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The Journal of Neuroscience

Society for Neuroscience

Preprints posted in the last 90 days, ranked by how well they match The Journal of Neuroscience's content profile, based on 928 papers previously published here. The average preprint has a 0.47% match score for this journal, so anything above that is already an above-average fit.

1
Cholecystokinin released somatodendritically from dopamine neurons broadly alters synaptic strength across the ventral tegmental area

Sianati, S.; Ma, Y.; Kauer, J. A.

2026-03-16 neuroscience 10.64898/2026.03.12.711406 medRxiv
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Neuropeptides are found in nearly every brain neuron, and can modulate behaviors by regulating neuronal excitability, synaptic transmission, and plasticity. In contrast to the canonical view of neuropeptide release from nerve terminals, we previously reported the somatodendritic release of cholecystokinin (CCK) from ventral tegmental area (VTA) dopamine (DA) neurons. Release of CCK occurs during modest depolarization of VTA DA cells, and by activating CCK2Rs, potentiates synaptic transmission from GABAergic afferents. Here, recording from dopamine neurons in acute midbrain slices from male and female mice, we examined how somatodendritic release of CCK regulates synaptic plasticity and the extent of its influence. Depolarization of a dopamine neuron induced long-term potentiation (LTP) at GABAergic synapses, and in parallel somatodendritic CCK release produced long-term depression (LTD) at glutamatergic synapses. CCK-induced LTP persisted when postsynaptic G protein signaling in dopamine neurons was blocked, suggesting that CCK likely acts at GABAergic presynaptic terminals. Activation of kappa opioid receptors prevented CCK-dependent LTP of GABAergic synapses, indicating interaction between these two neuromodulatory signaling pathways in VTA. Surprisingly, depolarization of one dopamine neuron potentiated synapses onto both the depolarized neuron and neighboring dopamine neurons located up to [~]100 {micro}m away, indicating substantial spread of CCK signaling and synaptic modulation within the VTA region. Taken together, our findings demonstrate that somatodendritic CCK release bidirectionally coordinates synaptic strength across dopamine neurons, identifying a peptide-mediated feedback mechanism that shapes VTA circuit function. Significance StatementDopamine neurons in the ventral tegmental area (VTA) play central roles in reward, motivation, stress responses, and feeding behavior. While fast synaptic inputs regulate dopamine neuron firing on fast timescales, less is known about how slower neuromodulatory signals shape these circuits. We show that somatodendritic release of the neuropeptide cholecystokinin from dopamine neurons coordinately alters both inhibitory and excitatory synaptic strength and influences neighboring neurons within the VTA. This peptide-mediated feedback mechanism operates over a broader spatial scale than classical synaptic transmission and is regulated by kappa opioid signaling. These findings reveal how local peptide release can reshape dopamine circuit function and may contribute to changes in reward processing and feeding behavior.

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Low-frequency phase temporally coordinates multiple working memory operations

Ding, Y.; Cavanah, P. J.; Fiebelkorn, I. C.

2026-05-02 neuroscience 10.64898/2026.04.30.721949 medRxiv
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Working memory unfolds over time, yet how different working memory operations are temporally coordinated remains unclear. Building on prior links between low-frequency neural oscillations and working memory maintenance and retrieval, as well as evidence that low-frequency oscillations help coordinate cognitive functions, we tested whether low-frequency neural oscillations bridge and/or differentiate distinct working memory operations. Specifically, we tested whether low-frequency phase was linked to memory accuracy and event-related neural responses across three operations: (i) encoding, (ii) retrieval, and (iii) distractor processing during maintenance. Using EEG in human participants, we found that encoding and retrieval were most strongly linked to memory accuracy through theta phase ([~]4-7 Hz), measured just prior to each task event. Pre-encoding theta phase also modulated the neural response to memory item onset, suggesting that theta phase influences encoding strength. Critically, the theta phase associated with better memory accuracy differed significantly between encoding and retrieval, consistent with temporally distinct and functionally specific states supporting each working memory operation. In contrast, the influence of distractors on memory accuracy was linked to alpha phase ([~]8-10 Hz), with distractor occurrence also appearing to re-engage theta-dependent processes associated with encoding and retrieval. Together, these findings suggest that low-frequency neural oscillations provide a temporal framework that bridges multiple operations of working memory. SignificanceWorking memory (WM) relies on multiple operations that must be coordinated over time, yet how these processes are temporally organized remains unclear. Neural oscillations have been proposed as a timing mechanism for cognition, yet evidence linking distinct oscillatory phases to distinct WM operations remains limited. Here, we show that memory accuracy depends on the phase of low-frequency neural activity, with encoding and retrieval linked to opposing theta phases ([~]4-7 Hz), and distractor interference during maintenance linked to alpha phase ([~]8-10 Hz). These findings indicate that distinct WM operations are temporally coordinated within oscillatory cycles, providing evidence that low-frequency neural activity both coordinates and segregates cognitive processes over time.

