Learning & Memory

Brainstem arousal systems including the locus coeruleus noradrenaline system, re-spond 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 for-mation, for example in states of increased emotionality or attention.

Cognitive flexibility, switching behaviour responses to changing task demands, is classically attributed to the prefrontal cortex. Yet thalamocortical circuits involving the mediodorsal thalamus (MD) and thalamic nucleus reuniens (Re) are dysfunctional across a range of neurological conditions with cognitive flexibility deficits. Interventions involving thalamocortical interactions may offer therapeutic benefits. Here we examined the effects of MD or Re bilateral glutamatergic neurotoxic damage in rats on cognitive flexibility using the attentional set-shifting task. Rats must attend to a sensory dimension that reliably predicts reward (intradimensional shift, ID) followed by a shift in attention to a previously irrelevant sensory dimension when contingencies change (extradimensional shift, ED). We found MD rats required more trials to criterion in the ED, while Re rats showed significant impairments on the first of three ID subtasks (ID1) only. Both MD and Re rats required more trials to criterion to complete each subtask than Sham controls. Intraperitoneal noradrenaline (atipamezole 1mg/kg), given 30 minutes prior to the task reduced trials to criterion across all rats, improving cognitive flexibility even after thalamic damage. These findings demonstrate the influence MD and Re contribute to cognitive flexibility and support noradrenergic regulation of thalamocortical circuits as potential therapeutic targets for cognitive flexibility dysfunction.

Humans order numbers in space from left to right, with smaller quantities represented preferentially in the left hemispace and larger ones in the right hemispace. The direction of this mental number line (MNL), or more generally of number-space associations (NSA), is influenced by cultural habits such as reading and writing direction. However, a growing body of evidence from pre-verbal infants and non-human animals suggests that number-space mappings may also have biological foundations. In non-human primates, evidence for a directional MNL remains mixed, partly due to small sample sizes and methodological heterogeneity. Here, we tested samples of rhesus (Macaca mulatta) and crab-eating macaques (Macaca fascicularis) across two experiments using spontaneous food-related tasks. In Experiment 1, monkeys chose between identical food quantities (1x1 to 24x24) presented on the left and right. No systematic spatial choice bias emerged as a function of numerical magnitude, and hand use did not differ across exact numerical pairs, although exploratory analyses revealed magnitude-related modulations of manual responses. In Experiment 2, monkeys were habituated to small (4x4) or large (16x16) quantities and subsequently tested with the alternative quantity. Result showed significantly more leftward choices following numerical decreases (16[->]4) and more rightward choices following numerical increases (4[->]16), indicating that relative numerical context, rather than absolute magnitude, elicited directional spatial biases. These findings suggest that in macaques, number-space associations emerge most robustly in comparative contexts involving expectancy violations of magnitude.

Decisions based on evidence accumulated over time require rules governing when to end the accumulation process and commit to a choice. These rules control inherent trade-offs between decision speed and accuracy, which require careful balance to maximize quantities that depend on both like reward rate. We previously showed that, to maximize reward rate, normative decision rules adapt to changing task conditions (Barendregt et al., 2022). Here we used a novel task to examine whether and how people use adaptive rules for individual decisions under a variety of conditions, including changes in decision outcomes across trials and changes in evidence quality both across and within trials. We found that the participants tended to use rules that adjusted, at least partially, to predictable changes in task conditions to improve reward rate, consistent with a rationally bounded implementation of normative principles. These findings help inform our understanding of the extent and limits of flexible decision formation in the brain.

