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Neurobiology of Learning and Memory

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match Neurobiology of Learning and Memory's content profile, based on 40 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

1
Safety learning produces rapid fear suppression and distinct amygdala-prefrontal engagement

Altaf, M.; Cho, C.; Maletta, T. A.; Lim, S.; Martin, L. J.; Lehmann, H.; Fournier, N. M.

2026-08-08 neuroscience 10.64898/2026.08.06.743388 medRxiv
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Animals detect and evaluate signs of danger and safety in their environment to ensure survival, yet the neural mechanisms that distinguish safety learning from other forms of conditioned inhibition, remain poorly understood. Here, we directly compared fear and safety learning in male rats. Fear conditioned rats showed high freezing to the tone and the conditioning context, whereas safety conditioned rats showed significant tone-specific reduction in freezing. This safety cue could also generalize to a novel, previously unassociated threat context leading to suppressed freezing when presented demonstrating that inhibitory actions of safety cues are not tied to its original training environment but can modify fear expression across settings. Fear and safety learning also produced unique patterns of neuronal activation and glutamatergic receptor expression in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and central amygdala (CeA), as measured by c-Fos immunohistochemistry and Western blotting. Fear conditioning induced greater Fos expression in the BLA and CeA, as well as elevated amygdalar NMDA receptor (GluN1) levels, whereas safety learning increased amygdalar PSD-95 and AMPA receptor (GluA1) expression. Both safety and fear learning increased mPFC Fos expression without affecting glutamatergic receptors levels. Finally, safety conditioning was associated with lower tone-evoked freezing than fear conditioned rats across early extinction sessions and was accompanied by distinct patterns of prefrontal and amygdala activation across extinction. Together, these findings suggest that safety learning engages neural and behavioral mechanisms distinct from fear learning and extinction, while modifying amygdala-prefrontal circuits towards more rapid fear suppression.

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Active control modulates memory-related activity during encoding and encoding-retrieval similarity

Ding, Z.; Yuan, S.; Xu, J.; Zhang, S.; Hanslmayr, S.; Liu, X.; Zhang, M.

2026-08-27 neuroscience 10.64898/2026.08.23.746434 medRxiv
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Self-directed learning allows learners to actively control their learning experience and has been shown to enhance memory compared with matched yoked learning. However, it remains unclear when and how active control modulates memory-related neural activity during learning and retrieval. We recorded electroencephalography (EEG) while participants encoded objects under active and yoked learning conditions and again during a delayed recognition test approximately 24 h later. We examined event-related potential (ERP) activity across earlier processing windows, including pre-stimulus slow potentials and early N2 activity, and later processing windows, including P300, late slow-wave, and post-stimulus slow-potential activity. We also examined encoding-retrieval similarity (ERS) between neural patterns during encoding and retrieval. Behaviorally, active control improved delayed recognition, with the advantage selectively expressed in detailed recognition. In the ERP analyses, earlier processing windows showed memory-related effects, with pre-stimulus slow-potential and N2 activity differentiating subsequently remembered from forgotten items, but were not modulated by active control. By contrast, active control modulated later memory-related ERP activity, with remembered-forgotten differences expressed during late stimulus-related and immediate post-stimulus processing only in the active condition. ERS showed a similar active-control modulation: memory-related encoding-retrieval pattern similarity was evident under active learning, but not under yoked learning, with this effect involving relatively late encoding and retrieval windows. Together, these findings support a constructive-processing account, suggesting that memory formation under active control depends more strongly on rich, detailed encoding representations that can be reinstated during retrieval.

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The influence of sleep on emotional and social recognition memory and gist abstraction in children

Meyer-Jajkov, P. T.; Kurz, E.-M.; Höpfner, F. M.; Tuncel, Z.; Hebborn, L.; Paetow, J.; Kölle, K.; Ngo-Dehning, H.-V. V.; Conzelmann, A.; Prehn-Kristensen, A.

2026-08-19 psychiatry and clinical psychology 10.64898/2026.08.18.26360653 medRxiv
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Sleep is proposed to have a beneficial effect on the consolidation of memories and gist abstraction in adults. For children, gist abstraction is of special relevance to transform new information from social and emotional contexts into stable representations. This study investigated the effect of sleep on emotional and social recognition and gist abstraction on N=34 typically developing children assessed in a sleep and a wake condition. In an emotional memory task, reward-associated stimuli were presented, while a social memory task used face-stimuli to implement social acceptance or rejection from peers. Both paradigms relied on a hidden rule to be abstracted. In general, children were able to remember emotional and social stimuli and to abstract gist information. With respect to sleep, we found a beneficial effect of sleep on the recognition of emotional stimuli but no sleep-dependent enhancement for either social recognition or emotional or social gist abstraction. Overall, our results indicate, that sleep-dependent recognition might depend on the type of memory task. Furthermore, nighttime sleep as compared to daytime wakefulness has no differential influence on gist abstraction in children as assessed in our paradigms, contrasting previous results found in adults.

