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Learning & Memory

Cold Spring Harbor Laboratory

Preprints posted in the last 30 days, ranked by how well they match Learning & Memory's content profile, based on 23 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Rearing and Head Scanning as Functionally Equivalent Information-Seeking Behaviors

Troha, R.; Burks, D.; Petro, A.; Kirkpatrick, K.; Newman, E.

2026-05-05 animal behavior and cognition 10.64898/2026.04.30.721974 medRxiv
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Spatial memory is crucial for navigation and adapting to changing environmental conditions. Known neurophysiological mechanisms of spatial memory center on the importance of hippocampal activity and its spatial tuning. Yet, the behavioral strategies that support adaptive spatial encoding remain poorly understood. We have shown that dorsal hippocampal activity during rearing is necessary for spatial working memory, highlighting a role of information seeking behaviors for spatial memory encoding. Similarly, spatial tuning by dorsal hippocampal neurons is substantially updated during another information seeking behavior: attentive head scanning. However, the functional relationship between these behaviors is unknown. Here, to assess the relevance of environmental context for the expression of these behaviors, we quantified rearing and head scanning in a radial-arm-maze spatial working memory task while manipulating the height of the maze walls. Our goal was to test whether the stereotyped patterns of rearing that rats generate with tall walls are replaced with attentive head scanning when the walls are short enough to reach the top without rearing. We found that rats reared significantly less often when the walls were shortened and, instead, exhibited frequent attentive head scanning. The head scanning was done when and where the rats had previously exhibited stereotyped rearing. These results support the hypothesis that rearing and head scanning are functionally related behaviors. Future work should test two key inferences: 1) Head scanning is a critical epoch of spatial memory encoding, and 2) Spatial tuning by hippocampal neurons is updated during rearing. Significance statementSpatial memory is a core cognitive function, essential for healthy independent living. Though the hippocampus is critical for spatial memory, it remains unclear when and how. Separate prior studies link rearing and lateral head scanning to key periods of hippocampal processing, suggesting both behaviors support sensory information gathering for updating cognitive maps. However, their relationship is unresolved. Here, we test whether these behaviors are functionally interchangeable, with environmental structure determining expression. In a radial-arm maze, rats reared frequently with 21 cm walls but showed reduced rearing when walls were shortened to 4.6 cm, instead increasing head scanning at similar locations. These findings suggest rearing and head scanning share underlying motivations and provide a basis for comparing hippocampal activity during exploration.

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Space-based and object-based saccadic selection in visual working memory

Shurygina, O.; Wirth, L. A.; Rolfs, M.; Ohl, S.

2026-05-10 neuroscience 10.64898/2026.05.05.723053 medRxiv
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Saccades made during memory maintenance prioritize memory for the saccade target, but it is unclear if this benefit is specific to a location or extends across memorized objects. In three experiments, we examined whether saccadic selection spreads to other locations within the same object. In Experiment 1, we asked observers to remember three oriented Gabors presented either within contour-defined objects or without object structure. A subsequent movement cue prompted observers to move their eyes to the indicated location. We then probed memory for stimuli at locations equidistant from the saccade target, in either the same or a different object. Memory was best for stimuli at locations congruent with the saccade target, and consistently weaker for other stimuli presented in the same or a different object than the saccade target. In Experiment 2, we created more complex objects by adding more object features to the stimulus. Again, memory performance was best for stimuli congruent with the saccade target location, whereas memory in incongruent trials was worse and similar for stimuli in the same and different object as the saccade target. In Experiment 3, we tested if saccadic selection is present and propagates within the object in a change detection task. Again, memory performance (i.e., change detection) was best at the saccade target location. However, this memory benefit also spread to other locations within the same object. Our results imply that saccadic selection in visual working memory is primarily space-based but can also spread towards locations within the object where a saccade was directed.

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The role of the ventral midline thalamus in the retrieval of precise temporal memories

Lorenzo Gonzalez, A. P.; Allen, T. A.

