Neuronal mechanisms of attentional selection in primary auditory cortex

描述(由申请人提供)：选择性注意通过以牺牲无关刺激为代价来增强任务相关刺激的神经表征，使感觉处理适应观察者的直接目标。先前对人类和猴子的研究表明，注意力调节视网膜后视觉处理的每一个阶段的神经元反应。虽然听觉选择性注意在人类中已经得到了广泛的研究，但在猴子身上的研究几乎没有触及这个话题。这个R21建议的主要目标是通过直接电生理记录在猴子的初级听觉皮质(A1)启动选择性注意的神经机制的研究。越来越多的证据表明，神经元振荡反映了神经元在不同空间和时间尺度上兴奋性的有组织的节律性转移，这些振荡是正常大脑功能的基本组成部分，在感觉、认知和运动操作中起着至关重要的作用。特别值得一提的是，最近对视觉皮质的研究表明，正在进行的振荡活动的结构可以适应或“缠绕”到所关注的感觉刺激流的时间(节奏)结构。夹带使神经元振荡的高兴奋性阶段与参与流中的事件的时间相一致，从而放大了它们的神经元表征。由于节奏结构对许多生物意义重大的声学刺激(如语音)来说是必不可少的，因此振荡夹带作为听觉系统中注意力选择的一种机制将显得特别有用。这一命题有很强的心理物理支持，但尚未在神经生理学层面上得到直接检验。我们将评估总体假设，即神经元振荡对出席的声流的时间结构的夹带导致神经元对组成该流的事件的反应增强，并抑制神经元对沿听觉处理的两个基本组织维度-时间(节奏)和频率-偏离它的刺激的反应。行为测量，以及在任务执行过程中在A1中采样的层流电流源密度和多单位活动轮廓，将解决确定1)注意节奏和2)注意音调频率对听觉处理的影响的具体目标。由于神经元振荡的注意夹带似乎对复杂环境中有效的适应行为至关重要，因此它的破坏可能会导致认知障碍。定义注意力牵引的神经基础是理解认知功能和功能障碍机制的关键一步。 公共卫生相关性：神经元振荡的注意力诱导性被认为是有效利用正在进行的生理过程对复杂的自然刺激进行适应性处理的关键，然而管理它及其功能的规则在很大程度上仍不清楚。我们建议探索振荡夹带作为听觉选择性注意的一种机制。由于听觉加工缺陷是许多神经精神障碍的关键症状，我们的研究结果将对改善对这些障碍的理解和治疗，以及促进我们对动态脑操作的总体理解具有重要意义。

DESCRIPTION (provided by applicant): Selective attention adapts sensory processing to the immediate goals of an observer by enhancing the neural representation of task relevant stimuli at the expense of irrelevant stimuli. Prior studies in both humans and monkeys show that attention modulates neuronal responses at every stage of visual processing after the retina. While auditory selective attention has been extensively studied in humans the topic is almost untouched by studies in monkeys. The broad goal of this R21 proposal is to initiate studies of the neural mechanisms of selective attention by direct electrophysiological recording in primary auditory cortex (A1) of the monkey. Accumulating evidence indicates that neuronal oscillations reflect organized rhythmic shifting of excitability in neuronal ensembles on different spatial and temporal scales, and that these oscillations are fundamental components of normal brain function with a crucial role in sensory, cognitive and motor operations. In particular, recent studies in visual cortex reveal that the structure of ongoing oscillatory activity can adapt or "entrain" to the temporal (rhythmic) structure of an attended sensory stimulus stream. Entrainment aligns the high excitability phase of neuronal oscillations with the timing of events in the attended stream, thus amplifying their neuronal representation. As rhythmic structure is essential to many biologically significant acoustic stimuli (e.g., speech sounds), oscillatory entrainment would appear particularly useful as a mechanism of attentional selection in the auditory system. This proposition has strong psychophysical support, but has not been directly tested at a neurophysiological level. We will evaluate the overall hypothesis that the entrainment of neuronal oscillations to the temporal structure of an attended acoustic stream results in enhanced neuronal responses to events that comprise that stream, and suppressed neuronal responses to stimuli that deviate from it along the two fundamental organizing dimensions of auditory processing, time (rhythm) and frequency. Behavioral measures, along with laminar current source density and multiunit activity profiles sampled in A1 during task performance will address the specific aims of defining the effects of 1) attended rhythm, and 2) attended tone frequency on auditory processing. Since attentional entrainment of neuronal oscillations appears critical to efficient, adaptive behavior in a complex environment, its disruption would likely result in cognitive impairment. Defining the neural underpinnings of attention entrainment is a crucial step in understanding the mechanisms of cognitive function and dysfunction. PUBLIC HEALTH RELEVANCE: Attention entrainment of neuronal oscillations is believed to be crucial to the effective use of ongoing physiological processes in adaptive processing of complex natural stimuli, yet the rules that govern it and its function are still largely unknown. We propose to explore oscillatory entrainment as a mechanism of auditory selective attention. Since deficits of auditory processing are key symptoms in numerous neuropsychiatric disorders, our findings will have important implications for improved understanding and treatment of these disorders, and for advancing our understanding of dynamic brain operations in general.