Gratton Caterina, Yousef Sahar, Aarts Esther, Wallace Deanna L, D'Esposito Mark, Silver Michael A
Neurology Department, Washington University, St. Louis, Missouri 63110,
School of Optometry, University of California, Berkeley, California 94720.
J Neurosci. 2017 Apr 19;37(16):4405-4415. doi: 10.1523/JNEUROSCI.2405-16.2017. Epub 2017 Mar 23.
The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker distance. We found that cholinergic enhancement with the cholinesterase inhibitor donepezil improved target detection, and modeling suggested that this was mainly due to a narrowing of the extent of facilitatory perceptual spatial interactions. In Experiment 2, we tested whether these effects were selective to the cholinergic system or would also be observed following enhancements of related neuromodulators dopamine or norepinephrine. Unlike cholinergic enhancement, dopamine (bromocriptine) and norepinephrine (guanfacine) manipulations did not improve performance or systematically alter the spatial profile of perceptual interactions between targets and distractors. These findings reveal mechanisms by which cholinergic signaling influences visual spatial interactions in perception and improves processing of a visual target among distractors, effects that are notably similar to those of spatial selective attention. Acetylcholine influences how visual cortical neurons integrate signals across space, perhaps providing a neurobiological mechanism for the effects of visual selective attention. However, the influence of cholinergic enhancement on visuospatial perception remains unknown. Here we demonstrate that cholinergic enhancement improves detection of a target flanked by distractors, consistent with sharpened visuospatial perceptual representations. Furthermore, whereas most pharmacological studies focus on a single neurotransmitter, many neuromodulators can have related effects on cognition and perception. Thus, we also demonstrate that enhancing noradrenergic and dopaminergic systems does not systematically improve visuospatial perception or alter its tuning. Our results link visuospatial tuning effects of acetylcholine at the neuronal and perceptual levels and provide insights into the connection between cholinergic signaling and visual attention.
神经调质乙酰胆碱通过改变产生神经元感受野的输入平衡来调节视觉皮层中的空间整合。这些胆碱能效应可能为视觉空间注意力对视觉表征的调节提供一种神经生物学机制。然而，胆碱能增强对人类视觉空间感知的影响尚不清楚。我们进行了两项实验，以测试增强胆碱能信号是否会选择性地改变人类受试者视觉空间相互作用的感知指标。在实验1中，一项双盲安慰剂对照药理学研究中，我们测量了侧翼干扰物如何影响外周目标小对比度降低的检测，作为目标-干扰物距离的函数。我们发现，使用胆碱酯酶抑制剂多奈哌齐增强胆碱能作用可改善目标检测，并且建模表明这主要是由于促进性感知空间相互作用范围的缩小。在实验2中，我们测试了这些效应是否对胆碱能系统具有选择性，或者在相关神经调质多巴胺或去甲肾上腺素增强后是否也会观察到。与胆碱能增强不同，多巴胺（溴隐亭）和去甲肾上腺素（胍法辛）操作并未改善表现或系统地改变目标与干扰物之间感知相互作用的空间分布。这些发现揭示了胆碱能信号影响视觉空间相互作用感知并改善干扰物中视觉目标处理的机制，这些效应与空间选择性注意力的效应显著相似。乙酰胆碱影响视觉皮层神经元如何跨空间整合信号，这可能为视觉选择性注意力的效应提供一种神经生物学机制。然而，胆碱能增强对视觉空间感知的影响仍然未知。在这里，我们证明胆碱能增强可改善干扰物侧翼目标的检测，这与锐化视觉空间感知表征一致。此外，虽然大多数药理学研究集中在单一神经递质上，但许多神经调质可对认知和感知产生相关影响。因此，我们还证明增强去甲肾上腺素能和多巴胺能系统不会系统地改善视觉空间感知或改变其调谐。我们的结果将乙酰胆碱在神经元和感知水平上的视觉空间调谐效应联系起来，并为胆碱能信号与视觉注意力之间的联系提供了见解。
