Biology subjects

Nuiten, S. A.

Publications and source records attributed to Nuiten, S. A..

8 recordsLinked to original sources

bioRxiv2026

Global nonequilibrium cortical dynamics tie mid-level pupil-linked arousal to optimal task performance in humans

Ongoing fluctuations in brain state, largely driven by neuromodulators of arousal, shape how sensory inputs are processed and decisions are made. Here, we combined pharmacological manipulations and pupillary proxies of arousal to examine how global cortical state dynamics relate to perceptual sensitivity. We applied the thermodynamics-inspired INSIDEOUT framework to electroencephalography (EEG) recordings from two visual discrimination tasks performed under placebo, atomoxetine (noradrenergic enhancer), and donepezil (cholinergic enhancer) challenges. INSIDEOUT quantifies the strength of functional hierarchies within the brain via the computation of temporal irreversibility in neural activity. Trial-wise global irreversibility increased linearly with pupil-indexed arousal and exhibited a nonlinear inverted-U relationship with perceptual sensitivity, while showing no differences across drug conditions. A nonlinear mediation analysis revealed that temporal irreversibility can account for a significant portion of the association between pupil-linked arousal and perceptual sensitivity. At lower arousal, increases in prestimulus irreversibility improved perceptual accuracy, whereas at higher arousal, pre- and poststimulus irreversibility had different effects. These results bridge intrinsic whole-brain dynamics with perceptual decision-making, demonstrating that neuromodulator-linked arousal tunes cortical states and, in turn, perceptual performance. More broadly, the results shed new light on how arousal may reconfigure neural global dynamics.

neuroscience↗

bioRxiv2026

Baseline activity of V1 interneurons connects pupil-linked arousal to engaged behavioral state

AO_SCPLOWBSTRACTC_SCPLOWHumans and rodents alternate between discrete, persistent behavioral states during perceptual decision-making. For example, trials can be clustered into states of engaged, disengaged, and biased decision-making strategies. In mice, the probability of being in an engaged state exhibits an inverted-U relationship with baseline pupil-linked arousal, consistent with the Yerkes-Dodson Law. We replicated this relationship in mice (N=11; audio-visual change detection task) and showed that it generalizes to humans (N=69; auditory detection task). We then examined its neural basis, using simultaneous pupillometry and electrophysiological recordings in mouse V1. A nonlinear mediation model revealed that baseline activity of putative fast-spiking interneurons, but not putative pyramidal neurons, made a significant statistical contribution to the inverted-U shaped relationship between pupil-linked arousal and engaged-state probability. These findings are consistent with the idea that arousal may shape behavioral states by modulating baseline inhibitory activity within a primary sensory region.

neuroscience↗

bioRxiv2024

Adaptive arousal regulation: Pharmacologically shifting the peak of the Yerkes-Dodson curve by catecholaminergic enhancement of arousal

Performance typically peaks at moderate arousal levels, consistent with the Yerkes-Dodson law, as confirmed by recent human and mouse pupillometry studies. Arousal states are influenced by neuromodulators like catecholamines (noradrenaline; NA and dopamine; DA) and acetylcholine (ACh). To explore their causal roles in this law, we pharmacologically enhanced arousal while measuring human decision-making and spontaneous arousal fluctuations via pupil size. The catecholaminergic agent atomoxetine (ATX) increased overall arousal and shifted the entire arousal-performance curve, suggesting a relative arousal mechanism where performance adapts to arousal fluctuations within arousal states. In contrast, the cholinergic agent donepezil (DNP) did not affect arousal or the curve. We modeled these findings in a neurobiologically plausible computational framework, showing how catecholaminergic modulation alters a disinhibitory neural circuit that encodes sensory evidence for decision-making. This work suggests that performance adapts flexibly to arousal fluctuations, ensuring optimal performance in each and every arousal state.

neuroscience↗

bioRxiv2023

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

Perceptual decision-making is highly dependent on the momentary arousal state of the brain, which fluctuates over time on a scale of hours, minutes, and even seconds. The textbook relationship between momentary arousal and task performance is captured by an inverted U-shape, as put forward in the Yerkes-Dodson law (Yerkes and Dodson, 1908). This law suggests optimal performance at moderate levels of arousal, and impaired performance at low or high arousal levels. However, despite its popularity, the evidence for this relationship in humans is mixed at best. Here, we use pupil-indexed arousal and performance data from various perceptual decision-making tasks to provide converging evidence for the inverted U-shaped relationship between spontaneous arousal fluctuations and performance across different decision types (discrimination, detection) and sensory modalities (visual, auditory). To further understand this relationship, we built a neurobiologically plausible mechanistic model and show that it is possible to reproduce our findings by incorporating two types of interneurons that are both modulated by an arousal signal. The model architecture produces two dynamical regimes under the influence of arousal: one regime in which performance increases with arousal, and another regime in which performance decreases with arousal, together forming an inverted U-shaped arousal-performance relationship. We conclude that the inverted U-shaped arousal-performance relationship is a general and robust property of sensory processing. It might be brought about by the influence of arousal on two types of interneurons that together act as a disinhibitory pathway for the neural populations that encode the available sensory evidence used for the decision. Significance statementWhen people are repeatedly performing the exact same task, their performance fluctuates over time. One of the causes of this behavioral variability is spontaneous fluctuations in arousal. According to the Yerkes-Dodson law, task performance is optimal at moderate levels of species arousal, with impaired performance at very low or high arousal levels. However, until now, the evidence supporting this law as a general mechanism in human decision-making is mixed, and a neural mechanism that may explain the inverted U-shaped arousal-performance relationship is lacking. We show that the Yerkes-Dodson law is a general law that holds for human observers across decision-making tasks and settings. Furthermore, we present a simple and neurobiologically plausible mechanistic model that can explain its existence.

