Biology subjects

Nieuwenhuis, S.

Publications and source records attributed to Nieuwenhuis, S..

12 recordsLinked to original sources

bioRxiv2026

Pulsed taVNS-elicited pupil dilation: effects of intermixed stimulation, sham location and respiratory phase

Transcutaneous auricular vagus nerve stimulation (taVNS) may offer a powerful, noninvasive way to stimulate activity of brainstem arousal systems, including the locus coeruleus-norepinephrine (LC-NE) system. Pulsed taVNS is known to elicit pupil dilation, a marker of LC activity. However, studies reporting taVNS effects on pupil dilation have delivered taVNS and sham stimulation in separate blocks of trials or in separate sessions, hindering the integration of taVNS into rapid, event-related task designs of cognitive neuroscientists. In two experiments, we examined the effectiveness of pulsed taVNS in eliciting pupil dilation when active and sham stimulation were intermixed within the same blocks of trials, and whether these effects depend on sham location and respiratory phase. In Experiment 1 (N = 40), intermixed taVNS and (earlobe) sham pulses of 3.4 seconds produced inconclusive evidence for increased taVNS-evoked pupil dilation. In contrast, in Experiment 2 (N = 60), taVNS pulses of 1.0 seconds had a strong effect on pupil dilation, but only in a group of participants that received sham stimulation at the earlobe; this effect was abolished in a group that received sham stimulation at the upper scapha, a non-vagal control area with a similar density of sympathetic nerve fibers as the cymba concha. Furthermore, taVNS-evoked pupil dilation was not enhanced when stimulation was delivered during exhalation, as would be expected if pupil effects were mediated by the vagus nerve-nucleus tractus solitarius-LC pathway. Together, these findings show that the effect of pulsed taVNS on pupil dilation can be preserved when taVNS and (earlobe) sham are delivered in the same blocks of trials. However, the null finding with the scapha as sham location, and the absence of an enhanced taVNS effect during exhalation call into question the assumption that taVNS-induced pupil dilation is mediated by activation of the vagal afferent pathway.

neuroscience↗

bioRxiv2025

A dynamical systems model of arousal-driven behavioural state transitions

When completing a task, animals switch between being engaged and disengaged. What neural and physiological processes trigger these behavioural state transitions? We estimated the engagement state of mice performing a visual decision-making task using a hidden Markov model of response times and found that intermediate arousal, as measured using baseline pupil size, was associated with more engagement in the task. Additionally, we show that changes in arousal (both mean and variability of the pupil baseline) predict changes in behavioural state. To explain this, we propose a double-well model, in which arousal causes behavioural state transitions by reshaping the attractor landscape of population neural activity. These results highlight a possible mechanism of arousal-related changes in behaviour.

animal behavior and cognition↗

bioRxiv2024

Subcortical nuclei of the human ascending arousal system encode anticipated reward but do not predict subsequent memory

Subcortical nuclei of the ascending arousal system play an important role in regulating brain and cognition. However, functional MRI of these nuclei in humans involves unique challenges due to their size and location deep within the brain. Here, we used ultra-high-field MRI and other methodological advances to investigate the activity of six subcortical nuclei during reward anticipation and memory encoding: the locus coeruleus, basal forebrain, median and dorsal raphe nuclei, substantia nigra and ventral tegmental area. Participants performed a monetary incentive delay task, which successfully induced a state of reward anticipation, and a 24-hour delayed surprise memory test. Region-of-interest analyses revealed that activity in all subcortical nuclei increased in anticipation of potential rewards as opposed to neutral outcomes. In contrast, activity in none of the nuclei predicted memory performance 24 hours later. These findings provide new insights into the cognitive functions that are supported by the human ascending arousal system.

neuroscience↗

bioRxiv2024

Neuromodulatory influences on propagation of brain waves along the unimodal-transmodal gradient

