European Journal of Neuroscience最新文献

{"title":"Assessing the Clinical Relevance of Blood Soluble Triggering Receptor Expressed on Myeloid Cells 2 in Neurological Diseases","authors":"Luisa Agnello,&nbsp;Caterina Maria Gambino,&nbsp;Giuseppe Salemi,&nbsp;Vincenzo Di Stefano,&nbsp;Tommaso Piccoli,&nbsp;Anna Masucci,&nbsp;Sabrina Novara,&nbsp;Anna Maria Ciaccio,&nbsp;Fabio Del Ben,&nbsp;Daniela Capello,&nbsp;Marcello Ciaccio","doi":"10.1111/ejn.70690","DOIUrl":"10.1111/ejn.70690","url":null,"abstract":"<p>Triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial and peripheral myeloid cell function, with its soluble form (sTREM2) emerging as a biomarker of neuroinflammation. Although cerebrospinal fluid (CSF) sTREM2 is consistently elevated in neurodegenerative diseases, the clinical relevance of blood sTREM2 remains unclear. We performed a retrospective observational study including 547 individuals: Alzheimer's disease (<span>AD</span>, <i>n</i> = 142), mild cognitive impairment (MCI, <i>n</i> = 42), multiple sclerosis (MS, <i>n</i> = 105), hereditary transthyretin amyloidosis with polyneuropathy (ATTR-PN, <i>n</i> = 23), asymptomatic ATTR mutation carriers (<i>n</i> = 25), and controls (<i>n</i> = 210). Plasma sTREM2 concentrations were measured using Lumipulse automated chemiluminescent enzyme immunoassay platform (Fujirebio, Tokyo, Japan). Age-adjusted multivariate analysis was performed to compare disease groups with controls. In controls, plasma sTREM2 levels increased with age, with a significant breakpoint at 68 years, after which the rate of increase markedly accelerated. Across diagnostic groups, <span>AD</span>, MCI, and MS patients exhibited significantly lower plasma sTREM2 levels (11%–18% reduction) compared to controls (<i>p</i> &lt; 0.05), independent of age. No significant differences were observed in ATTR-PN patients or asymptomatic carriers. Age remained a strong positive predictor of sTREM2 levels across all groups. In conclusions, plasma sTREM2 levels are reduced in <span>AD</span>, MCI, and MS despite known elevations in CSF, indicating a divergence between peripheral and central TREM2 biology. The lack of alteration in ATTR-PN suggests tissue-specific regulation of sTREM2. These findings highlight that blood sTREM2 does not directly mirror central nervous system microglial activation but may reflect peripheral immune dynamics, warranting further investigation into its role as a biomarker of systemic immune dysfunction in neurodegenerative diseases.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929329","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":"Early Musical Predictions in the Brain as Indexed by the Mismatch Negativity—From Acoustic Deviants to Cognitive Musical Errors","authors":"Elvira Brattico,&nbsp;Giovanni Marco Lorusso,&nbsp;Francesco Carlomagno,&nbsp;Giulio Carraturo","doi":"10.1111/ejn.70662","DOIUrl":"10.1111/ejn.70662","url":null,"abstract":"<p>Since the early 1990s, mismatch negativity (MMN) has been widely used to investigate sensory memory traces and predictive processing of musically relevant acoustic features, including timber, relational pitch, and rhythm. Evidence consistently demonstrates that the human brain possesses innate musical abilities, which can be further refined through training. The interplay between innate predispositions and experience is supported by robust associations between MMN parameters and behavioral measures of listening ability in both musically trained and untrained children and adults, with these associations further modulated by the duration of musical training. These findings align with hierarchical predictive-processing accounts of MMN, according to which mismatch responses can index prediction error signals whose amplitude is modulated by the precision of internal auditory models: MMN amplitudes decrease with increasing contextual complexity and show more frontal scalp distributions in musicians. As stimulation paradigms have become increasingly ecologically valid, distinguishing low-level sensory prediction errors indexed by MMN from higher level frontal prediction errors has grown more challenging, supporting an integrative perspective in which generative models dynamically merge bottom-up sensory input with top-down priors across hierarchical levels of the central nervous system. In this review, we summarize evidence for a “musical intelligence” of the MMN mechanism, highlighting its role within hierarchical auditory predictive processing.