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Frontiers in Human Neuroscience

Frontiers Media SA

All preprints, ranked by how well they match Frontiers in Human Neuroscience's content profile, based on 67 papers previously published here. The average preprint has a 0.08% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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The impact of thermal and auditory unpleasant stimulus on motor imagery in healthy individuals

Cohen-Aknine, G.; Raphaël, P.; Denis, M.; Dupeyron, A.

2025-03-12 pain medicine 10.1101/2025.03.06.25323546 medRxiv
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Motor imagery is the ability to mentally simulate a motor task without actually performing it. Pain is an unpleasant sensory experience that involves different dimensions - sensory-discriminative, motivational-affective, and cognitive-evaluative - that are known to interfere with motor imagery. However, it remains unclear which specific pain dimension most significantly impairs motor imagery. This study aims to compare the effects of unpleasant auditory (primarily affective and cognitive) and thermal (primarily sensory) stimuli, which can be assimilated to pain, on discrete and continuous explicit motor imagery modalities. Eighteen healthy participants were exposed to unpleasant stimuli in addition to a control condition. Participants rated their motor imagery abilities after tasks involving rest, motor execution, and motor imagery in discrete and continuous wrist movement modalities. Results showed that during discrete motor imagery, only the aversive auditory stimulus significantly reduced motor imagery abilities, whereas thermal pain had no effect. In contrast, motor imagery abilities were preserved during the continuous modality. These findings suggest that explicit motor imagery may be more affected by the affective dimension of pain induced by aversive auditory stimuli. The preservation of motor imagery abilities in the continuous modality provides insight into the optimization of rehabilitation programs.

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Peripheral magnetic stimulation of the upper-limb nerves: evoked sensations, phantom-pain relief, and cortical responses

Grigoreva, O.; Samsonov, T.; Dolgoarshinnaia, A.; Lebedev, M.; Soghoyan, G.

2025-12-05 pain medicine 10.64898/2025.12.05.25341696 medRxiv
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Peripheral magnetic stimulation (PMS) is a noninvasive technique applicable to post-stroke rehabilitation, treatment of phantom limb pain (PLP) and generating neuroprosthetic sensations. Here we aimed to test whether PMS could be utilized to enable sensory feedback from hand prostheses and suppress PLP. Accordingly, we induced somatic sensations with PMS and conducted EEG measurements to assess sensory evoked potentials (SEPs) in 30 able-bodied participants (controls) and 11 individuals with transradial amputation. Single PMS pulses of varying amplitude were applied to the left arm locations overlying the median, radial, and ulnar nerves. Subjective accounts of sensations were collected using PerceptMapper, the University of Pittsburghs multitouch interface. After the best location for PMS was found, continuous stimulation (20 or 40 Hz, delivered in 5-min blocks with 5-7 min interblock intervals for patricipant breaks and EEG setup checks) was applied. The control participants reported experiencing sensations in their hands. The amputees felt sensations in their phantom hands. PMS evoked SEPs in both the controls and amputees. The analysis of intertrial coherence showed significant phase consistency of the stimulus-locked EEG responses across trials for the controls and amputees. The measurements of visual analogue scale (VAS) scale showed that PMS did not change PLP in 2 participants, increased it in 4, and decreased in 3. We propose that PMS could be used to assess the effects of peripheral nerve stimulation on somatic sensations, PLP and cortical activity prior to the surgical placement of electrode implants. Significance StatementPeople with amputation have two critical needs: (1) their prosthetic limbs being augmented with naturalistic somatic sensations, and (2) their PLP, which develops in the majority of cases, being suppressed. Electrical stimulation with peripheral nerve implants offers a solution for both needs, but invasiveness of this procedure poses a number of problems. Here we show that PMS offers a noninvasive tool for testing the effects of peripheral nerve stimulation before any invasive implants are placed. PMS causes somatic sensations, modulates PLP and evokes cortical responses evident in EEG recordings. These effects of PMS were documented in both healthy controls and amputees. The results suggest that PMS combined with EEG measurements could serve as tools for testing potential implantation sites.

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Altered Functional Networks during Gain Anticipation in Fibromyalgia

Park, S. H.; Michael, A. M.; Baker, A. K.; Lei, C.; Martucci, K. T.

