Pub Date : 2026-01-01DOI: 10.1016/j.nicl.2026.103943
Natalie L. Voets , Oiwi Parker Jones , Mohamed L. Seghier , Puneet Plaha
Background
Selecting optimal tasks for language mapping in neurosurgical patients poses challenges that are exacerbated by mismatches in practice between presurgical and intraoperative evaluations. To help align practices, we evaluated a functional MRI version of a semantic association task increasingly used during intra-operative assessment of awake neurosurgery patients. Using a recently proposed consistency mapping approach, we characterise task fMRI activation reliability across individuals, visits, and scan cohorts.
Methods
FMRI data were acquired during an adapted Pyramids and Palm Trees Task (PPTT) in 15 healthy controls and 54 pre-surgical patients with a glioma. A new implementation of threshold-weighted overlap mapping (TWOM) was used to evaluate: 1. inter-individual variability in task activations among individuals; 2. test–retest variability in controls scanned twice (16 ± weeks apart); 3. between-scanner reliability across two patient cohorts scanned on a 3 T Siemens Prisma (n = 27) or Verio (n = 24) scanner using standard (TR = 3 s, voxel size 3 × 3 × 3 mm) or advanced (TR = 0.93 s, voxel size 2x2x2 mm) fMRI acquisitions, respectively.
Results
Task-related activations in the core language network were highly consistent between individuals and across test–retest sessions. Several brain regions showed variable activations, reflecting atypical language dominance (confirmed during neurosurgery), or differences in regional involvement during semantic processing.
Conclusion
The PPTT engaged widespread brain networks including but not limited to regions implicated in semantic processing. Overlap mapping is a powerful way to visualise meaningful variations in neural processing at the individual level, supporting alignment of pre- and intra-operative mapping for any given task.
{"title":"Separating the forest from the palm trees: Individual variation in a presurgical language mapping task","authors":"Natalie L. Voets , Oiwi Parker Jones , Mohamed L. Seghier , Puneet Plaha","doi":"10.1016/j.nicl.2026.103943","DOIUrl":"10.1016/j.nicl.2026.103943","url":null,"abstract":"<div><h3>Background</h3><div>Selecting optimal tasks for language mapping in neurosurgical patients poses challenges that are exacerbated by mismatches in practice between presurgical and intraoperative evaluations. To help align practices, we evaluated a functional MRI version of a semantic association task increasingly used during intra-operative assessment of awake neurosurgery patients. Using a recently proposed consistency mapping approach, we characterise task fMRI activation reliability across individuals, visits, and scan cohorts.</div></div><div><h3>Methods</h3><div>FMRI data were acquired during an adapted Pyramids and Palm Trees Task (PPTT) in 15 healthy controls and 54 pre-surgical patients with a glioma. A new implementation of threshold-weighted overlap mapping (TWOM) was used to evaluate: 1. inter-individual variability in task activations among individuals; 2. test–retest variability in controls scanned twice (16 ± weeks apart); 3. between-scanner reliability across two patient cohorts scanned on a 3 T Siemens Prisma (n = 27) or Verio (n = 24) scanner using standard (TR = 3 s, voxel size 3 × 3 × 3 mm) or advanced (TR = 0.93 s, voxel size 2x2x2 mm) fMRI acquisitions, respectively.</div></div><div><h3>Results</h3><div>Task-related activations in the core language network were highly consistent between individuals and across test–retest sessions. Several brain regions showed variable activations, reflecting atypical language dominance (confirmed during neurosurgery), or differences in regional involvement during semantic processing.</div></div><div><h3>Conclusion</h3><div>The PPTT engaged widespread brain networks including but not limited to regions implicated in semantic processing. Overlap mapping is a powerful way to visualise meaningful variations in neural processing at the individual level, supporting alignment of pre- and intra-operative mapping for any given task.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103943"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.nicl.2026.103947
Giordano Cecchetti , Jacopo Lanzone , Luca Zanchi , Giulia Rugarli , Silvia Basaia , Marco Cursi , Federico Coraglia , Edoardo G. Spinelli , Alma Ghirelli , Elisa Canu , Elisa Sibilla , Francesca Caso , Roberto Santangelo , Davide Curti , Giovanna Franca Fanelli , Anna Bellini , Giuseppe Magnani , Federica Agosta , Massimo Filippi
Background
Scalable biomarkers are needed for early Alzheimer’s disease (AD) detection. Plasma p-tau217 reflects AD pathology, while resting-state EEG captures functional brain alterations. Their relationship remains unclear.
