Neural Mechanisms of Selective Attention

描述(申请人提供)：在拥挤的视觉场景中，需要注意从相关刺激中选择性地处理信息，并过滤掉无关的分心因素。因此，对人类和动物的研究表明，当注意力被引导到它们的接受区时，几个不同大脑结构中的神经元显示出增强的反应。然而，对于这些无处不在的注意效应是如何通过这些结构之间的相互作用而产生的，尤其是当注意线索来自认知因素和任务需求时，人们仍然知之甚少。为了设计有效的神经假体或治疗注意力障碍患者，我们需要在系统水平上更好地理解注意力。前额叶皮质、后顶叶皮质和枕叶被认为是向视觉皮质提供反馈以调节注意效应的三个关键结构。在计划中的实验中，我们将比较这三个结构中的每一个在向视觉皮质V4区提供反馈方面的作用。V4区在沿着作为物体识别基础的腹侧流传递视觉信息方面起着中心作用，我们之前已经证明，V4神经元的反应受到注意力的调制，V4区的损伤会导致注意障碍。我们最近还发现，前额叶皮质中的神经元具有足够短的注意潜伏期，足以介导对V4神经元反应的一些注意效应，并且前额叶神经元与V4中的细胞具有一致的活动。这种相干活动在很大的频率范围内被时移约10ms，这可能是允许功能相互作用的关键时间。在目标1中，我们将把来自顶叶后皮质的记录添加到前额叶记录中，以比较这两个结构在调节V4活动中的作用。枕骨为来自前额叶和顶叶皮质的信号影响V4提供了另一条解剖学途径。因此，在目标2中，我们将在枕区和V4区同时记录，以测试枕区神经元的特性是否与这种反馈作用一致。然而，仅有神经生理记录只能提供活动相关性的证据，而不能提供因果关系的证据。因此，在目标3中，我们将在神经记录中补充前额叶、顶叶皮质和枕叶的活动抑制，以检验关于每个结构的反馈在调节V4反应中的作用的因果假说。对于这些实验，我们将使用我们和我们的合作者最近开发的技术，使用由慢病毒提供的质子泵Arch-T来抑制神经活动的光遗传。有了Arch-T，我们将能够在关键时间点以数十毫秒的分辨率抑制活动，以获得对V4的反馈的新的机械性见解。总而言之，我们希望这些研究能为我们提供到目前为止最好的解释，说明多个大脑结构之间的相互作用如何导致有效的注意力视觉处理。

DESCRIPTION (provided by applicant): In crowded visual scenes, attention is needed to selectively process information from relevant stimuli and to filter out irrelevant distracters. Accordingly, studies in humans and animals have shown that neurons in several different brain structures show enhanced responses when attention is directed into their receptive fields. However, there is still little understanding of how these ubiquitous attentional effects are actually generated through the interactions among these structures, particularly when the attentional cues arise from cognitive factors and task demands. To design an effective neural prosthesis or to treat people with attentional disorders, we need a better understanding of attention at the systems level. Three key structures thought to provide feedback to visual cortex that mediates attentional effects are the prefrontal cortex, the posterior parietal cortex and the pulvinar. In the planned experiments, we will compare the roles of each of these three structures in providing feedback to area V4 in visual cortex. Area V4 plays a central role in the relay of visual information along the ventral stream that underlies object recognition, and we have previously shown that V4 neuronal responses are modulated by attention and that damage to V4 causes attentional impairments. We have also recently shown that neurons in prefrontal cortex have attentional latencies that are short enough to mediate some of the attentional effects on V4 neuronal responses, and that prefrontal neurons have coherent activity with cells in V4. This coherent activity is time-shifted across a wide range of frequencies by about 10 ms, which may be the critical time to allow for functional interactions. In Aim 1, we will add recordings from the posterior parietal cortex to the prefrontal recordings, to compare the roles of these two structures in modulating activity in V4. The pulvinar provides an alternative anatomical route for signals from prefrontal and parietal cortex to influence V4. Therefore, in Aim 2, we will record simultaneously in the pulvinar and area V4, to test whether pulvinar neuronal properties are consistent with this feedback role. However, neurophysiological recordings alone can only provide evidence for correlations in activity, not for causality. Therefore, in Aim 3, we will supplement the neural recordings with suppression of activity in prefrontal and parietal cortex and pulvinar, to test causal hypotheses about the role of feedback from each structure in modulating V4 responses. For these experiments, we will use techniques that we and our collaborators have recently developed for the optogenetic suppression of neural activity using the proton pump, Arch-T, which is delivered by lentivirus. With Arch-T we will be able to suppress activity with resolution in the tens of milliseconds, at critical time points, to gain new mechanistic insights into the feedback to V4. In total, we expect these studies to give us the best account so far of how the interactions among multiple brain structures leads to effective visual processing with attention.