neuroscience↗

bioRxiv2022

Catecholaminergic neuromodulation and selective attention jointly shape perceptual decision making

Perceptual decisions about sensory input are 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 perceptual decision-making and/or whether neuromodulatory systems in fact control attentional processes. To investigate the effects of two distinct neuromodulatory systems and spatial attention on perceptual decisions, we pharmacologically elevated cholinergic (through donepezil) and catecholaminergic (through atomoxetine) levels in humans performing a visuo-spatial attention task, while we measured electroencephalography (EEG). Both attention and catecholaminergic enhancement improved decision-making at the behavioral and algorithmic level, as reflected in increased perceptual sensitivity and the modulation of the drift rate parameter derived from drift diffusion modeling. Univariate analyses of EEG data time-locked to the attentional cue, the target stimulus, and the motor response, further revealed that attention and catecholaminergic enhancement both modulated pre-stimulus cortical excitability, cue- and stimulus-evoked sensory activity as well as parietal evidence accumulation signals. Interestingly, we observed both similar, unique, and interactive effects of attention and catecholaminergic neuromodulation on these behavioral, algorithmic, and neural markers of the decision-making process. Thereby, this study reveals an intricate relationship between attentional and catecholaminergic systems and advances our understanding about how these systems jointly shape various stages of perceptual decision-making.

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bioRxiv2020

Intact sensory processing but hampered conflict detection when stimulus input is task-irrelevant

Conflict detection in sensory input is central to adaptive human behavior. Perhaps unsurprisingly, past research has shown that conflict may even be detected in absence of conflict awareness, suggesting that conflict detection is an automatic process that does not require attention. To test the possibility of conflict processing in the absence of attention, we manipulated task relevance and response overlap of potentially conflicting stimulus features across six behavioral tasks. Multivariate analyses on human electroencephalographic data revealed neural signatures of conflict only when at least one feature of a conflicting stimulus was attended, regardless of whether that feature was part of the conflict, or overlaps with the response. In contrast, neural signatures of basic sensory processes were present even when a stimulus was completely unattended. These data reveal an attentional bottleneck at the level of objects, suggesting that object-based attention is a prerequisite for cognitive control operations involved in conflict detection.

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bioRxiv2019

Decreased alertness reconfigures cognitive control networks

Humans remarkable capacity to flexibly adapt their behaviour based on rapid situational changes is termed cognitive control. Intuitively, cognitive control is thought to be affected by the state of alertness, for example, when drowsy we feel less capable of adequately implementing effortful cognitive tasks. Although scientific investigations have focused on the effects of sleep deprivation and circadian time, little is known about how natural daily fluctuations in alertness in the regular awake state affect cognitive control. Here we combined a conflict task in the auditory domain with EEG neurodynamics to test how neural and behavioural markers of conflict processing are affected by fluctuations in alertness. Using a novel computational method, we segregated alert and drowsy trials from two testing sessions and observed that, although participants (both sexes) were generally sluggish, the typical Conflict Effect reflected in slower responses to conflicting information compared to non-conflicting information was still intact, as well as the moderating effect of previous conflict (Conflict Adaptation). However, the typical neural markers of cognitive control-local midfrontal-theta band power changes-that participants show during full alertness were no longer noticeable when alertness decreased. Instead, when drowsy, we found an increase in long-range information sharing (connectivity) between brain regions in the same frequency band. These results show the resilience of the human cognitive control system when affected by internal fluctuations of alertness, and suggest neural compensatory mechanisms at play in response to physiological pressure during diminished alertness. Significance StatementThe normal variability in alertness we experience in daily tasks is rarely taking into account in cognitive neuroscience. Here we studied neurobehavioral dynamics of cognitive control with decreasing alertness. We used the classic Simon Task where participants hear the word "left" or "right" in the right or left ear, eliciting slower responses when the word and the side are incongruent - the conflict effect. Participants performed the task both while fully awake and while getting drowsy, allowing for the characterisation of alertness modulating cognitive control. The changes in the neural signatures of conflict from local theta oscillations to a long-distance distributed theta network suggests a reconfiguration of the underlying neural processes subserving cognitive control when affected by alertness fluctuations.

neuroscience↗

bioRxiv2019

The brain detects stimulus features, but not stimulus conflict in task-irrelevant sensory input

Cognitive control over conflicting sensory input is central to adaptive human behavior. It might therefore not come as a surprise that past research has shown conflict detection in the absence of conscious awareness. This would suggest that the brain may detect conflict fully automatically, and that it can even occur without paying attention. Contrary to this intuition, we show that task-relevance is crucial for conflict detection. Univariate and multivariate analyses on electroencephalographic data from human participants revealed that when auditory stimuli are fully task-irrelevant, the brain disregards conflicting input entirely, whereas the same input elicits strong neural conflict signals when task-relevant. In sharp contrast, stimulus features were still processed, irrespective of task-relevance. These results show that stimulus properties are only integrated to allow conflict to be detected by prefrontal regions when sensory information is task-relevant and therefore suggests an attentional bottleneck at high levels of information analysis.

neuroscience↗