Methods
We enrolled 128 patients with subjective cognitive decline (SCD), mild cognitive impairment due to AD (AD-MCI), or AD dementia (AD-DEM), who underwent 32-channel EEG and plasma biomarker assessment. EEG features included spectral, aperiodic, phase–amplitude coupling, and complexity metrics. Machine learning was used to classify p-tau217 positivity.
Results
AD-MCI and AD-DEM patients showed increased p-tau217 and spectral slowing (higher theta, lower alpha). While no correlations survived correction for multiple comparisons, stage-specific analyses revealed positive associations between theta power and p-tau217 in AD-MCI and AD-DEM. A random forest classifier achieved an AUC of 0.75 in predicting p-tau217 positivity.
Conclusions
EEG captures functional alterations reflecting AD pathology beyond molecular measures, supporting its value as a complementary, non-invasive biomarker for early stratification in clinical settings.
{"title":"Resting-State EEG captures functional network correlates of plasma p-Tau-217 in Alzheimer’s disease","authors":"Giordano Cecchetti , Jacopo Lanzone , Luca Zanchi , Giulia Rugarli , Silvia Basaia , Marco Cursi , Federico Coraglia , Edoardo G. Spinelli , Alma Ghirelli , Elisa Canu , Elisa Sibilla , Francesca Caso , Roberto Santangelo , Davide Curti , Giovanna Franca Fanelli , Anna Bellini , Giuseppe Magnani , Federica Agosta , Massimo Filippi","doi":"10.1016/j.nicl.2026.103947","DOIUrl":"10.1016/j.nicl.2026.103947","url":null,"abstract":"<div><h3>Background</h3><div>Scalable biomarkers are needed for early Alzheimer’s disease (AD) detection. Plasma p-tau217 reflects AD pathology, while resting-state EEG captures functional brain alterations. Their relationship remains unclear.</div></div><div><h3>Methods</h3><div>We enrolled 128 patients with subjective cognitive decline (SCD), mild cognitive impairment due to AD (AD-MCI), or AD dementia (AD-DEM), who underwent 32-channel EEG and plasma biomarker assessment. EEG features included spectral, aperiodic, phase–amplitude coupling, and complexity metrics. Machine learning was used to classify p-tau217 positivity.</div></div><div><h3>Results</h3><div>AD-MCI and AD-DEM patients showed increased p-tau217 and spectral slowing (higher theta, lower alpha). While no correlations survived correction for multiple comparisons, stage-specific analyses revealed positive associations between theta power and p-tau217 in AD-MCI and AD-DEM. A random forest classifier achieved an AUC of 0.75 in predicting p-tau217 positivity.</div></div><div><h3>Conclusions</h3><div>EEG captures functional alterations reflecting AD pathology beyond molecular measures, supporting its value as a complementary, non-invasive biomarker for early stratification in clinical settings.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103947"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.nicl.2025.103932
Songhong Yue , Jintao Wang , Jiahao Yan , Wanjun Hu , Jun Wang , Yucheng Ding , Laiyang Ma , Pengfei Wang , Na Han , Yurong Ma , Jing Zhang
Objectives
Atrial fibrillation (AF) is linked to cognitive impairment even without overt stroke, potentially via neurovascular coupling (NVC) dysfunction. We aimed to determine whether alterations in NVC mediate the relationship between cardiac structural remodeling and cognitive deficits in stroke‐free AF (sfAF) patients.