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Elucidating the Role of Cerebellar Nuclei Parvalbumin Activity on Adolescent Reversal Learning

Lyle, T.; Berkley, A.; Verpeut, J.

2026-08-25 neuroscience 10.64898/2026.08.20.746009 medRxiv
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The cerebellar nuclei (CN) has demonstrated its influence on cognitive behavior via the cerebello-cortico circuit, yet the role of CN critical period mechanisms and how they may influence cognitive behavior, such as parvalbumin (PV) expressing interneurons enwrapped by perineuronal nets (PNNs), is still unclear. Therefore, we investigated the role of the lateral CN (LCN) PV cell calcium activity while animals performed a visual discrimination touchscreen cognitive task. All animals received the PV cell calcium indicator GCaMP6f at postnatal day 21 (P21). We targeted the LCN critical period by manipulating neural activity in male mice using the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) from postnatal day 21 to 35 or by injecting an Hapln1-AAV vector to selectively target LCN PNN development. After animals completed the visual discrimination task, cerebellar tissue was collected for viral recovery and antibody staining for PNN components, Hapln1 and aggrecan. Results revealed DREADD animals showed improved reversal learning, an increase in calcium response to learning-related activity and altered PNN expression (Hapln1 and aggrecan). Hapln1 treated animals displayed a decrease in final day acquisition performance, lower reversal performance compared to DREADD groups, a decrease in reversal calcium learning-related activity, and an increase in PNN expression (Hapln1). Together, these data provide further evidence of LCN mechanisms associated with learning as well as the importance of understanding region-specific critical periods of plasticity.

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Distinct Working Memory for Near and Far in a T-Maze Delayed Alternation Task: Evidence for Dual-Process Dynamics in Hippocampal-Prefrontal Coordination

Takita, M.; Ichitani, Y.

2026-08-11 neuroscience 10.64898/2026.08.06.743185 medRxiv
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We recently reported that rats performed better at a task distance of 2 m than at 0 m in a T-maze delayed alternation paradigm using a movable home cage in the longer-delay condition (Takita & Ichitani, 2026). We simultaneously recorded local field potentials from the bilateral prefrontal cortex, intermediate hippocampus, and ventral hippocampus. Across task epochs, coherence and two cross-frequency measures (phase-locking value and modulation index [MI]) revealed differences between correct and error trials in prefrontal interactions with hippocampal subregions. Among these measures, only MI was affected by task distance during the pre-task delay epoch. MI was highest in 2-m error trials and lowest in correct trials. In 0-m error trials, MI transiently increased during arm entry to levels comparable to those in 2-m error trials before declining toward the levels observed in correct trials during the later post-task delay. These MI dynamics appeared to be consistent with distance-dependent differences in behavioral performance. In addition, normalized Correct-Error Indices calculated for each electrophysiological measure revealed differential contributions of prefrontal coupling with the intermediate and ventral hippocampus across task distances. These findings suggest the existence of distinct near and far working memory states underlying distance-dependent behavioral differences, with distinct yet complementary contributions of the intermediate and ventral hippocampus to prefrontal interactions.

6
Targeted Memory Reactivation During Non-Rapid Eye Movement Sleep Strengthens Consolidated Declarative Memories

Moyano, M. D.; Capurro, L.; Gonzalez, M. C.; Brusco, L. I.; Forcato, C.

