Biology subjects

O'Reilly, J. X.

Publications and source records attributed to O'Reilly, J. X..

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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bioRxiv2024

Noradrenaline causes a spread of association in the hippocampal cognitive map

The mammalian brain stores relationships between items and events in the world as cognitive maps in the hippocampal system. However, the neural mechanisms that control cognitive map formation remain unclear. Here, using a double-blind study design with a pharmacological intervention in humans, we show that the neuromodulator noradrenaline elicits a significant spread of association across the hippocampal cognitive map. This neural spread of association predicts overgeneralisation errors measured in behaviour, and is predicted by physiological markers for noradrenergic arousal, namely an increase in the pupil dilation response and reduced cortical GABAergic tone. Thus, noradrenaline sets the width of the smoothing kernel for plasticity across the cognitive map. Elevated noradrenaline can allow disparate memories to become linked, introducing potential for distortions in the cognitive map that deviate from direct experience. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=137 HEIGHT=200 SRC="FIGDIR/small/610602v3_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@85d4ceorg.highwire.dtl.DTLVardef@564073org.highwire.dtl.DTLVardef@a16111org.highwire.dtl.DTLVardef@ebe1fc_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2024

Memory consolidation during rest forms shortcuts in a cognitive map

Rest and sleep not only strengthen existing memories but also reorganise memories to generate new knowledge that extends beyond direct experience. However, it remains unclear both how memories are reorganised and the effect of this reorganisation on behaviour. Here, we designed a novel protocol to casually manipulate memory consolidation during rest using awake, contextual targeted memory reactivation (TMR). We found that promoting memory consolidation during rest qualitatively reorganises memories by forming shortcuts between memories which have not been experienced together. These shortcuts in memory extend beyond direct experience to facilitate our ability to make novel inferences. A series of control tests indicate that inference performance cannot be explained by quantitative strengthening of the experienced component links but are rather explained by qualitative changes in the cognitive map which involve formation of new shortcuts. Interestingly, we show that representing a shortcut may come with limitations, as shortcuts cannot be readily updated in response to rapid changes in the environment. Together, these findings reveal how memories are reorganised during awake rest to construct a cognitive map of our environment, while highlighting the constraints set by a trade-off between efficient and flexible behaviour.

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bioRxiv2023

The neurocomputational link between defensive cardiac states and approach-avoidance arbitration under threat

Fearful avoidance is a hallmark of anxiety disorders and often comes at a cost. It reduces the probability of threat and of obtaining rewards. Theoretical models predict that threat-induced psychophysiological states, such as freezing-related bradycardia, facilitate arbitration of approach-avoidance decisions. We indeed show that bradycardia states are linked to the neurocomputational underpinnings of approach-avoidance arbitration when facing varying reward and threat magnitudes. Bradycardia was not only linked to aversive value-related avoidance decisions but also to value comparison (a stronger tendency to approach vs. avoid when expected reward outweighs potential threat). An amygdala-striatal-prefrontal neural circuit supported approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating subjective outcome values and bradycardia states. These findings highlight the role of human freezing states in value-based decision making, relevant for optimal threat coping. They point to a specific role for amygdala/dACC in state-value integration under threat.

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bioRxiv2023

VmPFC supports persistence during goal pursuit through selective attention

Striking the balance between persistence with a goal and flexibility in the face of better options is critical for effectively organizing behaviour across time. While people are often biased towards completing their current goal (e.g. sunk cost biases), it is unclear how these biases occur at a mechanistic level, still allowing for some flexibility for goal abandonment. We propose that ventromedial prefrontal cortex (vmPFC) plays a critical role in orienting attention towards a current goal, prioritising goal completion but allowing for abandonment, particularly when the current goal fails. We developed a novel incremental goal pursuit task to study goal-directed attention and action in healthy individuals with functional magnetic resonance imaging (fMRI), and in an independent group of individuals with brain lesions. The task required participants to make sequential decisions between continuing to persist with a current goal (commitment), versus abandoning progress for a better alternative goal (flexibility). We show that individuals who persist more show greater goal-oriented attention outside the decision period. Increasing attentional capture by the current goal is also revealed in decision-making: people remain more likely to abandon from frustration (collapse of value of the current goal) than from temptation (attraction from valuable alternative goals). Strikingly, we find that our stable inter-individual metrics of persistence and goal-oriented attention were both predicted by baseline activity in vmPFC, tracking goal progress. We present converging evidence from an independent lesion patient study demonstrating the causal involvement of vmPFC in goal persistence: damage to the vmPFC reduces biases to over-persist with the current goal, leading to a performance benefit in our task.

