Biology subjects

de Gee, J. W.

Publications and source records attributed to de Gee, J. W..

18 recordsLinked to original sources

bioRxiv2026

Change-point oddball elicits pupil-linked signatures of Bayesian belief updating

The auditory oddball protocol is widely used to study neural responses to unexpected events. In conventional designs, however, stimulus statistics are stationary: deviants do not indicate environmental change and therefore should not drive learning. Here, we introduce change-point oddball, a passive, no-report protocol in which the standard-oddball mapping reverses at unpredictable change points, requiring inference over latent environmental states. We measured pupil-linked arousal in three human cohorts. Pupil responses were larger for state-specific oddballs than standards, decayed across newly established standards after state changes, and scaled with model-derived change-point probability. A many-standards control experiment implicated a prediction-based rather than repetition-based mechanism. Finally, within participants, stronger pupil encoding of change-point probability during the passive task was associated with greater change-point-sensitive belief updating in a separate active navigation task. Thus, passive change-point oddball preserves core signatures of adaptive belief updating, enabling cross-species and clinical investigations.

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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.

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bioRxiv2025

Task-irrelevant stimuli boost phasic pupil-linked arousal but not memory formation

AO_SCPLOWBSTRACTC_SCPLOWBrainstem arousal systems including the locus coeruleus noradrenaline system, respond transiently to behaviorally relevant events. Locus coeruleus activity also drives dilations of the pupil, which are often observed during cognitive tasks. The strength of pupil responses during encoding of stimulus material predicts the success of its later retrieval, which might reflect the impact of noradrenaline on synaptic plasticity and memory formation. The pupil also dilates in response to task-irrelevant sounds, which could therefore serve as a valuable tool for investigating causal effects of phasic, pupil-linked arousal on cognition. Here, we evaluated whether task-irrelevant white noise sounds affect memory formation and memory-based decisions. These sounds were played before, during or after the presentation of memoranda (images or spoken words). Memory success was measured in recognition and free recall tasks the day after. Trial-to-trial variations in the amplitude of pupil dilations during word encoding without task-irrelevant sounds predicted memory success. Task-irrelevant white-noise sounds also robustly dilated the pupil but did not improve memory formation for the words or the images. We conclude that pupil-linked arousal processes triggered by task-irrelevant sounds differ from those recruited endogenously during memory formation, for example in states of increased emotionality or attention.

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bioRxiv2024

Catecholamines reduce choice history biases

Theoretical accounts postulate that the catecholaminergic neuromodulator noradrenaline shapes cognition and behavior by reducing the impact of prior expectations on learning, inference, and decision-making. A ubiquitous effect of dynamic priors on perceptual decisions under uncertainty is choice history bias: the tendency to systematically repeat, or alternate, previous choices, even when stimulus categories are presented in a random sequence. Here, we directly test for a causal impact of catecholamines on these priors. We pharmacologically elevated catecholamine levels in human participants through the application of the noradrenaline reuptake inhibitor atomoxetine. We quantified the resulting changes in observers history biases in a visual perceptual decision task. Choice history biases in this task were highly idiosyncratic, tending toward choice repetition or alternation in different individuals. Atomoxetine decreased these biases (toward either repetition or alternation) compared to placebo. Behavioral modeling indicates that this bias reduction was due to a reduced bias in the accumulation of sensory evidence, rather than of the starting point of the accumulation process. Atomoxetine had no significant effect on other behavioral measures tested, including response time and choice accuracy. Atomoxetine and variations of pupil-linked arousal at slower and faster timescales had analogous effects on choice history bias. We conclude that catecholamines reduce the impact of a specific form of prior on perceptual decisions.

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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.

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bioRxiv2024

Task-irrelevant stimuli reliably boost phasic pupil-linked arousal but do not affect decision formation

The arousal systems of the brainstem, specifically the locus coeruleus-noradrenaline system, respond "phasically" during decisions. These central arousal transients are accompanied by dilations of the pupil. Mechanistic attempts to understand the impact of phasic arousal on cognition would benefit from the ability to experimentally manipulate arousal in a temporally precise manner. Here, we evaluated a non-invasive candidate approach for such a manipulation in humans: presenting task-irrelevant auditory stimuli at different latencies during the execution of a challenging task. Task-irrelevant auditory stimuli drive responses of brainstem nuclei involved in the control of pupil size. But it is unknown whether such sound-evoked responses mimic the central arousal transients evoked during cognitive computations. A large body of evidence has implicated central arousal transients in a bias reduction during challenging perceptual decisions. We thus used challenging visual decisions as a testbed, combining them with task-irrelevant sounds of varying onset latency or duration. Across three experiments, the sounds consistently elicited well-controlled pupil responses that superimposed onto task-evoked responses. While we replicated a negative correlation between task-evoked pupil responses and bias established in previous work, the task-irrelevant sounds had no behavioral effect. This dissociation suggests that cognitive task engagement and task-irrelevant sounds may recruit distinct neural systems contributing to the control of pupil size.

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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.