Spatialization in working memory refers to the spatial coding of non-spatial information along a mental horizontal line when encoding verbal material. This phenomenon is thought to support working memory by facilitating order encoding. Although it has been observed for both visually and auditorily presented stimuli, no direct comparison has yet examined whether these modalities rely on similar neural mechanisms. In this study, we investigated whether spatialization in visual and auditory modalities involves shared or distinct patterns of activity within the working-memory network. Forty-nine participants performed both a visual and an auditory working memory SPoARC task of the same verbal material, allowing to study the cortical patterns associated with distinct serial positions at both encoding and recognition across sensory modalities. Whole-brain analyses revealed similar frontoparietal networks across conditions. In addition, a representational similarity analysis (RSA) was conducted to assess the similarity of neural patterns between early and late serial positions in a sequence and across sensory modalities. This multivoxel pattern analysis revealed modality-dependent patterns distinguishing early and late positions in the inferior frontal gyrus. Additional modality-specific effects were observed in the anterior intraparietal sulcus in the visual modality and in the posterior hippocampus in the auditory modality. Drawing on the framework proposed by Bottini & Doeller (2020), we propose that order decoding in the IPS might reflect a low-dimensional spatial coding of order (e.g., along a horizontal axis), whereas order decoding in the hippocampus might reflect higher-dimensional spatial representations or temporal representations.

Numerical abilities are widespread in the animal kingdom and are not exclusive to humans. Domestic chicks (Gallus gallus) have been shown to discriminate numerosities spontaneously, but prior research has focused exclusively on the visual modality. Whether chicks can discriminate numerical information in the auditory domain remains unknown, despite evidence that they can perceive other auditory features such as tone and rhythm. In this study, we investigated spontaneous numerical discrimination in the auditory modality in naive domestic chicks. In Experiment 1, newly-hatched chicks were tested for their ability to discriminate between two auditory sequences differing in numerosity (4 vs. 12 identical sounds), with and without controlling for continuous variables such as duration and total sound amount. Experiment 2 examined chicks filial imprinting responses to familiar or unfamiliar numerosities. Experiment 3 controlled for potential spontaneous preferences for a single longer sound versus a shorter one. Our results showed a preference for the 12-sound sequence only when duration and total sound amount were not matched. When these continuous variables were controlled, no spontaneous numerical preference emerged. Experiment 2 revealed an overall preference for the 12-sound sequence regardless of imprinting conditions, while Experiment 3 confirmed that chicks do not have an inherent preference for longer sounds. These findings suggest that chicks are sensitive to overall magnitude in the auditory domain but do not spontaneously discriminate numerical differences when other continuous variables are held constant. Future studies will explore how specific stimulus features, such as heterogeneity of sounds, influence these preferences.

Despite growing evidence that many animals can evaluate quantities, the ecological relevance of numerical cognition remains debated, particularly outside vertebrates. Would individuals still rely on numerousness if less computationally demanding cues, visual features extracted at the early stage of visual processing, were available to assess quantity? In primates, individuals show a numerical bias as they tend to rely on the number of items rather than non-numerical cues, such as total area, to categorize quantities. In this study, we trained free-flying honeybees to discriminate between two and four items in conditions where numerosity covaried with the total area and perimeter (Experiment Size) or the convex hull (Experiment Space) cues, mimicking ecological contexts. Transfer tests assessed which numerical or non-numerical cues were learned and preferentially used by the bees. Bees primarily relied on numerousness over these non-numerical cues. Individual analyses revealed two consistent strategies: a "numerical bias" strategy, in which bees encoded numerical information while ignoring non-numerical cues, and a "generalist" strategy, where bees flexibly switched between cues and favored non-numerical information when cues conflicted. We further reported improved discrimination when smaller quantities appeared on the left and larger ones on the right, consistent with an oriented mental number line. Together, these findings demonstrate a spontaneous numerical bias in honeybees and reveal that individuals within the same species can adopt distinct strategies when evaluating quantity. Our findings also suggest that distantly related taxa like bees and primates may have independently evolved comparable mechanisms for quantity evaluation.

Working memory (WM) provides a flexible but capacity-limited workspace for maintaining information over short intervals, whereas long-term memory (LTM) serves as a vast and enduring repository for preserving information over extended periods. Decades of research suggest that they are two distinct yet connected systems that together enable adaptive behavior. The link between WM and LTM may not be straightforward, however, as recent evidence has shown that activation-dependent competition among items in WM can weaken their representations in LTM. In the current study, we examined how dynamic competition among items for limited WM resources affects their retention in LTM. We induced competition between items by manipulating temporal expectations in a WM task with either a short (1 s) or a long (4 s) memory delay. Human participants (N = 20) initially prioritized items expected to be tested early, but shifted their priority to items expected to be tested later when the early test did not occur. Using electroencephalography (EEG) and multivariate pattern analysis (MVPA), we tracked the dynamic fluctuations in WM contents based on expected task relevance across the delay window. We linked these temporal profiles during WM with the long-term recognition performance of each item and found that forgetting was associated with a marked decrease in neural evidence for items deemed no longer relevant during the later delay period. These results demonstrate that WM representations fluctuate with temporal expectations and that the de-prioritization of items during WM maintenance is what drives their long-term forgetting.