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bioRxiv2022

Decision-making in dynamic, continuously evolving environments: quantifying the flexibility of human choice

During perceptual decision-making tasks, centroparietal EEG potentials report an evidence accumulation-to-bound process that is time locked to trial onset. However, decisions in real-world environments are rarely confined to discrete trials; they instead unfold continuously, with accumulation of time-varying evidence being recency-weighted towards its immediate past. The neural mechanisms supporting recency-weighted continuous decision making remain unclear. Here, we use a novel continuous task design to study how the Centroparietal Positivity (CPP) adapts to different environments that place different constraints on evidence accumulation. We show that adaptations in evidence weighting to these different environments are reflected in changes in the CPP. The CPP becomes more sensitive to fluctuations in sensory evidence when large shifts in evidence are less frequent, and the potential is primarily sensitive to fluctuations in decision-relevant (not decision-irrelevant) sensory input. A complementary triphasic component over occipito-parietal cortex encodes the sum of recently accumulated sensory evidence, and its magnitude covaries with parameters describing how different individuals integrate sensory evidence over time. A computational model based on leaky evidence accumulation suggests these findings can be accounted for by a shift in decision threshold between different environments, which is also reflected in the magnitude of pre-decision EEG activity. Our findings reveal how adaptations in EEG responses reflect flexibility in evidence accumulation to the statistics of dynamic sensory environments.

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bioRxiv2021

Computational specialization within the cortical eye movement system

Animals actively sample their environment through orienting actions such as saccadic eye movements. Saccadic targets are selected based both on sensory evidence immediately preceding the saccade, and a salience map or prior built up over multiple saccades. In the primate cortex, the selection of each individual saccade depends on competition between target-selective cells that ramp up their firing rate to saccade release. However it is less clear how a cross-saccade prior might be represented, either in neural firing or through an activity-silent mechanism such as modification of synaptic weights on sensory inputs. Here we present evidence from magnetoencephalography for two distinct processes underlying the selection of the current saccade, and the representation of the prior, in human parietal cortex. While the classic ramping decision process for each saccade was reflected in neural firing rates (measured in the event related field), a prior built up over multiple saccades was represented via modulation of the gain on sensory inputs from the preferred target, as evidenced by rapid frequency tagging. A cascade of computations over time (initial representation of the prior, followed by evidence accumulation and then updating) provides a mechanism by which a salience map may be built up across saccades in parietal cortex. It also provides insight into why evidence accumulation signals are present in parietal cortex, when inactivation of the region has been shown not to affect performance on single-trial tasks.

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bioRxiv2021

Defensive freezing and its relation to approach-avoidance decision-making under threat

Successful responding to acutely threatening situations requires adequate approach-avoidance decisions. However, it is unclear how threat-induced states-like freezing-related bradycardia-impact the weighing of the potential outcomes of such value-based decisions. Insight into the underlying computations is essential, not only to improve our models of decision-making but also to improve interventions for maladaptive decisions, for instance in anxiety patients and first-responders who frequently have to make decisions under acute threat. Forty-two participants made passive and active approach-avoidance decisions under threat-of-shock when confronted with mixed outcome-prospects (i.e., varying money and shock amounts). Choice behavior was best predicted by a model including individual action-tendencies and bradycardia, beyond the subjective value of the outcome. Moreover, threat-related bradycardia interacted with subjective value, depending on the action-context (i.e., passive vs. active). Specifically, in action-contexts incongruent with participants intrinsic action-tendencies, strong freezers showed diminished effects of subjective value on choice. These findings illustrate the relevance of testing approach-avoidance decisions in relatively ecologically valid conditions of acute and primarily reinforced threat. These mechanistic insights into approach-avoidance conflict-resolution may inspire biofeedback-related techniques to optimize decision-making under threat. Critically, the findings demonstrate the relevance of incorporating internal psychophysiological states and external action-contexts into models of approach-avoidance decision-making.

