Biology subjects

Jocham, G.

Publications and source records attributed to Jocham, G..

13 recordsLinked to original sources

bioRxiv2026

Cholinergic and noradrenergic modulation of perceptual decision making and learning

Decision making often requires the integration of noisy bottom-up sensory evidence with top-down prior expectations learned from past experiences. Acetylcholine and noradrenaline have been proposed to shape these computations, yet it remains unclear whether they directly influence the weighting of sensory evidence and prior expectations during decision making or instead shape the learning process that gives rise to these expectations. To disentangle this, healthy participants (n = 62) completed a perceptual decision-making task under the influence of either the muscarinic acetylcholine receptor antagonist biperiden, the {beta}-adrenoceptor antagonist propranolol, or placebo, in a within-subject crossover design. The task required the integration of sensory evidence with learned expectations. The reliability of these two sources of information varied independently. We show that both drugs led to a faster updating of current beliefs in response to new evidence. Under propranolol, these effects were specific to reward outcomes, whereas under biperiden, faster updating in response to both reward and non-reward outcomes resulted in less stable beliefs. Notably, neither drug affected the degree to which choices were governed by the strength of the sensory evidence. Together, these findings suggest that acetylcholine and noradrenaline guide perceptual decision making by modulating the updating of top-down prior expectations in response to new bottom-up evidence during learning.

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bioRxiv2026

Role of GABA and NMDA receptors in shaping cortical timescales and large-scale network dynamics

Cortical brain regions integrate information across different timescales, ranging from fast sensory processing to longer integration windows, allowing cognitive functions like working memory. At the large-scale, brain regions organize into transient network states that rapidly switch over time and similarly contribute to cognition. Both cortical timescales and large-scale network dynamics are proposed to be determined by the balance between recurrent synaptic excitation and GABAergic inhibition. Here, we pharmacologically manipulated synaptic transmission at GABAA and NMDA receptors in 60 healthy male participants and acquired resting-state magnetoencephalography. Neuronal timescales followed a hierarchical gradient with shorter timescales in early sensory regions. Increasing GABAergic activity prolonged neuronal timescales across cortical regions. This effect was most prominent in the frontal default mode and in the dorsal attention network. Notably, dynamic network analyses revealed that the occurrence probability of the frontal default mode network increased, whereas the occurrence of the dorsal attention network was reduced. NMDA receptor modulation resulted in no significant changes. Together, these findings provide causal evidence that GABAergic inhibition is a key regulator of cortical temporal organization, linking microscale synaptic mechanisms to neuronal timescales and network dynamics that support diverse cognitive function.

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bioRxiv2024

A role for acetylcholine in reinforcement learning and decision making under uncertainty

The neuromodulator acetylcholine has been suggested to govern learning under uncertainty. Here, we investigated the role of muscarinic acetylcholine receptors in reward-guided learning and decision making under different degrees of uncertainty. We administered the muscarinic antagonist biperiden (4 mg) to healthy male participants (n = 43) in a within-subjects, placebo-controlled design. Participants performed a gambling and a learning task involving different levels of uncertainty, while magnetoencephalography (MEG) was recorded. We show that biperiden did not affect decision making in the gambling task, where no learning was required. However, in the learning task, where option values were associated with uncertainty, biperiden reduced the sensitivity to probabilities, particularly when choice-outcome-contingencies switched frequently. Reinforcement learning models revealed that the change in behaviour was caused by noisier estimates of probabilities resulting from increased learning rates for rewarded choices under biperiden. These behavioural findings were paralleled by elimination of the lateral prefrontal representation of learnt reward probability in high-beta (20 - 30 Hz) power under biperiden. Together, these findings suggest that muscarinic acetylcholine transmission controls learning in highly uncertain contexts, when the demand for carefully calibrated adjustments is highest.

