{"title":"Pain Perception and Modulation: Fundamental Neurobiology and Recent Advances","authors":"Willem W. J. van Strien, Markus W. Hollmann","doi":"10.1111/ejn.70275","DOIUrl":"https://doi.org/10.1111/ejn.70275","url":null,"abstract":"<p>Chronic pain is a major mental health burden with significant individual and societal impact. A major challenge in clinical practice is the considerable variability in treatment responses, reflecting the complexity of associated biopsychosocial factors and their neurobiological underpinnings. This narrative review presents an up-to-date overview of neural structures, circuits, and neurochemical systems involved in pain perception and modulation, integrating foundational and recent findings from human and animal studies. We outline current models of nociceptive processing and pain perception, emphasizing dynamic interactions between ascending nociceptive input, descending modulation, and distributed cortical networks. Additionally, we describe mechanisms at spinal, subcortical, and cortical levels, along with neuroplastic changes in chronic pain. Finally, we review key neuromodulators, including opioids, monoamines, cannabinoids, and GABA. Together, these insights support the development of personalized pain management strategies grounded in systems-level neurobiology.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kayleigh Kanakis, Richard G. M. Morris, Francesco Gobbo
{"title":"Modelling of What-Where-When Everyday Memories in Rats","authors":"Kayleigh Kanakis, Richard G. M. Morris, Francesco Gobbo","doi":"10.1111/ejn.70278","DOIUrl":"10.1111/ejn.70278","url":null,"abstract":"<p>Episodic memories contain information about the nature of an event, the place where it happened and the time when it occurred. In animals, the term ‘episodic-like memory’ is preferred to refer to mnemonic instances containing these three features, commonly referred to as ‘what-where-when’. Models to study episodic-like memory have been proposed in corvidae and rodents, although their use in neuroscience research has been limited due to certain limitations and potential ambiguities. Although the neurological correlates of ‘what-where-when’ have been identified in neuronal types such as place and time cells, it is unclear how they contribute to form a unitary representation or how this information can be accessed during memory recall, either holistically or differentially. Here, we outline two new behavioural paradigms based on the everyday memory task that we have developed to model what and when components as well as ‘where’ information. In Experiment 1 (E1), we demonstrate that rats are able to learn two distinct food positions on a daily basis and retrieve them independently. In E2, we establish that rats can learn that two flavours are replenished at different times after an initial sampling, thus using the temporal component to guide their decision making. These two tasks can therefore provide the basis to study how the item, location and time information of a memory are stored and accessed by the brain. This should be observable in single-unit recording or calcium-imaging studies.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Systematic Review of Aperiodic Neural Activity in Clinical Investigations","authors":"Thomas Donoghue","doi":"10.1111/ejn.70255","DOIUrl":"https://doi.org/10.1111/ejn.70255","url":null,"abstract":"<p>Aperiodic neural activity—activity with no characteristic frequency—has increasingly become a common feature of study, including in clinical work. Reports investigating aperiodic activity from patients from a broad range of clinical disorders have sought to evaluate aperiodic activity as a putative biomarker relating to diagnosis or treatment response and/or as a potential marker of underlying physiological activity. However, there is thus far no clear consensus on if and how aperiodic neural activity relates to clinical disorders. This systematic literature review, following PRISMA guidelines, examines reports of aperiodic activity in electrophysiological recordings from human patients with psychiatric and/or neurological disorders, finding 177 reports across 38 disorders. Results are summarized to evaluate current findings and examine what can be learned as pertains to the analysis, interpretations and overall utility of aperiodic neural activity in clinical investigations. Aperiodic activity is commonly reported to relate to clinical diagnoses, with 32 of 38 disorders reporting a significant effect in diagnostic and/or treatment-related studies. However, there is variation in the consistency of results across disorders, with the heterogeneity of patient groups, disease aetiologies and treatment status arising as common themes. Overall, the current variability of results, potentially confounding covariates, and limitations in current understanding of aperiodic activity suggest further work is needed before aperiodic activity can be established as a potential biomarker and/or marker of underlying pathological physiology. A series of recommendations are proposed to assist with guiding productive future work on the clinical utility of studying aperiodic neural activity.