2023-04-29 pain medicine 10.1101/2023.04.28.23289290 medRxiv
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Reward motivation is essential in shaping human behavior and cognition. Previous studies have shown altered reward motivation and reward brain circuitry in chronic pain conditions, including fibromyalgia. Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, cognitive problems, and mood-related symptoms. In this study, we analyzed brain reward networks in patients with fibromyalgia by using a data-driven approach with task-based fMRI data. fMRI data from 24 patients with fibromyalgia and 24 healthy controls were acquired while subjects performed a monetary incentive delay (MID) reward task. Functional networks were derived using independent component analysis (ICA) focused on the gain anticipation phase of the reward task. Functional activity in the motor, value-driven attention, and basal ganglia networks was evaluated during gain anticipation in both patient and healthy control groups. Compared to controls, the motor network was more engaged during gain anticipation in patients with fibromyalgia. Our findings suggest that reward motivation may lead to hyperactivity in the motor network, possibly related to altered motor processing, such as restricted movement or dysregulated motor planning in fibromyalgia. As an exploratory analysis, we compared levels of motor network engagement during early and late timepoints of the gain anticipation phase. Both groups showed greater motor network engagement during the late timepoint (i.e., closer to response), which reflected motor preparation prior to target response. Importantly, compared to controls and consistent with the initial findings described above, patients exhibited greater engagement of the motor network during both early and late timepoints. In summary, by using a novel data-driven ICA approach to analyze task-based fMRI data, we identified elevated motor network engagement during gain anticipation in fibromyalgia.

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Pain-related white-matter changes following mild traumatic brain injury: A longitudinal diffusion tensor imaging pilot study

Yang, H.-C.; Nguyen, T.; White, F. A.; Naugle, K. M.; Wu, Y.-C.

2024-08-06 pain medicine 10.1101/2024.08.05.24310944 medRxiv
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IntroductionPost-traumatic headache (PTH) is a common consequence of mild traumatic brain injury (mTBI) that can severely impact an individuals quality of life and rehabilitation. However, the underlying neuropathogenesis mechanisms contributing to PTH are still poorly understood. This study utilized diffusion tensor imaging (DTI) to detect microstructural alterations in the brains of mTBI participants with or at risk of developing PTH. MethodThis study investigated associations between DTI metrics 1-month postinjury and pain sensitivity, as well as psychological assessments 6-months postinjury to identify differences between mTBI (n = 12) and healthy controls (HC; n = 10). MRI scans, including T1-weighted anatomical imaging and DTI were acquired at 1-month postinjury. Pain sensitivity assays included quantitative sensory testing and psychological assessment questionnaires at 1-month and 6-months postinjury. ResultsSignificant aberrations of mean axial diffusivity in the forceps major were observed in mTBI relative to HCs at 1-month postinjury (p =0.02). Within the mTBI group, DTI metrics at 1-month postinjury were significantly associated (ps < 0.05) with pain-related measures and psychological outcomes at 6-month postinjury in several white matter tracts (right sagittal stratum, left anterior thalamic radiation, left corticospinal tract, left insula, left superior longitudinal fasciculus). Notably, the associations between DTI metrics at 1-month postinjury and pain-related measures at 6-month postinjury showed significant group differences in the right sagittal stratum (ps < 0.01), white matter tract in left insula (p < 0.04), and left superior longitudinal fasciculus (ps < 0.05). ConclusionThis study suggests that "Post-Traumatic Stress Disorder for DSM-5" and "Center for Epidemiological Studies-Depression Scale" are the most sensitive psychological measures to early microstructural changes after mTBI, and that the DTI metrics are predictive of pain and psychological measures in mTBI. Together, these results suggest that white matter microstructure plays an important role in the PTH following mTBI.

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Women with fibromyalgia: Insights into behavioral and brain imaging

Elkana, O.; Beheshti, I.

2024-09-16 pain medicine 10.1101/2024.09.15.24313716 medRxiv
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Fibromyalgia (FM) is a chronic condition marked by widespread pain, fatigue, sleep problems, cognitive decline, and other symptoms. Despite extensive research, the pathophysiology of FM remains poorly understood, complicating diagnosis and treatment, which often relies on self-report questionnaires. This study explored structural and functional brain changes in women with FM, identified potential biomarkers, and examined their relationship with FM severity. MRI data from 33 female FM patients and 33 matched healthy controls were utilized, focusing on T1-weighted MRI and resting-state fMRI scans. Functional connectivity (FC) analysis was performed using a machine learning framework to differentiate FM patients from healthy controls and predict FM symptom severity. No significant differences were found in brain structural features, such as gray matter volume, white matter volume, deformation-based morphometry, and cortical thickness. However, significant differences in FC were observed between FM patients and healthy controls, particularly in the default mode network (DMN), somatomotor network (SMN), visual network (VIS), and dorsal attention network (DAN). The FC metrics were significantly associated with FM severity. Our prediction model differentiated FM patients from healthy controls with an area under the curve of 0.65. FC measures accurately estimated FM symptom severities with a significant correlation (r = 0.45, p = 0.007). Functional connections in the DMN, VIS, and DAN were crucial in determining FM severity. These findings suggest that integrating brain FC measurements could serve as valuable biomarkers for early detection of FM and predicting FM symptom severity, improving diagnostic accuracy and facilitating the development of targeted therapeutic strategies.