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Prediction from Statistical Learning Aids Auditory Scene Analysis

Viswanathan, V.; Narayanan, S.; Johnsrude, I. S.; Saffran, J. R.; Shinn-Cunningham, B. G.

2026-04-23 neuroscience 10.64898/2026.04.21.719938 medRxiv
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Statistical regularities support auditory scene analysis across multiple levels. While acoustic regularities like comodulation and harmonicity aid bottom-up perceptual grouping, higher-level regularities like linguistic or musical structure must be learned to form a mental "schema" of statistical patterns. Although learned schemas may benefit comprehension by helping listeners perceptually separate and/or attend to a target sound stream in an acoustic mixture, the underlying mechanisms are unclear. Here, we used a statistical learning paradigm to expose listeners to sequences of speech syllables with fixed transitional probabilities, forming an artificial "language" of trisyllabic words. Following exposure, participants attended to one of two concurrent syllable streams and detected target syllables. Detection performance improved when the attended stream conformed to the statistical structure learned implicitly during exposure, with a larger benefit in the presence of a competing stream than in quiet. In contrast, predictability of the unattended stream had no effect on performance. Electroencephalography revealed that predictable targets elicited earlier parietal P300 "target-recognition" responses and enhanced neural tracking of the attended stream, with additional signatures of predictive processing observed even in the absence of targets. These findings demonstrate that learned statistical regularities enhance listening in noise by enabling predictive, schema-based selection of relevant input. Rather than facilitating automatic segregation of competing sounds, learned lexical schemas support auditory scene analysis through attentional template matching. Our findings establish a direct mechanistic link to the role of prediction in schema-based listening in noise. SignificanceOur remarkable ability to isolate a target sound source, such as a persons voice, in noisy environments is essential for effective communication. This process--termed auditory scene analysis--is known to rely on low-level acoustic regularities, but it is unclear whether learned higher-level regularities, like linguistic structure, also contribute. Combined electroencephalography and behavioral experiments reveal that statistical prediction of upcoming target syllables based on learned syllable-transition probabilities of an artificial language improves attentional selection to a target sound stream in an acoustic mixture. Prediction enhances neural tracking of the attended stream and speeds neural recognition of auditory targets. These findings have implications for auditory training approaches to rehabilitate hearing-impaired individuals who struggle to understand speech in noise.

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Domain Specific Functional Plasticity of Visual Processing Constrained by General Cognitive Ability in Deaf Individuals

Dong, C.; Wang, Z.; Zuo, X.; Wang, S.

2026-03-26 neuroscience 10.64898/2026.03.25.714101 medRxiv
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Interpersonal communication relies on integrating facial and vocal signals to extract multidimensional communicative information. How the absence of audition reshapes the communicative system remains unclear. We compared the performance of deaf (N=136) and hearing (N=135) adults across multiple domains, facial identity, emotional expression, speech, and global motion, through a series of unisensory and audiovisual psychophysical tasks. The results showed that, in hearing individuals, reliance on facial versus vocal signals differed across domains. In deaf individuals, auditory deprivation did not produce uniform enhancement or impairment of visual processing. Instead, they exhibited reduced sensitivity to dynamic emotional expressions and global motion, preserved sensitivity to facial identity (both static and dynamic) and static expressions, and enhanced categorization of facial speech. Notably, sensitivity to dynamic facial expressions and global motion was correlated, and both were explained by variations in fluid intelligence. Our results provide a systematic characterization of visual function across domains in deaf individuals, suggesting that the consequences of hearing loss are shaped both by the functional roles of audition within each domain and by broader cognitive adaptations. These findings advance understanding of cross-modal plasticity and inform the development of targeted ecologically valid accessibility and sensory-substitution strategies.

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Neural correlates of licking behavior modulated by target position in the striatal matrix compartment

Kimoto, T.; Yoshizawa, T.; Ishimaru, Y.; Inui, T.; Nakamura, K.; Yawaka, Y.; Funahashi, M.