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145272792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Loss of Neuropeptide Signalling Alters Temporal Expression of Mouse Suprachiasmatic Neuronal State and Excitability”","authors":"","doi":"10.1111/ejn.70272","DOIUrl":"10.1111/ejn.70272","url":null,"abstract":"<p>\u0000 <span>Wegner, S.</span>, <span>Belle, M. D. C.</span>, <span>Chang, P.-S.</span>, <span>Hughes, A. T. L.</span>, <span>Conibear, A. E.</span>, <span>Muir, C.</span>, <span>Samuels, R. E.</span>, and <span>Piggins, H. D.</span> (<span>2024</span>). <span>Loss of Neuropeptide Signalling Alters Temporal Expression of Mouse Suprachiasmatic Neuronal State and Excitability</span>. <i>European Journal of Neuroscience</i>, <span>60</span>(<span>11</span>), <span>6617</span>–<span>6633</span>. https://doi.org/10.1111/ejn.16590.\u0000 </p><p>In the attributions of the funder in Funding Information, some identifications of the grant numbers were inadvertently omitted. These are the following: BB/R019223 should be reported as BB/R019223/1, while T008741 should be reported as BB/T008741/1. Similarly in the Acknowledgements, BB/R019223 needs to be corrected to BB/R019223/1 and T008741 to BB/T00874/1.</p><p>We apologize for this error.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Narges Moein, Cindy Nguyen, Douglas Cheyne, Luc De Nil
{"title":"The Effects of tDCS on Speech Fluency in People Who Stutter: A Narrative Review","authors":"Narges Moein, Cindy Nguyen, Douglas Cheyne, Luc De Nil","doi":"10.1111/ejn.70267","DOIUrl":"10.1111/ejn.70267","url":null,"abstract":"<p>To improve the outcomes of current treatments for stuttering, researchers have explored adjunct tools such as transcranial Direct Current Stimulation (tDCS). The purpose of this paper is to review the literature investigating the effectiveness of tDCS for people who stutter (PWS) and offer some directions for future research. To achieve the objective of this study, we conducted a narrative review of the existing literature. Articles were selected using these inclusion criteria: participants, tDCS protocol, control group and primary outcomes. Our literature search was limited to studies published in English with no limits on the publication year. We only extracted data from studies that investigated the effects of tDCS on PWS. Systematic reviews, meta-analyses and other forms of reviews regarding tDCS were not included. We identified 101 studies during the exploratory phase. Ultimately, seven studies met our inclusion criteria. Of the included papers, five studies reported mixed effects, one study showed no effect and one study showed positive effects of tDCS. We summarized the studies in terms of several methodological features and the observed effects from tDCS. We also used SimNIBS modelling to compare the effects of different stimulation parameters on brain activity and outcomes. The studies reviewed in this study have reported a variable effectiveness of tDCS for enhancing speech fluency in PWS. As a result, it remains unclear whether tDCS is an effective tool for stuttering intervention, and the optimal stimulation parameters are not yet established. Several suggestions for future research are offered.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cecilia Steinwurzel, Maria Concetta Morrone, Ele Ferrannini, Francesca Frijia, Domenico Montanaro, Giuseppe Daniele, Paola Binda
