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Abstract

Purpose: Neuromodulators alter the input-output relationship of neural circuits and their energy expenditure, with concomitant effects on the hemodynamic response, and thereby neuromodulators can affect functional magnetic resonance (fMRI) signals as well. Yet, the effects of neuromodulation on fMRI responses are still unclear, limiting our ability to interpret the effects of changes in behavioural states using fMRI. For instance, cholinergic neuromodulation is involved in sensory processing [1], attention [2], learning and memory [3]. But despite the known role of ACh in sensory processing, we still lack a clear understanding about how to differentiate the effects of ACh from sensory evoked activity, and how exactly cholinergic neuromodulation affects the sensory evoked hemodynamic responses. Nearly all cortical regions receive cholinergic projections from the basal forebrain (BF) [4]. However, despite anatomical evidence indicating a differential distribution of choline acetylcholinesterase (AChE) in various brain areas, it has been generally assumed that the cholinergic system exerts uniform effects across all cortical areas. Electrical stimulation of BF and pharmacologically induced increases in ACh, have been shown to enhance the encoding efficiency of sensory signals in primary sensory areas, and to increase the cerebral blood flow (CBF) [1, 5]. Yet, whether these effects are the result of local changes in ACh, or the result of a chain of events instantiated by global changes in ACh is unknown. Here, we evaluated the extent to which local cholinergic neuromodulation changes the spatial correspondence between neural activity and hemodynamic signals in the primary visual cortex (V1) of anesthetized macaques. Intracortical injection of ACh in anesthetized animals allowed us to investigate the mechanisms by which ACh locally affects the neural and hemodynamic signals without potentially confusing effects of behavioural processes like attention [2] or learning [3].