Episodic memory depends on neural representations encoded in the hippocampus. Experimental and computational evidence suggests that the hippocampus encodes pattern-separated representations that support later recall of episodic event elements. While extant data in humans predominantly focus on assaying the relationship between the similarity of spatial neural patterns at encoding and later memory performance, similarity of neural patterns in the temporal domain may also reveal encoding computations predictive of future memory. To examine how the similarity among temporal patterns of hippocampal activity during encoding relates to later episodic retrieval (associative cued recall and recognition memory), hippocampal activity was recorded from human participants (n=7) with implanted intracranial electrodes while they encoded arbitrary (A-B) paired-associates. Subsequent memory analyses first revealed that hippocampal high-frequency broadband power (HFB; 70-180Hz) was linked to a graded increase in memory strength; HFB power was greater during the encoding of pairs later correctly recalled relative to events later recognized and was lowest for events later forgotten. Second, and critically, subsequent memory analyses further revealed that more distinctive temporal patterns in the hippocampus during encoding -- indexed by the similarity of the HFB timeseries elicited by a given event to that elicited by other events -- were associated with superior subsequent memory performance. Finally, exploratory analyses revealed stimulus category effects on hippocampal HFB power during encoding and retrieval cuing. These results indicate that the temporal distinctiveness of hippocampal traces during encoding is important for subsequent retrieval of episodic event elements, consistent with theories that posit that pattern separation facilitates future remembering.

Mental fatigue is known to impair cognitive and motor performance, but its impact on motor learning remains unclear. This study examined how mental fatigue affects skill acquisition in a sequential finger-tapping task. Twenty-eight participants were assigned to either a mental fatigue group, which completed a thirty-minute Stroop task, or a control group, which watched a documentary of equivalent duration. Both groups then trained on the finger-tapping task across multiple practice blocks with brief rest periods. Overall motor skill improved similarly in both groups. However, mental fatigue altered the pattern of acquisition: participants in the fatigue group showed decreased performance during practice blocks, which was compensated by larger gains during inter-block rest periods. A strong negative correlation was observed between online decrements and offline improvements, indicating that greater declines during practice were associated with larger gains during rest. This study highlights the critical role of rest periods in maintaining learning under cognitively demanding conditions and provides insight into how internal states, such as mental fatigue, can selectively influence the expression of performance without compromising overall learning.

The exploration-exploitation trade-off refers to the conflict between using known strategies that reliably yield reward (exploitation) and sampling uncertain options that might yield better outcomes (exploration). Dysregulation of this balance is implicated in neuropsychiatric disease, and while sex differences in this balance have been described, the biological bases remain unclear. To quantify sex differences in this trade-off, we tested mice (n=74 male, 62 female) on four home-cage based foraging tasks with an operant pellet dispensing device, Feeding Experimentation Device 3 (FED3). Mice completed the tasks continuously over multiple days and the tasks were their only source of food. Across multiple tasks, males showed higher win-stay behaviour than females, indicating greater exploitation of previously rewarded actions, an effect that was modest in size but highly significant. Power analyses revealed that >30 mice per sex were needed to detect these modest but significant sex differences with 80% power. No consistent sex differences were observed in pellet intake, suggesting that differences in exploitation did not reflect differences in hunger drive or demand for pellets. Exploitation is a more efficient strategy when environmental parameters are fixed, while exploration can be more advantageous when parameters such as reward locations are changing and uncertain. We tested this idea by re-running our mice in a probabilistic foraging task, where actions led to uncertain probabilities of reward. While males continued to show higher levels of win-stay behaviour on this task, this no longer led to increases in accuracy. Behavioural modelling also supported this framework, demonstrating that stronger win-stay behaviour was most advantageous in deterministic models, and less advantageous in probabilistic models. Together, our findings demonstrate that male and female mice have small but significant differences in their exploration-exploitation balance, which leads to more accurate foraging in certain, but not uncertain, environments.

