The role of attractor dynamics and feed-forward integration in working memory

吸引子动力学和前馈积分在工作记忆中的作用

• 批准号: 8526992
• 负责人: David A Markowitz
• 金额: $ 4.55万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526992
• 关键词: Age-associated memory impairment; Attention Deficit Disorder; Behavior; Behavior Control; Behavioral; Biological Assay; Brain; Brain region; Computational Technique; Computer Simulation; Conflict (Psychology); Data; Decision Making; Delayed Memory; Disease; Electrodes; Etiology; Exhibits; Fire - disasters; Functional disorder; Generations; Human; Link; Memory; Mind; Modeling; Monkeys; Motor; Movement; Neurons; Noise; Output; Photic Stimulation; Prefrontal Cortex; Primates; Process; Recovery; Recurrence; Role; Schizophrenia; Sensory; Short-Term Memory; Staging; Stimulus; Sum; Testing; Time; Visual; Work; base; cognitive function; design; feeding; improved; memory process; oculomotor; operation; prevent; public health relevance; research study; response; sensory stimulus

DESCRIPTION (provided by applicant): Working memory (WM) is a fundamental component of higher cognitive function that enables the persistent encoding of information during movement planning and decision-making. Dysfunction of WM has been linked to schizophrenia, attention deficit disorder, and age-related cognitive decline. In humans and monkeys, the prefrontal cortex (PFC) functions as the hub of a distributed network of brain regions that collectively supports WM, and damage to PFC abolishes WM function entirely. Therefore, understanding the mechanisms of WM function in PFC may be helpful to understanding the etiology of WM-related disorders in humans. Primate WM function has been linked to neurons in PFC whose firing rates remain persistently elevated during a delay period after the termination of a sensory stimulus and preceding a motor response. The mechanisms of persistent activity in PFC remain unknown, but theoretical work presents two competing hypotheses for how network interactions in PFC may give rise to persistent activity during WM. The "attractor" hypothesis proposes that mutually excitatory interactions produce a temporally invariant mode of network activity that persists after sensory input terminates and is stable in time. By contrast, the "feed forward integrator" hypothesis proposes that persistent activity results from the transient flow of sensory input through a sequence of modules. WM function then arises from the summed, time-varying outputs from these modules, approximating a step function. Computational models based on both hypotheses reproduce the firing rate responses of isolated PFC neurons during a spatial WM task. However, the experimental data needed to properly distinguish between these two competing frameworks is currently lacking. This proposal combines multiple-electrode recordings, behavioral manipulations and computational techniques to test three opposing predictions made by attractor and feed-forward models about firing rate dynamics and correlated variability during spatial WM. In all experiments, PFC neurons will be isolated and their responses recorded from an electrode array of up to 32 electrodes in monkeys performing a memory-guided oculomotor delayed response (ODR) task. Aim 1 will test conflicting model predictions about correlated variability among pairs of persistently active neurons during WM, by analyzing spike count correlations in paired single unit recordings during the memory ODR task. Aim 2 will test conflicting model predictions about the response of persistently active neurons to sustained visual stimulation, by analyzing single unit firing rate changes over time during a visually-guided ODR task. Finally, Aim 3 will test conflicting model predictions about the response of persistently active neurons to distracter stimuli during WM, by studying differences between single unit firing rates before and after a briefly flashed distracter stimulus. The result of these experiments will improve our understanding of WM function by supporting an existing model or pointing toward a new model of persistent activity generation in PFC.

描述（由申请人提供）：工作记忆（WM）是高级认知功能的基本组成部分，它能够在运动规划和决策过程中持续编码信息。WM功能障碍与精神分裂症、注意力缺陷障碍和与年龄相关的认知衰退有关。在人类和猴子中，前额叶皮层（PFC）作为一个分布式的大脑区域网络的枢纽，共同支持WM，并且PFC的损伤完全废除了WM功能。因此，了解PFC中WM功能的机制可能有助于了解WM相关疾病的病因。灵长类动物的WM功能与PFC中的神经元有关，PFC中的神经元在感觉刺激终止后和运动反应之前的延迟期内放电率持续升高。PFC中持续活动的机制仍然未知，但理论工作提出了两个相互竞争的假设，PFC中的网络相互作用可能会引起WM期间的持续活动。“吸引子”假说提出，相互兴奋的相互作用产生了一种时间不变的网络活动模式，这种模式在感觉输入终止后仍然存在，并且在时间上是稳定的。相比之下，“饲料 “前向积分器”假设提出，持续的活动是由 通过一系列模块进行感官输入。WM函数然后从这些模块的求和的时变输出产生，近似于阶跃函数。基于这两种假设的计算模型再现了空间WM任务期间孤立PFC神经元的放电率响应。然而，目前缺乏正确区分这两种竞争框架所需的实验数据。该建议结合了多电极记录，行为操纵和计算技术来测试三个相反的预测由吸引子和前馈模型的放电率动态和相关的变异性在空间WM。在所有实验中，PFC神经元将被分离，并从执行记忆引导的眼延迟反应（ODR）任务的猴子中的多达32个电极的电极阵列记录它们的反应。目的1将测试冲突模型预测相关的变异性之间的持续活跃的神经元对在WM，通过分析尖峰计数的相关性在成对的单单位记录在记忆ODR任务。目标2将通过分析视觉引导ODR任务期间单个单位放电率随时间的变化，测试关于持续活跃神经元对持续视觉刺激的反应的相互冲突的模型预测。最后，目标3将测试冲突的模型预测持续活跃的神经元分心刺激的反应，在WM，通过研究单个单位的放电率之间的差异之前和之后，短暂闪烁的分心刺激。这些实验的结果将通过支持现有的模型或指向PFC中持续活动生成的新模型来提高我们对WM功能的理解。