2026-04-21 neuroscience 10.64898/2026.04.18.719363 medRxiv
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The striatum is a major cortical input site of the basal ganglia and plays a critical role in the control of orofacial movements such as licking. However, how striatal activity relates to the spatial features of licking behavior remains unclear. In this study, we examined whether neural activity in the striatal matrix and striosomal compartments is associated with the spatial position of a licking target during an operant task. Head-fixed mice performed a licking task in which the target positions were varied across three spatial dimensions. Using fiber photometry in Calb1-IRES-Cre and Pdyn-IRES-Cre mice, we recorded calcium signals from matrix and striosomal neurons. Associations between neural activity, target position, and behavioral variables were quantified using linear mixed-effects modeling with cross-validation. Matrix activity prior to licking onset was primarily associated with the dorsal-ventral target position and reaction time. During licking, matrix activity was modulated by anterior-posterior and medial-lateral positions, independent of reaction time and lick count. In contrast, striosomal activity during licking was predominantly associated with the dorsal-ventral position. These findings demonstrate that neural matrix activity is systematically associated with spatial features of licking behavior, with distinct contributions before and during movement. Our results suggest that striatal matrix circuits provide task-relevant spatial signals for the control of orofacial actions. Significant StatementWe show that neural activity in the striatal matrix is associated with the three-dimensional position of a licking target during an operant task. Activity prior to licking onset reflects dorsal-ventral position, whereas activity during licking is modulated by the anterior-posterior and medial-lateral positions. These findings indicate that matrix activity represents spatial aspects of licking behavior, supporting a role for the striatum in integrating motor execution with task-specific spatial information and pointing to the matrix compartment as a substrate for transforming spatial coordinates into action-specific motor commands.

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Visuospatial coding by theta oscillations in human hippocampus

Rostowsky, K.; Issa, N. P.; Wu, S.; Tao, J. X.; Haider, H. A.; Rose, S. L.; Warnke, P. C.; Satzer, D.; Braga, R. M.; Schuele, S. U.; Shinn, A.; Shi, L.; Voss, J. L.; Kragel, J. E.

2026-05-20 neuroscience 10.64898/2026.05.19.725196 medRxiv
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The hippocampus has been proposed to support visual processing and perception, challenging longstanding accounts that emphasize navigation or declarative memory. A key prediction of visual-processing accounts is that the hippocampus should exhibit similar visuospatial coding properties to those of higher-order visual neocortical areas, such as sensitivity to the size of visual stimuli and contralateral visual field biases. We tested for these properties using intracranial EEG to measure hippocampal neural activity during a retinotopic mapping task. The hippocampus exhibited characteristic slow ([~]2 Hz) and fast ([~]8 Hz) theta oscillations throughout the task. Fast theta was responsive to the presence but not the amount of visual stimulation. In contrast, slow theta did not generally respond to stimulus presence but scaled with the size of the visual stimulus, consistent with larger receptive fields. Slow theta also showed a contralateral bias, an effect that was specific to the right hippocampus. None of these effects were attributable to microsaccades or performance of the concurrent vigilance task. These findings provide electrophysiological evidence for visual field coding by human hippocampus, supporting accounts of hippocampal function that emphasize its role atop the visual hierarchy. Visual processing of this kind may combine with self-motion, memory, and other signals to support the broader spatial and mnemonic functions with which hippocampal theta oscillations have long been associated.

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From Face to Person: Disentangling the Neural Origins of the N170, N250, and SFE in Familiar Face Recognition

Li, M.; Li, C.

2026-05-08 neuroscience 10.64898/2026.05.04.722329 medRxiv
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Recognizing familiar faces is essential in our everyday life. ERP studies have identified three components sensitive to face familiarity (N170, N250, and SFE), but whether these signals arise from visual experience, identity information, or semantic knowledge remains to be directly tested. Using a sequential familiarization paradigm, we progressively trained the same initially unfamiliar faces with visual exposure, identity associations, and biographical knowledge, recording EEG after each phase. The N250 emerged immediately after visual familiarization and remained stable thereafter; the N170 appeared only after identity familiarization; and the SFE exhibited a graded, enhanced pattern: absent after visual exposure, emerging after identity training, and reaching maximum effect after semantic familiarization. These findings provide the first direct evidence that these three ERP markers are differentially driven by distinct types of information, revealing the temporal dynamics through which person-related knowledge transforms a face percept into the recognition of a known person.

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Opioids modulate Curiosity-Driven Exploration in Music

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

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

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Fixation-locked hippocampal activity reflects semantic content and temporal order of visual exploration during scene encoding

San Agustin, A.; Voss, J. L.; Kragel, J. E.