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70662","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929350","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":"Reduced Motor Preparation and Altered EEG Signatures of Prediction in Autistic Adults","authors":"Soroush Bagheri,&nbsp;Annie Cardinaux,&nbsp;Lindsay Bungert,&nbsp;Cindy E. Li,&nbsp;Amanda M. O'Brien,&nbsp;Pawan Sinha,&nbsp;Jonathan Cannon","doi":"10.1111/ejn.70673","DOIUrl":"10.1111/ejn.70673","url":null,"abstract":"<p>A standing hypothesis proposes that the social and behavioral diagnostic features of autism may develop as a result of more fundamental difficulties in forming and utilizing predictions. More specifically, in the present study, we hypothesized that autistic individuals are less likely to mobilize motor preparatory processes when given reason to anticipate an imperative cue. In a preregistered experiment, we asked participants to respond as quickly as possible to target sounds embedded in a regular periodic sequence of tones, and informed them that the three distinct auditory tones in the sequence signal different probabilities of a target on the next beat. We found that a group of autistic participants showed significantly less benefit of cues signaling high target probability on target response time than an IQ- and language-matched control group of non-autistic participants. In concurrent electroencephalography (EEG) recordings, the autistic group also showed a reduced effect of high probability cues on the late CNV, a motor preparatory ramping potential. Group differences in anticipatory desynchronization of motor-related mu and beta oscillations were less straightforward—rather than showing broadly weaker predictive desynchronization, the autistic group showed reduced desynchronization specifically following medium probability cues. We also found evidence of a group difference in neural entrainment to the 1 Hz periodic sequence: the autistic group showed shallower ramping potentials anticipating the next event across all cue types, and reduced phase entrainment at posterior electrodes. Our results focus attention on reduced spontaneous predictive motor preparation as a possible sensorimotor contribution to autism's more visible manifestations.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929398","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":"Cholecystokinin Induces Ca2+ Transients in Brainstem Neurons, Astrocytes and Central Vagal Terminals in Jugular/Nodose Ganglia–Brainstem Slice Cultures","authors":"Adam Ujhelyi,&nbsp;Rana Soylu Kucharz,&nbsp;Jens Christian Rekling","doi":"10.1111/ejn.70686","DOIUrl":"10.1111/ejn.70686","url":null,"abstract":"<p>Cholecystokinin is a well-established neuromodulator of brainstem homeostatic circuits, including circuits implicated in satiety and visceral sensation. To better understand the cellular basis of brainstem cholecystokinin signalling, we developed a novel jugular/nodose ganglion–brainstem slice culture, where microdissection isolated bilateral jugular/nodose ganglia attached to a slice of the brainstem via intact vagal rootlets. This preparation preserves the functional vagal afferent pathway to the nucleus of the tractus solitarius and allows for targeted viral transduction of genetically encoded Ca²⁺ indicators. We show that electrical jugular/nodose ganglion stimulation evokes glutamate-driven Ca²⁺ transients in second-order brainstem neurons, confirming functional connectivity. Using nuclear-targeted Ca²⁺ imaging, we demonstrate that cholecystokinin directly activates a specific subpopulation of neurons in the dorsal and ventrolateral medulla, independent of action potential generation. Furthermore, we identify distinct populations of central vagal terminals: those recruited by electrical stimulation of the jugular/nodose ganglion and a separate subpopulation directly activated by cholecystokinin. Multiplex imaging revealed that cholecystokinin and Substance P triggered robust Ca²⁺ waves in brainstem astrocytes, and muscarine and thyrotropin-releasing hormone selectively activate neuronal populations without recruiting astrocytic networks. Finally, we found that the jugular/nodose ganglion–brainstem slice cultures generate spontaneous respiratory-like rhythmic bursting in the preBötzinger Complex, with a frequency significantly increased by cholecystokinin. Together, these findings establish jugular/nodose ganglion–brainstem slice cultures as a powerful model for dissecting the complex neuro-astrocytic circuitry of cholecystokinin signalling in the brainstem.