2026-08-27 neuroscience 10.64898/2026.08.24.746831 medRxiv
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Targeted memory reactivation (TMR) during sleep can benefit recently acquired memories, but whether it can also influence memories after an initial period of consolidation remains unclear. Here, we tested whether auditory reactivation during non-rapid eye movement (NREM) sleep could strengthen declarative memories learned 24 h earlier. Twenty-six healthy young adults learned 30 sound word associations and returned the following day for a 90 min nap. During NREM sleep, participants in the Reactivation group received incomplete reminders consisting of the learned sound followed by the first syllable of the associated word, whereas the No-Reactivation group slept under the same conditions without memory related cues. Participants who received reminders showed significantly less forgetting, despite comparable training performance and sleep macroarchitecture. Across NREM sleep, reactivation was associated with greater slow oscillation and delta power, more slow oscillations and fast spindles, and greater slow oscillation spindle cooccurrence. The memory benefit remained significant after adjusting for NREM physiological measures and in sensitivity analyses restricted to overlapping physiological ranges between groups. Cue locked analyses revealed significant responses in the slow oscillation, delta, theta, and fast-spindle ranges, but the magnitude of these responses was not associated with memory change. These findings show that TMR during NREM sleep can benefit declarative memories after a 24 h consolidation interval and suggest that its effects extend beyond the immediate post-learning sleep period.

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Vestibular Perturbation Disrupts Source and Reality Monitoring

Bates, C. M.; Lingawi, L.; Perry, E.; Gallagher, M.; Martin, A. K.

2026-08-13 neuroscience 10.64898/2026.08.07.743488 medRxiv
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The vestibular system has been implicated in several aspects of self-representation, including bodily self-location, yet its role in episodic source and reality monitoring remains unclear. Moreover, symptoms of depersonalisation and derealisation (DPDR) have been associated with both vestibular dysfunction and altered source and reality monitoring. We tested whether noisy galvanic vestibular stimulation (nGVS) modulates source and reality monitoring during a word-encoding paradigm and whether this increased symptoms of DPDR. Sixty young adults (N = 30 active nGVS, N = 30 sham) encoded words that varied by context (spoken vs. imagined), agentic source (self vs. other), and valence (positive vs. threat) before completing source/reality judgments. Active nGVS reduced overall accuracy relative to sham on both reality and source monitoring. Across conditions, self-referential items were remembered with greater sensitivity compared to other-referential items, and spoken items were recalled with greater sensitivity than imagined items. We additionally show an interaction effect whereby active nGVS reduced accuracy specifically for imagined and threat-valenced items. Trait DPDR did not moderate the effects of stimulation, although higher trait DPDR was associated with a more liberal reality-monitoring response criterion. Results indicate that transient vestibular perturbation via nGVS can impair source monitoring for internalised and threatening stimuli and impairs cognitive distinctions between internally and externally generated events in general, supporting a role for vestibular input in maintaining self-other and reality boundaries in episodic memory.

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Causal contributions of the dorsolateral prefrontal cortex and temporoparietal junction to source and reality monitoring

Bates, C.; Ring, L.; Tolfrey, M.; Martin, A.

2026-08-27 neuroscience 10.64898/2026.08.25.746632 medRxiv
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Source and reality monitoring enable individuals to distinguish the origins of remembered information, including whether information was self- or other-generated and whether it was perceived or imagined. Although the dorsolateral prefrontal cortex (dlPFC) and temporoparietal junction (TPJ) have been implicated in these processes, their independent causal contributions remain unclear. We investigated whether focal transcranial direct current stimulation (f-tDCS) of the left dlPFC and left TPJ differentially modulates source and reality monitoring. One hundred participants were randomly assigned to receive anodal or sham stimulation of the left dlPFC or TPJ before completing an episodic memory task manipulating agent (self, experimenter), context (spoken, imagined), and emotional valence (positive, negative). Discrimination sensitivity (d') and response criterion (c) were examined separately. For source monitoring, stimulation interacted with context and cortical region: anodal dlPFC stimulation was associated with a greater spoken-imagined difference in self-experimenter discrimination than sham stimulation, whereas no equivalent context-dependent effect emerged following TPJ stimulation. For reality monitoring, stimulation effects also differed by cortical target, with reduced spoken-imagined discrimination following anodal relative to sham TPJ stimulation and no significant effect of dlPFC stimulation. These effects were not accompanied by corresponding stimulation effects on response criterion. Independent of stimulation, source discrimination was substantially greater for spoken than imagined information, while reality-monitoring sensitivity was enhanced for self-generated relative to experimenter-generated negative information. Together, these findings provide evidence that the dlPFC and TPJ make dissociable contributions to source and reality monitoring, while highlighting the importance of contextual and affective features in determining how the origins of memories are evaluated.

9
Repeated swim exposure and PKN1a knockout enhance group I mGluR-dependent excitability associated with reduced EAAT3 expression in mouse dentate granule cells

Yasuda, H.; Kubouchi, K.; Hanamura, K.; Kurihara, T.; Nakasone, Y.; Mukai, H.