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MMA athletes demonstrate different Brain Vital Sign profiles compared to matched controls at baseline

Munce, T. A.; Fickling, S. D.; Nijjer, S. R.; Poel, D. N.; D'Arcy, R. C. N.

2024-03-27 sports medicine 10.1101/2024.03.26.24304733 medRxiv
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We investigated objective brain vital signs derived from event-related potentials (ERPs) for mixed martial arts (MMA) athletes and matched controls (N=24). Brain vital sign scans were acquired from 9 MMA athletes and 15 age- and sex-matched controls. Our analysis specifically compared differences in brain vital signs between MMA athletes and controls at baseline. We predicted that MMA athletes would show significant differences relative to controls due to their ongoing exposure to repetitive head impacts. Participants were scanned to extract three well-established ERPs: N100 for auditory sensation; P300 for basic attention; and N400 for cognitive processing. Scans were verified using automated reports, with N100, P300, and N400 amplitudes and latencies manually identified by a blinded reviewer. Groups were evaluated at the waveform level with a mass-univariate analysis using non-parametric resampling. Brain vital signs were compared across groups with a Kruskal-Wallis H-test for independent samples, with FDR correction for multiple comparisons. We identified significant differences between MMA athletes and controls. Specifically, there were significant N400 amplitude reductions, indicating that exposure to repetitive head impacts in MMA may be associated with changes in brain function.

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From Perception to Appraisal: Hierarchical Brain Responses to Natural and Built Features in Urban Environments

Zaehme, C.; Sander, I.; Koselevs, A.; Kuehn, S.; Gramann, K.

2025-11-01 neuroscience 10.1101/2025.10.31.685763 medRxiv
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Exposure to urban rather than natural environments has been linked to elevated stress and diminished well-being, prompting interest in the underlying mechanisms and influences of specific urban elements. This study investigated how semantic and lower-level visual characteristics of urban scenes influence subjective experience and underlying neural processes. A total of 63 adults viewed street-level photographs depicting urban environments with varying proportions of vegetation, buildings, vehicles, and sky visibility while electroencephalography (EEG) was recorded. Subjective ratings indicated that urban scenes with more greenery compared to built elements were consistently perceived as more positive. In terms of lower-level image features, images with higher non-straight edge density also led to scenes being perceived as more positive. In contrast, a more visible sky area and a higher mean metric depth led to more negative scene appraisal. On a neural level, urban scenes with higher greenery/built ratios enhanced visual evoked P1 amplitudes, while higher straight-edge density led to more pronounced N1 amplitudes. Further analysis showed that later P3 and LPP components predicted subjective ratings on higher-level evaluative but not basic affective dimensions. These results partially replicate previous studies, suggesting that urban greenery exerts an effect on subjective well-being and influences early visual processing. Moving forward, Neuro-Urbanism research should employ more diversified stimuli and leverage immersive or in situ paradigms to refine our understanding of the relationship between greenery in urban environments and well-being to inform evidence-based urban design strategies. HighlightsO_LIHigher proportions of greenery in urban environments lead to more positive responses across a variety of subjective rating scales. C_LIO_LIMore urban greenery elicited more pronounced P1 amplitudes, replicating previous findings. C_LIO_LIEarliest visual processing (P1) responds to natural elements of the environment, before processing of visual features characteristic of artificial elements (N1). C_LIO_LILater ERP components (P3, LPP) predict subjective scene appraisal of higher level and aesthetic evaluation, pointing to a hierarchical separation between perceptual and evaluative processes. C_LI

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Atypical influence of biomechanical knowledge in Complex Regional Pain Syndrome-Towards a different perspective on body representation

Filbrich, L.; Verfaille, C.; Vannuscorps, G.; Berquin, A.; Barbier, O.; Libouton, X.; Fraselle, V.; Mouraux, D.; Legrain, V.