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bioRxiv2024

Patch-leaving decisions and pupil-linked arousal systems

Deciding when to abandon a depleting resource in favour of potentially richer alternatives is fundamental to adaptive behaviour. Such patch-leaving decisions require balancing the expected advantage of leaving against both the cost of moving and the reward foregone in the current environment. Previous research suggests that activity of noradrenergic (NE) neurons in the locus coeruleus (LC) underpins patch-leaving. In the current study, we used pupil dilation as a time-resolved readout of subcortical neuromodulation during patch-leaving. We hypothesised that leave decisions will be preceded by a transient pupil dilation. Participants harvested from exponentially depleting patches (blueberry bushes) with three initial reward values, in two environments, which differed in the variability of initial reward values. Behavioural results show that, as predicted by the mathematically optimal solution, participants adjusted their decisions based on the instantaneous reward rate, but also displayed a bias to overharvest (stay longer in compared to the optimum), which was more pronounced in the high variability environment. Pupil size was overall larger in the high variability environment, associated with increased uncertainty. Importantly, we observed an increased transient pupil dilation in response to reward outcomes immediately preceding leave compared to stay decisions, as well as an increase in pupil dilation (and RT) across successive stay trials, leading up to leave decisions, presumably indicating an increased LC-NE activity associated with abandoning current options to explore alternatives.

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bioRxiv2024

Bidirectional modulation of reward-guided decision making by dopamine

RationaleThe neuromodulator dopamine is known to play a key role in reward-guided decision making, where choice options are often characterized by multiple attributes. Different decision strategies can be used to merge these choice attributes with personal preferences (e.g., risk preferences) and integrate them into a single subjective value. While the influence of dopamine on risk preferences has been investigated, it is unknown whether dopamine is also involved in arbitrating between decision strategies. ObjectiveIn the present study, we investigate the effects of pharmacological dopamine manipulations on arbitrating between different decision strategies in a healthy sample. Methods31 healthy male participants performed a reward-guided decision-making task under the influence of the dopamine D2/D3-receptor antagonist amisulpride (400 mg), the dopamine precursor L-DOPA (100 mg L-DOPA + 25 mg cardidopa), or placebo in a double-blind within-subject design. The effect of dopamine on reward-guided decisions and decision strategies was analyzed using hierarchical implementations of regressions and Bayesian models. ResultsNotably, we observed that the dopaminergic interventions shifted the (overall) weighting of option attributes without changing how option attributes are integrated into a subjective value (decision strategy). These effects were bidirectional: Amisulpride reduced whereas L-DOPA increased the degree to which choices were influenced by both reward magnitude and reward probability. These effects occurred in the absence of changes in statistically optimal behavior. ConclusionTogether, our data provide evidence for a role of dopamine in controlling the influence of value parameters on choice irrespective of decision strategies.

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bioRxiv2023

Dopaminergic and Cholinergic Modulation of Human Cost-Benefit Decision Making

In everyday life, we encounter situations that require tradeoffs between potential rewards and associated costs, such as time and (physical) effort. The literature indicates a prominent role for dopamine in discounting of both delay and effort, with mixed findings for delay discounting in humans. Moreover, the reciprocal antagonistic interaction between dopaminergic and cholinergic transmission in the striatum suggests a potential opponent role of acetylcholine in these processes. We found opposing effects of dopamine D2 (haloperidol) and acetylcholine M1 receptor (biperiden) antagonism on specific components of effort-based decision making in healthy humans: haloperidol decreased, whereas biperiden increased the willingness to exert physical effort. In contrast, delay discounting was reduced under haloperidol, but not affected by biperiden. Together, our data suggest that dopamine, acting at D2 receptors, modulates both effort and delay discounting, while acetylcholine, acting at M1 receptors, appears to exert a more specific influence on effort discounting only.