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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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bioRxiv2022

Auditory accessory stimulus boosts pupil-linked arousal and reduces choice bias

AO_SCPLOWBSTRACTC_SCPLOWRecent work indicates that pupil-linked phasic arousal signals reduce the impact of prior expectations and biases on decision formation. It has remained unclear whether phasic arousal (i) causes the bias reduction, if (ii) choosing against ones bias causes phasic arousal, or if (iii) a third variable is driving both. Here, using an auditory accessory stimulus, we found evidence for the first scenario: on accessory stimulus vs normal trials, pupil-linked phasic arousal was robustly elevated and choice bias was reduced. With computational modeling of behavior, we established that the bias reduction was not due to a change in response caution (i.e., speed-accuracy tradeoff), but due to a change in a bias in the accumulation of evidence leading up to a choice. Thus, pupil-linked phasic arousal shapes choice behavior.

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bioRxiv2022

Brainstem fMRI signaling of surprise across different types of deviant stimuli

The detection of deviant stimuli is crucial to orient and adapt our behavior. Previous work showed that infrequent (hence deviant) stimuli elicit phasic activation of the brainstem locus coeruleus (LC), which releases noradrenaline and controls central arousal. However, it is unclear whether the detection of behaviorally-relevant deviant events selectively trigger LC responses, or also other neuromodulatory systems related to dopamine, acetylcholine, and serotonin. Here, we combined human fMRI recordings optimized for brainstem imaging with pupillometry (a peripheral marker of central arousal) to perform a mapping of deviant-related responses in subcortical structures. Participants had to detect deviant items in a "local-global" paradigm that distinguishes between deviance based on the stimulus probability and the sequence structure. fMRI responses to deviant stimuli were quite distributed, detected in the LC but also other subcortical nuclei and many cortical areas. Both types of deviance elicited responses in the pupil, LC and other neuromodulatory systems. Our results reveal that the detection of task-relevant deviant items recruits the same multiple subcortical systems across computationally different types of deviance.

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bioRxiv2022

Mice regulate their attentional intensity and arousal to exploit increases in task utility

Changes in autonomic arousal, such as mounting sleep pressure, and changes in motivation, such as fluctuating environmental reward statistics, both profoundly influence behavior. Our experience tells us that we have some capacity to control our arousal when doing so is important, such as staying awake while driving a motor vehicle. However, little is known about how decision computations are jointly influenced by arousal and motivation, including whether animals, such as rodents, can adapt their arousal state to their needs. Here, we developed and show results from an auditory feature-based sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply novel signal detection theoretic and accumulation-to-bound modeling approaches in a large behavioral cohort. We find that both pupil-linked arousal and task utility have major impacts on multiple aspects of performance. Although substantial arousal fluctuations persist across utility conditions, mice partially stabilize their arousal near an intermediate, and optimal, level when task utility is high. Behavioral analyses show that multiple elements of behavior improve during high task utility and that arousal influences some, but not all, of them. Specifically, arousal influences the likelihood and timescale of sensory evidence accumulation, but not the quantity of evidence accumulated per time step while attending. In sum, the results establish specific decision-computational signatures of arousal, motivation, and their interaction, in attention. So doing, we provide an experimental and analysis framework for studying arousal self-regulation in neurotypical brains and diseases such as attention-deficit/hyperactivity disorder.

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bioRxiv2020

Pupil dilation and P3 reflect subjective surprise about decision outcome

Central to human and animal cognition is the ability to learn from feedback in order to optimize future rewards. Such a learning signal might be encoded and broadcasted by the brains arousal systems, including the noradrenergic locus coeruleus. Pupil responses and the positive slow wave component of event-related potentials reflect rapid changes in the arousal level of the brain. Here we ask whether and how these variables may reflect surprise: the mismatch between ones expectation about being correct and the outcome of a decision, when expectations fluctuate due to internal factors (e.g., engagement). We show that during an elementary decision-task in the face of uncertainty both physiological markers of phasic arousal reflect surprise. We further show that pupil responses and slow wave ERP are unrelated to each other, and that prediction error computations depend on feedback awareness. These results further advance our understanding of the role of central arousal systems in decision-making under uncertainty.

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bioRxiv2020

Comparing fMRI responses measured at 3 versus 7 Tesla across human cortex, striatum, and brainstem

Significant progress has been made in ultra-high field functional magnetic resonance imaging (fMRI) at 7 Tesla (T). While fMRI at 7 T promises a general increase in sensitivity compared to lower field strengths, the benefits may be most pronounced for specific applications. The current study aimed to evaluate the relative benefit of 7 T over 3 T fMRI for the assessment of task-evoked fMRI responses in different brain regions. We compared the amplitude of task-evoked responses between 3 T and 7 T measured from the same human participants. Participants performed a challenging random dot motion discrimination task with delayed monetary feedback, which animal physiology has linked to several cortical and subcortical structures including extrastriate (dorsal) visual cortical areas, the striatum, and the brainstem including dopaminergic midbrain nuclei. We quantified the evoked fMRI responses in each of these brain regions during the decision interval and the post-feedback interval of the task, and compared them between brain regions and field strengths. The dependence of response amplitudes on field strength during the decision interval differed between cortical, striatal, and brainstem regions, with a generally bigger 7 T vs. 3 T benefit in subcortical (in particular brainstem) structures. We also found stronger differential responses during easy than hard decisions at 7 T for the dopaminergic nuclei, possibly reflecting reward expectation. Our results demonstrate the potential of 7 T fMRI for illuminating the contribution of small brainstem nuclei to the orchestration of cognitive computations in the human brain. HighlightsO_LIWe compared 7 T to 3 T fMRI during perceptual decision-making under uncertainty. C_LIO_LIDifferences between 7 T and 3 T evoked responses and tSNR varied across the brain. C_LIO_LIEvoked responses in dopaminergic brainstem nuclei were bigger at 7 T than 3 T. C_LIO_LIThe responses of dopaminergic nuclei are consistent with reward expectation. C_LIO_LIResults highlight the potential of 7 T fMRI for imaging small brainstem nuclei. C_LI

