Cholinergic, But Not Dopaminergic or Noradrenergic, Enhancement Sharpens Visual Spatial Perception in Humans.
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.SIGNIFICANCE STATEMENTAcetylcholine 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.
Neurology Department, Washington University, St. Louis, Missouri 63110, cgratton@wustl.edu.
Caterina
0000-0003-4607-7401
C
Gratton
School of Optometry, University of California, Berkeley, California 94720.|Vision Science Graduate Group, University of California, Berkeley, California 94720.
Sahar
0000-0003-0199-3481
S
Yousef
Donders Institute, Centre for Cognitive Neuroimaging, Radboud University, Nijmegen 6525 EN, The Netherlands.
Esther
0000-0001-6360-6200
E
Aarts
Department of Neurosurgery, University of California, San Francisco, California 94122, and.
Deanna L
DL
Wallace
Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720.
Mark
0000-0002-3462-006X
M
D'Esposito
School of Optometry, University of California, Berkeley, California 94720.|Vision Science Graduate Group, University of California, Berkeley, California 94720.|Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720.
Michael A
0000-0002-7145-5657
MA
Silver
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D001971:Bromocriptine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D015350:Contrast Sensitivity / Q000187:drug effects*; D000077265:Donepezil; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D016316:Guanfacine / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011897:Random Allocation; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D058647:Adrenergic alpha-2 Receptor Agonists; D002800:Cholinesterase Inhibitors; D018491:Dopamine Agonists; D007189:Indans; D010880:Piperidines; D016316:Guanfacine; D001971:Bromocriptine; D000077265:Donepezil
acetylcholine; attention; dopamine; norepinephrine; pharmacology; visuospatial perception