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bioRxiv2020

Medial frontal cortex activity predicts information sampling in economic choice

Decision-making not only requires agents to decide what to choose, but also how much information to sample before committing to a choice. Previously established frameworks for economic choice argue for a deliberative process of evidence accumulation across time. These tacitly acknowledge a role of information sampling, in that decisions are only made once sufficient evidence is acquired, yet few experiments have explicitly placed information sampling under the participants control. Here, we use functional MRI to investigate the neural basis of information sampling in economic choice, by allowing participants to actively sample information in a multi-step decision task. We show that medial frontal cortex (MFC) activity is predictive of further information sampling prior to choice. Choice difficulty (inverse value difference) was also encoded in MFC, but this effect was explained away by the inclusion of information sampling as a co-regressor in the general linear model. A distributed network of regions across prefrontal cortex encoded key features of the sampled information at the time it was presented. We propose that MFC is an important controller of the extent to which information is gathered before committing to an economic choice. This role may explain why MFC activity has been associated with evidence accumulation in previous studies, in which information sampling was an implicit rather than explicit feature of the decision.

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bioRxiv2019

Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques

One of the most influential accounts of central orbitofrontal cortex- that it mediates behavioral flexibility - has been challenged by the finding that discrimination reversal in macaques -the classic test of behavioral flexibility -is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.

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bioRxiv2018

A network for computing value homeostasis in the human medial prefrontal cortex

Humans and other animals make decisions in order to satisfy their goals. However, it remains unknown how neural circuits compute which of multiple possible goals should be pursued (e.g. when balancing hunger and thirst) and combine these signals with estimates of available reward alternatives. Here, humans undergoing functional magnetic resonance imaging (fMRI) accumulated two distinct assets over a sequence of trials. Financial outcomes depended on the minimum cumulate of either asset, creating a need to maintain \"value homeostasis\" by redressing any imbalance among the assets. BOLD signals in the dorsal anterior cingulate cortex (dACC) tracked the level of homeostatic imbalance among goals, whereas the ventromedial prefrontal cortex (vmPFC) signalled the level of homeostatic redress incurred by a choice, rather than the overall amount received. These results suggest that a network of medial frontal brain regions compute a value signal that maintains homeostatic balance among internal goals.

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bioRxiv2018

Causal explanation of individual differences in human sensorimotor memory formation

Sensorimotor cortex mediates the formation of adaptation memory. Individuals differ in the rate at which they acquire, retain, and generalize adaptation. We present a mechanistic explanation of the neurochemical and computational causes of this variation in humans. Neuroimaging identified structural, functional and neurochemical covariates of a computational parameter that determines memory persistence. To establish causality, we increased sensorimotor cortex excitability during adaptation, using transcranial direct current stimulation. As predicted, this increased retention. Inter-individual variance in the stimulation-induced E:I increase predicted the computational change, which predicted the memory gain. These relations did not hold, and memory was unchanged, with stimulation applied before adaptation. This cognitive state dependent effect was modulated by the BDNF val66met genetic polymorphism. Memory was enhanced by stimulation in Val/Val carriers only, implicating a mechanistic role for activity-dependent BDNF secretion. Sensorimotor cortex E:I causally determines the time constant of memory persistence, explaining phenotypic variation in adaptation decay.

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bioRxiv2017

Towards a neuro-computational account of prism adaptation

Prism adaptation has a long history as an experimental paradigm used to investigate the functional and neural processes that underlie sensorimotor control. In the neuropsychology literature, functional explanations of prism adaptation are typically framed within a traditional cognitive psychology box-and-arrow framework that distinguishes putative component functions thought to give rise to behaviour (i.e. strategic control versus spatial realignment). However, this kind of theoretical framework lacks precision and explanatory power. Here, we advocate for a computational framework that offers several advantages: 1) an algorithmic explanatory account of the computations and operations that drive behaviour; 2) expressed in quantitative mathematical terms; 3) embedded within a principled theoretical framework (Bayesian decision theory, state-space modelling); 4) that offers a means to generate and test quantitative behavioural predictions. This computational framework offers a route toward mechanistic explanations of prism adaptation behaviour. Thus it constitutes a conceptual advance compared to the traditional theoretical framework. In this paper, we illustrate how Bayesian decision theory and state-space models offer principled explanations for a range of behavioural phenomena in the field of prism adaptation (e.g. visual capture, magnitude of visual versus proprioceptive realignment, spontaneous recovery and dynamics of adaptation memory). We argue that this explanatory framework offers to advance understanding of the functional and neural mechanisms that implement prism adaptation behaviour, by enabling quantitative tests of hypotheses that go beyond mere descriptive mapping claims that brain area X is (somehow) involved in psychological process Y.

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