2026-05-19 neuroscience 10.64898/2026.05.15.725376 medRxiv
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Memory formation relies on the hippocampus and unfolds over time across experience, such as during the visual exploration of complex, naturalistic scenes. Eye movements evoke hippocampal activity, including fixation-locked field potentials and phase resets of theta oscillations. This suggests that hippocampal encoding is temporally structured by the sequence of visual fixations. Because eye-movement sequences sample semantically meaningful portions of scenes, they provide temporal structure to semantic content in memory. However, it remains unclear how the semantic content and temporal order of fixations jointly shape medial temporal lobe activity. We therefore tested whether intracranial EEG recordings from human hippocampus and amygdala reflect the semantic content and temporal order of individual fixations during encoding of naturalistic scenes. Relative to other semantic content, fixations on people were particularly relevant for memory, with the first fixation on a person predicting subsequent scene recognition. Fixation-locked hippocampal responses were enhanced for fixations to people relative to other semantic content, expressed in both larger fixation-evoked potentials and stronger theta phase locking. These effects were strongest for the first fixation relative to subsequent fixations. Theta phase locking was also enhanced in both hippocampus and amygdala for first fixations on people relative to later fixations and to other semantic content. These findings indicate that medial temporal lobe activity is structured by discrete fixation-level events during scene encoding, suggesting that theta-paced sampling contributes to the transformation of semantic and temporal components of visual experiences into memory. Significance StatementThis study shows that the semantic content and order of eye fixations jointly influence human hippocampal activity during memory encoding. Combining intracranial recordings, eye-movement tracking, and deconvolutional modeling, we show that the first glance at a person within naturalistic scenes is a privileged event, associated with increased hippocampal activity, theta-phase resetting in hippocampus and amygdala, and subsequent memory success. These findings recast eye movements not as mere motor acts, but as an important process that helps medial-temporal structures prioritize and integrate behaviorally relevant information into episodic memory.

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Task-irrelevant stimuli boost phasic pupil-linked arousal but not memory formation

Hebisch, J.; Van Puyenbroeck, P.; Schwabe, L.; de Gee, J. W.; Donner, T. H.

2026-03-28 neuroscience 10.64898/2025.12.23.696068 medRxiv
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Brainstem arousal systems including the locus coeruleus noradrenaline system, re-spond transiently to behaviorally relevant events. Locus coeruleus activity also drives dilations of the pupil, which are often observed during cognitive tasks. The strength of pupil responses during encoding of stimulus material predicts the success of its later retrieval, which might reflect the impact of noradrenaline on synaptic plasticity and memory formation. The pupil also dilates in response to task-irrelevant sounds, which could therefore serve as a valuable tool for investigating causal effects of phasic, pupil-linked arousal on cognition. Here, we evaluated whether task-irrelevant white noise sounds affect memory formation and memory-based decisions. These sounds were played before, during or after the presentation of memoranda (images or spoken words). Memory success was measured in recognition and free recall tasks the day after. Trial-to-trial variations in the amplitude of pupil dilations during word encoding without task-irrelevant sounds predicted memory success. Task-irrelevant white-noise sounds also robustly dilated the pupil but did not improve memory formation for the words or the images. We conclude that pupil-linked arousal processes triggered by task-irrelevant sounds differ from those recruited endogenously during memory for-mation, for example in states of increased emotionality or attention.

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Distinct SMA beta bursts support the development of anticipatory postural control in children

Manyukhina, V.; Barlaam, F.; Vergne, J.; Bain, A.; Abdoun, O.; Daligault, S.; Delpuech, C.; Jerbi, K.; Sonie, S.; Bonnefond, M.; Schmitz, C.

