Neurobiology of Learning and Memory

Accurate and efficient memory processing is essential for survival. Recent work in human subjects and animal models has suggested that memory processing may differ in meaningful ways between males and females. In mice, contextual fear memory (CFM) encoding, consolidation, and recall have been well studied, and the mouse hippocampus and amygdala have been implicated in these processes. The present study addresses how the specific contribution of these brain regions to each stage CFM processing in female vs. male mice. We find that male and female mice show no differences in CFM recall, nor in sleep behavior in the hours following single-trial contextual fear conditioning (CFC), which is essential for CFM consolidation. However, females - but not males - show significantly increased expression of cFos in dorsal hippocampal CA1 and CA2 neurons during CFM encoding. On the other hand, males - but not females - show increased cFos expression among DG granule cells during CFM consolidation. These findings highlight the fact that the neurobiological underpinnings of memory processing may differ between males and females, even when recall performance is identical. Scope statementHistorically, research on the neurobiological basis of memory processing has been carried out mainly in male subjects. Thus, our understanding of these mechanisms is biased towards male brain neurophysiology. Recent studies have variously reported performance differences for episodic memory tasks, in which male subjects perform better, worse, or the same as females. Here, we find that male and female mice perform similarly on a well-studied experimental memory task but nonetheless have differences in the relative activity of different brain structures during sequential stages of memory processing. This emphasizes the importance of including both males and females in memory studies, due to potential sex differences in the neurobiological substrates of memory.

RationaleRecent research on habits and skills has produced a wave of new theories regarding the shift in control from medial to lateral regions of the dorsal striatum, and how these regions are implicated in the selected and executed of action sequences. ObjectivesTo examine the comparative effects of muscimol/baclofen inactivation and dopamine D1 and D2 receptor agents in the dorsomedial (DMS) and dorsolateral (DLS) striatum on the performance of skilled action sequences. MethodsInfusions were made in well-trained rats using the five-step nose poke task to isolate the effects on initiation, execution and termination components of skilled action sequences. ResultsDLS inactivation produced sequencing deficits like those observed with pre-training lesions, indicating that the DLS is critical for both the acquisition and performance of sequences. Behaviour was unchanged following DMS inactivation, consistent with models of DMS disengagement following training. Infusions of D1 and D2 antagonists did not alter behaviour, however the D2 receptor agonist quinpirole increased sequence errors at a low dose and reduced sequences at the high dose in the DLS. DLS manipulations impaired sequence initiation and termination as well as reward transitions, while the chunking ballistic response pattern was largely unaltered, indicating that between-but not within-sequence actions rely on the DLS. ConclusionsSkilled action sequencing, including chunk transitions was dependent on DLS and its modulation by D2 receptors, but not on DMS function. Using a novel sequencing task, these results support the dissociable and dopamine-dependent role of the dorsal striatum subregions in performing skilled motor actions.

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.

Cerebellar communication with the prefrontal cortex (PFC) may play a significant role in cognitive functions. Our previous studies found that rule-based (RB) category learning depends on the PFC in humans and rats. The PFC is also crucial for behavioral flexibility following rule-changes in various tasks. Very little is known regarding the role of the cerebellum in RB category learning. The current study was designed to determine whether the cerebellum plays a role in RB category learning, and in categorization following a rule switch. Female and male rats were given bilateral lesions of the lateral cerebellar nuclei (LCN) or a control surgery and trained on an RB category learning task followed by a category rule switch. A subset of rats was trained on a control discrimination task with the same trial procedures as the categorization task. Rats with LCN lesions took significantly longer to learn both the first and second category rules but were not impaired on the control task. Computational modeling revealed less task engagement and increased switching between engaged and non-engaged states in the LCN lesion group. Several measures of task performance indicated that the category learning deficit was not caused by a motor impairment, response bias, or an inability to discriminate the stimuli. The category learning deficits with LCN lesions were related to reduced accuracy of stimulus classification, an inability to maintain task engagement, and loss of flexibility. The results show, for the first time, that the cerebellum plays a crucial role in category learning and category rule-switching.

