Investigating the neural mechanisms of human cognitive function through intracranial recordings

2013财年在建立研究基础设施和实现这些目标方面取得了重大进展。 我们已经开发了我们的实验室基础设施，用于在参与者参与旨在探索记忆编码和提取的认知任务时捕获和分析颅内记录。在临床中心接受颅内电极和手术治疗的难治性癫痫患者被招募进行这些研究。在一组研究中，我们主要感兴趣的是研究从记忆编码到记忆提取是否恢复了神经元振荡功率的模式，并检查了这种恢复的精确时空动力学。使用配对联想情景记忆任务，我们直接考察了这些问题。我们首先研究了在记忆编码过程中观察到的振荡活动的变化。然后，我们实施了分析技术，聚合了多个大脑皮层位置和多个频段的振荡功率分布模式，以探索这种活动在回忆过程中是否会恢复。我们已经证明，在成功的回忆过程中，这种跨空间和跨频率的振荡功率模式的恢复程度要大得多。此外，我们还开发了分析，证明了这种振荡活动的准确时间，以及在各个频率和位置上的恢复。在第二组研究中，我们主要感兴趣的是了解注意机制如何调节成功记忆的形成。我们设计了一项行为任务，专门问这个问题，并允许我们比较那些被关注并成功记住的项目与那些没有被关注但仍然记得的项目之间的神经活动。我们感兴趣的是了解注意力本身是如何调节记忆的。基于我们对几个参与者的初步分析，我们发现了明确的证据，即注意线索显著地触发了精确空间位置的神经活动，这与成功的记忆编码相关。 我们还开发并继续我们的工作，捕捉和分析在脑深部刺激手术期间从基底节捕捉到的局部场电位和单个单位的放电活动。我们重点研究了丘脑底核的活动，以了解当参与者执行知觉决策任务时，这一结构在调节决策冲突中所起的作用。我们已经证明，决策阶段的显著特征是丘脑底核的theta振荡能力显著增加，而且在涉及更大冲突的决策中，这些振荡明显更强。此外，使用头皮脑电测量的前额叶皮质和丘脑底核之间的直接一致性在受试者调解高冲突决策时显著更高。这些数据表明，在决策过程中，theta振荡活动可能会将信息从大脑皮层传递到基底节。我们已经扩展了这项工作，以研究丘脑底核单位放电活动的作用，以及这种活动如何与观察到的振荡功率的变化有关。我们已经确定了不同的神经元群体，它们表现出不同的时间动力学，而不同的时间动态受到冲突的不同调节。重要的是，我们已经证明了这些神经元群体中的放电活动受到theta和beta振荡的影响，这表明用于向丘脑下核传递决策冲突信息的皮质振荡最终调节了该结构中的放电活动。我们设计了一组新的实验，以这些发现为基础，使用DBS手术期间临时放置的硬膜下电极直接测量前额叶皮质活动，以便准确地了解这些结构是如何通信的。

FY2013 has seen significant progress towards establishing the research infrastructure and towards realizing these goals and objectives. We have developed our lab infrastructure for capturing and analyzing intracranial recordings while participants engage in cognitive tasks designed to probe memory encoding and retrieval. Patients with medically refractory epilepsy receiving intracranial electrodes and surgical treatment at the Clinical Center have been recruited for these studies. In one set of studies, we have principally been interested in investigating whether patterns of neuronal oscillatory power are reinstated from memory encoding to memory retrieval, and in examining the precise spatiotemporal dynamics of such reinstatement. Using a paired associates episodic memory task, we have directly examined these questions. We have first examined the changes observed in oscillatory activity during memory encoding. We then implemented analysis techniques that aggregate the distributed pattern of oscillatory power across multiple cortical locations and across multiple frequency bands in order to probe whether this activity is reinstated during recall. We have demonstrated that, during successful recall, there is significantly greater reinstatement of this pattern of oscillatory power across space and across frequencies. Furthermore, we have developed analyses that demonstrate the precise timing of such oscillatory activity and reinstatement across individual frequencies and locations. In a second set of studies, we have been principally interested in understanding how attentional mechanisms mediate the formation of successful memories. We have designed a behavioral task that specifically asks this question and allows us to compare neural activity between items that are attended to and successfully remembered versus those that were not attended to yet still remembered. Our interest is in understanding how attention itself mediates memory. Based on our preliminary analyses from several participants, we have found clear evidence that attentional cues significantly trigger neural activity in precise spatial locations that correlate with successful memory encoding. We have also developed and continued our work in capturing and analyzing local field potential and single unit spiking activity captured from the basal ganglia during deep brain stimulation surgery. We have focused on activity in the subthalamic nucleus in order to understand the role this structure plays in mediating decision conflict as participants performed perceptual decision tasks. We have demonstrated that decision periods are marked by significant increases in theta oscillatory power in the subthalamic nucleus, and that these oscillations are significantly stronger during decisions that involve greater conflict. Furthermore, directed coherence between the prefrontal cortex, measured using scalp EEG, and the subthalamic nucleus is significantly higher when subjects are mediating high conflict decisions. These data suggest that theta oscillatory activity may communicate information from the cortex to the basal ganglia during decision processes. We have extended this work to investigate the role of subthalamic nucleus single-unit spiking activity and how this activity relates to the observed changes in oscillatory power. We have identified distinct neuronal populations that exhibit different temporal dynamics that are differentially mediated by conflict. Importantly, we have shown that spiking activity in these populations of neurons is entrained by theta and beta oscillations, suggesting that the cortical oscillations used to convey information regarding decision conflict to the subthalamic nucleus ultimately modulate spiking activity in that structure. We have designed a new set of experiments to build upon these findings and to directly measure prefrontal cortical activity using intracranial subdural electrodes temporarily placed during DBS surgery in order to precisely understand how these structures communicate.