Previous research has demonstrated that children exhibit superior - as compared to adults - consolidation of newly acquired motor sequences across post-learning periods of wakefulness. Given that consolidation is thought to be supported by the reactivation of learning-related patterns of brain activity during the rest periods following active task practice, we hypothesized that the childhood advantage in offline consolidation may be linked to greater reactivation during post-learning wakefulness. Twenty-two children (7-11 years) and 23 adults (18-30 years) completed two sessions of a motor sequence learning task, separated by a 5-hour wake interval. Multivoxel analyses of task-related and resting-state functional magnetic resonance imaging data were employed to assess the persistence of learning-related patterns of neural activity into post-task rest epochs, reflective of reactivation processes. Behavioral results demonstrated the previously reported childhood advantage in offline consolidation over a post-learning wake interval. Imaging results revealed that children exhibited greater persistence of task-related hippocampal - but not putaminal - activity into post-learning rest as compared to adults. These findings suggest that the childhood advantage in awake motor memory consolidation may be supported, at least partially, by enhanced reactivation of task-dependent hippocampal activity patterns during offline epochs.

We assessed whether pigs provide consolation, referring to targeted affiliation that attenuates a partners stress, under experimental conditions that manipulated exposure to stressed partners. Using a within-subject design, 74 pigs were tested in three contexts: a helping task in which group members could observe and help a trapped focal pig to return to the group, a direct-reunion, in which group members were naive to the experience of a separated focal pig until reunion, and an undisturbed control. We measured affiliative and non-affiliative interactions, anxiety behaviours and changes in salivary cortisol. Only the helping context satisfied most consolation criteria: there were selective increases in unidirectional affiliative contacts from the observer to the focal pig, non-affiliative interactions remained at baseline, and focal pigs showed fewer anxiety behaviours. In contrast, direct-reunions triggered increases in affiliative and non-affiliative interactions and higher anxiety. Cortisol increased during both direct-reunions and helping, but its level was not linked to affiliation. Results add to growing evidence for consolation behaviour in pigs and suggest best practices for reintegrating pigs into groups. Graded reintroductions that allow observers to assess the emotional state of targets may promote social buffering, whereas abrupt regrouping may trigger more generalized arousal or personal distress.

The ability to evaluate ones own knowledge states is often studied using paradigms in which participants make a decision and subsequently report their confidence. This structure has motivated hierarchical models in which confidence arises from a metacognitive process, distinct from the decision process itself, that estimates the probability that the choice is correct (Meyniel et al., 2015; Pouget et al., 2016; Fleming and Daw, 2017). Here, we contrast this framework with an alternative based on an intentional architecture (Shadlen et al., 2008). In this account, choice and confidence are determined simultaneously through a multidimensional drift-diffusion process, where each dimension represents one choice-confidence combination (Ratcliff and Starns, 2009, 2013). Choice, response time, and confidence jointly emerge when one of these accumulators reaches a decision bound. To adjudicate between these accounts, we fit both models to behavioral data from two perceptual tasks: a random-dots motion discrimination task with incentivized confidence reports, and a luminance discrimination task without feedback or incentives. The integrated model provided a superior fit for the incentivized motion task, whereas the hierarchical model more accurately captured behavior in the un-incentivized luminance task. These results suggest that confidence does not rely on a single computational mechanism, but rather its implementation may adapt to the specific demands and structure of the task.