Methods
This prospective cohort study evaluated participants who underwent MR brain scans, transthoracic echocardiography, and completed neuropsychological assessments. We used a neurovascular coupling approach, combining fMRI metrics (amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC)) with regional cerebral blood flow maps. Mediation analysis were conducted to explore the relationships among NVC metrics, cardiac parameters, and cognitive performance in sfAF.
Results
Compared with healthy controls, the sfAF patients exhibited significant cardiac remodeling, marked by increased LA and LVEDd and decreased LVEF, alongside poorer cognitive performance on AVLT-Immediate and MoCA. They also showed widespread disruptions in neurovascular coupling, with notably reduced fALFF-CBF coupling in the orbital inferior frontal gyrus. Moreover, this reduction in fALFF-CBF coupling mediated the relationship between elevated LVEDd and short-term memory impairment.
Conclusion
NVC dysfunction mediates the adverse effects of cardiac remodeling on cognitive function in sfAF, supporting a heart-brain axis model as a potential target for early intervention.
{"title":"Neurovascular coupling, cognition, and cardiac function in stroke-free atrial fibrillation","authors":"Songhong Yue , Jintao Wang , Jiahao Yan , Wanjun Hu , Jun Wang , Yucheng Ding , Laiyang Ma , Pengfei Wang , Na Han , Yurong Ma , Jing Zhang","doi":"10.1016/j.nicl.2025.103932","DOIUrl":"10.1016/j.nicl.2025.103932","url":null,"abstract":"<div><h3>Objectives</h3><div>Atrial fibrillation (AF) is linked to cognitive impairment even without overt stroke, potentially via neurovascular coupling (NVC) dysfunction. We aimed to determine whether alterations in NVC mediate the relationship between cardiac structural remodeling and cognitive deficits in stroke‐free AF (sfAF) patients.</div></div><div><h3>Methods</h3><div>This prospective cohort study evaluated participants who underwent MR brain scans, transthoracic echocardiography, and completed neuropsychological assessments. We used a neurovascular coupling approach, combining fMRI metrics (amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC)) with regional cerebral blood flow maps. Mediation analysis were conducted to explore the relationships among NVC metrics, cardiac parameters, and cognitive performance in sfAF.</div></div><div><h3>Results</h3><div>Compared with healthy controls, the sfAF patients exhibited significant cardiac remodeling, marked by increased LA and LVEDd and decreased LVEF, alongside poorer cognitive performance on AVLT-Immediate and MoCA. They also showed widespread disruptions in neurovascular coupling, with notably reduced fALFF-CBF coupling in the orbital inferior frontal gyrus. Moreover, this reduction in fALFF-CBF coupling mediated the relationship between elevated LVEDd and short-term memory impairment.</div></div><div><h3>Conclusion</h3><div>NVC dysfunction mediates the adverse effects of cardiac remodeling on cognitive function in sfAF, supporting a heart-brain axis model as a potential target for early intervention.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103932"},"PeriodicalIF":3.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.nicl.2025.103927
Nick Steele , Ahmed Hussain , Delin Sun , Courtney Russell , Ashley A. Huggins , Nicholas D. Davenport , Seth G. Disner , Scott R. Sponheim , Thomas Straube , David Hofmann , Shmuel Lissek , Hannah Berg , Daniel W. Grupe , Jack B. Nitschke , Richard J. Davidson , Ruth Lanius , Maria Densmore , Jean Théberge , Richard W.J. Neufeld , Sophia I. Thomopoulos , Rajendra A. Morey
The thalamus exhibits widespread connectivity to the entire cortical mantle, yet distinct thalamic subregions possess unique connectivity profiles and functional roles. While the thalamus has been consistently implicated in posttraumatic stress disorder (PTSD), fine-grained investigations examining thalamic subregions and nuclei remain sparse. We examined how resting-state functional connectivity (RSFC) of thalamic nuclei with the cortex and large-scale brain networks may contribute to PTSD using high-resolution functional magnetic resonance imaging (fMRI) data from a multi-site dataset of PTSD cases and controls (n = 397). We show that the pulvinar nuclei exhibit weaker RSFC with sensorimotor and salience regions, while the medial geniculate nucleus (MGN) exhibits stronger RSFC with the sensorimotor cortex in PTSD. Greater PTSD severity correlated with weaker RSFC between both the pulvinar and mediodorsal thalamus and cortical sensory/motor regions in the frontal, parietal, and occipital lobes. We identified that the default mode network of PTSD participants had stronger RSFC with the mediodorsal thalamus, while the salience and somatosensory networks exhibited stronger RSFC with somatomotor thalamic nuclei. Fine-grained thalamic mapping is important for uncovering thalamocortical disruptions in PTSD. Thalamic RSFC shows a shift toward heightened subcortical sensory responsivity and diminished voluntary control and cognitive regulation in PTSD.
