Abstract
The ascending modulatory systems of the brain stem are powerful regulators of global brain state. Disturbances of these systems are implicated in several major neuropsychiatric disorders. Yet, how these systems interact with specific neural computations in the cerebral cortex to shape perception, cognition, and behavior remains poorly understood. Here, we probed into the effect of two such systems, the catecholaminergic (dopaminergic and noradrenergic) and cholinergic systems, on an important aspect of cortical computation: its intrinsic variability. To this end, we combined placebo-controlled pharmacological intervention in humans, recordings of cortical population activity using magnetoencephalography (MEG), and psychophysical measurements of the perception of ambiguous visual input. A low-dose catecholaminergic, but not cholinergic, manipulation altered the rate of spontaneous perceptual fluctuations as well as the temporal structure of “scale-free” population activity of large swaths of the visual and parietal cortices. Computational analyses indicate that both effects were consistent with an increase in excitatory relative to inhibitory activity in the cortical areas underlying visual perceptual inference. We propose that catecholamines regulate the variability of perception and cognition through dynamically changing the cortical excitation–inhibition ratio. The combined readout of fluctuations in perception and cortical activity we established here may prove useful as an efficient and easily accessible marker of altered cortical computation in neuropsychiatric disorders.
Highlights
The modulatory systems of the brain stem send widespread, ascending projections to the specialized circuits of the cerebral cortex that mediate perception, cognition, and goal-directed behavior
We tested for changes in intrinsic fluctuations of perception and cortical population activity under placebo-controlled, within-subjects pharmacological manipulations of catecholamine and acetylcholine levels (Fig 1A, see Materials and methods for details on the pharmacological interventions)
In a third condition that was only used for the analysis of perceptual fluctuations, subjects immediately reported the perceptual alternations by button press (“Task-pressing,” i.e., associated with movement-related transients in cortical activity)
Summary
The modulatory systems of the brain stem send widespread, ascending projections to the specialized circuits of the cerebral cortex that mediate perception, cognition, and goal-directed behavior. These systems regulate ongoing changes in brain state, even during periods of wakefulness [1,2,3,4]. They are recruited during, and in turn, shape cognitive processes such as perceptual inference, learning, and decision-making [5,6,7,8]. An important challenge for neuroscience is to uncover the mechanistic principles by which neuromodulatory systems interact with the cortical computations underlying cognition
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