2026-05-12 neuroscience 10.64898/2026.05.11.724442 medRxiv
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Interval timing (IT) is the ability to time events in the range from seconds to a few minutes, allowing animals to organize behavior in time at short durations. IT relies on two cognitive functions: 1) Measuring the passage of time; 2) Storing and retrieving temporal memories in a context appropriate manner. The hippocampus (HC) and medial prefrontal cortex (mPFC) have been shown critical to the accuracy and precision of time-contingent instrumental responses in IT. The anatomy supporting mPFC-HC interactions, required for memory encoding and retrieval, include projections from HC to mPFC, and indirect bidirectional connections through the ventral midline thalamus (VMT), most notably reuniens. Here, we explored VMTs role in retrieving fixed-interval (FI) temporal memories. Rats were trained on a 5s FI signaled by an auditory cue and demonstrated temporal memory by poking predominantly at the time of the expected reward. Timing responses on individual trials were classified into on-time, early, and random response. Across sessions, random response trials decreased following training. Next, we switched training to longer intervals (20s or 80s; daily sessions for weeks). To probe the role of the VMT in temporal memory retrieval, we infused the GABAA-agonist muscimol, or saline, before training sessions. Results show that VMT muscimol infusions decreased timing precision. Also, at both intervals, the number of on-time response trials decreased, and the number of random response trials significantly increased. The number of early response trials had no significant change at 20s, and significantly decreased at 80s. Overall, our results suggest that the VMT is critical for precise retrieval of temporal memories. We also describe per-trial response patterns with characteristics consistent across all trained intervals, suggesting multiple behavioral strategies at play during interval timing.

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Artificial Reactivation of a Cocaine-Associated Engram in the Dorsal Dentate Gyrus Attenuates Cocaine Prime-Induced Reinstatement of Drug-Seeking

Edwards, L. H.; Papanikolaou, L. F.; Wilson, M. R.; Brody, M. V.; Wade, W. F.; Cutler, M.; Arora, S. A.; Stratmann, A.; Canuelas del Valle, S.; Grella, S. L.

2026-05-21 animal behavior and cognition 10.64898/2026.05.19.726387 medRxiv
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Relapse-prevention strategies aimed at reducing relapse following abstinence, primarily focus on reducing cravings that lead to drug-seeking triggered by stress, drug-related cues, or re-exposure to the drug. Because addictive drugs form persistent associative contextual memories, we investigated how reactivation of cocaine-related hippocampal memories influences subsequent drug-seeking. Here, we tagged dorsal dentate gyrus (dDG) memory ensembles involved in encoding either a first or fourth cocaine exposure (15mg/kg, i.p) in male and female c57BL/6 mice using a TetTag approach. Mice underwent cocaine conditioned place preference (CPP), extinction, and reinstatement. We assessed whether optical reactivation of tagged cocaine-related ensembles could substitute for a cocaine priming injection to reinstate CPP, whether reactivation altered cocaine-induced reinstatement, and if these effects differed depending on stage of drug exposure. We also compared these effects to reactivation of saline-associated ensembles. Cocaine produced robust locomotor activation during conditioning, and sensitization developed across repeated drug exposures. Reactivation of a cocaine-related engram alone did not reinstate CPP. However, reactivation of the first cocaine exposure engram attenuated cocaine-induced reinstatement. In contrast, reactivation of the fourth exposure engram did not confer this protective effect. Interestingly, reactivation of saline-associated ensembles also reduced cocaine-induced reinstatement specifically in females, suggesting dDG ensemble reactivation may modulate relapse-related behavior through interference or neuromodulatory disruption of cocaine-associated representations, consistent with our prior work. These findings raise the possibility that early contextual experiences form competing or destabilizing representations that interfere with later cocaine-seeking when reactivated. Females also displayed greater sensitivity to locomotor-inducing effects of cocaine memory reactivation, although this was dissociated from CPP. Together, these findings show that cocaine memories are distinct across drug experience and selective reactivation of dDG engrams can differentially influence drug-seeking.

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Sympathetic activation of sensory input and learning

Flo, E. E.; Flo, G. M.

2026-05-05 neuroscience 10.64898/2026.05.01.722216 medRxiv
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Summary paragraphA hallmark of learning is the need for sensory stimuli (Ginns, 2015; McGraw et al., 2009; Reinwein, 2012; Spence, 1950) so that learning is fundamentally based on sensory input signals affecting behaviour, physiology, and neurology. If behavioural measures of learning can be causally linked to physiological and neurological variables, a broader understanding of the mechanisms related to learning in schools, learning disabilities, and learning and health issues may emerge (McGraw et al., 2009). Despite decades of research on the physiological/neurological variable of sympathetic activation, learning, and achievement (Horvers et al., 2021), any causal relation remains unclear (Cowley et al., 2014; Mason et al., 2020; Pijeira-Diaz et al., 2016; Sung et al., 2023; Yu et al., 2024) and issues with instrument validation remain (Costantini et al., 2023; Hu et al., 2024; Milstein & Gordon, 2020; Van Der Mee et al., 2021). Here we investigate the effect of sensory input on sympathetic activation by using validated instruments for skin conductance measurement (Batista et al., 2019) and whether sympathetic activation is connected to learning in a cognitive laboratory context and an ecologically valid classroom context. In both contexts, we found a physiological variable which correlated with learning and that sensory input affected this variable while student movement did not. These sensory inputs varied depending on the different instructional activities the students participated in. Together, these findings bring us one step closer to a model linking sensory input to behavioural, physiological, and neurological variables.