{"title":"Disrupted thalamocortical functional connectivity and canonical resting-state network integration in posttraumatic stress disorder","authors":"Nick Steele , Ahmed Hussain , Delin Sun , Courtney Russell , Ashley A. Huggins , Nicholas D. Davenport , Seth G. Disner , Scott R. Sponheim , Thomas Straube , David Hofmann , Shmuel Lissek , Hannah Berg , Daniel W. Grupe , Jack B. Nitschke , Richard J. Davidson , Ruth Lanius , Maria Densmore , Jean Théberge , Richard W.J. Neufeld , Sophia I. Thomopoulos , Rajendra A. Morey","doi":"10.1016/j.nicl.2025.103927","DOIUrl":"10.1016/j.nicl.2025.103927","url":null,"abstract":"<div><div>The thalamus exhibits widespread connectivity to the entire cortical mantle, yet distinct thalamic subregions possess unique connectivity profiles and functional roles. While the thalamus has been consistently implicated in posttraumatic stress disorder (PTSD), fine-grained investigations examining thalamic subregions and nuclei remain sparse. We examined how resting-state functional connectivity (RSFC) of thalamic nuclei with the cortex and large-scale brain networks may contribute to PTSD using high-resolution functional magnetic resonance imaging (fMRI) data from a multi-site dataset of PTSD cases and controls (<em>n</em> = 397). We show that the pulvinar nuclei exhibit weaker RSFC with sensorimotor and salience regions, while the medial geniculate nucleus (MGN) exhibits stronger RSFC with the sensorimotor cortex in PTSD. Greater PTSD severity correlated with weaker RSFC between both the pulvinar and mediodorsal thalamus and cortical sensory/motor regions in the frontal, parietal, and occipital lobes. We identified that the default mode network of PTSD participants had stronger RSFC with the mediodorsal thalamus, while the salience and somatosensory networks exhibited stronger RSFC with somatomotor thalamic nuclei. Fine-grained thalamic mapping is important for uncovering thalamocortical disruptions in PTSD. Thalamic RSFC shows a shift toward heightened subcortical sensory responsivity and diminished voluntary control and cognitive regulation in PTSD.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103927"},"PeriodicalIF":3.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1016/j.nicl.2025.103921
Elisabeth Klint , Johan Richter , Teresa Nordin , Ida Blystad , Martin Hallbeck , Alexandra Golby , Carl-Fredrik Westin , Karin Wårdell
High-grade glioma characteristics such as heterogeneity and diffuse growth present a major diagnostic and therapeutic challenge, making accurate imaging essential for diagnosis and surgical planning. Diffusion MRI (dMRI) shows promise in tissue identification through a negative correlation between the dMRI apparent diffusion coefficient and tumor cellularity. Further, tissue disorganization due to tumor growth is correlated with decreased fractional anisotropy (FA) from diffusion tensor imaging (DTI). Q-space trajectory imaging (QTI) through free gradient waveform encoding during dMRI acquisition has been suggested as a framework for dMRI scalar map generation, enabling disentangled measures of shape, size, and orientation. We aimed to extend a clinically integrated workflow for optical guidance in frameless navigated brain tumor biopsies to include DTI and QTI scalars for multimodal analysis. Diffusion scalars were compared to tumor indications on tissue fluorescence, conventional imaging, and neuropathology in navigated brain tumor biopsy procedures.