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929324","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":"Bidirectional EEG Neurofeedback of Sensorimotor Beta Oscillations Reveals Asymmetric Modulation and Strategy-Dependent Learning","authors":"Krithika Anil,&nbsp;Stephen Hall,&nbsp;Jennifer A. Freeman,&nbsp;Jonathan Marsden,&nbsp;Giorgio Ganis","doi":"10.1111/ejn.70681","DOIUrl":"10.1111/ejn.70681","url":null,"abstract":"<p>EEG-based neurofeedback (ENF) may be utilised as an intervention for improvement of motor performance in Parkinson's movement impairment. This exploratory study aimed to determine the ability of healthy participants to bidirectionally modulate sensorimotor beta power using ENF in real time and examine learning trends. The protocol trained participants to increase and decrease the amplitude of their individual beta power over C3 using a double-blind sham-controlled and within-subjects design. Fifteen healthy participants completed the study (mean age = 38.9, SD = 14.9, age range = 20–66; nine female and six male). Thirteen participants successfully decreased beta activity, three participants successfully increased it and two participants demonstrated bidirectional control. A Wilcoxon signed-rank test showed that successful EEG control during real ENF was significantly higher than sham ENF when participants received the sham condition first (<i>Z</i> = 3.80, <i>p</i> &lt; 0.001). When participants received the real condition first, the difference in success was not statistically significant (<i>Z</i> = 1.19, <i>p</i> = 0.233), indicating a transfer learning effect from real to sham sessions. ENF performance varied across ENF training based on modulation direction and cognitive variables, including mental strategy, engagement and fatigue. This study showed that initial ENF performance depends critically on how performance is defined and measured. Learning trends between real and sham conditions further suggest that early ENF performance primarily reflects strategy-dependent, effort-based control rather than stable neurophysiological plasticity. These findings highlight the need for a more precise framework for ENF evaluation, one that separates transient modulation, strategic learning and durable physiological adaptation.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70681","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919032","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":"Modifiable Physiological Factors Associated With Human Glymphatic and Interstitial Fluid Dynamics-Related Measures: A Scoping Review","authors":"Miray Başer,&nbsp;Betül Taşpınar,&nbsp;Ferruh Taşpınar","doi":"10.1111/ejn.70682","DOIUrl":"10.1111/ejn.70682","url":null,"abstract":"<div>\u0000 \u0000 <p>Human glymphatic and interstitial fluid (ISF) dynamics are increasingly studied using direct, fluid-dynamic, and surrogate measures, but modifiable physiological correlates have not been comprehensively mapped. To map human evidence on non-pharmacological modifiable physiological factors associated with glymphatic- and ISF dynamics-related measures and characterize the methods used. PubMed and Web of Science Core Collection were searched through July 31, 2026. Eligible human studies evaluated at least one modifiable physiological factor and a glymphatic- or ISF-related outcome. Measures were classified as direct/near-direct transport or clearance (Level I), functional or diffusion-based imaging (Level II), CSF/ISF fluid dynamics (Level III), or indirect structural/tissue surrogates (Level IV). Of 4134 records, 105 studies were included. Sleep quality, efficiency, architecture, or insomnia was the largest domain (<i>n</i> = 45), followed by blood pressure/hypertension (<i>n</i> = 25). Other domains included sleep deprivation, sleep duration, circadian timing, obstructive sleep apnea, hemodynamics/vasomotion, metabolic factors, physical activity, respiration, and nutrition. Measurement memberships were Level I (<i>n</i> = 5), Level II (<i>n</i> = 41), Level III (<i>n</i> = 14), and Level IV (<i>n</i> = 59), with some studies spanning multiple levels. Human evidence supports associations between modifiable physiological states and glymphatic/ISF-related measures, especially for sleep and vascular physiology, but is dominated by observational studies and surrogate outcomes. Standardized multimodal and interventional studies using more direct measures are needed.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929450","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}

