Integrating the neural and biochemical basis of attention in humans

选择性注意是大脑中的一组核心操作，它控制着与行为相关的信息流。自从第一次展示注意力的神经基础以来，研究人员几乎只专注于注意力如何改变神经元的放电率--通过实验试验中神经元活动的平均值来表示。然而，在对非人类动物模型中神经活动的复杂新探索的推动下，我们对注意力的理解正在发生巨大变化。从最近的这项工作中，出现了一种新的注意力机制基础，这是传统的通过试验平均神经活动的方法看不到的。除了增加神经元的平均反应外，注意力还可以减少神经元试验到试验反应的方差或噪声。注意力驱动的噪音减少可以对群体神经活动产生很大影响，因为单个神经元的噪音通常与邻近神经元的噪音相关。通过减少人群中的共享噪音，注意力可以极大地影响在任何给定时间代表多少信息。有趣的是，大脑的核心神经调节化学物质之一--乙酰胆碱能引起神经元之间噪音相关性的快速变化，这与定向注意的效果非常相似。这些发现共同揭示了一种以群体编码噪音及其神经化学基础来表达注意力的有效机制。然而，用来推进这些发现的侵入性记录方法在人类身上是不可行的。因此，跨物种的翻译速度变慢了。此事体大。目前对人群活动的非侵入性探测，如功能磁共振成像(FMRI)，几乎完全依赖于试验平均方法。因此，在人类研究中，注意对群体噪声的大规模影响被忽略了，尽管它们在大脑皮层信息处理中起着基础作用。此外，由于最常用的神经成像技术，如fMRI和EEG，对大脑的神经化学环境不敏感，我们对人类认知和神经调节之间的联系的理解仍然非常基础。*我的实验室将使用人类活体神经成像来检查神经元噪音的机制基础，以便翻译和推广非人类动物研究的最新发现。由fMRI索引的大量神经元反应对注意驱动的噪声相关性变化敏感吗？如果是这样的话，注意力驱动的噪音相关性变化与种群代码中携带的信息量有何关系？皮层胆碱能调制是否可以用非侵入性成像探头，如1H磁共振波谱来检测？如果是这样的话，注意力驱动的噪音相关性变化依赖于胆碱能调制吗？我的研究计划将开发新的人类神经成像方法，以三角测量定向注意、胆碱能调制和群体编码之间的联系。**

Selective attention is a set of core operations in the brain that control the flow of behaviourally relevant information. Since the first demonstrations of a neural basis of attention, researchers have focused almost exclusively on how attention changes the firing rate of neuronsexpressed by the mean of their activity over experimental trials. However, driven by sophisticated new probes of neural activity in non-human animal models, our understanding of attention is changing dramatically.******From this recent work, a novel mechanistic basis of attention has emerged, which is invisible to traditional approaches of averaging neural activity over trials. In addition to increasing a neuron's average responses, attention can reduce the variance, or noise, of a neuron's trial-to-trial responses. Attention-driven reductions in noise can have large effects on population neural activity because an individual neuron's noise is often correlated with the noise of neighboring neurons. By reducing shared noise in a population, attention can dramatically influence how much information is represented at any given time. Intriguingly, one of the brain's core neuromodulatory chemicalsacetylcholineinduces rapid changes in the noise correlations among neurons which closely mimic the effects of directed attention.******Together, these discoveries reveal a potent mechanism of attention expressed in the noise of population coding and its neurochemical basis. However, the invasive recording methods used to advance these discoveries are not feasible in humans. As a result, cross-species translation has slowed. This is a big problem. Current non-invasive probes of population activity, such as functional magnetic resonance imaging (fMRI), almost exclusively rely on trial-averaging methods. Large-scale effects of attention on population noise are therefore neglected in human research despite their fundamental role in cortical information processing. Moreover, because the most commonly used neuroimaging techniques, such as fMRI and EEG, are not sensitive to the brain's neurochemical environment, our understanding of the links between cognition and neuromodulation in humans remains very basic. ******My lab will examine the mechanistic basis of neuronal noise using human in vivo neuroimaging in order to translate and extend recent findings from non-human animal research. Are the mass neuronal responses indexed by fMRI sensitive to attention-driven changes in noise correlation? If so, how do attention-driven changes in noise correlation relate to the amount of information carried in the population code? Is cortical cholinergic modulation detectable with non-invasive imaging probes such as 1H magnetic resonance spectroscopy? If so, do attention-driven changes in noise correlation rely on cholinergic modulation? My program of research will develop novel human neuroimaging methods to triangulate the links among directed attention, cholinergic modulation and population coding. **