Learning dance of a motor sequence involves the coordination of both oculomotor and manual motor systems through the practiced repetition of a fixed sequence of actions, resulting in automatized execution of movement through habit learning. This study aims to address whether a sequence-based learning paradigm centered on the visual-motor system can feasibly be measured while listening to music (Bar and DeSouza 2016). It aims to develop a new visual-motor-based learning paradigm with music, potentially promoting neuroplasticity and creating new interventional tools, building upon prior research that shows behavioural and putative neural changes following dance-based neurorehabilitation in people with Parkinson's disease (Bearss et al. 2024). Eye movements of 10 participants (8 female, 2 male) were tracked using the Eyelink 1000 Plus system during a 68-second eye-dance sequence. The experiment consisted of a learning phase, where participants observed the sequence five times with 30-second breaks, and a performance phase, where they performed the sequence five times from memory on a grey screen without visual cues. Music was incorporated into both phases to aid memorization of the 4 spatial locations. After each performance, the participant was shown a visual reinforcer and asked for their thoughts on how well they executed the dance. A visual reinforcer flashes one of three different colours: red, yellow, or green. Each colour corresponds to how many steps in the dance a participant performed correctly, with key points being: under one third, between one to two thirds, and over two thirds of total steps correct. Participants were scored based on timing of the steps as well for exact (1.00), good (0.66), slightly off (0.33) or missed (0) steps. Data was analyzed using R4.3.1, MATLAB, and Experiment Builder: Data Viewer software. Results showed a significant improvement in performance accuracy between the first session (g1; M = 40%, SD = 7.2%) and the last session (g5; M = 69.7%, SD = 22.8%). A repeated-measures ANOVA revealed a significant main effect of session on performance accuracy, F(4, 36) = 6.99, p < 0.001, 2G = 0.26, indicating that accuracy significantly improved over sessions. Post-hoc Bonferroni comparisons showed that accuracy in later sessions was significantly higher than earlier sessions, suggesting a defined learning curve and consolidation of performance pattern across repeated practice. Similarly, there was significant improvement in timing accuracy between the first session g1; M = 0.29, SD = 0.06) and the fifth session (g5; M = 0.46, SD = 0.12). A repeated-measures ANOVA revealed a significant main effect of session on timing precision, F(4, 36) = 11.67, p < 0.001, 2G = 0.25, indicating significant improvements in temporal control and coordination over sessions. Post-hoc Bonferroni comparisons showed that timing precision significantly improved between early and late sessions (e.g, g1-g4, p <0.01; g1-g5, p < 0.001), suggesting a defined learning curve and increase in precision across repeated practice. These findings suggest that visual-motor-based interventions have the potential to enhance motor and non-motor symptoms like depression and anxiety for neurodegenerative diseases such as Parkinson's Disorder (PD). The results provide a foundation for developing targeted therapies that integrate learning paradigms to improve functional outcomes, warranting further exploration of their long-term efficacy.

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.

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.

Retrieval training (i.e., cued recall) is theorised to induce rapid memory consolidation, similarly to sleep. Across consolidation, related neural representations become increasingly similar; yet, this representational change has never been directly compared between sleep and retrieval training. In this study, 30 subjects (27F, 18-34, M=22.17) completed four separate sessions in which they (1) learnt object-word pairs, followed by (2) immediate recognition testing, (3) one of four 120-min interventions (retrieval training, restudy, sleep, or wake), and (4) delayed recognition testing. We compared EEG phase similarity between similar and different objects to assess the time, frequency, and anatomical distribution of representational similarity across encoding (learning to immediate recognition), and each intervention (immediate to delayed recognition). We hypothesised that EEG phase patterns for similar objects would become more similar (i.e., representational merging) across retrieval training and sleep interventions, and predict a greater endorsement of similar-object lures. Indeed, we found increased representational similarity between similar objects across the encoding shift in the theta-band and occipital sources. Crucially, additional representational merging was only observed across the retrieval training intervention, in the alpha-band and parieto-occipital sources. Despite retrieval training leading to reduced performance in discriminating similar-objects lures, greater representational merging across retrieval training predicted greater discrimination of similar-object lures. Together, these findings suggest that sleep and retrieval training induce different memory transformations across the same timescale. Retrieval training may generally provoke rapid gist extraction, with greater neocortical integration supporting episodic discrimination. Conversely, sleep may selectively maintain task-relevant episodic and semantic details in the short-term.