Pretend play is a hallmark behavior in childhood where children create nonliteral meanings. Empirical data supporting the role of social cognition and the decoupling from literality are still scarce during early development. We explored here how the comprehension of pretense affects the visual exploratory behavior of toddlers (n = 44) and adults (n = 65) when they were exposed to short video clips in which an actress performed either real actions (e.g., eating jelly) or pretend actions (e.g., pretending to eat with imaginary food), while varying the complexity of those actions. We analyzed participants exploration of the face in the videos as exploitation of social information. We showed that all observers paid more attention to the face in pretend scenarios than in real ones, measured as longer total looking time in adults and more fixations and revisits to the face in both age groups. We also found more gaze shifts (a measure of information sampling) between the face and the moving hand in the pretend videos in both age groups, mainly at the initial stages of the actions. Additionally, analyses of the scanpaths structure using gaze entropy showed less order in the exploration of pretend videos in both age groups, suggesting that pretense involved greater uncertainty and increased information seeking. The less structured trajectories were observed again mainly in complex pretend scenarios. Taken together, our gaze results indicate that from its developmental origins, the comprehension of pretense relies on social processes linked with information seeking and exploration. Significance StatementDevelopmental theories have long debated whether pretend games are born in conjunction with social capacities in the second year or become integrated later in life. Our study shows that, much like adults, toddlers visually explore pretend scenes gathering more social information and in a less structured manner compared to real-world scenarios, suggesting that the emerging capacity to play with the meaning of things is linked with that of thinking of other minds early in life.

Stressors are commonly used in rats to induce models of anxiety or depression. The effectiveness of these stressors is often evaluated using specific behavioural tests. In a previous meta-analysis of chronic variable stress (CVS) procedures, we predicted that longer and more intensive stress procedures would result in larger effect sizes in behavioural tests. However, we found that the duration or intensity of CVS procedures did not correlate strongly with the magnitude of the effect sizes reported in behaviouraltests. In that study, we were concerned that the large and unexplained diversity in CVS procedure design, both in terms of duration and the types of stressors used, made it challenging to detect the factors that were influencing effect size. In an effort to address this, we explore here the use of a much simpler stress procedure - chronic restraint stress (CRS) - to study the relationship between the duration of CRS procedures and the effect sizes obtained in subsequent behavioural tests. We searched PubMed for articles using CRS procedures with rats, systematically documented the total duration of restraint, and carried out a meta-analysis of the effect sizes obtained in four behavioural tests: the forced swim test (FST), the sucrose preference test (SPT), the elevated plus maze (EPM) and the open field test (OFT). We found that chronic restraint stress increased immobility in the FST, decreased sucrose preference in the SPT, decreased time spent in the open arms of the EPM but had no effect on time spent in the centre of the OFT. However, the effect sizes in all behavioural tests, except the SPT, were not moderated by the duration of the CRS procedure, indicating that longer CRS procedures are associated with larger effect sizes in the SPT but not in the FST or EPM.

The muscarinic acetylcholine receptor 1 (mAChR1, M1) has been identified as a primary target for Alzheimers disease (AD) and better understanding of the receptor biology, especially in regard to biased signalling of the receptor, will allow for the development of improved drugs targeting cholinergic dysfunction in AD. The aim of this study was to determine the contribution of phosphorylation of M1 to the learning and memory (LM) effects of M1 agonism. The contribution of M1 phosphorylation dependent signalling in LM was assessed using the mAChR1 positive allosteric modulator, VU0486846, in a scopolamine (1.5 mg/kg) induced LM deficit model in mice expressing HA-tagged M1 (M1-WT), phosphorylation deficient HA-tagged M1 (M1-PD), or mice deficient in M1 (M1-KO). LM was assessed using a fear conditioning (FC) testing paradigm where context and cued memory retrieval was measured 24 hrs after training and a higher level of freezing indicated intact memory. Results demonstrated that scopolamine induced a significant LM deficit in both context and cued retrieval in M1-WT mice which was partially rescued by VU0486846 confirming a contribution of M1 signalling in LM. The scopolamine induced deficit in contextual retrieval in M1-KO mice was not rescued by VU0486846, which is an M1 selective ligand, while scopolamine did not induce a deficit in cued retrieval in M1-KO mice. In M1-PD mice, scopolamine induced a LM deficit in contextual retrieval, however this was also not rescued by VU0486846 treatment. Similarly to M1-KO animals, M1-PD mice did not display a scopolamine induced deficit in cued retrieval. When freezing responses were compared across strains, M1-PD mice displayed a deficit compared to M1-WT and M1-KO mice in contextual retrieval, while both M1-PD and M1-KO mice displayed a deficit compared to M1-WT mice in cued retrieval. These results demonstrate that although M1 agonism can restore a LM deficit in both contextual and cued testing paradigms, only the cued retrieval response is dependent on the M1. Additionally, biased Gq M1 signalling is not sufficient to restore contextual memory and requires phosphorylation of the receptor. Furthermore, biased M1 signalling results in LM deficits not seen with KO of the receptor. Overall, these results reiterate the importance of considering the bias of ligands when developing M1 agonists for dementia in the future.