2026-08-24 neuroscience 10.64898/2026.08.19.745661 medRxiv
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Stress-related experiences alter glutamatergic signaling and neuronal excitability, but the mechanisms that couple experience to dentate granule cell function remain incompletely understood. Here, we examined how protein kinase N1a (PKN1a), a protein kinase C-like serine/threonine kinase, and repeated swim exposure regulate mouse hippocampal dentate granule cell excitability, with a focus on the neuronal glutamate transporter excitatory amino acid transporter 3 (EAAT3) and group I metabotropic glutamate receptors (mGluRs). Five days of repeated swim exposure increased spike firing in mature dentate granule cells from wild-type mice. PKN1a knockout produced a similar increase, and repeated swim did not further enhance firing in knockout mice. The enhanced firing observed after repeated swim exposure and in PKN1a knockout mice was reduced by co-application of an mGluR1 antagonist (LY367385) and an mGluR5 antagonist (MPEP). Inhibition of glutamate transporters with DL-TBOA increased granule cell firing in control wild-type mice but did not further increase firing in repeated-swim wild-type or PKN1a knockout mice, suggesting occlusion of transporter-dependent regulation of excitability. Repeated swim exposure and PKN1a knockout also reduced total and surface expression of EAAT3 in the hippocampus, whereas expression of the glial glutamate transporter EAAT2 was not significantly altered. Finally, PKN1a knockout and repeated swim exposure reduced anxiety-related behavior in the elevated plus maze test. Thus, PKN1a-dependent regulation of EAAT3 may restrain group I mGluR-dependent excitability in dentate granule cells, whereas repeated swim exposure and PKN1a knockout shift this system toward a lower-EAAT3, higher-excitability state accompanied by reduced anxiety-related behavior.

10
Sex differences in diverse conditioned fear behaviors following systemic naloxone administration

Greiner, E. M.; Shansky, R. M.; Laine, M. A.; Fourte, J.

2026-08-20 neuroscience 10.64898/2026.08.20.745978 medRxiv
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Fear conditioning studies have historically relied on freezing as the primary measure of conditioned fear despite evidence that defensive responding is behaviorally diverse and sexually dimorphic. The endogenous opioid system, particularly mu-opioid receptor (MOR) signaling, is known to regulate fear learning and conditioned analgesia, yet its role in alternative fear-related behaviors and sex differences remains unclear. Here, we investigated the effects of systemic naloxone administration prior to auditory fear conditioning on freezing, darting, shock responsivity, and ultrasonic vocalizations (USVs) in male and female rats. Adult Sprague Dawley rats received naloxone (5 mg/kg, i.p.) or saline prior to conditioning and underwent fear recall testing 24 hours later. Naloxone produced sex- and behavior-specific effects across conditioning and recall. During conditioning, naloxone increased freezing in males during baseline and early tone presentations, while females exhibited reduced shock-response velocity and increased post-shock freezing. Naloxone did not significantly alter darting or USV production during conditioning. During recall, freezing behavior did not differ across groups. Naloxone-treated females, however, exhibited a distinct alarm-calling pattern, with fewer callers overall but increased call output among those that vocalized. These findings suggest that MOR antagonism differentially alters distinct components of fear expression in a sex-dependent manner and support the idea that freezing and alarm calling may reflect separable aspects of fear processing.

11
Hippocampal-midbrain interactions link encoding-related pupil response to memory success

Kafkas, A.; Baek, H. Y.-J.; Kukkonen, N.; Montaldi, D.

2026-08-19 neuroscience 10.64898/2026.08.10.743973 medRxiv
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Encoding-related pupil responses predict later memory performance, but the neural mechanisms linking these autonomic dynamics to memory formation remain unclear. This study examined whether pupil responses during encoding track activity in the brains memory network and whether they reflect functional interactions between memory-related regions and neural systems involved in pupil control. Participants performed an incidental encoding task involving object stimuli while undergoing simultaneous fMRI and pupillometry; recognition memory was subsequently assessed outside the scanner. Greater pupil constriction during encoding predicted both the strength and quality of later memory. These pupil dynamics correlated with activity in memory-related brain regions, notably the hippocampus and the parahippocampal cortex. Connectivity analyses indicated that encoding-related pupil responses were supported by functional interactions between the hippocampus and the midbrain Edinger-Westphal nucleus, the striatum, and the orbitofrontal cortex. The findings suggest that interactions between memory-related regions and parasympathetic pupil-control systems may modulate encoding efficiency. Together, the results identify encoding-related pupil constriction as a non-invasive marker of memory-network engagement and suggest a hippocampal-midbrain pathway through which autonomic pupil dynamics are coupled with successful memory formation.