{"title":"Acute Supplementation of Beta-Hydroxybutyrate Increases Visual Cortical Excitability in Humans: A Combined Electro-EncephaloGraphy and Magnetic Resonance Spectroscopy Study","authors":"Cecilia Steinwurzel, Maria Concetta Morrone, Ele Ferrannini, Francesca Frijia, Domenico Montanaro, Giuseppe Daniele, Paola Binda","doi":"10.1111/ejn.70270","DOIUrl":"10.1111/ejn.70270","url":null,"abstract":"<p>Increasing plasma levels of ketone bodies via supplementation has been recently found to modulate the neurometabolic profile in the healthy human brain. Here, we aimed to explore the physiological consequences of these neurometabolic changes by assessing visual cortical function. Ten young adult human volunteers (mean age 27 years, range 23–34) were orally administered a single dose of a β-hydroxybutyrate (βHB) ester (one of the main ketone bodies), and we measured neurometabolic change after supplementation. We used Electroencephalography (EEG) to assess cortical responsivity to visual stimuli and endogenous rhythms, and magnetic resonance spectroscopy (MRS) to quantify glutamate and GABA+ concentrations in the occipital cortex. βHB supplementation increased the amplitude of steady-state visual evoked potentials and increased resting-state EEG alpha power (8–13 Hz). These electrophysiological changes were paralleled by an increase in glutamate (but not GABA+) concentration in the occipital cortex. The glutamate increase was correlated with the increased steady-state visual evoked potentials amplitude. This suggests that acute βHB supplementation increases the excitability of the brain cortex, as assessed neurometabolically and electrophysiologically. We discuss how these effects of acute supplementation may differ from the long-term effects of chronic interventions in healthy or pathological brains.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genc Hasanaj, Iris Jaeger, Berkhan Karsli, Enrico Schulz, Emanuel Boudriot, Lukas Roell, Maxim Korman, Marcel S. Kallweit, Fanny Dengl, Nicole Klimas, Kristin Fischer, Katharina Hanken, Verena Meisinger, Joanna Moussiopoulou, Vladislav Yakimov, Susanne Karch, Alkomiet Hasan, Andrea Schmitt, Peter Falkai, CDP Working Group, Oliver Pogarell, Florian J. Raabe, Elias Wagner, Matin Mortazavi, Daniel Keeser
{"title":"Periodic and Aperiodic Alterations of Resting-State EEG in Schizophrenia Spectrum Disorders: Cognitive and Clinical Insights","authors":"Genc Hasanaj, Iris Jaeger, Berkhan Karsli, Enrico Schulz, Emanuel Boudriot, Lukas Roell, Maxim Korman, Marcel S. Kallweit, Fanny Dengl, Nicole Klimas, Kristin Fischer, Katharina Hanken, Verena Meisinger, Joanna Moussiopoulou, Vladislav Yakimov, Susanne Karch, Alkomiet Hasan, Andrea Schmitt, Peter Falkai, CDP Working Group, Oliver Pogarell, Florian J. Raabe, Elias Wagner, Matin Mortazavi, Daniel Keeser","doi":"10.1111/ejn.70263","DOIUrl":"https://doi.org/10.1111/ejn.70263","url":null,"abstract":"<p>Schizophrenia spectrum disorders (SSD) are marked by cognitive deficits and clinical symptoms linked to disrupted neural oscillations. While changes in spectral power are well documented in SSD, many studies have not clearly separated rhythmic (periodic) from the nonrhythmic (aperiodic) brain activity. This study examined both periodic and aperiodic resting-state EEG components in SSD, recorded from 152 healthy controls and 97 SSD participants. EEG features (periodic power, bandwidth, center frequency; aperiodic exponent and offset) were extracted from global scalp averages and frontoinsular regions, including the dorsal anterior cingulate cortex (dACC), right anterior insula (R-INS), and left anterior insula (L-INS). At the scalp level, SSD individuals exhibited a global increase in theta power, along with a decreased alpha center frequency. Aperiodic activity showed increased exponent and offset in SSD. In frontoinsular regions, increased theta power was observed in the dACC, R-INS, and L-INS, along with lower alpha center frequency in L-INS. No significant differences were found for aperiodic activity in these regions. Increased frontoinsular theta power, especially in the dACC, was associated with worse cognitive performance, particularly global cognition and working memory. These findings highlight the importance of separating periodic and aperiodic EEG activity in SSD, suggesting that periodic alterations, particularly in frontoinsular theta oscillations, may underlie cognitive dysfunction in SSD.