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bioRxiv2023

Tonic and phasic transcutaneous auricular Vagus Nerve Stimulation both evoke rapid and transient pupil dilation

BackgroundTranscutaneous auricular vagus nerve stimulation (tVNS or taVNS) is a non-invasive method of electrical stimulation of the afferent pathway of the vagus nerve, suggested to drive changes in putative physiological markers of noradrenergic activity, including pupil dilation. ObjectiveHowever, it is unknown whether different taVNS modes can map onto the phasic and tonic modes of noradrenergic activity. The effects of taVNS on pupil dilation in humans are inconsistent, largely due to differences in stimulation protocols. Here, we attempted to address these issues. MethodsWe investigated pupil dilation under phasic (1 s) and tonic (30 s) taVNS, in a pre-registered, single-blind, sham-controlled, within-subject cross-over design, in the absence of a behavioural task. ResultsPhasic taVNS induced a rapid increase in pupil size over baseline, significantly greater than under sham stimulation, which rapidly declined after stimulation offset. Tonic taVNS induced a similarly rapid (and larger than sham) increase in pupil size over baseline, returning to baseline within 5 s, despite the ongoing stimulation. Thus, both active and sham tonic modes closely resembled the phasic effect. There were no differences in tonic baseline pupil size, and no sustained effects of stimulation on tonic baseline pupil size. ConclusionsThese results suggest that both phasic- and tonic-like taVNS under the standard stimulation parameters may modulate primarily the phasic mode of noradrenergic activity, as indexed by evoked pupil dilation, over and above somatosensory effects. This result sheds light on the temporal profile of phasic and tonic stimulation, with implications for their applicability in further research.

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bioRxiv2022

Removal of reinforcement improves instrumental performance in humans by decreasing a general action bias rather than unmasking learnt associations

Performance during instrumental learning is commonly believed to reflect the knowledge that has been acquired up to that point. However, recent work in rodents found that instrumental performance was enhanced during periods when reinforcement was withheld, relative to periods when reinforcement was provided. This suggests that reinforcement may mask acquired knowledge and lead to impaired performance. In the present study, we investigated whether such a beneficial effect of removing reinforcement translates to humans. Specifically, we tested whether performance during learning was improved during non-reinforced relative to reinforced task periods using signal detection theory and a computational modelling approach. To this end, 60 healthy volunteers performed a novel visual go/no-go learning task with deterministic reinforcement. To probe acquired knowledge in the absence of reinforcement, we interspersed blocks without feedback. In these non-reinforced task blocks, we found an increased d, indicative of enhanced instrumental performance. However, computational modelling showed that this improvement in performance was not due to an increased sensitivity of decision making to learnt values, but to a more cautious mode of responding, as evidenced by a reduction of a general response bias. Together with an initial tendency to act, this is sufficient to drive differential changes in hit and false alarm rates that jointly lead to an increased d. To conclude, the improved instrumental performance in the absence of reinforcement observed in studies using asymmetrically reinforced go/no-go tasks may reflect a change in response bias rather than unmasking latent knowledge. Author SummaryIt appears plausible that we can only learn and improve if we are told what is right and wrong. But what if feedback overshadows our actual expertise? In many situations, people learn from immediate feedback on their choices, while the same choices are also used as a measure of their knowledge. This inevitably confounds learning and the read-out of learnt associations. Recently, it was suggested that rodents express their true knowledge of a task during periods when they are not rewarded or punished during learning. During these periods, animals displayed improved performance. We found a similar improvement of performance in the absence of feedback in human volunteers. Using a combination of computational modelling and a learning task in which humans performance was tested with and without feedback, we found that participants adjusted their response strategy. When feedback was not available, participants displayed a reduced propensity to act. Together with an asymmetric availability of information in the learning environment, this shift to a more cautious response mode was sufficient to yield improved performance. In contrast to the rodent study, our results do not suggest that feedback masks acquired knowledge. Instead, it supports a different mode of responding.

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bioRxiv2022

Intermediately Synchronised Brain States optimise trade-off between Subject Identifiability and Predictive Capacity

Functional connectivity (FC) refers to the statistical dependencies between activity of distinct brain areas. To study temporal fluctuations in FC within the duration of a functional magnetic resonance imaging (fMRI) scanning session, researchers have proposed the computation of an edge time series (ETS) and their derivatives. Evidence suggests that FC is driven by a few time points of high-amplitude co-fluctuation (HACF) in the ETS, which may also contribute disproportionately to interindividual differences. However, it remains unclear to what degree different time points actually contribute to brain-behaviour associations. Here, we systematically evaluate this question by assessing the predictive utility of FC estimates at different levels of co-fluctuation using machine learning (ML) approaches. We demonstrate that time points of lower and intermediate co-fluctuation levels provide overall highest subject specificity as well as highest predictive capacity of individual-level phenotypes.