12
Systemic diazepam alters local hippocampal CA1 circuits and differentially affects entorhinal and CA3 inputs

Peterson, J. G.; Erickson, M. T.; Sheehan, A.; Damphousse, C. C.; Redish, A. D.

2026-08-23 neuroscience 10.64898/2026.08.18.745488 medRxiv
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The GABAA positive allosteric modulator diazepam is taken systemically by millions of people daily. GABAA signaling is essential for hippocampal circuit function, but the effects of systemic diazepam on hippocampal information processing during behavior has not been studied. To answer this question, large neural ensembles were recorded from rats running a linear track under systemic diazepam administration. A cross-correlation of spiking activity revealed significantly increased inhibition from interneurons, aligned with the timescale of GABAA, suggesting a direct effect on local circuits. Local field potentials (LFP) showed an increase in theta and lo-gamma (30-50 Hz) power but a decrease in hi-gamma (80-120 Hz) power. We also found decreased amplitude and rate of sharp wave ripple (SWR) events and a reduction of firing rate and proportion of cells recruited to the SWRs. An autocorrelation of single-cell spike trains revealed a decrease and shift from shorter to longer timescales, aligning differently with theta frequencies. Phase coupling measurements showed decreased cellular coupling to theta and increased coupling to lo-gamma and hi-gamma. Finally, entropy of decoding along the track was increased, suggesting less precise spatial representations under diazepam. These changes suggest mechanisms that would likely disrupt hippocampal memory storage and consolidation processes under systemic diazepam.

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Anxiety-Related Traits Are Associated with Subjective Biases but not Altered Threat-Safety Discrimination

Ehlers, M. R.; Stiffel, H.; Kastrinogiannis, A.; Koppold, A.; Lonsdorf, T. B.

2026-09-01 neuroscience 10.64898/2026.08.27.747474 medRxiv
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Anxiety-related traits (ARTs) have been linked to altered fear learning, but previous studies have typically examined different experimental phases and response systems, limiting the comparability of findings and the accumulation of consistent evidence. Here, we comprehensively examined associations between ARTs and fear conditioning across acquisition, extinction and renewal and across subjective, physiological and neural response systems in a well-powered sample (N = 267) using a two-day differential conditioning paradigm. ARTs were operationalized as a composite of trait anxiety, neuroticism, and intolerance of uncertainty and conditioned responding was assessed using skin conductance responses, fear-potentiated startle, US expectancy ratings, fear ratings, and functional magnetic resonance imaging. Higher ARTs were consistently associated with elevated subjective fear and US expectancy to both threat and safety cues during extinction and renewal, without corresponding elevations in physiological responding. At the same time, ARTs were not associated with threat-safety discrimination in subjective or physiological measures across phases, while neural associations were limited to reduced dorsal anterior cingulate cortex discrimination during early renewal. These findings suggest that ARTs are characterized by a CS unspecific cognitive bias toward heightened threat expectancy and evaluation rather than altered associative fear learning, highlighting the importance of distinguishing conditioned discrimination from general levels of responding across response systems.

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Contextual Inference Drives Motor Memory Protection and Disruption

Sannamath, S.; Kaur, R.; Kumar, A. D.; Kumar, A.; Kumar, N.

2026-08-28 neuroscience 10.64898/2026.08.25.746912 medRxiv
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Newly acquired memories are initially fragile and are consolidated into long-term memory over time. Although consolidated memories were once thought to be resistant to interference, accumulating evidence shows that memory reactivation renders them transiently labile, making them susceptible to modification or interference before reconsolidation. Crucially, however, there is substantial variation in whether reactivated memories are disrupted by new information, remain protected from it, or even strengthened by it. The factors that guide this modification are largely unknown. To systematically investigate this, we examined motor memory interference using a classic A-B-A visuomotor rotation paradigm. Participants adapted to a 30-degree clockwise rotation (A) on Day1. On Day2, an interfering 30-degree counter-clockwise rotation (B) was introduced under varied conditions: directly without reactivation, after brief reactivation of A, after expression of A without feedback, or following a gradual transition from A to B. The final experiment used explicit contextual cues (a secondary follow-through target) to distinguish A and B trials. Contrary to the simple prediction that reactivation should increase vulnerability to interference, reactivating the original memory before introducing interference protected it, as evidenced by significant savings during relearning on Day3. In contrast, introducing interference directly, without reactivation, disrupted the original memory. This protection was consistent with a contextual-inference account: the large sensory prediction error experienced during the abrupt transition from A to B served as a latent contextual cue, signaling a new context and thereby shielding the original memory from being overwritten. Eliminating this prediction error through an immediate washout session with a similar error profile or through a gradual A-to-B transition abolished the protective effect and disrupted the original memory. Furthermore, when explicit contextual cues distinguished the two perturbations, memories were protected even in the absence of a salient prediction error. Our findings are consistent with a contextual inference account in which the fate of a consolidated memory, whether it is modified or protected, is shaped by the availability of explicit cues or latent signals such as sensory prediction error at the time when interference is introduced.

