Catecholaminergic neuromodulation and selective attention jointly shape perceptual decision-making

Abstract

Perception of sensory input is influenced by fluctuations in ongoing neural activity, most prominently driven by attention and neuromodulator systems. It is currently unknown if neuromodulator activity and attention differentially modulate neural activity and perception or whether neuromodulatory systems in fact control attentional processes. We pharmacologically enhanced cholinergic (through donepezil) and catecholaminergic (through atomoxetine) levels in humans performing a visual attention task to investigate the effects of neuromodulatory drive and spatial attention on neural activity and behavior. Attention and catecholaminergic enhancement both improved perceptual sensitivity by increasing the rate of evidence accumulation towards a decision threshold (cholinergic effects were negligible). Electroencephalographic recordings revealed that attention and catecholaminergic enhancement both modulated pre-stimulus cortical excitability, evoked sensory processes and parietal evidence accumulation. Crucially however, the spatial profile and timing of these effects were remarkably different. This suggests that selective attention and neuromodulatory systems shape perception largely independently and in qualitatively different ways.

A disinhibitory circuit mechanism explains a general principle of peak performance during mid-level arousal

“…To test this, we performed polynomial regression for each sensory modality and decision type separately, averaging across tasks that fell into each category (see Methods for details). This allowed us to step aside from specific experimental manipulations of each of the six tasks individually, which will be reported elsewhere (in the future) (see e.g., (Nuiten et al, 2023), and focus on generalities across these tasks, namely which sensory modality was recruited (visual or auditory) and what was the task to be performed (discrimination or detection). Additionally, this ensured a sufficient number of trials per analysis to reliably compute regressions across pupil bins.…”

“…This allowed us to step aside from specific experimental manipulations of each of the six tasks individually, which will be reported elsewhere (in the future) (see e.g., ref. 46 , and focus on generalities across these tasks, namely which sensory modality was recruited (visual or auditory) and what was the task to be performed (discrimination or detection). Additionally, this ensured enough trials per analysis to reliably compute regressions across pupil bins.…”

“…For the auditory tasks, we thus analyze the data from all sessions. Below, we provide a brief description of the behavioral tasks, for more details on the pharmacological manipulation, visual tasks and additional results please see (Nuiten et al, 2023). During all tasks, participants were seated 80cm from a computer monitor (69x39cm, 60Hz, 1920x1080 pixels) in a darkened, sound isolated room.…”

“…The visual tasks were titrated to 75% performance in a similar fashion in a separate intake session (Nuiten et al, 2023).…”

Pharmacological Elevation of Catecholamine Levels Improves Perceptual Decisions, But Not Metacognitive Insight

“…Recent empirical work also suggests that the arousal state of an organism, driven by neuromodulator systems ( Aston-Jones and Cohen, 2005 ; McCormick et al, 2020 ), may differentially affect perceptual and metacognitive decision-making. For example, pharmacological elevation of baseline levels of catecholamines (i.e., noradrenaline and dopamine) improves perceptual sensitivity ( d ’; Gelbard-Sagiv et al, 2018 ; Nuiten et al, 2023 ), whereas antagonizing catecholaminergic receptors selectively improves metacognitive sensitivity (meta- d ’; Hauser et al, 2017 ). This suggests that perceptual and metacognitive processing are oppositely affected by fluctuations in (catecholaminergic) neuromodulator levels.…”