Brain activity fluctuates over time, and understanding the factors that influence such fluctuations is important to understand the flexible nature of the brain and cognition. Growing evidence suggests that fMRI brain activity shows spatio-temporal patterns of propagation following specific gradients. In particular, activity around global peaks propagates as a travelling wave following a gradient from unimodal to associative areas. Some properties of these travelling waves seem to be related to behavioral and arousal states, however their meaning remains unknown. Here we assess the possibility that travelling waves explain the finding that there are specific time points when the brain presents larger brain integration. We reasoned that a faster speed of propagation would be related to more brain integration as measured with fMRI. Furthermore, we explored whether increased pupil-linked arousal, which has been related to more integration in specific brain regions, would be increased during periods of whole brain propagation. To test these hypotheses, we detected brain travelling waves and characterized them in terms of speed, directionality and ratio. We compared these features between different task conditions, and after a pharmacological challenge affecting neuromodulatory tone. We then studied the relation between travelling wave speed, pupil size and a graph-based measure of brain integration. Our results suggest that neuromodulatory tone affects travelling wave propagation, and that this propagation reflects changes in arousal and integrated functional connectivity features. This study provides a novel view of brain dynamics in terms of the effects of neruomodulatory influences across time scales.

neuroscience↗

bioRxiv2024

Phasic alertness generates urgency and amplifies competition between evidence accumulators

Although phasic alertness generally benefits cognitive performance, it often increases the interference caused by distracting information, resulting in impaired decision-making and cognitive control. However, it is unclear why phasic alertness has these negative effects. Here, we present a novel, biologically-informed account, according to which phasic alertness generates an evidence-independent urgency signal. This urgency signal shortens overall response times, but also amplifies competition between evidence accumulators, thus slowing down decision-making and impairing cognitive control. The key assumptions of this account are supported with pupil measurements and electrophysiological data from human decision-makers performing an arrow flanker task. We also show that a computational model of the flanker task that incorporates time-varying urgency can reproduce the behavioral effects of phasic alertness, but only when the evidence accumulators compete with each other through lateral inhibition. Our results reveal a close interplay between dynamic changes in urgency, cognitive control and evidence accumulation.

neuroscience↗

bioRxiv2024

Strength of low-frequency phase entrainment to external stimuli is associated with fluctuations in the brain's internal states

The brain attends to environmental rhythms by aligning the phase of internal oscillations. However, the factors underlying fluctuations in the strength of this phase entrainment remain largely unknown. In the present study we examined whether the strength of low-frequency EEG phase entrainment to rhythmic stimulus sequences varied with pupil size and posterior alpha-band power, thought to reflect arousal level and excitability of posterior cortical brain areas, respectively. We recorded pupil size and scalp EEG while participants carried out an intermodal selective attention task, in which they were instructed to attend to a rhythmic sequence of visual or auditory stimuli and ignore the other perceptual modality. As expected, intertrial phase coherence (ITC), a measure of entrainment strength, was larger for the task-relevant than for the task-irrelevant modality. Across the experiment, pupil size and posterior alpha power were strongly linked with each other. Interestingly, ITC tracked both variables: larger pupil size was associated with a selective increase in entrainment to the task-relevant stimulus sequence, whereas larger posterior alpha power was associated with a decrease in phase entrainment to both the task-relevant and task-irrelevant stimulus sequences. Exploratory analyses showed that a temporal relation between ITC and posterior alpha power emerged in the time periods around pupil maxima and pupil minima. These results indicate that endogenous sources contribute distinctly to the fluctuations of EEG phase entrainment. Significance statementFluctuations in cortical state powerfully shape the perception of external stimuli. Understanding the physiological signatures of cortical state fluctuations is crucial to understand how the brain selectively attends and switches between internal and external content. Here we studied how two signatures of attentional state, pupil-linked arousal and power in the alpha band, shape the entrainment of brain activity to low-frequency rhythmic stimuli. Our results reveal common and dissociable influences of these signatures at slow time scales. Furthermore, measuring and including pupil size and posterior alpha power as covariates in statistical models can help increase statistical power in studies focusing on EEG phase entrainment. Our study provides new evidence on a direct influence of cortical state on the perception of rhythmic stimuli.

animal behavior and cognition↗

bioRxiv2023

Non-invasive vagus nerve stimulation and the motivation to work for rewards: a replication