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bioRxiv2020

Reinstatement of cortical outcome representations during higher-order learning

Naturalistic learning scenarios are characterized by infrequent experience of external feedback to guide behavior. Higher-order learning mechanisms like second-order conditioning (SOC) may allow stimuli that were never experienced together with reinforcement to acquire motivational value. Despite its explanatory potential for real-world learning, surprisingly little is known about the neural mechanism underlying such associative transfer of value in SOC. Here, we used multivariate cross-session, cross-modality searchlight classification on functional magnetic resonance imaging data obtained from humans during SOC. We show that visual first-order conditioned stimuli (CS) reinstate cortical patterns representing previously paired gustatory outcomes in the lateral orbitofrontal cortex (OFC). During SOC, this OFC region showed increased functional covariation with amygdala, where neural pattern similarity between second-order CS and outcomes increased from early to late stages of SOC. Our data suggest a mechanism by which motivational value is conferred to stimuli that were never paired with reinforcement.

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bioRxiv2020

A causal role for estradiol in human reinforcement learning

The sex hormone estrogen is hypothesized to play a key role in human cognition via its interactions with the dopaminergic system. Work in rodents has shown that estrogens most potent form, estradiol, impacts striatal dopamine functioning predominately via increased D1-receptor signalling, while human work has suggested that high estradiol levels are associated with altered reward sensitivity. Here, we addressed two fundamental questions: 1) whether estradiol causally alters reward sensitivity in men, and 2) whether this effect of estradiol is moderated by individual variation in polymorphisms of dopaminergic genes. To test this, we performed a double-blind placebo-controlled administration study in which hundred men received either a single dose of estradiol (2 mg) or placebo. We found that estradiol administration increased reward sensitivity, which was moderated by baseline dopamine. This was observed in choice behaviour and increased learning rates. These results confirm a causal role of estradiol in reinforcement learning in men that is moderated by the striatal dopaminergic pathway.

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bioRxiv2019

Dissociable roles of cortical excitation-inhibition balance during patch-leaving versus value-guided decisions

In a dynamic world, it is essential to decide when to leave an exploited resource. Such patch-leaving decisions involve balancing the cost of moving against the gain expected from the alternative patch. This is in contrast with value-guided decisions that typically involve maximizing reward by selecting the current best option. Patterns of neuronal activity pertaining to patch-leaving decisions have been reported in the dorsal anterior cingulate cortex (dACC), whereas competition via mutual inhibition in the ventromedial prefrontal cortex (vmPFC) is thought to underlie value-guided choice. Here, we show that the balance between cortical excitation and inhibition (E/I balance), measured by the ratio of GABA and glutamate concentrations, plays a dissociable role for the two kinds of decisions. Patch-leaving decision behaviour was related to E/I balance in dACC. In contrast, value-guided decision making was related to E/I balance in vmPFC. These results support previous mechanistic accounts of value-guided choice and provide novel evidence for a role of dACC E/I balance in patch-leaving decisions.

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bioRxiv2019

Decisions bias future choices by modifying hippocampal associative memories

Decision making is guided by memories of option values. However, retrieving items from memory renders them malleable. Here, we show that merely retrieving values from memory and making a choice between options is sufficient both to induce changes to stimulus-reward associations in the hippocampus and to bias future decision making. After allowing participants to make repeated choices between reward-conditioned stimuli, in the absence of any outcome, we observed that participants preferred stimuli they had previously chosen, and neglected previously unchosen stimuli, over otherwise identical-valued options. Using functional brain imaging, we show that decisions induced changes to hippocampal representations of stimulus-outcome associations. These changes were correlated with future decision biases. Our results indicate that choice-induced preference changes are partially driven by choice-induced modification of memory representations and suggest that merely making a choice - even without experiencing any outcomes - induces associative plasticity.

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