2021-10-07 pain medicine 10.1101/2021.10.05.21264512 medRxiv
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Part of the multifaceted pathophysiology of Complex Regional Pain syndrome (CRPS) has been ascribed to a lateralized maladaptive neuroplasticity in sensorimotor cortices, a finding that has been corroborated by behavioral studies indicating that CRPS patients indeed present difficulties in mentally representing their painful limb. Hand laterality judgment tasks (HLT) are widely used to measure such difficulties, with the laterality of hand stimuli corresponding to the affected hand judged more slowly than the one of hand stimuli corresponding to the unaffected hand. Importantly, the HLT is also regularly used in the rehabilitation of CRPS and other chronic pain disorders, with the aim to activate motor imagery and, consequently, restoring the cortical representation of the limb. The potential of these tasks to elicit motor imagery is thus critical to their use in therapy. Yet, the influence of the biomechanical constraints (BMC) on HLT reaction time, supposed to reflect the activation of motor imagery, is rarely verified. In the present study we investigated the influence of the BMC on the perception of hand postures and movements. The results of a first experiment, in which a HLT was used, showed that CRPS patients were significantly slower than controls in judging hand stimuli, whether or not the depicted hand corresponded to their affected hand, but that their performance did not differ from controls when they judged non-body stimuli. Results regarding reaction time patterns reflecting the BMC were inconclusive in CRPS and controls, questioning the validity of the task in activating motor imagery processes. In a second experiment we therefore directly investigated the influence of implicit knowledge of upper-limb BMC on perceptual judgments of hand movements with the apparent body movement perception task. Participants judge the perceived path of movement between two depicted hand positions, with only one of the two proposed paths that is biomechanically plausible. While the controls chose the biomechanically plausible path most of the time, CRPS patients did not, indicating that the perception and/or use of the BMC seems to be disturbed in CRPS. These findings show a non-lateralized body representation impairment in CRPS, which might be related to difficulties in using correct knowledge of the bodys biomechanics. Most importantly however, our results, in agreement with previous studies, indicate that it seems highly challenging to measure motor imagery and the indexes of BMC with the classical HLT task, which has important implications for the rehabilitation of chronic pain with these tasks.

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Agency and responsibility over virtual movements controlled through different paradigms of brain-computer interface

Nierula, B.; Spanlang, B.; Martini, M.; Borrell, M.; Nikulin, V. V.; Sanchez-Vives, M. V.

2019-08-15 neuroscience 10.1101/735548 medRxiv
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Agency is the attribution of an action to the self and is a prerequisite for experiencing responsibility over its consequences. Here we investigated agency and responsibility by studying the control of movements of an embodied avatar, via brain computer interface (BCI) technology, in immersive virtual reality. After induction of virtual body ownership by visuomotor correlations, healthy participants performed a motor task with their virtual body. We compared the passive observation of the subjects own virtual arm performing the task with (1) the control of the movement through activation of sensorimotor areas (motor imagery) and (2) the control of the movement through activation of visual areas (steady-state visually evoked potentials). The latter two conditions were carried out using a brain-computer interface (BCI) and both shared the intention and the resulting action. We found that BCI-control of movements engenders the sense of agency, which is strongest for sensorimotor areas activation. Furthermore, increased activity of sensorimotor areas, as measured using EEG, correlates with levels of agency and responsibility. We discuss the implications of these results for the neural bases of agency, but also in the context of novel therapies involving BCI and the ethics of neurotechnology.\n\nKey points summaryO_LIWe induced embodiment of a virtual body and its movements were controlled by two different BCI paradigms - one based on signals from sensorimotor versus one from visual cortical areas.\nC_LIO_LIBCI-control of movements engenders agency, but not equally for all paradigms.\nC_LIO_LICortical sensorimotor activation correlates with agency and responsibility.\nC_LIO_LIThis has significant implications for neurological rehabilitation and neuroethics.\nC_LI

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Effects of childhood adversity on socially learned placebo analgesia in virtual reality: A cross-sectional study

Watson, L.; Wang, Y.; White, J. N.; Shafir, R.; Colloca, G.; Heagerty, J.; Li, S.; Brawn, B.; Varshney, A.; Chen, S.; Colloca, L.

