Neurobiology of Learning and Memory

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.

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.

The midsession reversal (MSR) task is frequently used to study behavioral flexibility and decision strategies in animals. In a typical version of the task, subjects complete 80 trials in which they choose between two simultaneously presented stimuli, S1 and S2. During the first 40 trials, responses to S1 are reinforced, whereas responses to S2 are not. The contingencies then reverse without warning: From trial 41 to 80, only responses to S2 are reinforced. In birds, performance in this task is often characterized by anticipatory and perseverative errors around the reversal point, suggesting a reliance on elapsed time since the session began. In contrast, rats tested in operant conditioning chambers typically show near-optimal performance with few errors, a pattern often interpreted as evidence that rats rely primarily on local reinforcement cues rather than temporal information. The present study investigated whether rats exclusively rely on local cues in the MSR task or whether temporal information also contributes to the decision process. Two groups of rats were trained with different intertrial intervals (ITIs; 5 s or 10 s) while the reversal point remained fixed at Trial 41. During acquisition, both groups diplayed similar learning rates and near-optimal steady-state performance with minimal anticipatory or perseverative errors. However, when the ITI was manipulated in probe sessions, systematic shifts in switching behavior emerged. Rats adjusted their choices according to the temporal midpoint experienced during training rather than the nominal trial number of the reversal. These results suggest that rats rely on a mixed strategy that integrates local reinforcement cues with global timing information. Temporal control may therefore be present even when it is not expressed during standard training conditions.

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.

Motor memory retention is impaired in Parkinsons disease (PD), affecting long-term rehabilitation outcomes. It appears that NREM sleep could be beneficial for consolidation processes in PD, and could be leveraged with non-invasive sleep interventions. This study examined the effect of auditory targeted memory reactivation (TMR) during NREM sleep on the retention of a motor sequence learning finger tapping task in 20 PD and 20 healthy older adults (HOA). TMR was applied during a 2-hour nap and its effect on motor retention was post-nap, after 24-hours and with a dual-task. The impact of TMR on sleep electrophysiology was also evaluated. Results showed no effect of TMR on motor retention or dual-tasking, with no difference between the groups. However, the TMR intervention did increase slow-wave density and decreased spindle density in both groups, and slow-wave amplitude during the presentation of the auditory cues was positively associated with performance in HOA. In conclusion, TMR applied during a 2 hour nap did not enhance motor retention, but the changes in sleep physiological features could be linked to a possible underlying effect on memory processing that warrants further investigation.

Traumatic stress can cause long-lasting changes in cognition and affect, sometimes leading to diagnoses such as post-traumatic stress disorder (PTSD). The stress-enhanced fear learning (SEFL) model recapitulates understudied components of PTSD, such as stress-induced sensitization of fear learning. The SEFL procedure entails exposing mice to footshock stress followed later by fear conditioning in a different context. When tested later for recall of fear conditioning, previously stressed mice exhibit enhanced freezing compared to non-stressed controls. Studies have shown that dorsal and ventral dentate gyrus (DG) generates neural ensemble representations of contextual fear, such that fear recall involves reactivation of a sparse set of "engram cells" that were active during fear memory acquisition. How stress affects these hippocampal ensemble representations is unknown. We used SEFL and activity-dependent neuronal tagging with FosTRAP2 mice to investigate effects of stress on fear memory ensembles in rostral and caudal hippocampal DG. FosTRAP2/Ai6 mice received footshock stress or equivalent context exposure without shock in Context A on day 1. Five days later, mice received 1-shock conditioning in Context B and immediately received an injection of 4-OHT (55mg/kg) to tag fear acquisition neurons with the zsGreen reporter. One day later, mice were tested for fear recall in Context B and were perfused 90 minutes after testing. Confirming prior studies, prior stress potentiated 1-shock conditioning in Context B, with stressed mice displaying higher freezing in the Context B test session than non-stressed mice. At the level of neural activity, results showed stress had no effect on the number of zsGreen+ fear ensemble cells or the number of cfos+ recall-activated cells in rostral or caudal DG. However, stress increased reactivation (percentage of zsGreen+ cells expressing cfos) in the caudal but not rostral DG. The results suggest stress potentiates later fear learning by enhancing fear representations in caudal hippocampus, a region of the hippocampus specialized for integrating emotional and motivational valence into memory.

