Investigating the neural mechanisms of human cognitive function through intracranial recordings

通过颅内记录研究人类认知功能的神经机制

• 批准号: 8940131
• 负责人: Kareem Zaghloul
• 金额: $ 152.57万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8940131
• 关键词: Attention; Basal Ganglia; Behavioral; Cells; Clinical; Cognition; Cognitive; Complex; Conflict (Psychology); Cues; Data; Decision Making; Deep Brain Stimulation; Electrodes; Electroencephalography; Epilepsy; Episodic memory; Exhibits; Frequencies; Functional Magnetic Resonance Imaging; Goals; Human; Implant; Individual; Knowledge; Learning; Location; Measures; Mediating; Memory; Methods; Neurodegenerative Disorders; Neurons; Neurosciences; Neurosurgical Procedures; Operative Surgical Procedures; Participant; Patients; Pattern; Physiological; Play; Population; Prefrontal Cortex; Process; Psychological reinforcement; Recruitment Activity; Refractory; Research; Research Infrastructure; Role; Scalp structure; Seizures; Signal Transduction; Structure; Structure of subthalamic nucleus; Techniques; Time; Work; base; cognitive function; design; improved; insight; interest; memory encoding; memory recall; memory retrieval; neuromechanism; neuronal patterning; neurophysiology; neurosurgery; relating to nervous system; research study; response; spatiotemporal; tool

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.

2013财政年度在建立研究基础设施和实现这些目标和目的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，用于捕获和分析颅内记录，而参与者参与旨在探测记忆编码和检索的认知任务。 这些研究招募了在临床中心接受颅内电极和手术治疗的难治性癫痫患者。 在一组研究中，我们主要感兴趣的是调查是否模式的神经元振荡功率恢复从记忆编码到记忆检索，并在检查精确的时空动态恢复。使用成对的联想情景记忆任务，我们直接检查了这些问题。 我们首先研究了记忆编码过程中振荡活动的变化。 然后，我们实施了分析技术，聚合的分布模式的振荡功率在多个皮层位置和多个频带，以探测是否恢复这种活动在回忆。 我们已经证明，在成功的回忆，有显着更大的恢复这种模式的振荡功率跨越空间和频率。 此外，我们已经开发了分析，证明了这种振荡活动的精确时间和在各个频率和位置的恢复。 在第二组研究中，我们主要感兴趣的是了解注意力机制如何介导成功记忆的形成。 我们设计了一个行为任务，专门提出这个问题，并允许我们比较被注意并成功记住的项目与那些没有被注意但仍然记住的项目之间的神经活动。 我们的兴趣在于理解注意力本身是如何调节记忆的。 根据我们对几名参与者的初步分析，我们发现了明确的证据，即注意力线索显著触发了与成功记忆编码相关的精确空间位置的神经活动。 我们还开发并继续我们的工作，捕获和分析局部场电位和单个单位尖峰活动捕获的基底神经节在脑深部电刺激手术。 我们专注于活动在丘脑底核，以了解这个结构在调解决策冲突的参与者进行知觉决策任务中发挥的作用。 我们已经证明，决策期的特点是丘脑底核的θ振荡功率显着增加，并且这些振荡在涉及更大冲突的决策期间显着更强。 此外，使用头皮EEG测量的前额叶皮层与丘脑底核之间的定向一致性在受试者调解高冲突决策时显着更高。 这些数据表明，在决策过程中，θ振荡活动可能会将信息从皮层传递到基底神经节。 我们已经扩展这项工作，以调查的作用，丘脑底核单单位尖峰活动，以及如何这种活动与所观察到的振荡功率的变化。 我们已经确定了不同的神经元群体，表现出不同的时间动态，差异介导的冲突。 重要的是，我们已经证明，这些神经元群体中的尖峰活动是由θ和β振荡夹带的，这表明用于向丘脑底核传达决策冲突信息的皮质振荡最终调节该结构中的尖峰活动。 我们设计了一组新的实验，以这些发现为基础，并直接测量前额叶皮质活动使用颅内硬膜下电极暂时放置在DBS手术，以准确地了解这些结构如何沟通。