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Evaluating Cognitive Impact of Traumatic Brain Injury and Risk for Post-Traumatic Epilepsy

Zink, T.; Noren, H.; Valdivia, D.; Yohn, C.; Hundal, J.; Chen, S.; Scarisbrick, D.; Sun, H.

2026-09-01 neurology 10.64898/2026.08.30.26361760 medRxiv
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Abstract: Objective: Post-traumatic epilepsy (PTE) is a common sequela of traumatic brain injury (TBI). Research indicates that individuals with PTE tend to experience greater cognitive difficulties compared to those with TBI alone. However, it is plausible that a distinct cognitive profile exists that distinguishes between TBI cases with and without PTE. We aimed to identify longitudinal changes in cognitive measures among TBI patients to better assess the changes associated with developing PTE. Setting: Outpatient. Participants: Prospective subjects who had suffered TBI within 6 months post-injury (TBI-6M, n=32), retrospective subjects with pre-existing PTE diagnoses (PTE, n=20), and healthy control subjects (HC, n=41). Design: We examined cognitive performance for TBI patients within 6 months post-injury, then again within 12 months (TBI-12M, n=26), and within 18-months (TBI-18M, n=25), and compared this with cognitive performance among HC and PTE. Main Measures: Cognitive tests administered yielded 15 test components for analysis. We utilized linear mixed effects modeling to examine cohort-level differences cognitive function. Results: 11/15 tests showed a significant performance deficit in the PTE subjects compared to HC. TBI-6M was not significantly different from the PTE subjects; with time, 9/15 tests showed some degree of recovery in TBI subjects. Tests for information processing speed/working memory and executive function showed strong recovery (TBI-6M vs. TBI-18M, SDMT written: p<0.0001, SDMT oral and COWAT: p<0.001). Tests for visual attention/working memory also showed a smaller but significant recovery (TBI-18M vs. PTE, p<0.05). By contrast, tests for verbal memory [HVLT-R Delayed Recall] showed chronic impairment in TBI (TBI-18M vs HC, p<0.0001). TBI subjects generally trend towards recovery in cognitive performance post-TBI. Conclusions: Information processing speed/working memory are strong indicators for TBI recovery, while auditory learning/memory shows chronic impairment. The stagnation of recovery in cognitive domains typically characterized by robust recovery may correlate with an elevated risk of developing PTE.

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Episodic memory rescues working memory via pattern separation, pattern completion, and predictive recall

Bai, Z.; Fougnie, D.; Michelmann, S.

2026-09-01 neuroscience 10.64898/2026.08.26.746101 medRxiv
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Working memory is capacity-limited, but interactions with episodic memory may offset this constraint. We tested moment-by-moment contributions of episodic representations to working memory by combining the N-back and Mnemonic Similarity tasks. Thirty-one participants, undergoing eye-tracking, first encoded items in a one-back task, classifying them as "same" or "similar" to their predecessor. In a subsequent two-back task, mnemonic discrimination showed a graded, item-specific benefit of prior experience: performance was best for previously compared items, whereas recognition of identical repeats was unaffected. Successful discrimination of previously compared items was accompanied by greater pupil dilation, gradually emerging gaze patterns resembling those elicited by their similar pair-mate, and higher gaze-similarity between one-back and two-back target viewing. Diverging gaze patterns between pair-mates during one-back further predicted two-back discrimination. These findings challenge working memory's characterization as an isolated system, demonstrating how it recruits episodic computations - encoding distinct traces, predicting upcoming content, and reinstating it at retrieval.