BackgroundGrowing evidence suggests that sleep plays an important role in PTSD outcomes, potentially due to its influence on emotional memory consolidation, though these mechanisms remain unknown. This study sought to test the hypotheses that sleep neurophysiology, PTSD status, and sex moderates the degree to which the late positive potential (LPP) mediates memory accuracy for affective visual stimuli. MethodsN = 39 participants (18 female) viewed 75 negative and 75 neutral IAPS images while EEG was recorded. After viewing the images, participants took a two-hour long nap which was followed by a memory assessment. Memory accuracy was measured using d = Z(hit rate) - Z(false alarm rate), where hit rate refers to the proportion of images seen during the memory assessment that are correctly identified as being previously seen, false alarm rate refers to the proportion of images seen during the memory assessment that are incorrectly identified as being previously seen, and Z() is the inverse cumulative distribution function of the standard normal distribution function. ResultsThe early (300 - 1000 ms) and late (1000 - 1500 ms) LPP mediated enhanced discrimination accuracy for emotional compared to neural stimuli (d) (ps < 0.001). The association between the late LPP and d was moderated by sleep such that the association was stronger when participants spent proportionately more time in N3 and REM (p = 0.02). The differences in reactivity between emotional and neutral images for both the early and late LPP were attenuated in PTSD+ individuals vs. controls (ps < 0.001). Despite mediation results showing greater d for emotional compared to neutral stimuli, women showed overall worse memory accuracy for negative compared to neutral stimuli (p < 0.001) whereas men showed no difference (p = 0.64). ConclusionsN3 and REM sleep play a critical role for memory of stimuli that produce large and sustained neural responses. PTSD is marked by a diminished ability to distinguish between negative and neutral information. More research is critical to understand sex effects on emotional memory.

Memory impairment is a common and sometimes overlooked feature of major depressive disorder, and cognitive deficits may precede the onset of depressive symptoms in some cases. However, the cognitive benefits of first-line treatments such as SSRIs are mixed. Tianeptine is an atypical antidepressant and cognitive enhancer that neither interacts with monoamine receptors nor inhibits the reuptake of their neurotransmitters. Its antidepressant efficacy in animal models requires activation of the mu-opioid receptor (mu-OR) and phosphorylation of the AMPA receptor. However, the receptors that mediate its memory enhancing actions have never been investigated. We therefore tested the ability of tianeptine to improve spatial memory in a cross-maze task in wild-type (WT) mice compared to its effects in mice with global knockout of either the mu-OR or delta-OR. In parallel, we assessed the effects of tianeptine on hippocampal oscillatory activity and spontaneous locomotion in the same genotypes. Adult male and female WT, mu -/-, and delta -/- mice on a C57BL/6J background were implanted with hippocampal electrodes for the recording of local field potential (LFP) oscillations. Consistent with our previous observations in anaesthetised rats, injection of tianeptine (10 mg/kg and 30 mg/kg SC) caused a dose-dependent increase in beta-frequency power in WT mice that was maximal at circa 25 Hz. The same effect was observed in delta -/- mice, but the increase in beta was completely absent in mu -/- animals. As others have reported previously, tianeptine also caused a mu-OR-dependent increase in spontaneous locomotor activity, but with a time-course that was distinct from the increase in beta power. Separate groups of WT, mu -/-, and delta -/- mice were tested for their ability to learn a food-rewarded spatial memory task in a cross-maze. Over a 20-day training period, sub-groups of each genotype received either tianeptine (10 mg/kg SC) or vehicle injection 30 min before testing. Tianeptine increased the percentage of correct trials and the number of allocentric (place) responses in WT mice, but did not enhance memory in either mu -/- or delta -/- mice, even though both genotypes were able to learn the task. These results indicate that the ability of tianeptine to drive hippocampal beta oscillations is dependent on the mu-OR, whereas its memory-enhancing actions require the presence of both mu- and delta-ORs. The latter result is consistent with the actions of tianeptine on postsynaptic AMPA receptors, and we are currently exploring the signalling pathways involved in this process.

