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How does Cholinergic Enhancement Modulate Neural Correlates of Bottom-Up and Top-Down Processing in Human Visual Cortex?

Paul Bentley
Wellcome Department of Imaging Neuroscience, Institute of Neurology, University College London, UK

Effects of acetylcholine on early sensory cortices include enhancement of input activity; reduction of feedback from higher areas, and an improvement in signal-to-noise ratio. Additionally, cholinergic input to prefrontal and parietal cortices is necessary for normal sustained attention, especially in the presence of distraction (i.e. with selective attention). This might suggest that feedback influences on sensory cortices is enhanced, through selective inhibition of task-irrelevant inputs. Since we know that during attention-demanding conditions, acetylcholine is released diffusely throughout cerebral cortex, the question remains of what is the net effect of cholinergic neuromodulation on top-down versus bottom-up processing in sensory cortices?

Functional imaging provides the means to discern stimulus-driven from attention-driven effects in sensory cortices, and these effects have direct parallels with primate neurophysiological recordings, e.g. enhancement of neural activity in retinotopic visual cortex secondary to selective attention. Our laboratory has been engaged in fMRI studies that have specifically manipulated visual stimulus and attentional factors, and the interaction of these with the administration of the cholinergic enhancer physostigmine.

In study one, we examined the interaction of physostigmine with selective spatial attention in discrete object-processing regions of extrastriate visual cortex (viz. ‘face’ and ‘house’ areas). Unexpectedly, the effects of the drug on attention-driven responses were opposite between the two regions, even in the absence of stimulus.  

In study two, we compared effects of physostigmine between conditions of low and high spatial visual attention, keeping stimulus constant. In striate cortex, physostigmine reduced activity to stimulus independent of task, but in extrastriate cortex physostigmine enhanced activity specifically with high-attention. However, the selective spatial biasing of extrastriate cortex observed with selective spatial attention was decreased (due to a relatively greater increase in activity on the occipital side ipsilateral to cued direction (i.e. coding for the ‘less task-relevant’ side). This BOLD-effect correlated with an equivalent behavioural effect, viz. relative performance on invalid versus valid trials.

Our results demonstrate modulation of both stimulus-driven and attention-driven responses in visual cortex with cholinergic enhancement. Comparing studies, it is apparent that such effects may vary between visual regions and tasks. In occipital regions, both studies found physostigmine resulted in an enhanced effect of combined high-attention and stimulation (relative to low-attention or no stimulation), as well as a diminution of the orthogonal effect of selective spatial attention (task-relevant versus irrelevant locations). In inferior temporal regions, physostigmine enhanced both attention-driven activity (relative to baseline) and the effect of selective spatial attention.