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.

By relying on the observation of others experiences, humans learn about threat while avoiding harmful experiences. Yet, previous neuroscience research has focused on observational threats that are predictable. While the neurobiological distinction between temporally predictable (cued) and unpredictable (contextual) threats has been well-characterized in firsthand learning. In this study, we developed a novel observational paradigm in which participants learned from predictable (P) and unpredictable (U) observational threats, as well as a no-threat (N) condition and encountered the same conditions during an expression phase based on the NPU paradigm to investigate how the brain encodes predictable and unpredictable threat cues observed in others. Participants in Experiment 1 (n=20, male and female) and Experiment 2 (n=23, male and female) successfully learned threat contingencies, showing heightened threat expectations for predictable cues and unpredictable contexts. This converged with neural (fMRI, Experiment 2) responses in the anterior insula during the expression phase. Reflecting the dynamic process of learning, the amygdala responded to predictable threat cues with a linear decrease across trials. Interestingly, we found that responses to others pain was enhanced within the amygdala, insula and hippocampus, when participant could learn to predict threats, as compared to unpredictable conditions. Our findings suggest that humans learn to resolve temporal uncertainty, relying solely on observation, which thereby lays a foundation to the concept of fear and anxiety in social groups.

BACKGROUND AND OBJECTIVESPatients with epilepsy (PWE), especially temporal lobe epilepsy (TLE), experience impaired memory for personally experienced events. However, current assessments of episodic memory are limited in their ecological validity with a potential to miss detection of subtle cognitive decline. We conducted an exploratory study to determine whether a naturalistic film-viewing task with open-ended spoken recall could detect memory differences between TLE patients and healthy controls (HCs). METHODSTLE patients (ages 18-60, fluent in English, not legally blind) were recruited from a Level 4 Epilepsy Center (2018-2024). TLE diagnosis was based on seizure semiology, MRI Brain, and EEG. TLE patients scored [&ge;]22/30 on the Montreal Cognitive Assessment (MOCA); HCs scored [&ge;]26/30. Subjects watched 6 short films and then freely recalled film details. Spoken responses were recorded, transcribed, segmented, and scored for film- and event-level recall. Recall order was assessed using the Damerau-Levenshtein distance. Semantic and causal centrality were quantified using sentence embeddings and rater-identified causal links, respectively. Beta regression with cluster-robust standard errors assessed group and centrality effects on recall probability. Beta regression evaluated the influence of age, MOCA, and testing platform on sequence recall error. RESULTSWe recruited 51 subjects (27 TLEs; 24 HCs, 70.1% F, mean 29.9 {+/-}8.3 years). TLE patients and HCs showed similar recall of films (HC 89% {+/-}11% vs TLE 88% {+/-}18%, p = 0.54), coarse events (HC 50% {+/-}16% vs TLE 44% {+/-}18%, p = 0.19) and fine events (HC 25%{+/-}10% vs. TLE 22%{+/-}12%, p=0.17). Both groups recalled high causal centrality events better. For coarse event sequence recall, TLE patients showed a numerical trend toward greater sequence errors compared to HCs (HC 10.8% {+/-} 10.5% vs. TLE 19.5% {+/-} 18%, p = 0.06), although this difference did not reach statistical significance. However, TLE patients showed significantly greater fine event sequence errors at recall than HCs (HC 15% {+/-}13% vs 23% {+/-}18%, p = 0.02, Hedges g = 0.85, Cliffs {delta} = 0.51), with RTLE demonstrating more sequence errors than HCs (15%{+/-}13 vs. 29%{+/-}21% p = 0.021) Age, education, MOCA, and performance on standard verbal and visual memory tasks were unrelated to film, event, and sequence recall performance. DISCUSSIONWe demonstrate that a short film task with spontaneous spoken recall can identify sequence memory impairment in TLE patients despite intact film- and event-level recall. Sequence memory may represent a subtle manifestation of memory impairment that is not detected by standard cognitive testing. Key PointsO_LIWe asked whether a naturalistic film recall task could detect episodic memory impairment in a temporal lobe epilepsy cohort. C_LIO_LIPatients with temporal lobe epilepsy showed comparable film and event recall compared to healthy controls but were found to have impaired sequence memory. C_LIO_LISequential memory for temporal order is an overlooked aspect of episodic memory that may detect subtle memory decline. C_LI