Study ObjectivesSleep spindles are implicated in memory consolidation. Yet direct evidence linking spindle dynamics to declarative memory outcomes remains limited. We thus tested whether targeted memory reactivation (TMR) time-locked to sleep spindles enhances declarative memory, and whether the temporal organization of stimulated spindles-trains versus isolated events-is selectively associated with distinct memory outcomes. MethodsTwenty-eight healthy young adults learned image locations from two categories (animals, clothing) in a grid, each paired with a distinct auditory cue. During overnight NREM sleep, one cue was replayed time-locked to spindles detected in real-time using a closed-loop system (TMR condition); the other served as the non-reactivated control (No-TMR condition). Category-cue assignment was counterbalanced. Post-sleep recall, recognition accuracy, and movement time were assessed. ResultsRecall accuracy was significantly higher in the TMR than the No-TMR condition (93.96% vs. 90.61%, p = .024), whereas recognition accuracy (p = .139) and movement time (p = .651) did not differ. Stimulation intensity within spindle trains correlated with the TMR effect on recall (Spearman {rho} = .531, p = .004), whereas the proportion of isolated spindle stimulations correlated with the TMR effect on recognition ({rho} = .563, p = .002). Cross-associations were not significant. ConclusionsSpindle-locked TMR enhances recall-based declarative memory retention. The selective association between spindle temporal clustering and memory outcomes suggests that train-embedded and isolated spindles support different aspects of memory consolidation, highlighting spindle temporal context as a functionally relevant dimension of sleep-dependent memory processing.

Exteroception is attenuated during sleep, while interoceptive signals may remain active. If so, they can trigger responses in their target areas, including the hippocampus, which is known to receive information from the internal organs and is susceptible to oversynchronization while triggered. We investigated whether the hippocampus is synchronized to various visceral events in sleep and wakefulness. Activity of hippocampal neurons and local field potentials (LFPs) was co-registered with respiration, heart rate and myoelectric signals of the stomach and duodenum in two adult female cats over multiple sleep-wake cycles. Visceral event-triggered and neuronal spike-triggered (bootstrapping-based) analyses were performed in wakefulness and SWS. Synchronization between visceral and hippocampal activities occurred in both wakefulness and SWS. However, hippocampal cells and LFPs showed preferences for one state only. Consistent with prior studies, we found the strongest link between high-amplitude respiratory events and hippocampal activity, with significantly higher occurrence during SWS. Both stomach and duodenal signals were also represented in hippocampal activity. Motility-associated duodenal myoelectric signals correlated with hippocampal activity more during wakefulness where gastrointestinal motility is more active, while synchronization between regular duodenal waves and the hippocampus was more frequent during SWS. We conclude that the interoceptive signals reach the hippocampus in both sleep and wakefulness and suggest that they have the potential to oversynchronize any ongoing synchronized slow-wave activities in the hippocampal network during slow wave sleep (SWS). Significance StatementWhat types of sensory input shapes hippocampal activity and regulates its rhythmical structure is important for understanding both normal and paroxysmal hippocampal dynamics. We find that synchronization between interoceptive signals and hippocampal neural activity exists during wakefulness and is preserved during SWS. Moreover, in some cases, this association increases in SWS for respiratory and periodic duodenal activities. Our data revealed specificity of hippocampal neurons to both type of visceral activity and state of vigilance, suggesting that hippocampal network is shaped by visceral activity in a state-dependent manner. Our results highlight the factors underlying the comorbidities of epilepsy with gastrointestinal, cardiac or respiratory disorders.

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.

