Neurophysiology and Anatomy of Multisensory Processing

描述（由申请人提供）：多感觉整合开始于初级听觉皮层（A1）或之前，并在更高的阶段建立。在A1区，这种效应似乎主要是对“驱动”听觉输入强度的非听觉“调制”，而在更高的区域，它可能越来越多地反映出听觉和非听觉信息的更高层次的“整合”。在A1阶段，听觉/非听觉相互作用使用神经元振荡作为听觉反应放大的工具，而在更高阶段，相互作用还包括经典的兴奋性收敛。自始至终，输入的显著性（自下而上）和自上而下的注意力控制的影响被认为是至关重要的。这些元素——神经元振荡、调节驱动的相互作用、自上而下的控制和潜在的解剖回路——无处不在，对大脑运作至关重要。在多感官相互作用的背景下研究它们提供了对关键输入的独特而明确的控制，因为它们来自不同的受体表面。我们的总体目标是研究听觉系统各层次的多感觉相互作用，作为大脑综合操作的一般模型。我们将解剖分析与电生理方法结合起来，索引突触活动和伴随动作电位的层流轮廓，以区分来自各种皮层和皮层下来源的“驱动”听觉输入和非听觉“调节”输入，并确定这些输入类型在注意辨别过程中如何在生理上相互作用。具体目标1是表征跨加工水平的多感觉表征的机制和进化。具体目标2是确定预测声音时间和位置的跨模态线索如何帮助听觉处理。具体目标3是描述听觉皮层驱动和调节回路的精细结构，强调目标1和目标2所检查的过程的解剖学相关性。提高对神经元振荡在驱动输入处理中的关键工具功能的理解，通过调节输入对它们的操纵，刺激显著性和注意力的影响，以及潜在的电路，将增强对正常听力的机制理解，以及那些导致许多病理条件的潜在听力破坏。

DESCRIPTION (provided by applicant): Multisensory Integration begins at or before the level of primary auditory cortex (A1) and builds over higher stages. In A1 the effect seems to be mainly a non-auditory "modulation" of the strength of "driving" auditory inputs, while in higher areas it may increasingly reflect a higher order "integration" of auditory and non-auditory information. In A1, auditory/non-auditory interactions use neuronal oscillations as instruments of auditory response amplification, while in higher stages, interactions also entail classic excitatory convergence. Throughout, the impact of inputs' salience (bottom-up), and that of top-down attentional control are believed to crucial. These elements - neuronal oscillations, modulatory-driving interactions, top-down control, and the underlying anatomic circuits - are ubiquitous and crucial to brain operation. Investigating them in the context of multisensory interactions affords a unique unambiguous control over the key inputs since they arise from different receptor surfaces. Our BROAD GOAL is to investigate multisensory interaction across levels of the auditory system as a general model for integrative operations in the brain. We combine anatomical analyses with electrophysiological methods indexing laminar profiles of synaptic activity and concomitant action potentials to differentiate "driving" auditory inputs and non-auditory "modulatory" inputs arising from various cortical and subcortical sources, and to determine how these input types interact physiologically during attentive discrimination. SPECIFIC AIM 1 is to characterize the mechanisms and evolution of multisensory representation across processing levels. SPECIFIC AIM 2 is to determine how cross modal cues that predict sound timing and location help auditory processing. SPECIFIC AIM 3 is to characterize the fine structure of driving and modulatory circuits in auditory cortex, emphasizing anatomical correlates of processes examined under Aims 1 and 2. Improved understanding of the critical instrumental functions of neuronal oscillations in processing of driving inputs, their manipulation by modulatory inputs, influences of stimulus salience and attention, and the underlying circuitry, will enhance the mechanistic understanding of normal hearing, as well as those underlying disruptions of hearing that contribute to a number of pathological conditions. PUBLIC HEALTH RELEVANCE: Improved mechanistic understanding of the instrumental functions of neuronal oscillations in the processing of driving inputs, their manipulation by modulatory inputs, the underlying circuitry, and the way that attention orchestrates these elements, will enhance our mechanistic understanding of perceptual/cognitive impairment specific to hearing disorders, and in a spectrum of disorders including ADHD, autism and schizophrenia, where defects in normal connectivity, disruptions of neuronal synchrony and attentional impairments are prominent