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Whole-Brain Connectome-Wide Signature of Transdiagnostic Depression Severity Across Major Depressive Disorder and Posttraumatic Stress Disorder","authors":"Runnan Yang, Minlan Yuan, Hanyi Zhang, Hua Xie, Changjian Qiu, Dorjnambar Balgansuren, Xiaoqi Huang, Su Lui, Qiyong Gong, Wei Zhang, Hongru Zhu","doi":"10.1111/ejn.70271","DOIUrl":"https://doi.org/10.1111/ejn.70271","url":null,"abstract":"<div>\u0000 \u0000 <p>Depressive symptoms are commonly observed in stress-related psychiatric disorders, such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). To date, emerging evidence from behavior and psychology suggests the possibility of underlying neurobiological mechanisms in transdiagnostic depression. This study aims to identify predictive signatures of depression severity across MDD and PTSD using a whole-brain connectivity machine learning analysis based on resting-state functional magnetic resonance imaging (rs-fMRI). Patients with MDD (<i>n</i> = 84) and PTSD (<i>n</i> = 65), all medication-free at the time of enrollment, underwent rs-fMRI scans along with a battery of clinical assessments. Using a multivariate machine learning approach, we applied sparse connectome predictive modeling to identify a functional connectivity signature that predicts individual depression severity, as assessed by Hamilton Depression Rating Scale-17 items. The cross-validated model explained 42% of the variance in depression severity across MDD and PTSD. The identified connectome signature predominantly involved regions in the fronto-limbic circuit (e.g., middle frontal gyrus and temporal pole), subcortical areas (e.g., hippocampal, caudate, and brainstem), and the cerebellum. Our findings highlight diffuse whole-brain dysfunction patterns associated with depressive symptom severity, emphasizing the importance of transdiagnostic research in understanding the neurobiological mechanisms underlying key clinical features across disorders.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Hausdorf, A. Ferdinand, P. Koo-Poeggel, M. Mölle, M. Bazhenov, L. Marshall
{"title":"Stimulating the Stimulated Cortex—Frontocortical Anodal Electric Stimulation Combined With Closed-Loop Acoustic Stimulation During Sleep Impairs Memory in Subjects With High Cognitive Ability","authors":"T. Hausdorf, A. Ferdinand, P. Koo-Poeggel, M. Mölle, M. Bazhenov, L. Marshall","doi":"10.1111/ejn.70266","DOIUrl":"10.1111/ejn.70266","url":null,"abstract":"<p>This study investigates the impact of simultaneous anodal transcranial direct-current stimulation (tDCS) and closed-loop acoustic stimulation (CLAS) during slow-wave sleep on memory consolidation and neural oscillations. In this experiment, anodal tDCS was used to modulate cortical excitability, aiming to alter the brain state and investigate the resultant impact of CLAS-induced effects on sleep electroencephalography and overnight memory consolidation. Twenty participants (aged 18–30) completed two experimental nights involving either CLAS alone or tDCS combined with CLAS (AmodCLAS). Offline detected spontaneous SOs were shifted toward negative potential values by AmodCLAS, SO duration was increased, and density decreased. AmodCLAS also decreased sleep efficiency and REM sleep in the second part of the night. Compared with CLAS alone, AmodCLAS failed to influence memory consolidation across all subjects. However, memory retention of participants with higher fluid intelligence (as measured by Raven's Advanced Progressive Matrices) was significantly decreased after AmodCLAS, together with a more pronounced negative shift of SO up-state intervals, yet a weaker reduction in REM sleep. Our findings suggest that individuals with higher cognitive ability exhibit greater susceptibility to sleep-based neuromodulation while possibly possessing greater resilience against sleep perturbance. This highlights the critical role of interindividual cognitive differences in shaping responsiveness to neuromodulation techniques and underscores the need for personalized approaches during such interventions.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Mismatch Negativity in Subjects at Clinical High Risk for Psychosis: No Evidence of Progressive Decline”","authors":"","doi":"10.1111/ejn.70273","DOIUrl":"https://doi.org/10.1111/ejn.70273","url":null,"abstract":"<p>\u0000 <span>J. Jang</span>, <span>E. Choe</span>, <span>M. Ha</span>, <span>M. Kim</span> (corresponding author), <span>J.S. Kwon</span>. <span>Mismatch Negativity in Subjects at Clinical High Risk for Psychosis: No Evidence of Progressive Decline</span>. <i>European Journal of Neuroscience</i>. <span>2025 Sep</span>; <span>62</span>(<span>5</span>):e70256. https://doi.org/10.1111/ejn.70256.\u0000 </p><p>In the published article, the corresponding author Minah Kim's affiliation was listed as affiliation 1 only. The correct affiliations are 1, 2, and 4.</p><p>We apologize for this error.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"62 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}