2025-12-09 pain medicine 10.64898/2025.12.04.25341572 medRxiv
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Early life adversity (ELA), indexed through Adverse Childhood Experiences (ACEs), is associated with long-term alterations in emotion regulation, stress responsivity, and social learning--factors that may shape learned pain modulation. Social observation in immersive virtual environments offers a powerful way to investigate these mechanisms. To examine whether ELA influences social observation-induced placebo analgesia and empathy responses in immersive and non-immersive contexts. Adults with self-reported low versus high ACE exposure completed an observational learning task in immersive virtual reality (VR) or a non-immersive format. Participants observed Human or Avatar demonstrators experiencing pain relief and then underwent self-pain testing. Measures included socially induced placebo analgesia and affective and cognitive components of state empathy. Individuals with high ACE exposure showed stronger social observation-induced placebo analgesia, particularly within immersive VR. High ACE participants exhibited reduced affective state empathy, while cognitive empathy remained comparable to the low ACE group. Elevated ELA is unexpectedly associated with enhanced responsiveness to socially learned placebo analgesia, especially in immersive VR settings. These findings highlight how early adversity may shape sensitivity to socially transmitted treatment cues, with implications for the design of VR-based therapeutic interventions.

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Behavioral evidence of reduced working memory capacity in fibromyalgia patients is not reflected in electrophysiological outcomes

Young, E. L.; Atum, Y.; Mista, C. A.; Arevalo, D.; Moglia, B.; Biurrun Manresa, J. A.

2025-09-21 pain medicine 10.1101/2025.09.20.25336159 medRxiv
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Fibromyalgia is characterized by widespread musculoskeletal pain accompanied by sleep disturbances and cognitive dysfunction, among other symptoms. Patients frequently report difficulties with memory, but objective assessment of these impairments remains limited. This study aimed to evaluate working memory performance in fibromyalgia patients using two established paradigms: the change detection task, which primarily measures storage capacity, and the n-back task, which assesses both storage and manipulation of information. For the change detection task, the behavioral outcomes assessed were the hit rate, false alarm rate, capacity estimate and response times. The electrophysiological measure evaluated was the contralateral delayed activity. For the n-back, the behavioral outcomes were the same, except for the capacity estimate. Electrophysiologically, the P2 and P3 from the evoked potentials were the outcomes of the task. Behaviorally, results demonstrated that fibromyalgia patients exhibited lower memory capacity than controls (1.90 vs 2.64), in the change detection task, which involved differences in the hit rate and false alarm rate, whereas no behavioral differences were found for the n-back task. In contrast, no differences were found for any of the electrophysiological outcomes in any of the tasks. Taken together, we found evidence supporting a reduction in working memory capacity in fibromyalgia, although it is not reflected in electrophysiological measures.

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Beats of the Brain: Mapping Neural Activation During Candombe Engagement

Agarwal, N.

2024-09-03 neuroscience 10.1101/2024.09.01.610692 medRxiv
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This research delves into the complex connection between traditional music in Uruguay, specifically candombe, and its cognitive advantages. Relying on real-life studies, we explore the impact of involvement with candombe music on diverse cognitive abilities such as cognitive flexibility, emotional regulation, and social cognition. Our results show that playing music, especially drumming, activates certain brain pathways related to cognitive function and emotional regulation. The sense of community and distinct rhythmic patterns found in candombe not only boost individual cognitive skills but also foster social bonding, ultimately leading to better mental well-being and strength. This study highlights how cultural heritage influences cognitive functions, showing that candombe is crucial for mental well-being in addition to being a significant cultural symbol. In summary, our research supports incorporating traditional Uruguayan music in educational and therapeutic environments, offering a new framework for cognitive and emotional growth. This research focuses on how Uruguays diverse musical traditions can be used to enhance cognitive abilities and mental health, offering possibilities for application in different cultural settings globally.

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Development of a Research Program Focused on Non-Invasive Brain Stimulation for Peripheral Neuropathy in Minoritized Communities

Wong, M. L.; McTeague, L. M.; Miller, C. A.; Gonzalez, G.; Tovin, M. M.; Penedo, F. J.; Widerstrom-Noga, E.