{"title":"Beyond Bulk: Cell-Type-Resolved Epigenomics as the Path Forward in Alzheimer's Disease Research","authors":"Lucía Cañizares-Moscato,&nbsp;Jose Ruiz-Iglesias,&nbsp;Javier Isoler-Alcaraz,&nbsp;Ernest Palomer","doi":"10.1111/ejn.70683","DOIUrl":"10.1111/ejn.70683","url":null,"abstract":"<p>Alzheimer's disease (AD) is a complex neurodegenerative disorder in which most risk variants are noncoding and are enriched at gene regulatory regions, implicating epigenetic mechanisms as central mediators of disease pathogenesis. For most of the history of AD epigenetics research, bulk tissue analysis has dominated, obscuring the fundamentally distinct epigenomic landscapes of individual brain cell types and masking cell-type-specific contributions to disease. Advances in single-cell and single-nucleus sequencing, fluorescence-activated nuclei sorting and multiplexed epigenomic platforms have transformed this landscape, enabling cell-type-resolved profiling of chromatin accessibility, DNA methylation, histone modifications and transcription across the major neuronal, glial and neurovascular populations of the human brain. Here, we review these advances, structured around the argument that cell-type resolution is not a methodological refinement but a conceptual necessity. We describe the distinct epigenomic programs disrupted in neurons, microglia, astrocytes, oligodendrocytes and neurovascular cells in AD, highlighting how each cell type responds to pathology. We discuss the discovery of epigenomic erosion, the progressive loss of cell-type-specific epigenomic identity across virtually all brain cell populations as AD advances, as a unifying disease mechanism linking chromatin dysregulation to cognitive decline. Finally, we identify critical gaps in current knowledge, including the near-complete absence of cell-type-resolved histone modification and DNA methylation data for most brain cell types, the underrepresentation of rare populations in standard preparations and the untapped potential of metabolic acylation marks as indicators of the epigenome–metabolism interface in neurodegeneration.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919045","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":"Hyperdopaminergic States Bias Explorations–Exploitation Trade-Off in Foraging and Impair Survival","authors":"Wanhao Chi,&nbsp;Wenqin Fu,&nbsp;Cristianne R. M. Frazier,&nbsp;Liwen Xu,&nbsp;Jeff A. Beeler,&nbsp;Xiaoxi Zhuang","doi":"10.1111/ejn.70669","DOIUrl":"10.1111/ejn.70669","url":null,"abstract":"<p>Dopamine plays central roles in reinforcement learning and motivation, allowing animals to evaluate energetic costs and gains for efficient foraging. However, how genetic variation in dopaminergic function influences survival remains poorly understood. Here, we used <i>Drosophila melanogaster</i>, an established model for studying fitness, to investigate the effects of hyperdopaminergic state on survival in energetically limited environments. We used the well-characterized dopamine transporter mutant <i>fumin</i> (<i>DAT</i>^<i>fmn</i>), thermogenetic activation and pharmacological manipulations to alter dopamine signalling. In free-feeding environment, <i>DAT</i>^<i>fmn</i> mutants displayed normal food consumption and survival. However, in a foraging environment with energetic scarcity, <i>DAT</i>^<i>fmn</i> mutants exhibited reduced meal frequency and impaired survival compared with controls. Dopaminergic contribution to survival was further supported by data from genetic rescue, pharmacological rescue and thermogenetic activation. Because dopamine modulates both learning and exploration-exploitation bias, we dissociated these processes experimentally. Amphetamine treatment during the post-learning phase, but not during learning, impaired survival, indicating that exploration–exploitation bias after learning, rather than impaired learning, accounts for the observed phenotype. Moreover, <i>DAT</i>^<i>fmn</i> flies showed increased exploratory activity and reduced exploitation of known food sources. These results demonstrate that hyperdopaminergic state disrupts the balance between exploration and exploitation, thereby compromising survival under conditions of limited energy availability.