2026-03-19 neuroscience 10.64898/2026.03.17.712353 medRxiv
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To compensate for self-generated movement-induced postural disturbances, the brain generates anticipatory postural adjustments (APA), ensuring smooth, coordinated actions. APA development continues into late adolescence, yet the specific pathways and mechanisms that remain immature in children are poorly understood. We studied APA mechanisms in 24 children (7-12 years old) using magnetoencephalography (MEG) while they performed the naturalistic bimanual load-lifting task (BLLT). In the BLLT, participants lift a load placed on one forearm with the contralateral hand while keeping the postural forearm horizontal, as if lifting a glass from a tray. To counteract forearm deflection caused by unloading, the brain generates APAs, which involve anticipatory inhibition of the postural Biceps brachii. We found that stronger anticipatory Biceps brachii inhibition was associated with reduced excitability, as indexed by high-gamma (90-130 Hz) suppression, and increased high-beta power (19-29 Hz) in the contralateral Supplementary Motor Area (SMA). Analysis of transient beta events revealed two functionally distinct burst types: (1) 19-24 Hz bursts: time-locked to immediate high-gamma suppression correlated with 26-28 Hz beta power; predicted stronger muscle inhibition and received directed input from middle frontal cortex and precentral gyrus; (2) 24-29 Hz bursts: linked to delayed ([~]100 ms) high-gamma suppression correlated with 8 Hz alpha power; predicted earlier and prolonged muscle inhibition and better forearm stabilization, but did not show directional influence from other regions. Results on anticipatory inhibition-related beta bursts replicated mechanisms reported in adults, suggesting that the efferent pathways and transient inhibitory processes underlying APA may already be mature in children. In contrast, higher-frequency beta bursts revealed a child-specific, complementary APA mechanism that may compensate for imprecise anticipatory inhibition. These results reveal two oscillatory mechanisms supporting APA in children and indicate that beta bursts may reflect both immediate cortical inhibition linked to muscle control and indirect alpha-mediated inhibition likely compensating for forearm instability.

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Homeostatic Coupling Of Cortical And Brainstem Delta Rhythms In Sleeping Infant Rats

Ahmad, M.; Sokoloff, G.; Blumberg, M. S.

2026-05-13 neuroscience 10.64898/2026.05.11.724416 medRxiv
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The emergence of the cortical delta rhythm (1-4 Hz) during quiet sleep (QS) is a major milestone in brain development. In rats, this milestone is achieved between 8 and 12 days of postnatal (P) age. We previously reported an age-dependent increase in PZ delta-rhythmic activity that is synchronized with cortical delta and entrained by breathing. Here, we ask whether this long-distance synchrony persists in response to perturbations to sleep homeostasis or respiration. First, using male and female P12 rats, we investigated the coupling strength between frontal cortex and PZ in response to a short but intense period of sleep deprivation. During recovery sleep, we observed a rebound in delta power in both PZ and cortex, even in the absence of increased QS duration, indicating that PZ and cortical delta power are equivalent markers of homeostatic sleep regulation. Analyses of phase-locking and lagged cross-correlation revealed persistent temporal coupling between the two rhythms such that cortical delta reliably lagged PZ delta regardless of changes in sleep pressure. Curiously, we also observed an increase in breathing depth during recovery sleep, which we confirmed in a separate cohort of pups. Next, using mild hypercapnia (5% CO2) to alter breathing frequency and depth, we produced decreases in cortical and PZ delta power along with decreases in the depth of breathing. These findings provide additional support for the notion that PZ and cortical delta rhythms function as distantly interconnected components within a developmentally emerging sleep-homeostatic system that is also intimately tied with the brainstem respiratory network. SIGNIFICANCE STATEMENTWe reported previously that the delta rhythm that defines slow-wave sleep is not confined to the forebrain but also occurs synchronously in the medulla. This study in infant rats uses two perturbations to assess the coupling strength of cortical and brainstem delta. Using sleep deprivation and hypercapnia, we show that delta power increases or decreases in lockstep in the two regions, respectively. Our results reinforce the notion that delta across these two regions is strongly coupled and adds a new dimension to our understanding of the interconnectedness of the delta rhythm and respiration.

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Individual Differences in Speech Monitoring: Functional and Structural Correlates of Delayed Auditory Feedback

Ozker, M.; Giglio, L.; Beyh, A.; Forkel, S.; Hagoort, P.