BackgroundThe vagus nerve is thought to be involved in the allostatic regulation of motivation and energy metabolism via gut-brain interactions. A recent study by Neuser and colleagues [1] provided novel evidence for this process in humans, by reporting a positive effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the invigoration of reward-seeking behaviors, especially for food rewards. ObjectiveWe conducted an independent direct replication of Neuser et al. [1], to assess the robustness of their findings. MethodsFollowing the original study, we used a single-blind, sham-controlled, randomized cross-over design. We applied left-sided taVNS in healthy human volunteers (n=40), while they performed an effort allocation task in which they had to work for monetary and food rewards. The replication study was purely confirmatory in that it strictly followed the analysis plans and scripts used by Neuser et al. [1]. ResultsAlthough, in line with Neuser et al. [1], we found strong effects of task variables on effort invigoration and effort maintenance, we failed to replicate their key finding: taVNS did not increase the strength of invigoration (p = .62); the data were five times more likely (BF10 = 0.19) under the null hypothesis. We also found substantial evidence against an effect of taVNS on effort maintenance (p = 0.50; BF10 = 0.20). ConclusionsOur results provide evidence against the idea that taVNS boosts the motivational drive to work for rewards. Our study also highlights the need for direct replications of influential taVNS studies.

neuroscience↗

bioRxiv2023

Short-term transcutaneous vagus nerve stimulation increases pupil size but does not affect EEG alpha power: a replication

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) is a promising brain stimulation method for the treatment of pharmaco-resistant epilepsy and depression. Its clinical efficacy is thought to depend on taVNS-induced activation of the locus coeruleus. However, unlike for invasive VNS, there is little evidence for an effect of taVNS on noradrenergic activity. ObjectiveWe attempted to replicate recently published findings by Sharon et al. (2021), showing that short bursts of taVNS transiently increased pupil size and decreased EEG alpha power, two correlates of central noradrenergic activity. MethodsFollowing the original study, we used a single-blind, sham-controlled, randomized cross-over design. We applied short-term (3.4 s) taVNS in healthy human volunteers (n=29), while collecting resting-state pupil-size and EEG data. To analyze the data, we used scripts provided by Sharon and colleagues. ResultsConsistent with Sharon et al. (2021), pupil dilation was significantly larger during taVNS than during sham stimulation (p = .009; Bayes factor supporting the difference = 7.45). However, we failed to replicate the effect of taVNS on EEG alpha power (p = .37); the data were four times more likely under the null hypothesis (BF10 = 0.28). ConclusionOur findings support the effectiveness of short-term taVNS in inducing transient pupil dilation, a correlate of phasic noradrenergic activity. However, we failed to replicate the recent finding by Sharon et al. (2021) that taVNS attenuates EEG alpha activity. Overall, this study highlights the need for continued research on the neural mechanisms underlying taVNS efficacy and its potential as a treatment option for pharmaco-resistant conditions. It also highlights the need for direct replications of influential taVNS studies.

neuroscience↗

bioRxiv2022

Assessing pupil size as an index of activation of subcortical ascending arousal system nuclei during rest

Neuromodulatory nuclei that are part of the ascending arousal system (AAS) play a crucial role in regulating cortical state and optimizing task performance. Pupil diameter, under constant luminance conditions, is increasingly used as an index of activity of these AAS nuclei. Indeed, task-based functional imaging studies in humans have begun to provide evidence of stimulus-driven pupil-AAS coupling. However, whether there is such a tight pupil-AAS coupling during rest is not clear. To address this question, we examined simultaneously acquired resting-state fMRI and pupil-size data from 74 participants, focusing on six AAS nuclei: the locus coeruleus, ventral tegmental area, substantia nigra, dorsal and median raphe nuclei, and cholinergic basal forebrain. Activation in all six AAS nuclei was optimally correlated with pupil size at 0-to 2-second lags, suggesting that spontaneous pupil changes were almost immediately followed by corresponding BOLD-signal changes in the AAS. These results suggest that spontaneous changes in pupil size that occur during states of rest can be used as a noninvasive general index of activity in AAS nuclei. Importantly, the nature of pupil-AAS coupling during rest appears to be vastly different from the relatively slow canonical hemodynamic response function that has been used to characterize task-related pupil-AAS coupling.

neuroscience↗

bioRxiv2020

Temporal expectation hastens sensory encoding but does not affect evidence quality