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Physical restraint induces conditioned place aversion and region-specific c-Fos activation in mice

Reinders, E.; Tondravi, M.; Lee, S. R.; Beyene, E.; Nguyen, T.; LeGates, T. A.

2026-05-12 neuroscience 10.64898/2026.05.07.723616 medRxiv
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Linking environmental contexts with stressful experiences is critical for engaging adaptive responses necessary to avoid future threats. Yet, active context-dependent avoidance remains poorly understood. Here, we establish a restraint-induced conditioned place aversion (CPA) paradigm to examine how an acute physiological stressor acquires negative motivational value through contextual association. We found that mice repeatedly exposed to physical restraint in a contextually distinguishable chamber later avoid that location, demonstrating that restraint stress can drive learned aversion in the absence of continued exposure. To identify potential neuronal correlates underlying this learned association, we quantified c-Fos expression in several areas implicated in aversive motivation, emotional salience, and contextual encoding. We found that restraint within the context of the CPA paradigm was associated with increased c-Fos in the nucleus accumbens (NAc) and basolateral amygdala (BLA) while c-Fos expression increased in the ventral hippocampus in response to exposure to the contextual cues alone. These findings reveal region-specific engagement in processing aversive contextual memories induced by restraint stress. This work bridges classical stress models with associative learning frameworks, providing a platform to further dissect the neural mechanisms underlying stress-related negative affect and avoidance behaviors.

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An Operant-based Touchscreen Morph Discrimination Task Does Not Detect Age-related Mnemonic Similarity Deficits in Rats

Ross, A.; Logan, C. N.; Thompson, J. J.; Johnson, S. A.; Watson, C.; Ramirez, M.; Lubke, K. N.; Maurer, A. P.; Burke, S. N. N.

2026-05-05 neuroscience 10.64898/2026.04.30.722044 medRxiv
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The Mnemonic Similarity Task (MST) is highly sensitive to age-related cognitive decline in humans and has been adapted for rodents using 3D objects, where aged animals show deficits in discriminating similar lures. To improve translational alignment with human testing and increase automation, we developed a touchscreen-based rat analog using a morphed Object-Cued Spatial Choice (OCSC) task with 2D image stimuli. Young (4-month) and aged (21-month) male and female Fischer 344 x Brown Norway hybrid rats were trained in Bussey-Saksida touchscreen chambers and tested on discrimination performance using image pairs that varied parametrically in feature overlap. We also assessed perirhinal cortical engagement in a subset of animals using Arc expression as a readout of activity-related principal cell firing following low-and high-overlap task epochs. Across shaping and procedural training, aged rats required more errors to reach criterion on one stimulus set, but both age groups successfully acquired the task. During morph testing, performance declined systematically as stimulus similarity increased, confirming that the task manipulated discrimination difficulty. However, contrary to expectations, young and aged rats performed similarly across overlap conditions, with no significant age-related impairment. In the Arc experiment, discrimination accuracy was again reduced by greater stimulus overlap, but Arc expression in perirhinal cortex did not differ reliably by age or overlap condition, although expression was associated with behavioral accuracy and deep layers showed higher ensemble similarity than superficial layers. These findings indicate that, while the touchscreen morph OCSC task is sensitive to stimulus similarity, it does not detect the robust age-related mnemonic discrimination deficits previously observed with 3D object-based rodent MST paradigms, underscoring the importance of considering ethological relevance when designing translational cognitive assays.

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Dynamics of Dentate Gyrus Place Cells and Dentate Spikes During Spatialand Nonspatial Changes in Environments

Demetrovich, P. G.; Colgin, L. L.

