来研究“疼痛网络”的心理物理学和神经科学。标准临床记录过程中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)。我们最近的研究表明，皮层模块之间以及皮质和丘脑模块之间的动态功能连接发生了变化，这是由于人们对痛苦的皮肤激光刺激的关注与分散。因此，这一提议有可能描述基于任务特定的、皮质和丘脑模块内部和之间的动态功能交互作用的人类动态“疼痛网络”。在人类身上的这些结果可能对设计和优化基于解剖学的疼痛疗法特别有用，例如通过经皮磁场或植入电极刺激大脑。

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.