In seven high-grade glioma patients, the biopsied tissue volume was associated with decreased dMRI features (anisotropy, kurtosis, and order parameters) and increased diffusivity in DTI when compared with contralateral white matter. Principal components of diffusion scalars depend on microstructural (QTI) and diffusivity (DTI) parameters, respectively. Redundancy analysis between the dMRI scalars revealed scalar pairs that offer novel information for tissue separation that could be of interest for fine-tuning of the MRI protocol before further evaluation of QTI for tumor tissue identification in the clinical setting.
{"title":"Mapping brain tumor microstructure: A multimodal study of diffusion MRI, intraoperative fluorescence, and neuropathology in navigated biopsies","authors":"Elisabeth Klint , Johan Richter , Teresa Nordin , Ida Blystad , Martin Hallbeck , Alexandra Golby , Carl-Fredrik Westin , Karin Wårdell","doi":"10.1016/j.nicl.2025.103921","DOIUrl":"10.1016/j.nicl.2025.103921","url":null,"abstract":"<div><div>High-grade glioma characteristics such as heterogeneity and diffuse growth present a major diagnostic and therapeutic challenge, making accurate imaging essential for diagnosis and surgical planning. Diffusion MRI (dMRI) shows promise in tissue identification through a negative correlation between the dMRI apparent diffusion coefficient and tumor cellularity. Further, tissue disorganization due to tumor growth is correlated with decreased fractional anisotropy (FA) from diffusion tensor imaging (DTI). Q-space trajectory imaging (QTI) through free gradient waveform encoding during dMRI acquisition has been suggested as a framework for dMRI scalar map generation, enabling disentangled measures of shape, size, and orientation. We aimed to extend a clinically integrated workflow for optical guidance in frameless navigated brain tumor biopsies to include DTI and QTI scalars for multimodal analysis. Diffusion scalars were compared to tumor indications on tissue fluorescence, conventional imaging, and neuropathology in navigated brain tumor biopsy procedures.</div><div>In seven high-grade glioma patients, the biopsied tissue volume was associated with decreased dMRI features (anisotropy, kurtosis, and order parameters) and increased diffusivity in DTI when compared with contralateral white matter. Principal components of diffusion scalars depend on microstructural (QTI) and diffusivity (DTI) parameters, respectively. Redundancy analysis between the dMRI scalars revealed scalar pairs that offer novel information for tissue separation that could be of interest for fine-tuning of the MRI protocol before further evaluation of QTI for tumor tissue identification in the clinical setting.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103921"},"PeriodicalIF":3.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.nicl.2025.103926
Beatriz E. Padrela , Sandra Tecelão , Bjørn-Eivind Kirsebom , Oliver Geier , Mario Tranfa , Federico Masserini , Markus H. Sneve , Maksim Slivka , Emilie Sogn Falch , Lene Pålhaugen , Amnah Mahroo , Klaus Eickel , David L. Thomas , Matthias Günther , Per Selnes , Atle Bjørnerud , Kristine B. Walhovd , Anders M. Fjell , Frederik Barkhof , Jan Petr , Henk J.M.M. Mutsaerts
Blood-brain barrier (BBB) water exchange may serve as a sensitive early biomarker for Alzheimer’s disease and age-related cognitive decline. This study applied a non-invasive multi-echo arterial spin labeling (ASL) technique to measure BBB water exchange time (Tex), cerebral blood flow (CBF), and arterial transit time (ATT) in 160 adults aged 50 years and older. Participants were classified as cognitively normal (CN), having subjective cognitive decline (SCD), or mild cognitive impairment (MCI). They were assessed for amyloid status and cerebrovascular burden. Compared to CN participants, Tex was significantly lower in both SCD (−9.5 %) and MCI (−14.5 %) groups, suggesting that reductions in BBB water exchange emerge early in the course of cognitive decline. In contrast, CBF was reduced only in MCI participants (−20.8 % compared to CN), and ATT was significantly increased only in individuals with severe cerebrovascular burden (Fazekas score 3). Notably, Tex showed a stepwise decrease with increasing Fazekas scores (1–2), supporting its sensitivity to moderate small vessel disease. No associations were found between Tex and amyloid positivity after adjusting for age and sex. These findings indicate that Tex alterations may precede changes in traditional perfusion markers and are more closely related to vascular and early cognitive changes than to amyloid pathology. BBB water exchange mapping may therefore provide a promising, non-invasive tool to detect early neurovascular dysfunction that contributes to cognitive decline in aging populations, potentially offering a useful biomarker for early intervention trials targeting vascular contributions to dementia.