2026-04-27 neuroscience 10.1101/2025.10.22.683659 medRxiv
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Sensory feedback is essential for the fine-tuning of motor actions, and speech production is no exception. It depends on continuous self-monitoring to ensure that produced sounds match intended targets. Delaying auditory feedback (DAF) disrupts this alignment and impairs fluency, providing a powerful tool to investigate sensorimotor control. We combined functional and diffusion-weighted MRI in 31 participants performing a word-production task under delayed (DAF) and immediate (no-DAF) auditory feedback. While all participants slowed their speech under DAF, the extent of this effect varied across individuals and was quantified using a susceptibility index (SI). At the group level, DAF elicited increased activation in a right-lateralized network encompassing the superior temporal gyrus, supramarginal gyrus, inferior frontal gyrus, supplementary motor area, and left cerebellum. Incorporating individual differences revealed that higher susceptibility was associated with greater activation in left-hemisphere speech motor homologues and larger volume of the right long arcuate fasciculus, a white-matter pathway connecting auditory and motor speech regions. This pattern suggests that vulnerability reflects increased recruitment of neural resources and a stronger reliance on auditory-motor coupling. In contrast, resilience was associated with greater engagement of the bilateral angular gyrus and higher fiber density in the right posterior arcuate fasciculus, which connects auditory and somatosensory speech regions. This finding indicates that resilience is supported by a posterior circuit that efficiently integrates multi-modal sensory feedback. Together, these findings link functional dynamics with underlying structural connectivity to reveal how a right-lateralized network supports speech control, while accounting for individual differences in susceptibility to fluency disruption. Significance StatementFluent speech depends on the brains ability to monitor self-produced sounds and sensations from articulatory organs to adjust motor commands in real time. To uncover the neural basis of this process, we combined a fluency-disrupting paradigm, delayed auditory feedback (DAF), with functional and structural neuroimaging. This multimodal approach revealed that while DAF processing relies on a right-lateralized network, more susceptible individuals show enhanced recruitment of left-hemisphere monitoring regions. We also found that stronger white-matter connections in the right posterior arcuate fasciculus predict greater resilience and fluency. These findings provide an anatomically grounded account of how auditory and somatosensory feedback interact to support speech production, offering new insight into why some individuals are more susceptible to fluency breakdowns and related disorders.

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Soft tactile stimulation engages parabrachial circuits traditionally associated with aversion

Anesten, F.; Simfors, S.; Ioneskou, K.; Hezso, M.; Gundogdu, B.; Tran, A.; Stjernvall, A.; Ratiglia, V.; Almasri, A.; Loken, L. S.

2026-03-18 neuroscience 10.64898/2026.03.15.711870 medRxiv
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Gentle tactile stimulation is associated with positive affect and social bonding, yet the central circuits engaged by such stimuli remain incompletely understood. The lateral parabrachial nucleus (lePB) is a key hub in ascending affective sensory pathways and is robustly activated by aversive stimuli, including pain. Here, we examined neuronal activation in the lePB and the likewise associated subparafascicular nucleus, parvocellular part (SPFp), following different tactile stimulation paradigms in mice. Behavioral analyses confirmed that the soft touch stimuli used in this study were not aversive: mice displayed low aversive facial grimace scores during brushing and von Frey stimulation compared with noxious heat, and showed a preference for a soft tactile environment in a place preference assay. Neuronal activation was assessed using Fos immunohistochemistry following exposure to brushing-based soft touch, a fur-roll paradigm, innocuous punctate touch (von Frey), or noxious heat. Soft touch protocols robustly increased Fos expression in the lePB compared with home cage controls, whereas innocuous punctate touch did not. Notably, the magnitude of activation produced by brushing-based stimuli was comparable to that induced by noxious heat. Using CalcaCre mice, we further found that soft touch recruited a subset of CGRP-expressing neurons in the lePB. In contrast, tactile stimulation produced only modest activation in the SPFp and did not strongly increase overall Fos expression in this region. Together, these findings demonstrate that affective tactile stimulation can engage neuronal populations within ascending parabrachial circuits, including CGRP neurons traditionally associated with nociceptive processing, suggesting that these pathways may encode the salience or affective significance of somatosensory stimuli rather than exclusively aversive input.

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Limb-Selective Regions in the Lateral Temporal Lobe Shrink from Childhood to Adulthood

Cohnen, S.; Kahler, L.; Yun, S. D.; Konrad, K.; Nordt, M.

2026-03-09 neuroscience 10.64898/2026.03.06.709762 medRxiv
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Perceiving hand gestures and inferring others actions and emotions from movements of hands and limbs play an important role in every-day interactions, especially in young children. The perception of categories such as limbs, bodies, or faces is supported by category-selective regions in the temporal lobe. Some category-selective regions, such as those reacting selectively to body parts or limbs, exist both on the ventral and on the lateral side of the temporal lobe, and are part of the ventral and lateral stream, respectively. While it was recently shown that limb-selective regions in the ventral stream shrink from childhood to adulthood, the developmental trajectory of limb-selective regions in the lateral stream remains unknown. To close this gap in knowledge, we acquired functional magnetic resonance imaging (fMRI) data in 21 children aged 10 - 12 years and 20 adults while they watched images of 10 visual categories including limbs and whole bodies. We first replicate the decrease of limb-selectivity from childhood to adulthood in the ventral temporal lobe. Across several analyses, our results further demonstrate that limb-selective regions in the lateral temporal lobe shrink as well, particularly in the left hemisphere. Underlining the specificity of our finding, we show that lateral body-selective regions show no significant development from childhood to adulthood. These findings advance our understanding of the developmental trajectories of limb- and body-selective regions and of the ventral and lateral visual streams more broadly.