From a behavioral and neuronal perspective, observational and physical practice conditions have been theorized to be equivalent during motor task learning. However, some paradigms can challenge such a functional equivalence hypothesis. The perception of difficulties experienced by others may play a role in observational learning by allowing learners to partially distance themselves from these episodes, thereby limiting their impact on learning. In contrast, during physical practice, performance difficulties are directly experienced, which may constrain such distancing mechanisms. Indeed, an observer watching a model that uses a wrong physical strategy can ignore erroneous trials in order to preserve action encoding. The main goal of the present study was to prevent such observer avoidance and to test the cognitive and neuronal functional equivalence between the physical and observational practice groups. During this experiment, both groups learned two motor sequences. Only one sequence was repeatedly interrupted to perturb encoding. Behavioral results revealed that both groups were equally negatively impacted by such interruptions. Together, these findings suggest that while physical and observational practice can lead to comparable behavioral outcomes under strong disruption, they rely on partially distinct neural strategies. Physical practice predominantly engages motor and striato-cerebellar feedback loops, whereas observational learning relies more strongly on fronto-cerebellar and episodic memory networks, highlighting a context-dependent functional equivalence between learning modalities.

Previously, electrophysiological differences between subpopulations of midbrain dopamine (DA) neurons were identified based on projection targets, including distinct responses to hyperpolarization and in the regularity of pacemaking. Here we explored single-compartment models of three subpopulations of DA neurons, projecting to medial shell of the nucleus accumbens (VTA-mNAcc), dorsomedial striatum (SNc-DMS) or dorsolateral striatum (SNc-DLS). We reduced the dimensionality to a phase plane consisting of membrane potential and one slow variable, either total slow potassium conductance or Kv4 channel inactivation. Nullclines are curves on which the rate of change of each variable is zero, given the value of the other variable. The voltage nullclines had three branches: upper spiking, unstable middle, and lower quiescent branch. Recruitment of Kv4 channels by the more prominent after-hyperpolarizing potential (AHP) in the DA-DMS and DA-DLS models channels stabilized pacemaking by creating a restorative moving fixed point along the quiescent branch. The slow inactivation of KV4 channels dominated and regularized the dynamics during the interspike interval; a dominant slow process may be a general mechanisn for stable regular pacemaking in a frequency range between 1-10 Hz. In contrast, the smaller AHP in VTA-mNAcc models prevented recruitment of this Kv4-mediated moving fixed point, which increased the sensitivity to synaptic inputs. On rebound from hyperpolarization the ability to produce robust ramps reverses between the DA neurons: now VTA-mNAcc projecting DA models fully recruited Kv4 channels and produced stable ramp-like pauses, whereas SNc-DLS projecting cells recruited significant regenerative inward CaV3 channels that overwhelmed Kv4 channels and produced rebound bursts. Author SummaryMidbraim dopamine (DA) neurons in the mammalian midbrain are linked to motivation, control of voluntary movement initiation, and reward-based learning. Their dysfunction is implicated in major disorders like Parkinsons disease, schizophrenia or substance use disorders. Firing patters like bursts or pauses in most DA subpopulations are thought to signal better or worse than expected outcomes. Here we use dynamic systems analysis to capture how functional diversity of DA neurons of their intrinsic properties results in differences of synaptic input integration leading to the generation of burst and pause patterns of electrical activity.

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.