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Block-Level Deep Sleep Consolidation and Environmental Modifiers in Long COVID with Dysautonomia: A Longitudinal N-of-1 Wearable Study

Hammer, M. F.

2026-08-10 neurology 10.64898/2026.08.06.26359860 medRxiv
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Background: Sleep architecture fragmentation is common in Long COVID and dysautonomia, yet the relationship between block-level deep sleep consolidation and next-day functional wellbeing has not been characterized longitudinally in this population. We tested the hypothesis that block-level deep sleep architecture predicts next-day wellness better than aggregate stage duration. Methods: A prospective N-of-1 longitudinal study was conducted across 78 nights between January 1 and March 25, 2026 using a consumer wearable (Garmin Index Sleep Monitor). Next-day wellbeing was assessed using the Overall Feeling Score (OFS; 0-10 scale). A five-tier Architecture Group (AG) classification operationalized consolidation quality. A custom predictive model (Pendulum v5.2) quantified consolidation through block-level weighting and contextual penalties. Space weather metrics (Kp index, daily electron fluence, Load Score) were correlated with sleep architecture and OFS across same-day and lagged alignments. A secondary hierarchical regression examined illness as an independent covariate across the full dataset. Results: Architecture Group explained 56.7% of next-day OFS variance (r = 0.753, p < 0.001), compared with 17.0% for total deep sleep duration (r = 0.412) and 4.8% for the Garmin Sleep Score (r = 0.220). Pendulum v5.2 explained 43.0% of variance (r = 0.656). The deep sleep fragmentation phenotype occurred on 25.6% of nights despite adequate total deep sleep. Space weather explained 14.2% of OFS variance through architecture degradation; Load Score at 1-day lag was the strongest space weather predictor (r = -0.328, p = 0.004). A binary illness indicator explained an additional 5.7% of OFS variance beyond architecture and space weather (full-model R{superscript 2} = 55.2%), with a mean illness-night residual of -0.56 (SD = 0.36; 95% CI [-0.72, -0.40]), consistent with immune/viral flares reducing OFS through pathways independent of sleep architecture. Conclusions: Block-level deep sleep consolidation quality is a substantially stronger predictor of next-day wellbeing than total stage duration in Long COVID with dysautonomia. Space weather constitutes a measurable environmental modifier operating through architecture degradation. Immune and viral flares constitute a significant architecture-independent confound consistent with direct neuroinflammatory effects on functional capacity. This framework may be applicable across conditions where sleep architecture fragmentation plays a pathophysiological role.

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Cue-Induced Retrieval and Reconsolidation with Episodic Future Thinking for Craving and Delay Discounting in Opioid Use Disorder: A Pilot Randomized Controlled Trial

Toulami, M.; Ghasemi, K.; Rafei, P.; Vassileva, J.; Salehi, M.; Ekhtiari, H.; Rezapour, T.

2026-08-22 addiction medicine 10.64898/2026.08.19.26360819 medRxiv
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Aims: To evaluate whether Cue-Induced Retrieval and Reconsolidation with Episodic Future Thinking (CIREF), which combines personalized drug-cue retrieval with structured future-oriented processing, produces greater changes in craving and delay discounting than a recent-past episodic active control in individuals with opioid use disorder receiving methadone maintenance treatment. Design: Multicentre, two-arm, parallel-group randomized controlled pilot trial with per-protocol analyses. Setting: Two outpatient addiction treatment and rehabilitation centres in Tehran, Iran. Participants: Thirty participants with opioid use disorder receiving methadone maintenance treatment were randomized to CIREF or Episodic Recent Thinking (ERT; n = 15 per group). Twenty-eight completed the intervention and were included in the analyses (n = 14 per group). Intervention and comparator: Participants completed one screening, baseline, and personalized cue-development session followed by three 75-minute intervention sessions. CIREF combined personalized drug-cue retrieval with future-oriented simulation, prediction, intention, and planning. ERT was structurally matched but anchored episodic processing to the recent past. Measurements: Primary craving outcomes comprised the three Desire for Drug Questionnaire (DDQ) subscales assessing session-level phasic/current craving immediately before and after each intervention session and the four Obsessive-Compulsive Drug Use Scale (OCDUS) subscales assessing tonic craving before and after the intervention period. The secondary outcome was Monetary Choice Questionnaire (MCQ) log(k), with more negative values indicating less steep delay discounting. Findings: After Holm correction across the three DDQ subscales, Group x Occasion interactions indicated greater reductions with CIREF for Desire and Intention to Drug Use, FGG(1.23, 32.09) = 24.37, pHolm < .001, partial eta-squared = .484, and Negative Reinforcement, FGG(1.35, 35.23) = 17.67, pHolm < .001, partial eta-squared = .405, but not Drug Abuse Control (pHolm = .172). After Holm correction across the four OCDUS subscales, only Desire and Mental Preoccupation with Drugs showed a significant Group x Time interaction, F(1, 26) = 12.35, pHolm = .007, partial eta-squared = .322; the remaining subscales were not significant (adjusted ps >= .177). MCQ log(k) showed a Group x Time interaction, F(1, 26) = 7.18, p = .013, partial eta-squared = .217; mean log(k) changed from -1.22 (0.36) to -1.80 (0.55) in CIREF and from -1.39 (0.32) to -1.44 (0.44) in ERT. Conclusions: In this small pilot sample, the future-oriented retrieval-based intervention produced greater changes than the recent-past active control in two dimensions of session-level phasic craving, one dimension of tonic craving, and monetary delay discounting. The results are preliminary and do not establish memory reconsolidation or effects on relapse or longer-term clinical outcomes.