Background and aimsPerseverative behaviours are commonly assessed using operant paradigms in which rodents work for drugs or food under physiological deprivation, limiting translational relevance to some behavioural addictions. Here we validated an operant paradigm in which the acquired behaviour is driven neither by physiological needs nor hedonic responses. MethodsMice were trained to lever-press for green light. Exp.1 used a within-subjects design to examine lever discrimination and whether responding could be "satiated" by light preexposure. Exp.2 examined instrumental contingency using a between-subjects design, with light delivery equated between contingent and non-contingent groups. Exp.3 replaced green light with dim red light producing less retinal photoreceptor excitation but comparable heat to assess non-photic cues. Exp.4 examined whether green light could affect food seeking different motivational states. ResultsIn Exp.1, green light supported lever discrimination. Among high responders, the satiation effect was modest (<15% reduction) and did not deter lever pressing. In Exp.2, instrumental contingency promoted response acquisition whereas random light delivery did not. In Exp.3, dim red light failed to sustain behaviour, producing [~]50% response decrement. In Exp.4, light potentiated food seeking under ad libitum feeding. Discussion and conclusionsResponse-contingent light serves as a reward to establish operant responding, which cannot be explained by alerting effects or thermal cues. Our study bridges the gap between animal models and findings from humans that coloured light may exacerbate smartphone use and that light therapy may reshape reward circuits in individuals with Internet gaming disorder symptoms [Li et al. (2026) Advanced Science 13:e14044].

Some images are consistently remembered better than others, suggesting that memorability reflects intrinsic image properties. We tested whether within-category distinctiveness underlies this effect. Across three experiments (N = 477), participants categorized indoor scenes previously rated for subjective typicality and then completed recognition memory tests. Typical scenes were categorized faster and more accurately, but were remembered worse and showed a more liberal response bias than atypical scenes. These opposing effects were robust across categories. To link subjective typicality to visual representations, we quantified image distinctiveness using a convolutional neural network (CNN). Across layers, CNN-derived distinctiveness closely tracked human typicality judgments and predicted both categorization speed and memorability, with strongest effects in higher, semantic layers. Critically, the memory advantage for atypical scenes persisted even when most images were atypical, ruling out rarity within the experimental context. Together, the results show that intrinsic scene memorability reflects an images position within a category-specific representational space.

Physical activity offers myriad benefits to health and well-being, in humans and other animals as well. In rodents, voluntary wheel running can attenuate the effects of both physical and social stressors on rodent social behavior. Whether wheel running affects rodent social behaviors per se remains less well understood. We conducted the current study to test whether home cage access to running wheels impacts the social behaviors of adult, group-housed C57BL/6J female mice during same-sex interactions with novel females. Group-housed females were either given continuous home cage running wheel access or a standard paper hut starting at weaning, and as adults, social behaviors were measured during interactions with novel females. In two cohorts, we found that 5 weeks of running wheel access during adolescence reduced the time that subject females spent investigating a novel female and also tended to reduce total ultrasonic vocalizations produced during interactions. These effects were not reversed by a 2-week period of running wheel removal but were recapitulated in a different cohort by 2 weeks of running wheel access in adulthood. Unexpectedly, we found that these effects on female social behavior were not due to wheel running per se, because females raised from weaning with immobile running wheels also showed low rates of social behaviors during same-sex interactions in adulthood. Overall, we find that the presence of a running wheel in the home cage has an enduring inhibitory influence on female social behavior during same-sex interactions, a finding that has implications for the design of studies that include same-sex interactions between female mice.