2026-05-14 neuroscience 10.1101/2025.10.24.684382 medRxiv
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The dentate gyrus (DG) is thought to play a key role in the formation of dissociable memory representations for similar contexts. Neurons in the DG receive highly processed spatial and nonspatial sensory information from the medial and lateral entorhinal cortices, respectively. Changes in spatially tuned firing patterns of DG place cells occur after spatial changes to an environment, but the degree to which DG place cells respond to ethologically relevant nonspatial stimuli is largely unknown. Spatial and nonspatial information is thought to be transmitted to the DG during discrete local field potential events called dentate spikes. Here, we tested the extent to which different spatial and nonspatial stimuli modulate place cell firing patterns and dentate spike dynamics. We performed extracellular recordings of DG place cells and local field potentials in rats of both sexes exploring a familiar spatial environment, in which social stimuli and nonsocial odors of varying ethological relevance were presented, and a novel spatial environment. As expected, DG place cells exhibited different firing patterns between familiar and novel environments. Significant changes in firing were not observed, however, with any of the nonspatial stimuli. Surprisingly, the occurrence of dentate spikes associated with lateral entorhinal cortex input increased during exploration of ethologically relevant stimuli, and this increase was greater for social stimuli. Altogether, these results suggest that the DG preferentially responds to social stimuli at the network level, providing novel insights into how spatial and nonspatial information is processed in the DG. Significance StatementThe dentate gyrus (DG) encodes spatial and nonspatial sensory information. Here, we investigated how place cells in the DG respond to changes in spatial and nonspatial cues in familiar and novel environments in rats. We found that DG place cell firing patterns significantly changed in a novel spatial environment but did not significantly change when nonspatial stimuli were presented in a familiar environment. Conversely, discrete dentate spike events reflecting presumed nonspatial inputs from the lateral entorhinal cortex increased during investigation of ethologically relevant nonspatial stimuli. These findings suggest novel mechanisms of nonspatial information processing in the DG.

9
Selective encoding failure of self-face identity in subthreshold depression

Wen, M.; Su, B.; Chen, Y.; Gu, T.; Qin, P.

2026-05-07 neuroscience 10.64898/2026.05.04.721614 medRxiv
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Subthreshold depression is associated with significant functional impairment and elevated risk of major depressive disorder. A negative self-concept may disrupt the implicit positive association evoked by ones own face, impairing incidental encoding of self-relevant information. Whether subthreshold depression involves a selective deficit in encoding self-face identity remains unclear. The attribute amnesia paradigm is well suited to address this question because it can dissociate attentional selection from working memory encoding. Using this paradigm, we examined the issue across two experiments. Experiment 1 employed nonsocial stimuli (animal drawings) and confirmed an intact attribute amnesia effect in subthreshold depression (n = 30) comparable to healthy controls (n = 30), ruling out a generalized encoding deficit. Experiment 2 replaced targets with faces (self or other) and revealed a selective enhancement of the attribute amnesia effect for self-face identity in subthreshold depression. Specifically, on the surprise trial, accuracy for self-face identity dropped to near-chance levels in the subthreshold depression group, whereas no such deficit emerged for other-faces or in controls. Encoding recovered rapidly once explicit memory expectations were introduced, indicating intact basic encoding capacity. These findings suggest that subthreshold depression is associated with a specific impairment in incidentally encoding self-face identity. This impairment likely stems from a negative self-concept that weakens self-face salience under incidental encoding conditions. By capturing this selective encoding failure, the present study reveals that the self-processing deficit in subthreshold depression can arise at the gating stage between attention and working memory consolidation.

10
Opioids modulate Curiosity-Driven Exploration in Music

Alvarez-Martin, C.; Buehler, R.; Cerda-Company, X.; Cardona, G.; Willeit, M.; Gottlieb, J. P.; Silani, G.; Rodriguez-Fornells, A.