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Altered Social Cognition Associated with Kleptomanic and Instrumental Thefts

Goto, Y.; Iclal Cakir, M.; Yoshino, S.; Kita, C.; Won, M.; Lee, Y.-A.

2026-08-24 neuroscience 10.64898/2026.08.19.745606 medRxiv
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Theft, including shoplifting, extorts a pervasive societal and economic burden. However, the neurobehavioral mechanisms underlying recurrent theft remain sparsely understood. In this study, we investigated social cognition deficits in theft recidivists with kleptomania (TR+K) and instrumental theft recidivists without kleptomania (TR-K) compared to control subjects without criminal records (CT), for which the Social Norms Questionnaire (SNQ-22) to assess explicit moral knowledge, alongside the Dictator Game (DG) and Hawk-Dove Game (HDG) to evaluate discretionary and competitive resource allocation with others, respectively, were administered. Bayesian statistical analyses revealed that all groups demonstrated comparable social norm recognition in SNQ-22 and prosociality in the DG. However, distinct behavioral profiles emerged in specific contexts, such that TR+K exhibited more unfairness than CT and TR-K at discretionary resource allocations in the DG, whereas in the HDG, TR-K demonstrated more aggressive, resource-monopolizing responses, particularly when against an aggressive opponent, than CT and TR+K. These results suggest that theft recidivism may stem from contextual failures rather than general deficits in moral knowledge, which are distinct between TR+K rooted in the internal factor, such as heightened loss aversion, and TR-K characterized by impulsivity over the external factor, such as social conflicts with others.

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Proficiency-Dependent Reorganisation of Language and Control Networks during Second Language Processing: An fMRI Study of Korean-English Bilinguals

Kim, J.; Choi, J.; Baik, Y.; van Heuven, W.; Nam, K.; Jung, J.

2026-08-21 neuroscience 10.64898/2026.08.14.744902 medRxiv
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Second language (L2) processing engages both language-specific and domain-general control systems, yet how these systems vary with L2 proficiency remains unclear. We used functional magnetic resonance imaging (fMRI) to examine neural activity during L2 English processing in Korean-English (K-E) bilinguals across three proficiency levels (beginner, intermediate, advanced). Participants performed rhyme and spelling judgement tasks manipulating orthographic-phonological conflict. Behaviourally, conflict conditions reduced accuracy, with proficiency effects observed selectively in the rhyme task. fMRI results showed that conflict processing recruited frontoparietal control regions, including inferior frontal and parietal cortices, accompanied by deactivation in default mode network regions. Critically, proficiency-related effects differed by task. During rhyme judgement, advanced bilinguals showed greater activation in the left supramarginal gyrus (SMG) and cerebellum, whereas intermediate bilinguals exhibited greater recruitment of the left middle orbital gyrus and dorsomedial prefrontal cortex. During spelling judgement, advanced bilinguals showed greater thalamic activation alongside greater deactivation of the right dorsolateral prefrontal cortex. Activity in the left SMG and cerebellum was positively associated with L2 reading score, and cerebellar activity was also associated with rhyme-task performance, whereas right DLPFC activity was negatively associated with the scores. These findings suggest that increasing L2 proficiency is associated less with altered recruitment of core reading regions than with task-specific shifts in the balance between phonological-specialized, subcortical attentional, and domain-general control systems supporting L2 processing.