The ability to predict the timing of forthcoming events, known as temporal expectation, has a strong impact on human information processing. Although there is growing consensus that temporal expectations enhance the speed and accuracy of perceptual decisions, it remains unclear whether they affect the decision process itself, or non-decisional (sensory / motor) processes. Here, healthy human participants (N = 21; 18 female) used predictive auditory cues to anticipate the timing of low-contrast visual stimuli they were required to detect. Modelling of the behavioral data using a prominent sequential sampling model indicated that temporal expectations speeded up non-decisional processes but had no effect on decision formation. Electrophysiological recordings confirmed and extended this result: temporal expectations hastened the onset of a neural signature of decision formation, but had no effect on its build-up rate. Anticipatory alpha-band power was modulated by temporal expectation, and co-varied with intrinsic trial-by-trial variability in behavioral and neural signatures of the onset latency of the decision process. These findings highlight how temporal predictions optimize our interaction with unfolding sensory events. SIGNIFICANCE STATEMENTTemporal expectation enhances performance, but the locus of this effect remains debated. Here, we contrasted the two dominant accounts: enhancement through (1) expedited decision onset, or (2) an increase in the quality of sensory evidence. We manipulated expectations about the onset of a dim visual target using a temporal cueing paradigm, and probed the locus of the expectation effect with two complementary approaches: drift diffusion modeling of behavior, and estimation of the onset and progression of the decision process from a supramodal accumulation-to-bound signal in simultaneously measured EEG signals. Behavioral modeling and neural data provided strong, converging evidence for an account in which temporal expectations enhance perception by speeding up decision onset, without affecting evidence quality.

neuroscience↗

bioRxiv2018

Amplification and Suppression of Distinct Brain-wide Activity Patterns by Catecholamines

The widely projecting catecholaminergic (norepinephrine and dopamine) neurotransmitter systems profoundly shape the state of neuronal networks in the forebrain. Current models posit that the effects of catecholaminergic modulation on network dynamics are homogenous across the brain. However, the brain is equipped with a variety of catecholamine receptors with distinct functional effects and heterogeneous density across brain regions. Consequently, catecholaminergic effects on brain-wide network dynamics might be more spatially specific than assumed. We tested this idea through the analysis of functional magnetic resonance imaging (fMRI) measurements performed in humans (19 females, 5 males) at rest under pharmacological (atomoxetine-induced) elevation of catecholamine levels. We used a linear decomposition technique to identify spatial patterns of correlated fMRI signal fluctuations that were either increased or decreased by atomoxetine. This yielded two distinct spatial patterns, each expressing reliable and specific drug effects. The spatial structure of both fluctuation patterns resembled the spatial distribution of the expression of catecholamine receptor genes: 1 norepinephrine receptors (for the fluctuation pattern: placebo > atomoxetine), D2-like dopamine receptors (pattern: atomoxetine > placebo), and {beta} norepinephrine receptors (for both patterns, with correlations of opposite sign). We conclude that catecholaminergic effects on the forebrain are spatially more structured than traditionally assumed and at least in part explained by the heterogeneous distribution of various catecholamine receptors. Our findings link catecholaminergic effects on large-scale brain networks to low-level characteristics of the underlying neurotransmitter systems. They also provide key constraints for the development of realistic models of neuromodulatory effects on large-scale brain network dynamics.\n\nSIGNIFICANCE STATEMENTThe catecholamines norepinephrine and dopamine are an important class of modulatory neurotransmitters. Because of the widespread and diffuse release of these neuromodulators, it has commonly been assumed that their effects on neural interactions are homogenous across the brain. Here, we present results from the human brain that challenge this view. We pharmacologically increased catecholamine levels and imaged the effects on the spontaneous covariations between brain-wide fMRI signals at rest. We identified two distinct spatial patterns of covariations: one that was amplified and another that was suppressed by catecholamines. Each pattern was associated with the heterogeneous spatial distribution of the expression of distinct catecholamine receptor genes. Our results provide novel insights into the catecholaminergic modulation of large-scale human brain dynamics.

neuroscience↗

bioRxiv2017

Catecholaminergic Manipulation Alters Dynamic Network Topology Across Behavioral States

The human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic reorganization of the functional connectome. The ascending catecholaminergic arousal systems of the brain are a plausible candidate mechanism for driving alterations in network architecture, enabling efficient deployment of cognitive resources when the environment demands them. We tested this hypothesis by analyzing both task-free and task-based fMRI data following the administration of atomoxetine, a noradrenaline reuptake inhibitor, compared to placebo, in two separate human fMRI studies. Our results demonstrate that the manipulation of central catecholamine levels leads to a reorganization of the functional connectome in a manner that is sensitive to ongoing cognitive demands.

neuroscience↗