2026-05-08 neuroscience 10.64898/2026.05.05.722646 medRxiv
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Curiosity, a key driver of exploration and learning, is reinforced by reward-related neurochemical systems, yet the role of the opioidergic system in modulating this behavior remains unclear. Music, as a highly rewarding stimulus, offers a unique context to investigate the neurochemical basis of curiosity, particularly the unexplored role of opioids in music-driven exploration. To fill this gap, we performed a double-blind within-subject pharmacological design, in which 26 participants received, in two different sessions, either a placebo or the opioid antagonist naltrexone. During each session, participants engaged in a music exploration/exploitation trade-off paradigm designed to assess their willingness to pay for exploring unfamiliar electronic music. Using logistic regression mixed-effects models, we found that while naltrexone did not affect overall curiosity ratings, it significantly reduced exploratory behavior in states of heightened curiosity. These findings suggest that the opioidergic system plays a critical role in regulating the relationship between curiosity and exploration, particularly in the context of novel and rewarding stimuli like music. Overall, the present research provides new and compelling evidence on the important relationship between curiosity and exploration and its regulation with the opioidergic neurotransmitter subsystem. Significance StatementThe present research aimed to advance our understanding of the neurochemical mechanisms underlying curiosity and information seeking. In our study, we employed a pharmacological design to examine the role of the opioidergic system in music-related exploration. Using a novel music exploration/exploitation paradigm, we found that while naltrexone, an opioid antagonist, did not affect baseline curiosity ratings, it markedly reduced exploratory behavior during high-curiosity states in the presence of potential monetary losses. These results provide new evidence that opioidergic modulation plays a critical role in regulating curiosity-driven exploration. This new evidence might be relevant in the future for better understanding how neurochemical systems shape learning, motivation, and affective responses in complex cognitive domains such as music.

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Sex-specific weighting of shoal size and movement speed but no evidence of asymmetric dominance effect in zebrafish shoal-size preference

Singh, A.; Mathew, N. M.; Aggarwal, A.; Ail, T.; Kohli, S.; Rajaraman, B. K.

2026-05-11 animal behavior and cognition 10.64898/2026.05.07.723409 medRxiv
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Social decisions often require animals to integrate information across multiple attributes of potential partners. Using biological motion stimuli, point-displays generated from tracked live shoals, we tested how adult zebrafish (Danio rerio) weigh shoal size and movement speed during social preference, and whether these preferences are susceptible to contextual manipulation by an asymmetrically placed alternative. In Experiment 1, we established a multi-attribute indifference point by presenting males and females with dichotomous contrasts in which shoal size and movement speed were traded off. Both sexes showed no preference when a larger, slower shoal (4 fish at 0.75x speed) was pitted against a smaller, faster shoal (2 fish at 1.25x speed), but preferred the smaller, faster shoal when the speed difference was greater (4 fish at 0.5x versus 2 fish at 1.25x), indicating that zebrafish are sensitive to graded differences in movement speed relative to numerical cues. In Experiment 2, unidimensional tests confirmed that both sexes preferred larger shoals when speed was held constant but revealed sex-based differences in speed sensitivity: males preferred faster-moving shoals at both shoal sizes tested, whereas females showed no significant speed preference. Male shoal size preferences were stronger at higher movement speeds, suggesting that speed modulates the strength of size preference. In Experiment 3, we tested the asymmetric dominance effect in males, the only sex sensitive to both dimensions, using the indifferent contrast from Experiment 1 as the primary options and four decoy shoals asymmetrically placed along either the size or speed dimension, under counterbalanced presentation orders. No decoy shifted male preference significantly from chance under any condition. These results indicate that zebrafish weigh social cues in a sex-specific manner, and that asymmetric decoy options do not induce preference biases in males when shoals vary along the dimensions of movement speed and size.

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The Two Lives of Visual Working Memory: Evidence for Distinct Conscious and Unconscious Representations.

Lipinska, A.; Ciupinska, K.; Rutiku, R.

2026-05-05 neuroscience 10.64898/2026.05.01.722131 medRxiv
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Visual working memory (vWM) is often linked to conscious experience and visual imagery, but it is typically described as a system that stores separate, independent items. These assumptions are difficult to reconcile, given the unified nature of conscious experience. Here, we test the hypothesis that vWM relies on at least two distinct representations: an underlying, unconscious memory trace and a consciously accessible, integrated representation. A total of 216 participants performed a change-detection task, in which they rated their perceptual awareness of the memory display during the maintenance interval. Critically, we manipulated the statistical properties of the displays (average item size and size variability) to probe sensitivity to unified ensemble-level structure. Results revealed a dissociation between subjective and objective measures. Perceptual awareness increased for displays with larger, more variable items, whereas objective performance improved for displays with smaller, less variable items. Despite this difference, subjective awareness still predicted performance, and even incorrect responses showed consistent biases rather than random guesses. Importantly, individual differences in imagery vividness (VVIQ) were selectively associated with subjective awareness and estimation bias, but not with objective correctness. These precision biases were further shaped by display statistics, suggesting that multiple representations can guide behavior. Together, our findings support a reinterpretation of vWM performance in which task responses can draw on both unconscious and consciously accessible representations. One possible explanation for these behavioral patterns is that subjective experience reflects integrated, ensemble-like representations, while objective performance depends more strongly on item-specific information. Public significance statementsWorking memory allows us to temporarily hold and use information, and differences in this ability are closely linked to broader cognitive skills such as intelligence. This study shows that these differences may not depend only on how much information people can store, but also on how they experience it: some individuals appear to rely more on consciously accessible, image-like representations, especially when memory is uncertain or prone to error. By demonstrating that subjective experience and the vividness of imagery can shape behavior independently of objective accuracy, these findings suggest that how we use memory may be as important as how much we can store, with implications for understanding individual differences in cognition.