Stored memories are useless unless they are available for retrieval. Thus, investigating different ways to modulate retrieval is crucial. Novelty has been extensively studied as a modulator of memory. In this study, we investigated whether exposure to a novel event, an innovative neuroscience lesson, can enhance memory retrieval and divergent thinking in high school students. Across three experiments, we assessed the timing and mechanisms underlying these effects. In experiment 1, we found that memory retrieval was enhanced when the novel lesson occurred immediately before a memory test, but not when it was presented one hour earlier. In experiment 2, we found that the same immediate novelty exposure improved divergent thinking performance. Finally, in experiment 3, we explored potential shared mechanisms using a competition protocol and revealed that novelty improved divergent thinking regardless of its timing relative to memory retrieval. However, memory retrieval benefited only when tested immediately before the divergent thinking task. These results suggest that novelty boosts both memory retrieval and divergent thinking, but through partially distinct mechanisms. Our findings demonstrate that a simple, real-world classroom intervention can effectively enhance key cognitive functions in students. Significance StatementStored memories are only valuable if they can be retrieved, and memory retrieval plays a key role in creative thinking. Here, we tested whether a simple, novel event, a neuroscience lesson, could enhance memory retrieval and creative thinking in a real-world classroom setting. We found that novelty improved both memory retrieval and divergent thinking, an aspect of creative thinking, when presented immediately before the task. Finally, we revealed a non-reciprocal competition effect between memory retrieval and divergent thinking. These findings highlight a practical, low-cost intervention to boost key cognitive functions in students, demonstrating that brief, well-timed novel experiences can support both learning and creative thinking in educational environments.

Background: Gait variability is a hallmark of Parkinson's disease (PD) and has been linked to cognitive deficits and fall risk. Rapid eye movement sleep behavior disorder (RBD) is a strong predictor of synucleinopathies, yet evidence for gait changes in RBD is inconsistent. Performing a dual task increases gait variability, an effect that can be quantified using a cost function. Objective: Determine the degree to which dual task cost differs between control, RBD, and PD participants at baseline, and between RBD converters versus non-converters at follow-up. Methods: 46 RBD, 23 control, and 14 PD participants completed standardized gait analysis at baseline. Parameters chosen for analysis included enhanced gait variability index (eGVI), functional ambulation performance (FAP), velocity, step length, cadence, base of support, and double support time. Medical records were surveilled for 3 years following participant enrollment, determining that 6 RBD participants converted to PD or dementia. Baseline gait indices and dual task costs were compared between control, RBD, and PD groups at enrollment, and between RBD stable and RBD converters at follow-up. Results: The PD group had greater eGVI, as well as greater dual task cost for FAP, cadence, width, and double support time. No differences in gait variability were identified between RBD and control groups at baseline. Compared to the stable group, RBD converters had greater dual task cost for FAP, velocity, cadence, and double support time. Conclusions: Increased gait variability during dual task may identify RBD patients at imminent risk of phenoconversion.

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.

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.

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.

BackgroundAttributional bias, a tendency to overinterpret others intentions as hostile (rather than situational or accidental), represents a component of social cognition and may affect everyday functioning. Neural models link attributional processing to fronto-temporal circuits and the default mode network, which are frequently altered in epilepsy. Difficulties in social participation and employment are common in people with epilepsy, and maladaptive attributional styles may contribute to these challenges. Attributional bias has not been systematically compared across epilepsy syndromes. MethodsWe examined attributional bias in 96 participants comprising 26 individuals with genetic generalised epilepsy (GGE), 27 with temporal lobe epilepsy (TLE), and 43 healthy controls (HC). Attributional style was assessed using the Ambiguous Intentions Hostility Questionnaire. Depressive symptoms were evaluated using the Neurological Disorders Depression Inventory in Epilepsy. Group differences were analysed, and potential clinical and demographical correlates were explored. ResultsThe GGE group exhibited higher hostility bias scores than HC (95% CI: 0.12-0.38, adjusted p = 0.014), whereas the difference between TLE and HC groups was moderate and not statistically significant (95% CI: 0.12-0.58, adjusted p = 0.059). Higher blame scores were positively associated with depressive symptoms (p = 0.016). Disease duration, seizure frequency, and antiseizure medication were not significantly associated with attributional bias. ConclusionsThese findings suggest that some individuals with genetic generalised epilepsy are more likely to interpret ambiguous situations as hostile. Altered attributional style may represent an under-recognised factor contributing to social difficulties in people with epilepsy and warrants further investigation as a potential target for psychosocial interventions. HighlightsO_LISome people with epilepsy are more prone to interpret social situations as hostile. C_LIO_LIHigher depression scores correlate with a tendency to blame external factors for misfortunes. C_LIO_LIDisease duration, antiseizure medication, and seizure frequency do not seem to influence the attributional bias. C_LI