2025-01-12 pain medicine 10.1101/2025.01.10.25320213 medRxiv
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Black and Hispanic/Latino communities experience disproportionate chronic pain and are underrepresented in pain research. Transcutaneous auricular vagus nerve stimulation (taVNS) and transcranial magnetic stimulation (TMS) are promising tools for pain management. Therefore, it is critical to ensure that research using these tools engages underrepresented communities to make research findings more generalizable and reach all who may benefit. Lack of diversity in the research workforce itself is a key barrier to improving Black and Hispanic/Latino representation in pain research, and video-enhanced recruitment and consenting may be a useful tool to better engage minoritized communities. Using community participatory research principles in an iterative process, we engaged key stakeholders, including neuromodulation researchers and minoritized community members, to create and test informational videos on taVNS and TMS. These videos were designed for Black English-speaking, Hispanic/Latino Spanish-speaking, and Haitian-Creole speaking people with chronic pain. Study 1 involved iterative feedback from stakeholders to develop test videos, which were then refined based on community member input. Study 2 was a pilot randomized controlled trial assessing the impact of these videos on participant expectations for pain relief with taVNS. Results indicated that the videos were well-received, and there was no significant difference in expectancy scores between those who viewed the videos and those who received traditional brochures. This suggests that while videos may improve engagement, they do not unduly influence expectations, potentially making them valuable tools for improving research participation in underrepresented populations. These videos will be freely available to help researchers to engage people from minority communities. PERSPECTIVEThis article presents the process of developing culturally sensitive informational videos on taVNS and TMS, and provides the field with these videos in English, Spanish, and Haitian-Creole language. These videos could potentially help researchers to engage people from minority communities to enhance the diversity and reach of research using noninvasive brain stimulation for pain.

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Resting-state functional connectivity after creativity training with music composing

Arkhipova, A.; Hok, P.; Trneckova, M.; Zatkova, G.; Zouhar, V.; Hlustik, P.

2026-01-29 neuroscience 10.64898/2026.01.29.701494 medRxiv
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Creativity is one of the unique cognitive constructs in human beings and its neurobiological correlates are one of the current hot topics in neuroscience. The "Different Hearing" program (DHP) is an educational activity aimed at stimulating musical creativity by means of group composing in the classroom, alternative to the mainstream model of music education in Czechia. In our previous study, the data from task-related functional MRI with passive listening was analyzed. The results suggested that DHP training modified the response to diverse sound samples, differentially changing the engagement of functional networks known to be related to creative thinking, namely, increasing default mode network activation and decreasing activation of executive and salience networks. In the present study, we hypothesized that the DHP short-term (2 days) intense workshop would also induce changes in the resting-state networks that were significantly modified during task. To investigate it, seed-based, ROI-to-ROI resting-state functional connectivity and degree centrality analysis were performed on the acquired resting-state fMRI data. The results showed no significant group-by-time interaction.

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Characterization of perceptual and electrophysiological responses to high-speed robot controlled pinprick stimulation

Poux, S.; Youssif, A.; Van Den Broeke, E.; Baumgartner, U.; Biurrun Manresa, J.; Mista, C.

2025-02-21 pain medicine 10.1101/2025.02.20.25322639 medRxiv
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ObjectiveThis work utilises a novel high-speed robot-controlled stimulator to evaluate the effects of different levels of mechanical impulse (force and duration) of pinprick stimuli on neurophysiological responses and subjective perception. MethodsTwenty-seven healthy volunteers received pinprick stimuli on the right volar forearm using different combinations of force and duration that configured three distinct levels: low, medium and high mechanical impulse stimuli. The robotic system recorded stimulus force and duration in real time, and participants rated the pinprick perceived intensity on a numerical rating scale (NRS). The peak amplitudes and latencies of the pinprick evoked potentials (PEPs) were compared across stimulation levels. Perceived intensity ratings were analysed using linear mixed models, and the PEP features were evaluated through spatio-temporal cluster permutation tests. ResultsPerceived intensity ratings, expressed as median [IQR], were 2.5 [1.14 - 8.15] for low, 16.4 [ 8.86 - 26.9] for medium and 28.5 [10.2 - 41.4] for high impulse stimuli. Differences in brain activity were found when comparing across stimulation levels: the N2 Peak latency was longer for high impulse compared to low impulse and for medium impulse compared to low impulse. The P2 peak latency showed no differences across levels. The N2 amplitude was larger for high vs. low impulse and for medium vs. low impulse, with no significant difference observed between high and medium impulse stimulation. ConclusionsHigh speed robot-controlled pinprick stimulation successfully elicited pinprick-evoked potentials (PEPs) across different mechanical impulse levels. The use of robot-controlled systems may help standardize the assessment of mechanical nociception.