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bioRxiv2019

Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

AO_SCPLOWBSTRACTC_SCPLOWVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an optimal zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.

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bioRxiv2018

Phasic arousal optimizes decision computations in mice and humans

Decisions are often made by accumulating ambiguous evidence over time. The brains arousal systems are activated during such decisions. In previous work in humans, we showed that evoked responses of arousal centers during decisions are reported by rapid dilations of the pupil, and predict a suppression of biases in the accumulation of decision-relevant evidence (de Gee et al. 2017). Here, we show that this arousal-related suppression in decision bias acts on both conservative and liberal biases, and generalizes across species (humans / mice), sensory systems (visual / auditory), and domains of decision-making (perceptual / memory-based). In challenging sound-detection tasks, the impact of spontaneous or experimentally induced choice biases was reduced under high arousal. Similar bias suppression occurred when evidence was drawn from memory. All these behavioral effects were explained by reduced evidence accumulation biases. Our results pinpoint a general principle of the interplay between phasic arousal and decision-making.

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bioRxiv2018

Task-evoked pupil responses reflect internal belief states

Perceptual decisions about the state of the environment are often made in the face of uncertain evidence. Internal uncertainty signals are considered important regulators of learning and decision-making. A growing body of work has implicated the brains arousal systems in uncertainty signaling. Here, we found that two specific computational variables, postulated by recent theoretical work, evoke boosts of arousal at different times during a perceptual decision: decision confidence (the observers internally estimated probability that a choice was correct given the evidence) before feedback, and prediction errors (deviations from expected reward) after feedback. We monitored pupil diameter, a peripheral marker of central arousal state, while subjects performed a challenging perceptual choice task with a delayed monetary reward. We quantified evoked pupil responses during decision formation and after reward-linked feedback. During both intervals, decision difficulty and accuracy had interacting effects on pupil responses. Pupil responses negatively scaled with decision confidence prior to feedback and scaled with uncertainty-dependent prediction errors after feedback. This pattern of pupil responses during both intervals was in line with a model using the observers graded belief about choice accuracy to anticipate rewards and compute prediction errors. We conclude that pupil-linked arousal systems are modulated by internal belief states.

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bioRxiv2018

Choice history biases subsequent evidence accumulation

AO_SCPLOWBSTRACTC_SCPLOWPerceptual choices depend not only on the current sensory input, but also on the behavioral context. An important contextual factor is the history of ones own choices. Choice history often strongly biases perceptual decisions, and leaves traces in the activity of brain regions involved in decision processing. Yet, it remains unknown how such history signals shape the dynamics of later decision formation. Models of perceptual choice construe decision formation as the accumulation of sensory evidence towards decision bounds. In this framework, it is commonly assumed that choice history signals shift the starting point of accumulation towards the bound reflecting the previous choice. We here present results that challenge this idea. We fit bounded-accumulation decision models to behavioral data from perceptual choice tasks, and estimated bias parameters that depended on observers previous choices. Across multiple task protocols and sensory modalities, individual history biases in overt behavior were consistently explained by a history-dependent change in the evidence accumulation, rather than in its starting point. Choice history signals thus seem to bias the interpretation of current sensory input, akin to shifting endogenous attention towards (or away from) the previously selected interpretation.

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bioRxiv2017

Criterion Setting Modulates Neural Excitability of Human Visual Cortex

Decision bias is traditionally conceptualized as an internal reference against which sensory evidence is compared. Instead, we show that individuals implement decision bias by shifting the rate of sensory evidence accumulation towards a decision bound. Participants performed a target detection task while we recorded EEG. We experimentally manipulated participants decision criterion for reporting targets using different stimulus-response reward contingencies, inducing either a liberal or a conservative bias. Drift diffusion modeling revealed that a liberal strategy biased sensory evidence accumulation towards target-present choices. Moreover, a liberal bias resulted in stronger midfrontal pre-stimulus 2-6 Hz (theta) power and suppression of pre-stimulus 8--12 Hz (alpha) power in posterior cortex. The alpha suppression in turn mediated the output activity of visual cortex, as expressed in 59--100 Hz (gamma) power. These findings show that observers can intentionally control cortical excitability to strategically bias evidence accumulation towards the decision bound that maximizes their reward.

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