ContextGrid cells in the medial entorhinal cortex (MEC) of head-fixed mice exhibit ultraslow (<0.01 Hz) oscillations (USO) during walking in a 1D running wheel in darkness. It was proposed that these oscillations may have a connection with navigational behavior. ProblemThere is no clear link between the functional role of these oscillations and path integration, a fundamental navigation strategy used by animals to calculate their current position and orientation by continuously summing self-motion cues. HypothesisGiven the synaptic projections from MEC to the hippocampus, we hypothesized that ultraslow oscillations have a role in linking spatiotemporal memories acquired during navigation. MethodologyA realistic computational model of entorhinal-grid with ultraslow oscillations and hippocampal-place cells is proposed using synaptic plasticity between cell types, sustaining path integration of a rodent-like simulated animal. ResultsUltraslow oscillations induced persistent changes in the grid cell dynamics, represented as a positional drift of grid fields. Such drift resulted in position estimation errors but generated new grid-place cell associations when combined with synaptic plasticity. >DiscussionsUltraslow entorhinal oscillations were found to shape spatial memory through grid cell drifting, which could serve as a mechanism for flexibly accessing different spatial memories during navigation. HIGHLIGHTSO_LIPath integration dynamics hide ultraslow oscillations despite coexistence. C_LIO_LIUltraslow oscillations significantly degrade position estimation in path integration. C_LIO_LIGrid and place fields drift after the effect of ultraslow oscillations. C_LIO_LINew spatial memories were created as a result of the ultraslow oscillation drift. C_LIO_LIUltraslow oscillations enable dynamic access of different spatial memories C_LI

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.

BackgroundPatients with Parkinsons disease (PD) almost inevitably experience cognitive impairments. These deficits have been linked to low frequency "theta" cortical activity [~]4 Hz, previously associated with cognitive control. ObjectiveOur study investigated effects of 4 Hz subthalamic nucleus (STN) deep brain stimulation (DBS) on cognitive performance in PD patients with cognitive impairments. MethodsWe recruited 17 PD participants with (n=10) and without (n=7) cognitive impairment. In these patients, we compared motor and cognitive performance during 4 Hz STN DBS, typical DBS for motor symptoms of PD ([~]130Hz) and DBS OFF. Motor performance was tested by Part III of the Movement Disorders Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS-III). Cognitive performance was tested during performance of the Multi-Source Interference Task (MSIT), which requires conflict resolution to respond accurately. ResultsMotor function improved with 4 Hz STN DBS and further improved with [~]130 Hz STN DBS. Compared to DBS OFF, reaction times were decreased during 4 Hz STN DBS and were further decreased at [~]130 Hz. Strikingly, 4 Hz DBS alone improved accuracy compared to both DBS OFF and compared to [~]130 Hz STN DBS. ConclusionsThese data suggest that theta-frequency 4 Hz STN stimulation is effective in PD patients with cognitive impairments. Our findings will help guide new therapies targeted at improving cognitive dysfunction in PD and could broaden applications for low-frequency brain stimulation.

Study ObjectivesIdiopathic hypersomnia (IH) is a central nervous system hypersomnia frequently accompanied by autonomic symptoms, yet objective physiological data are limited. We sought to characterize autonomic nervous system (ANS) dysfunction in IH using nocturnal heart rate variability (HRV) and diurnal autonomic reflex testing (ART), compared to individuals with type 1 narcolepsy (NT1) and healthy controls (HCs). MethodsTwenty-four adults with IH, 10 with NT1, and 14 HCs underwent overnight video polysomnography with HRV analyses in time and frequency domains during stable slow-wave sleep and REM sleep. Comprehensive ART included sympathetic adrenergic (head-up tilt (HUT), Valsalva BP responses), parasympathetic cardiovagal (HRV to deep breathing, Valsalva ratio), and sudomotor (Q-Sweat) measures. ResultsIH participants were predominantly female, with over half reporting long sleep duration. Compared to NT1 and HC, participants with IH demonstrated a greater magnitude of orthostatic tachycardia on tilt ({Delta}HR 41.0 {+/-} 16.3 vs. 26.3 {+/-} 9.3 vs. 30.8 {+/-} 9.3 bpm, p = 0.0086), as well as frequent sudomotor dysfunction (64.3%). IH participants demonstrated greater nocturnal and REM HR with reduced parasympathetic indices during REM, indicating diminished vagal modulation compared with HCs ConclusionsIH is characterized by a distinct pattern of autonomic dysfunction, including pronounced orthostatic tachycardia, frequent sudomotor abnormalities, and reduced parasympathetic activity during sleep. These findings provide objective physiological evidence of ANS involvement in IH and delineate features that distinguish IH from NT1 and HCs.