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Decoding Motivational States and Craving through Electrical Markers for Neural 'Mind Reading'

Proverbio, A. M.; Zanetti, A.

2024-11-22 neuroscience 10.1101/2024.11.22.624825 medRxiv
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The aim of this electroencephalogram (EEG) study was to identify electrical neuro-markers of 12 different motivational and physiological states such as visceral craves, affective and somatosensory states, and secondary needs. Event-related potentials (ERPs) were recorded in 30 right-handed participants while recalling a specific state upon the presentation of an auditory verbal command incorporating an evocative sound background consistent with that state (e.g. the chirping of cicadas associated with the verbal complaint about feeling hot). ERP data showed larger amplitude N400 responses in the affective and somatosensory states, while the P400 component displayed greater amplitudes for the secondary and visceral states. Furthermore, the two components were also discernibly responsive to the 12 micro-categories (e.g., joy vs. pain or hunger), by providing a distinctive electric pattern for mostly all microstates. The reconstruction of the intracranial generators of surface signals revealed common imagery-related activations, including the middle and superior frontal gyri, the fusiform and lingual gyri, supramarginal, and middle occipital regions, as well as the middle temporal region. Additionally, specific regions were identified that were active for distinct mentally represented content, such as that visceral needs were associated with activations in the medial and inferior frontal gyri, uncus, precuneus, and cingulate gyrus. Affective states were associated with activations in the medial frontal, superior temporal, and middle temporal gyri. Somatosensory states (e.g., pain or cold) activated regions in the parietal cortex and the crave for music was linked to activations in the auditory and motor regions. These findings support the use of ERP markers for BCI applications.

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Taking the perspective of an embodied avatar modulates the temporal dynamics of vicarious pain and pleasure: a combined Immersive Virtual Reality and EEG study

Nicolardi, V.; Lisi, M. P.; Mello, M.; Fusaro, M.; Tieri, G.; Aglioti, S. M.

2025-01-29 neuroscience 10.1101/2024.06.14.598683 medRxiv
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Observing negative and positive valence virtual stimuli can influence the onlookers subjective and brain reactivity. However, the relationship between vicarious pain and pleasure, observers perspective taking and cerebral activity remains underexplored. To address this gap, we asked 24 healthy participants to passively observe pleasant, painful, and neutral stimuli delivered to a virtual hand seen from a first-person (1PP) or third-person perspective (3PP) while undergoing time and time-frequency EEG recording. Participants reported a stronger sense of ownership over the virtual hand seen from a 1PP, rated pain and touch valence appropriately, and more intense than the neutral ones. Distinct EEG patterns emerged across early (N2, early posterior negativity, EPN), late (late positive potential, LPP) event-related potentials, and EEG power. The N2 and EPN components showed greater amplitudes for pain and pleasure than neutral stimuli, particularly in 1PP. The LPP component exhibited lower amplitudes for pleasure than pain and neutral stimuli. Further, theta-band power increased, and alpha power decreased for pain and pleasure stimuli viewed from a 1PP versus a 3PP perspective. In the ultra-late time window, we observed decreased theta, alpha, and beta-band power specifically associated with pleasure stimuli. Our study provides novel evidence that perspective-taking modulates the temporal dynamics of vicarious pain and pleasure.

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Embodied Interoception Questionnaire (Intero-10): development, validation, and application in people with chronic pain

Fernandes, A. M.; Oliveira, V.; Millard, S.; Maia, M.; Campos, C.; Pentiado Junior, J.; Barbosa, M.; Martins, P.; Nogueira, S.; Cunha, P.; Fonseca, D.; LaFerreira, L.; Santos-Silva, P.; Carvalho, N.; Iamonti, V.; Carvalho, C.; Dale, C.; Kubota, G.; Yeng, L.; Teixeira, M. J.; Baptista, A. F.; Interoception Study Group, ; Ciampi de Andrade, D.