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Hippocampal patterns and associative memory: Distinct intracranial EEG temporal encoding patterns support memory

Xue, A. M.; Hsu, S.; LaRocque, K. F.; Raccah, O. M.; Gonzalez, A.; Parvizi, J.; Wagner, A. D.

2026-03-20 neuroscience 10.64898/2026.03.18.712716 medRxiv
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Episodic memory depends on neural representations encoded in the hippocampus. Experimental and computational evidence suggests that the hippocampus encodes pattern-separated representations that support later recall of episodic event elements. While extant data in humans predominantly focus on assaying the relationship between the similarity of spatial neural patterns at encoding and later memory performance, similarity of neural patterns in the temporal domain may also reveal encoding computations predictive of future memory. To examine how the similarity among temporal patterns of hippocampal activity during encoding relates to later episodic retrieval (associative cued recall and recognition memory), hippocampal activity was recorded from human participants (n=7) with implanted intracranial electrodes while they encoded arbitrary (A-B) paired-associates. Subsequent memory analyses first revealed that hippocampal high-frequency broadband power (HFB; 70-180Hz) was linked to a graded increase in memory strength; HFB power was greater during the encoding of pairs later correctly recalled relative to events later recognized and was lowest for events later forgotten. Second, and critically, subsequent memory analyses further revealed that more distinctive temporal patterns in the hippocampus during encoding -- indexed by the similarity of the HFB timeseries elicited by a given event to that elicited by other events -- were associated with superior subsequent memory performance. Finally, exploratory analyses revealed stimulus category effects on hippocampal HFB power during encoding and retrieval cuing. These results indicate that the temporal distinctiveness of hippocampal traces during encoding is important for subsequent retrieval of episodic event elements, consistent with theories that posit that pattern separation facilitates future remembering.

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Late Integration of Prior Expectations During Precision Weighted Perceptual Decisions

Gastrell, T.; Rangelov, D.; Mattingley, J. B.

2026-04-16 neuroscience 10.64898/2026.04.13.718329 medRxiv
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Adaptive perceptual decision-making relies on the ability to combine sensory evidence with prior expectations in a precision-weighted manner. Although Bayesian inference provides a clear normative account of how such integration should occur, the neural mechanisms through which the brain represents and combines priors and likelihoods remain poorly understood. Across two preregistered experiments, we investigated how the precision of prior expectations and sensory likelihoods influences visual motion judgements and associated neural activity patterns during a random-dot motion estimation task. Neurotypical adult participants (N=80, 58 female) reported directions of visual motion stimuli, with motion coherence varying randomly across trials. Prior expectations were manipulated block-wise by varying the probabilities with which different motion directions were presented. Consistent with precision-weighted inference, response accuracy improved as coherence increased with robust response biases toward the expected motion direction. Neural activity measured using electroencephalography (EEG) revealed reliable effects of prior expectation on the univariate central-parietal positivity (CPP), consistent with reduced accumulation of sensory evidence under informative priors. Multivariate analysis using inverted-encoding models revealed robust effects of prior informativeness on motion-specific neural representations, but only late, during response planning stages. Together, these findings demonstrate that precision-weighted inference primarily occurs at late stages of the decision process and challenge predictive-processing accounts that emphasise early sensory processing. Significance StatementPerceptual decisions require combining uncertain sensory information with prior expectations about what is likely to occur. Although behaviour often follows this principle, it remains unclear how the brain integrates prior expectations with incoming sensory evidence. Using a visual motion task and concurrent brain imaging, we show that expectations do not alter early sensory processing but instead influence later stages of decision formation and action planning. Neural representations of sensory evidence primarily reflect stimulus reliability, whereas prior expectations selectively enhance representations during response preparation. These findings challenge influential theories proposing that expectations affect early sensory processing and instead highlight their contribution to later decision-related processes. This work advances understanding of how the brain uses experience to optimise perceptual decisions under uncertainty.

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Explicit knowledge gates expectation suppression in the motor system: Evidence from a TMS motor oddball paradigm

Cost-Chretien, M. E.; Rideaux, R.; Tran, D. M. D.