{"title":"Blood-brain barrier water exchange in relation to amyloid, cognition and cerebrovascular burden","authors":"Beatriz E. Padrela , Sandra Tecelão , Bjørn-Eivind Kirsebom , Oliver Geier , Mario Tranfa , Federico Masserini , Markus H. Sneve , Maksim Slivka , Emilie Sogn Falch , Lene Pålhaugen , Amnah Mahroo , Klaus Eickel , David L. Thomas , Matthias Günther , Per Selnes , Atle Bjørnerud , Kristine B. Walhovd , Anders M. Fjell , Frederik Barkhof , Jan Petr , Henk J.M.M. Mutsaerts","doi":"10.1016/j.nicl.2025.103926","DOIUrl":"10.1016/j.nicl.2025.103926","url":null,"abstract":"<div><div>Blood-brain barrier (BBB) water exchange may serve as a sensitive early biomarker for Alzheimer’s disease and age-related cognitive decline. This study applied a non-invasive multi-echo arterial spin labeling (ASL) technique to measure BBB water exchange time (Tex), cerebral blood flow (CBF), and arterial transit time (ATT) in 160 adults aged 50 years and older. Participants were classified as cognitively normal (CN), having subjective cognitive decline (SCD), or mild cognitive impairment (MCI). They were assessed for amyloid status and cerebrovascular burden. Compared to CN participants, Tex was significantly lower in both SCD (−9.5 %) and MCI (−14.5 %) groups, suggesting that reductions in BBB water exchange emerge early in the course of cognitive decline. In contrast, CBF was reduced only in MCI participants (−20.8 % compared to CN), and ATT was significantly increased only in individuals with severe cerebrovascular burden (Fazekas score 3). Notably, Tex showed a stepwise decrease with increasing Fazekas scores (1–2), supporting its sensitivity to moderate small vessel disease. No associations were found between Tex and amyloid positivity after adjusting for age and sex. These findings indicate that Tex alterations may precede changes in traditional perfusion markers and are more closely related to vascular and early cognitive changes than to amyloid pathology. BBB water exchange mapping may therefore provide a promising, non-invasive tool to detect early neurovascular dysfunction that contributes to cognitive decline in aging populations, potentially offering a useful biomarker for early intervention trials targeting vascular contributions to dementia.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103926"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Navigated transcranial magnetic stimulation (nTMS) has become a cornerstone in preoperative functional mapping for brain tumor patients. The resting motor threshold (RMT) derived from nTMS reflects motor cortex excitability and may be influenced by tumor-related and patient-specific factors. However, the specific contribution of tumor location within cortical motor networks to RMT remains insufficiently understood.
Methods
In this prospective study, 223 patients with motor-eloquent brain tumors underwent nTMS-based motor mapping. Individual RMTs were determined using the Rossini-Rothwell method. Preoperative MRIs were normalized to MNI space, and tumor lesions were manually segmented. Voxel-based lesion-symptom mapping (VLSM) was performed to assess voxel-wise associations between tumor location and RMT. Multivariate regression identified clinical and anatomical predictors of RMT.