2025-09-14 pain medicine 10.1101/2025.09.12.25335640 medRxiv
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Embodied interoception refers to the perception of the bodys state and is a multidimensional cognitive process. It is proposed that the experience of pain also feeds interoceptive networks with information from the state of the body, and the subjective experience of pain would be influenced by an individuals trait embodied interoceptive profile. Here we developed and validated the Intero-10, a questionnaire designed to specifically evaluate embodied interoception based on trait interoceptive channels. Healthy adults (n=381) and people with neuropathic pain (n=86) were enrolled. The relationship between trait and state interoceptive responses was examined during experimentally evoked interoceptive psychophysics tasks, which were specific for each interoceptive channel. During these tests, embodied interoceptive state scores only correlated with trait ones for unpleasantness (P<0.05), but not for intensity rating, suggesting that the predicted negative valence of lived experience provided lower prediction errors than intensity estimations. The Intero-10 final version included embodied interoceptive perception intensity (heartbeat, heat, itching, dyspnea, sleep, muscle fatigue, and anguish) and unpleasantness (heartbeat, dyspnea, and nausea) categories. Intero-10 demonstrated adequate content validity, good internal consistency (Cronbachs alpha=0.81), good reliability (>0.75), and a single-factor structure. Patients with neuropathic pain filled in the Intero-10 alongside traditional pain, mood, sleep, and quality of life assessments. Embodied interoception scores correlated with mood, and quality of life, and partially mediated the correlation between pain interference and quality of life ({beta}=-0.0093). The specific assessment of embodied interoceptive channels may broaden our current assessment of people with chronic pain and of those at risk to develop it.

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The Contextual Affects of Facial Expression

Cui, B.; Bex, P. J.

2025-10-27 neuroscience 10.1101/2025.10.23.683775 medRxiv
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Affect recognition and communication are critical for everyday social interaction. Traditional emotion research has often assumed that facial expressions reliably reflect internal emotional states and conform to a set of universal expressions. However, emerging evidence suggests that facial expressions are highly individualized and influenced by context. To investigate these factors, we used genetic algorithms to enable participants to generate personalized facial expressions that best matched their subjective interpretation of affect within written contextual scenarios. 12 participants read standardized scenarios drawn from Howard Schatzs Actors Acting, which had been independently rated (0-4) across 13 primary emotions (Amusement, Anger, Awe, Contempt, Disgust, Embarrassment, Fear, Happiness, Interest, Pride, Sadness, Shame, Surprise). Each primary emotion was paired with all 12 secondary emotions that were either maximized (Condition 1) or minimized (Condition 2). Participants completed 26 such randomly interleaved trials, followed by the last condition (Condition 3) in which they selected faces corresponding directly to each of the 13 emotion words. Faces were generated within the 199-dimensional coefficient space of the Basel Face Database, with a genetic algorithm presenting 12 unique faces across 6 generations per scenario. Faces selected by participants as matching a given scenario were semi-randomly combined to generate 6 offspring per generation, with the remaining 6 faces created randomly to maintain genetic diversity. A 4-way ANOVA (factors: affect, context, generation, participant) on the cosine distances among faces revealed a significant main effect of affect (p =.0061) and a significant interaction between affect and context (p =.0003). These results indicate that distinct facial structures are associated with different emotions, but the representation of a given emotion is context-dependent. This work offers a novel approach to visualizing individual differences in emotion perception and has implications for advancing personalized tools in affective science, including clinical assessment and emotion recognition systems.

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Semantic Inhibition and Reactivation for Transcending from Semantic Understanding to Aesthetic Appreciation: fNIRS Evidence from Aesthetic Reading

Liu, H.; Xu, X.; Sun, W.; Zhang, D.; Zhang, Y.

2024-10-12 neuroscience 10.1101/2024.10.08.617173 medRxiv
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BackgroundAesthetic education is pivotal in shaping a comprehensive and harmonious humanity. However, the transition from semantic comprehension to aesthetic appreciation remains poorly understood. This study, informed by transactional theory, sought to elucidate the cognitive mechanisms of aesthetic reading by examining its neural dynamics through functional Near-Infrared Spectroscopy. MethodsParticipants were tasked with reading Tang poetry aesthetically, with fNIRS monitoring brain activity in frontal and temporal regions. ResultsCompared to an efferent reading task, the aesthetic reading task revealed a distinct three-stage neural dynamic pattern. Initially, aesthetic reading showed similar HbO activation in all regions, likely indicating the semantic processing phase. This was followed by a divergence, with a decrease in HbO over the left primary somatosensory cortex and the left superior, inferior, and middle temporal gyri, suggesting inhibition of semantic processing. Finally, a resurgence of activity in these areas was observed, along with an increase in HbO over the left dorsolateral prefrontal cortex, which could be associated with memory, imagination, and empathy. This reactivation correlated with participants self-reported aesthetic appreciation scores. ContributionThe findings reveal the temporal and spatial dynamics of brain activity during aesthetic reading, enhancing our comprehension of underlying cognitive processes.