2026-04-30 neuroscience 10.64898/2026.04.27.721216 medRxiv
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Models of predictive processing propose that the brain continuously generates predictions about incoming sensory input, updating an internal model of the environment through prediction errors when those predictions are violated. A foundational assumption of these models is that prediction error generation occurs automatically, independently of conscious awareness. Evidence from auditory oddball studies in unconscious patients appears to support this view, though findings are complicated by stimulus-specific adaptation confounds that make it difficult to isolate genuine predictive effects. To investigate whether expectation suppression or prediction-based attenuation extends to the motor system and whether it operates automatically, we developed a novel motor oddball paradigm using brain stimulation. Transcranial magnetic stimulation (TMS) delivered over the primary motor cortex elicit motor-evoked potentials (MEPs) in peripheral muscles, providing an index of corticospinal excitability. By varying stimulation intensity in an oddball-like manner using repeating and deviating sequences, we manipulated the predictability of TMS pulses and compared MEP amplitudes for expected versus unexpected intensity-matched stimulation. Incorporating experimental designs to control for adaptation and an instruction manipulation to test the role of awareness, expected TMS reliably produced smaller MEPs than unexpected TMS. Critically, this attenuation was observed only in participants with explicit knowledge of the sequence structure. These findings extend expectation suppression effects to the motor system and support the domain-generality of prediction-based neural attenuation while challenging the assumption that predictive processing operates entirely automatically.

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Experience shapes infants' electrophysiological responses to faces from 3 to 9 months

Ashton, K.; Sugden, N.; Xie, W.; Fernandez, F.; Pickron, C. B.; Moulson, M.; Bayet, L.

2026-05-21 neuroscience 10.64898/2026.05.20.726644 medRxiv
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The types of faces that infants see impact their developing ability to engage with and individuate people from familiar and unfamiliar social groups, a phenomenon known as perceptual narrowing. However, the neural mechanisms that underlie infants processing of different faces as a function of experience remain poorly understood. To address this gap, the present study analyzes electroencephalography data collected while 3-month-olds (N=24), 6-month-olds (N=26), and 9-month-olds (N=18) viewed female and male faces of a familiar or unfamiliar social group. Infants neural responses to faces differed by group familiarity from 3 months of age, with increased responses to the more familiar face types in early components (P1, N290), and to the more unfamiliar face types in later components (P400, Nc). Face sex and group familiarity interacted to shape N290 and P400 amplitudes at 3- and 9-months. Specifically, N290 amplitudes were greater in response to female faces of a familiar group at 3 months, and to male faces of a familiar group at 9 months. In contrast, P400 amplitudes were greater in response to male faces of an unfamiliar group at 3 months old, and greatest in response to both female faces of a familiar group and to male faces of an unfamiliar group at 9 months. Source reconstruction of the Nc revealed greater reconstructed current density in response to faces of an unfamiliar social group across all ages. These findings contribute to a growing body of knowledge examining how perceptual experiences shape infants understanding of their social world.

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Food preference is associated with distinct large-scale cortical functional connectivity patterns during food-image observation

Sugata, H.; Kim, S.; Ikeda, T.; Hara, M.

2026-04-23 neuroscience 10.64898/2026.04.22.720279 medRxiv
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Food preference influences behavior toward food-related stimuli, yet the large-scale neural mechanisms underlying this process remain unclear. This study investigated whether preferred and nonpreferred food cues are associated with distinct patterns of cortical functional connectivity during the observation of food images. Data from 25 of the 40 recruited healthy adults were included in the final analysis after excluding individuals with highly unbalanced response tendencies. Participants viewed 150 food images and rated each image on a four-point preference scale. Trials were classified as favorite food (FF) or disliked food (DF). High-density electroencephalography (EEG) was recorded during the task, and source-level ROI-to-ROI functional connectivity was analyzed using amplitude envelope correlation in the alpha (8-13 Hz) and beta (13-25 Hz) frequency bands over the 1000-ms period after food-picture onset. Response time did not differ significantly between FF and DF trials. However, distinct functional connectivity patterns were observed between conditions in both frequency bands. In the alpha band, FF trials involved a network including the cuneus, parietal regions, cingulate regions, and lateral occipital cortex, whereas DF trials involved the isthmus cingulate, caudal middle frontal gyrus, inferior temporal cortex, superior parietal lobule, and lateral occipital cortex. In the beta band, FF trials involved the isthmus cingulate, precuneus, parietal regions, and pericalcarine cortex, whereas DF trials additionally involved frontal regions, including the superior frontal gyrus and pars triangularis. These findings indicate that food preference is associated with distinct large-scale cortical functional connectivity patterns during food image observation, suggesting differential neural processing of preferred and nonpreferred food cues.