Neuronal Correlates of Memory in the Human Temporal Lobe

人类颞叶记忆的神经元相关性

• 批准号: 6383575
• 负责人: ITZHAK FRIED
• 金额: $ 30.71万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-16 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6383575
• 关键词: brain electrical activity; cerebral dominance; clinical research; cues; entorhinal cortex; epilepsy; hippocampus; human subject; memory; microelectrodes; neural information processing; single cell analysis; temporal lobe /cortex; visual stimulus

Our overall goal is to provide a better understanding of the neuronal basis of human memory function health and disease. We have taken the unique approach of directly recording single unity activity in humans during memory tasks, using depth electrodes implanted in medial temporal lobe (MTL) structures. This is only possible because our subjects are epilepsy patients who require placement of electrodes in the brain to identify the seizure focus for later resection. We have been successful, in our NIH-funded project (of which this proposal is a continuation), in demonstrating that the approach is not only feasible but also highly productive in terms of revealing some of the key characteristics of neuronal responses to complex visual stimuli during encoding and subsequent retrieval. Now we are in a position to use these data as a foundation for probing further into the neuronal correlates of memory. Specifically, our objective is to characterize neuronal responses during recall processes particularly during stimulus associations and episodic recall. Conscious recall cannot be studies in animals, and this will be the first such investigation at the neuronal level. The central hypothesis states: The same neurons in the hippocampus and entorhinal cortex that demonstrate selective excitatory responses during encoding are reactivated during conscious retrieval. This reactivation occurs when a stimulus or episode is recalled to mind in the absence of a visual stimulus, and also in episodic recall when a cure from the original episode is presented. Furthermore, reactivation has the same stimulus specifically as the original response during encoding and is set against prevalent reduction in neuronal activity ("inhibitory responses") in the hippocampus. It is the balance between excitatory and inhibitory responses that is important for successful retrieval. The specific aims are therefore to (1) compare neuronal responses during encoding with those during recall, (2) compare activity among the various regions of MTL during episodic recall, (3) compare responses of single neurons during recognition and recall, (4) correlate the inhibitory and excitatory responses of single neurons in the MTL to retrieval success, and (5) characterize differences between the epileptogenic hippocampus and contralateral hippocampus with respect to the neuronal responses during the memory tasks. Ours is the only group in a position to address these fundamental questions about the single neuron substrates or declarative memory function in humans. Our findings promise to be of value in understanding memory impairments in Alzheimer's disease, temporal love epilepsy and other neurological disorders involving memory impairment.

我们的总体目标是更好地了解人类记忆功能、健康和疾病的神经元基础。我们采用了一种独特的方法，在记忆任务中直接记录人类的单个活动，使用植入内侧颞叶（MTL）结构的深度电极。这是唯一可能的，因为我们的研究对象是癫痫患者，他们需要在大脑中放置电极来识别癫痫发作的病灶，以便以后切除。在美国国立卫生研究院资助的项目中，我们已经成功地证明了这种方法不仅可行，而且在揭示神经元在编码和随后的检索过程中对复杂视觉刺激的反应的一些关键特征方面也非常有效。现在我们可以利用这些数据作为进一步探索记忆的神经元关联的基础。具体来说，我们的目标是描述回忆过程中的神经元反应，特别是在刺激关联和情景回忆过程中。有意识的回忆不能在动物身上进行研究，这将是第一次在神经元水平上进行这样的研究。中心假说认为：在编码过程中表现出选择性兴奋反应的海马体和内嗅皮层中的神经元在有意识的检索过程中被重新激活。当在没有视觉刺激的情况下回忆起刺激或情节时，这种再激活就会发生，当出现原始情节的治疗方法时，这种再激活也会发生在情景回忆中。此外，在编码过程中，再激活具有与原始反应相同的特异性刺激，并且与海马中普遍存在的神经元活动减少（“抑制性反应”）相对应。兴奋性和抑制性反应之间的平衡是成功检索的重要因素。因此，具体的目标是：(1)比较编码过程中的神经元反应与回忆过程中的神经元反应，(2)比较情景回忆过程中MTL各区域之间的活动，(3)比较识别和回忆过程中单个神经元的反应，(4)MTL单个神经元的抑制和兴奋反应与检索成功之间的关系。(5)表征癫痫源性海马和对侧海马在记忆任务中神经元反应的差异。我们是唯一有能力解决这些关于单个神经元基质或人类陈述性记忆功能的基本问题的研究小组。我们的研究结果有望在理解阿尔茨海默病、颞叶性癫痫和其他涉及记忆障碍的神经系统疾病的记忆障碍方面具有价值。