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Hippocampal representations of partner and novel individuals in monogamous California mice during pair bond formation

Hernandez Palacios, K.; Golam, O.; Siegelbaum, S. A.; Bendesky, A.

2026-05-09 neuroscience 10.64898/2026.05.08.723922 medRxiv
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The hippocampal CA2 region is critical for social novelty recognition memory--the discrimination of whether a conspecific is novel or familiar. However, its role in forming a memory of a pair-bonded mate is unknown. To examine how social memories of pair-bonded individuals are encoded, we sought to understand if CA2 and the neighboring CA1 region participate in the memorization and recognition of a pair-bonded mate in monogamous Peromyscus californicus (California mice). Here, we report that CA2 and CA1 show distinct changes in social encoding of an opposite sex conspecific following pair-bonding. Using multi-channel silicon probes, we recorded single units from CA2 and CA1 in freely behaving male mice before and after pair bond formation during interactions with novel and partner females. We found that the strength of CA2 representations of a novel female mouse weakened after pair bond formation, indicating that CA2 may be preferentially important for novelty detection. In contrast, CA1 demonstrated an increase in the strength of encoding a female partner after pair-bond formation, suggesting that CA1 may encode partner memory. These findings indicate that pair bonding shifts the discrimination of social information from CA2 to CA1.

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Face in the facade: How face-likeness modulates memory and neural representations

Pauley, C.; Sztuka, I. M.; Tawil, N.; Kuehn, S.

2026-05-11 neuroscience 10.64898/2026.05.06.723204 medRxiv
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Evidence suggests that information represented more reliably in neural activity patterns across repeated exposures is more likely to be remembered. However, this relationship varies across category-selective regions of the ventral visual cortex. Specifically, for house stimuli neural reliability has been robustly linked to memory outcomes in the parahippocampal place area (PPA), but less consistently for faces in the fusiform face area (FFA). The reason for this mismatch is unknown. To address this discrepancy, we implemented a novel within-category manipulation by presenting highly face-like and non-face-like house stimuli during fMRI, followed by a memory test. Non-face-like houses were more likely to be remembered than face-like houses. Although face-likeness did not elicit face-selective responses in the FFA, representational reliability in ventral visual cortices, particularly in the FFA, showed an association with individual differences in memory performance. Finally, symmetry emerged as a potential perceptual factor underlying differences in mnemonic outcomes.

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Determinants of persistence in sequential effort-based decision-making

Chaigneau, A.; Moretti, R.; Iodice, P.; Pessiglione, M.; Pezzulo, G.

2026-05-14 neuroscience 10.64898/2026.05.11.723817 medRxiv
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Goal-directed behavior often requires sustained effort across a sequence of interdependent decisions, yet the determinants of persistence in such contexts remain poorly understood. Here, we investigated how individuals regulate persistence in a novel sequential effort-based task in which they controlled an avatar through successive checkpoints to reach a final goal and could make repeated attempts following failure. At each attempt, participants could choose either to persist in the same task or to disengage toward an easier but less rewarding alternative. We found that decisions to persist or disengage were jointly shaped by multiple interacting factors. Disengagement increased with task difficulty and lower skill level. It also increased with repeated attempts and time-on-task, indexing fatigue, and with accumulated errors, indexing lack of progress. Conversely, proximity to the goal promoted persistence and shaped decision dynamics by reducing choice conflict during persistence decisions and increasing hesitation during disengagement near the goal. Notably, clearing the first checkpoint produced a sharp increase in persistence, suggesting that early success plays a pivotal role. Furthermore, persistence reflected both retrospective and prospective evaluations of effort, with prior investment promoting commitment and anticipated effort reducing it. Finally, disengagement was preceded by short-term performance decline but not by gradual increases in decision conflict, suggesting relatively abrupt strategy shifts following repeated failures. Together, these findings provide a comprehensive account of persistence in sequential effortful tasks, showing that decisions to persist or disengage are jointly shaped by multiple factors related to fatigue, (lack of) progress, goal proximity, and early success.