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905584","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":"The Cortical Contribution to the Speech-Frequency–Following Response Is Not Modulated by Visual Information","authors":"Jasmin Riegel,&nbsp;Alina Schüller,&nbsp;Mike Thornton,&nbsp;Alexander Wißmann,&nbsp;Steffen Zeiler,&nbsp;Dorothea Kolossa,&nbsp;Tobias Reichenbach","doi":"10.1111/ejn.70680","DOIUrl":"10.1111/ejn.70680","url":null,"abstract":"<p>Seeing a speaker's face can significantly aid understanding, particularly in challenging acoustic environments. An early neural response implicated in audiovisual speech processing is the frequency-following response (speech-FFR), which occurs at the fundamental frequency of the speech signal. This response arises from both subcortical areas and the auditory cortex. A previous study showed that subcortical responses to speech can be enhanced when a listener can see the talker's face. Here, we examined the cortical contribution to the speech-FFR and its potential modulation by visual information, motivated in part by the growing use of artificially generated talking-face avatars to support speech comprehension. We recorded MEG responses to four types of audiovisual signals: a still image, an artificially generated avatar, a degraded video, and a natural video. The audio stimuli were presented in a substantial level of background noise to make behavioral audiovisual effects stand out. Speech-in-noise comprehension increased significantly from the audio-only condition to the avatar and the degraded video, and further to the natural video. Moreover, we found that all types of audiovisual stimuli yielded robust speech-FFRs in the auditory cortex at an early latency of around 30 ms. However, the magnitude of this neural response was neither enhanced nor attenuated by the videos, nor could the cortical contribution of the speech-FFR explain a significant portion of the variance in the behavioral comprehension scores. Our results suggest that visual modulation of the speech-FFR in the auditory cortex is, if existent, too small to be measurable in scenarios where speech occurs in considerable background noise.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911303","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":"Regional Organisation and Sex-Related Differences in Trigeminal Nerve DTI Metrics in Healthy Young Adults","authors":"Eduardo Rocha Arruda,&nbsp;Hohana G. Konell,&nbsp;Carlos E. Garrido Salmon","doi":"10.1111/ejn.70668","DOIUrl":"10.1111/ejn.70668","url":null,"abstract":"<p>Trigeminal neuralgia has been associated with microstructural alterations of the trigeminal nerve, particularly at the root entry zone, but region-specific reference data stratified by sex in healthy individuals are lacking. This study aimed to characterise the regional organisation of the trigeminal nerve using diffusion tensor imaging (DTI) metrics and volumetry in healthy young adults, describing regional heterogeneity, lateral asymmetry and sex effects. T1-weighted and diffusion-weighted images from 300 Human Connectome Project participants (150 women, 150 men; 22–35 years) were used to bilaterally segment four regions of the trigeminal nerve. For each region of interest, we derived absolute and relative volumes, fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity, computed asymmetry indices and coefficients of variation, and applied <i>t</i>-tests, MANOVA and effect sizes to assess regional, lateral and sex-related differences. We observed a pronounced regional gradient in fractional anisotropy, with highest values at the root entry zone and a progressive decrease towards Meckel's cave. Lateral asymmetries were generally small, and sex systematically influenced diffusion metrics and volumes in specific regions of interest, while preserving the same spatial pattern along the nerve. In healthy young adults, the trigeminal nerve exhibits a marked regional gradient in fractional anisotropy, accompanied by modest physiological lateral asymmetry and consistent sex-related differences. These findings establish region- and sex-specific reference ranges for diffusion metrics and volumes of the trigeminal nerve, providing a quantitative framework to distinguish expected variability from disease-compatible alterations in future studies.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905568","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}