Role of oscillatory dynamics in prefrontal control of cortical excitability durin

描述(申请人提供)：选择性地促进或抑制信息处理的能力对于更高层次的认知任务，如工作记忆是必不可少的。以前的工作已经确定前额叶皮质(PFC)是调节这一过程的区域。我们认为，在认知过程中，PFC利用振荡机制与低阶大脑皮层区域的网络活动进行交流和控制。这项拟议的工作试图研究PFC在工作记忆过程中调节感觉区域皮质兴奋性的振荡相互作用。对PFC参与这一过程的神经机制的了解具有理论和翻译意义，并可能导致开发有针对性的康复方法来治疗和监测脑损伤患者的康复进程。这项工作将以两个具体目标进行。在目标1中，我们将利用皮层电图(ECoG)来研究振荡耦合在感觉皮层兴奋性的前额叶控制中的作用。直接从接受难治性癫痫治疗的患者的大脑皮层获得的ECOG信号将是 在受试者执行多通道工作记忆任务时被记录下来，该任务需要选择性地注意不同感觉通道中的刺激。与非侵入性记录方法相比，ECoG方法具有许多优点，包括极高的空间和时间分辨率以及增强的信噪比。我们假设PFC使用振荡机制来控制和增强PFC和低阶大脑皮层之间的网络活动，以促进相关信息的处理，并将通过计算不同任务期间电极之间的相位一致性、谱Granger因果关系和交叉频率耦合等连通性指标来验证这一假设。此外，我们预测，PFC和感觉区域之间的更高水平的连接将与更好的任务表现相关，以及感觉区域上阿尔法(~10赫兹)振荡的调制增加，α(~10赫兹)振荡是皮层兴奋性的假定指标。在目标2中，我们将在前一个目标的基础上，利用中风患者和年龄匹配的对照组的脑电(EEG)记录，评估前额叶皮质在调节感觉加工中的因果作用和重组。当受试者执行与目标1类似的任务时，脑电将被记录下来。我们假设，当患者注意到受损的PFC对侧的刺激时，任务绩效下降的同时，患者在受损的PFC同侧感觉区域的阿尔法调制量将减少。我们进一步预测，与年龄匹配的对照组相比，完整的额叶皮质将补偿受损的皮质，这种补偿将通过患者完整的额叶半球和后部感觉区域之间更高水平的连接来体现。

DESCRIPTION (provided by applicant): The ability to selectively facilitate or suppress the processing of information is essential for higher-order cognitive tasks such as working memory. Previous work has identified the prefrontal cortex (PFC) as the region modulating this processing. We propose that the PFC utilizes oscillatory mechanisms to communicate with and control network activity in lower-order cortical areas during cognition. The proposed work seeks to investigate the oscillatory interactions which allow the PFC to modulate cortical excitability i sensory areas during working memory. Knowledge of the neural mechanisms of PFC engagement in this process has both theoretical as well as translational implications and may lead to development of targeted rehabilitation methods to treat and monitor the progress of recovery for patients suffering from brain injury. This work will be carried out with two specific aims. In Aim 1, we will utilize electrocorticography (ECoG) to investigate the role of oscillatory coupling in the prefrontal control of sensory cortex excitability. ECoG signals, which are obtained directly from the cortex of patients undergoing treatment for refractory epilepsy, will be recorded while subjects perform a multimodal working memory task requiring selective attention to stimuli in different sensory modalities. The ECoG method has many benefits compared with noninvasive recording methods including exceptionally high spatial and temporal resolutions as well as an enhanced signal to noise ratio. We hypothesize that the PFC uses oscillatory mechanisms to control and enhance network activity between PFC and lower-order cortical areas in order to facilitate the processing of relevant information, and this hypothesis will be tested by computing connectivity measures such as phase coherence, spectral Granger causality, and cross frequency coupling between electrodes during different task periods. Furthermore, we predict that greater levels of connectivity between PFC and sensory areas will be associated with better task performance, as well as with an increased modulation of alpha (~10Hz) oscillations, a putative index of cortical excitability, over sensory areas. In Aim 2, we wll build on our findings from the previous aim and assess the causal role and reorganization of prefrontal cortex in modulating sensory processing utilizing electroencephalographic (EEG) recordings from patients with focal frontal lobe damage due to stroke as well as age-matched controls. EEG will be recorded while subjects perform a task similar to that used in Aim 1. We hypothesize that, concurrent with decreased task performance when attending to stimuli contralateral to damaged PFC, patients will show a decreased amount of alpha modulation over sensory areas ipsilateral to damaged PFC. We further predict that intact frontal cortex will compensate for lesioned cortex and that this compensation will be manifested through a greater level of connectivity between the intact frontal hemisphere and posterior sensory areas in patients compared with age-matched controls.