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From flexible to anticipatory processing: alpha and beta oscillatory signatures of feedback-guided strategy adaptation and memory updating

Al Safadi, M.; Chatburn, A.; Cross, Z.; Dawson, S.; bornkessel-schlesewsky, I.

2026-05-11 neuroscience 10.64898/2026.05.10.724182 medRxiv
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When humans learn under conditions of uncertainty, they dynamically adjust how they prepare for and respond to feedback. In navigating uncertain environments, the brain minimizes error by continuously refining internal models via memory updating (MU). Feedback is critical for MU, and anticipatory neural mechanisms shape how feedback is processed, likely reflecting learned environmental certainty. However, the literature has largely focused on post-feedback activity, leaving pre-feedback certainty-related mechanisms less understood. The present study aims to address this gap by examining how certainty modulates anticipatory states, preceding feedback and subsequent MU. We examined oscillatory activity prior to performance feedback in a reanalysis of EEG data previously published by Hassall and colleagues (2023). Twenty-one participants (16 female, Mage = 25.81 years) predicted the strength of cartoon characters with varying predictability levels which were learned through exposure. Feedback on prediction accuracy was presented via an animated rising bar. Results revealed that theta power is modulated by accumulative feedback. Linear mixed-effects models revealed an interaction between predictability-related certainty and learning stage: in late learning, higher performance was associated with increased pre-feedback alpha and beta power for low-certainty trials, whereas in early learning, higher performance was associated with decreased beta power. These learning-related modulations in alpha and beta power suggest that initial learning is marked by adaptable exploratory processing. Subsequent learning exhibited increased alpha-mediated inhibition and beta-related anticipatory activity for lower certainty trials, indicative of dynamic strategy refinement and selective engagement of task-relevant information. These results demonstrate that certainty shapes preparatory oscillatory activity associated with MU.

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PALMS: A Computational Implementation for Pavlovian Associative Learning Models Simulation

Fixman, M.; Abati, A.; Jimenez Nimo, J.; Lim, S.; Mondragon, E.

2026-05-08 animal behavior and cognition 10.64898/2026.05.05.722899 medRxiv
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In contrast to static formalisms, computational definitions describe the operational mechanisms of a model. Simulations are an essential part of the cycle of theory development and refinement, assisting researchers in formulating the precise definitions that models require, and making accurate predictions. This manuscript introduces a computational implementation of Pavlovian learning models in a Python environment, termed Pavlovian Associative Learning Models Simulation (PALMS). In addition to the canonical Rescorla-Wagner model, attentional approaches are implemented, including Pearce-Kaye-Hall, Mackintosh Extended, Le Pelleys Hybrid, and a novel extension of the Rescorla-Wagner model featuring a unified variable learning rate that synthesises Mackintoshs and Pearce and Halls opposing conceptualisations. To our knowledge, only the first attentional model has been previously specified computationally in a general design tool. PALMS integrates a graphical interface that permits the input of entire experimental designs in an alphanumeric format, akin to that used by experimental neuroscientists. It uniquely enables the simulation of experiments involving hundreds of stimuli, such as those used with human participants, and the computation of configural cues and configural-cue compounds across all models, thereby substantially broadening their predictive capabilities. A comprehensive description of the models implementation and the environment functionalities is provided in the paper; these include efficient and accurate operation and instant visualisation of predicted results across different models within a single architecture and environment. We evaluate PALMS by simulating five published experiments in the associative learning literature that assessed the predictive scope of existing models, and we show that this implementation provides neuroscientists with a useful tool for identifying critical variables, refining experimental designs, making precise predictions, comparing model fitness, and formulating new theoretical approaches. PALMS is licensed under the open-source GNU Lesser General Public License 3.0. The environment source code and the latest multiplatform release build are accessible as a GitHub repository at https://github.com/cal-r/PALMS-Simulator. Author summaryResearch on associative learning is multidisciplinary, encompassing disciplines such as neuroscience, AI, psychology, psychiatry, behavioural sciences, planning, and marketing. Unlike static formalisms, precise computational definitions specify how a model operates, enabling model simulation, swift and error-free prediction calculations, which are essential for testing theories, comparing predictions, holding models accountable, and providing a common language across fields. We introduce Pavlovian Associative Learning Models Simulation (PALMS), a user-friendly, open-source Python environment for simulating classical conditioning and studying the role of attention in learning. PALMS implements the prescriptive Rescorla-Wagner and attentional models: Pearce-Kaye-Hall, Mackintosh Extended, Le Pelleys Hybrid, and a new hybrid model with a unified variable learning rate that blends Mackintosh and Pearce-Halls conflicting views. Its graphical interface makes it easy for neuroscientists to enter experiments. Our computational implementation supports simulations with hundreds of stimuli, configural cues, and compounds, broadening the models predictive power. Designed for efficiency, it offers instant visual results and useful features. We evaluate PALMS by simulating five published experiments, highlighting its value for model comparison and refinement, and, more generally, as a tool to assist research.