ObjectiveSeizure dogs are service animals trained to respond supportively to seizures in people with epilepsy; some are also trained to detect seizure-specific scents, particularly ictal volatile organic compounds (VOCs). This survey study examines feasibility and safety of incorporating a seizure service dog (SSD) into an inpatient setting, as well as patient perceptions of having an SSD in the Epilepsy Monitoring Unit (EMU). MethodsOur SSD underwent specialized training for seizure response and seizure recognition based on seizure-specific VOCs, and accompanied his epileptologist owner in the EMU on rounds for over four years prior to the study. We administered surveys to patients hospitalized in the EMU before and after interactions with a trained seizure dog. The surveys assessed the patients comfort with the dog, perceived usefulness of service dogs, safety, and tolerability. Select case examples are also presented in which seizure dog spontaneously alerted prior to epileptic seizures; seizures later confirmed by independent EEG review. ResultsPatient responses underscored overall high enthusiasm for seizure dog therapy, with 93% of participants reporting feeling "very comfortable" or "extremely comfortable" with a seizure dog present. No adverse concerns or negative experiences were reported by participants. 91% reported personally experiencing benefits of working with the seizure dog, citing emotional and comfort benefits during their hospitalization. 94% of participants were comfortable with physical contact with the dog or had no proximity preference. ConclusionThese findings suggest that seizure service dogs can be safely integrated into the inpatient EMU setting and have potential to enhance patient care and emotional well-being during EMU monitoring. Summary PointsO_LITotal of 98 patients admitted to EMU were surveyed about opinions regarding seizure dogs and comfort with integration of seizure dog in EMU setting, with 35 patients completing post-test surveys after interacting with the seizure dog. C_LIO_LI93% of surveyed EMU patients completing post-test surveys felt very or extremely comfortable with the seizure dog; no negative experiences or safety concerns were reported. C_LIO_LI91% reported personally experiencing emotional benefits of working with the seizure dog. C_LIO_LISelect case examples demonstrate that the trained seizure dog in our study may be able to spontaneously identify epileptic seizures. C_LI

Sleep deprivation is known to impair cognitive performance, yet its effects on error awareness and subsequent behavioral adjustments remain incompletely understood. Here, we investigated how sleep loss affects the use of subjective performance evaluation to guide post-error adaptations. Thirty healthy adults completed a novel, gamified error awareness multi-rule Simon task once while well rested and once after 24 h of total sleep deprivation. On each trial, participants reported both their task response and subjective evaluation of response accuracy. This design allowed us to dissociate objective performance from subjective error awareness and to examine their influence on subsequent behavior over time. Sleep deprivation slowed responses, reduced accuracy, increased missed responses, and decreased the proportion of consciously detected errors. These effects increased with time on task and were accompanied by greater instability in sustained attention. Critically, post-error adjustments were driven by subjective error awareness rather than factual error commission. Reaction times slowed most strongly after subjectively perceived errors, including instances in which the preceding response had been objectively correct. Accuracy showed post-error decreases that were most pronounced following unaware errors. Sleep deprivation further altered these awareness-dependent control processes, particularly in later task phases. Together, these findings indicate that sleep deprivation disrupts both error awareness and the effective use of awareness signals for behavioral regulation. Statement of significanceOne night of total sleep deprivation reduces behavioral error awareness and disrupts post-error adjustments in a time-dependent manner. Crucially, our findings show that adaptive cognitive control is strongly shaped by subjective error awareness--even when that awareness is inaccurate. By identifying conscious performance evaluation as a key mechanism linking sustained attention, sleep loss, and behavioral regulation, this work highlights the importance of considering subjective awareness when studying adaptive control under fatigue.

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.