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Anticipated Loss of Action Consequences Disrupts Motor Execution in Skilled Basketball Shooting

Nakao, A.; Yamada, N.; Wakatsuki, T.

2026-05-18 animal behavior and cognition 10.64898/2026.05.13.722224 medRxiv
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Internal forward models predict the sensory consequences of motor commands; however, whether the anticipated availability of post-action feedback contributes to the precision of the action itself remains unknown. We manipulated the predictability of post-release visual occlusion in skilled basketball players. Participants performed three-point shots while wearing liquid-crystal shutter goggles. The study tested three conditions: a no-occlusion baseline, certain-occlusion condition in which players knew that their vision would be occluded at ball release in every trial, and random-occlusion condition in which they could not predict whether an occlusion would occur. Shooting accuracy declined in the certain-occlusion condition relative to the no-occlusion condition (49.2% vs 41.7%). The random-occlusion condition did not differ from the baseline (46.1%). Within the random condition, the accuracy in occluded trials were virtually identical to that in non-occluded trials (46.6% vs 46.2%), even though the immediate visual occlusion was the same as in the certain-occlusion condition. These results demonstrate that it is not the absence of post-action information per se that disrupts motor execution, but the prior certainty that action consequences will be unavailable. We interpret this finding as a prospective influence of anticipated consequence loss, whereby motor execution depends on whether the prediction-outcome loop remains closable.

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Contingency degradation overwrites initial learning and depends on lateral orbitofrontal cortex

Mahmoudi, M.; Gladding, J.; Kendig, M. D.; Castorina, A.; Turner, K.; Soegyono, O.; Bradfield, L. A.

2026-05-19 animal behavior and cognition 10.64898/2026.05.18.726131 medRxiv
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Relapse after treatment for various mental health disorders has been linked to tendency for reductions in responding to increase over time or following re-exposure to motivating stimuli. Here we show that, in rats, responding reduced through non-contingent outcome delivery does not recover in these ways, and that this learning depends on an intact lateral orbitofrontal cortex. These findings suggest that contingency degradation overwrites original learning which may support the development of relapse-resistant behavioural interventions.

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Influence of distractors on spatial working memory and neural activity in marmoset prefrontal cortex

Wong, R. K.; Selvanayagam, J.; Johnston, K. D.; Zanini, A.; Loewith, M. S.; Everling, S.

2026-05-03 neuroscience 10.64898/2026.05.01.722299 medRxiv
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The prefrontal cortex (PFC) plays a critical role in maintaining working memory (WM) representations while filtering irrelevant distractors. In macaques, PFC neurons exhibit persistent delay period activity that is robust to distractor interference. The common marmoset has emerged recently as a complementary primate model for investigating the neural basis of cognitive processes including WM, in part because the relatively lissencephalic cortex of this species enables laminar recordings which could provide substantial insight into the microcircuit basis of these functions. It remains unknown however, whether marmoset WM performance is robust to distractors presented during delay periods of WM tasks, and how such distractor filtering may be implemented in PFC circuits. Here, we addressed this gap by conducting wireless recordings of PFC in freely moving marmosets performing a touchscreen-based delayed-match-to-location (DML) task in which a salient visual distractor was presented during the delay period on a subset of trials. Marmosets maintained WM performance on distractor trials, showing a decrease in accuracy of only 5%. Consistent with prior observations in both the macaque and marmoset models, we found that many PFC neurons exhibited activity related to the stimulus sample, during the delay period, and around the time of the behavioural response. In a subset of neurons, we observed distractor-mediated modulations of persistent delay period activity which were associated with a greater incidence of performance errors on the DML task. These findings reveal that marmoset WM is robust to distractor interference, and that the PFC mechanisms instantiating WM and distractor filtering are conserved in this primate species. Taken together, they support the common marmoset as a complementary model for investigating the contribution of PFC circuits to mnemonic and attentional processes.