Results
Lesions were predominantly located in the perirolandic region, involving the primary motor cortex (MC) as well as precentral (preMC) and postcentral (postMC) areas. Multivariate analysis revealed that postMC tumor location and age were significant negative predictors of RMT, while meningioma histology was a positive predictor. VLSM revealed that lesions in the postcentral gyrus, superior parietal lobule, and precuneus were associated with lower RMT (i.e., increased excitability), whereas lesions in the precentral gyrus, supplementary motor area (SMA), and dorsal premotor cortex (PMd) were associated with higher RMT (i.e., decreased excitability).
Conclusion
Motor cortex excitability in brain tumor patients is shaped by the functional integrity of interconnected cortical hubs. Disruption of inhibitory (e.g., sensory cortex) or facilitatory (e.g., premotor cortex) inputs to MC can modulate excitability in opposing directions. The combined use of nTMS and VLSM enables a network-level understanding of tumor-induced excitability changes and supports individualized surgical planning based on lesion topography.
{"title":"Lesion topography shapes motor thresholds in brain tumor patients","authors":"Alexia Stark, Kateryna Goloshchapova, Aldo Spolaore, Mykola Gorbachuk, Athanasios Gkampenis, Sophie Wang, Kathrin Machetanz, Marcos Tatagiba, Georgios Naros","doi":"10.1016/j.nicl.2025.103924","DOIUrl":"10.1016/j.nicl.2025.103924","url":null,"abstract":"<div><h3>Background</h3><div>Navigated transcranial magnetic stimulation (nTMS) has become a cornerstone in preoperative functional mapping for brain tumor patients. The resting motor threshold (RMT) derived from nTMS reflects motor cortex excitability and may be influenced by tumor-related and patient-specific factors. However, the specific contribution of tumor location within cortical motor networks to RMT remains insufficiently understood.</div></div><div><h3>Methods</h3><div>In this prospective study, 223 patients with motor-eloquent brain tumors underwent nTMS-based motor mapping. Individual RMTs were determined using the Rossini-Rothwell method. Preoperative MRIs were normalized to MNI space, and tumor lesions were manually segmented. Voxel-based lesion-symptom mapping (VLSM) was performed to assess voxel-wise associations between tumor location and RMT. Multivariate regression identified clinical and anatomical predictors of RMT.</div></div><div><h3>Results</h3><div>Lesions were predominantly located in the perirolandic region, involving the primary motor cortex (MC) as well as precentral (preMC) and postcentral (postMC) areas. Multivariate analysis revealed that postMC tumor location and age were significant negative predictors of RMT, while meningioma histology was a positive predictor. VLSM revealed that lesions in the postcentral gyrus, superior parietal lobule, and precuneus were associated with lower RMT (i.e., increased excitability), whereas lesions in the precentral gyrus, supplementary motor area (SMA), and dorsal premotor cortex (PMd) were associated with higher RMT (i.e., decreased excitability).</div></div><div><h3>Conclusion</h3><div>Motor cortex excitability in brain tumor patients is shaped by the functional integrity of interconnected cortical hubs. Disruption of inhibitory (e.g., sensory cortex) or facilitatory (e.g., premotor cortex) inputs to MC can modulate excitability in opposing directions. The combined use of nTMS and VLSM enables a network-level understanding of tumor-induced excitability changes and supports individualized surgical planning based on lesion topography.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103924"},"PeriodicalIF":3.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.nicl.2025.103922
Federica Cacciamani , Marion Houot , Sophie Tezenas du Montcel , Elina Thibeau-Sutre , Patrizia Vannini , Raffaella Lara Migliaccio
Impaired cognitive awareness—anosognosia—is a core symptom of Alzheimer’s disease (AD), yet its neural correlates remain poorly defined. This study examined how cognitive awareness, measured both cross-sectionally and longitudinally via subject-informant discrepancy on the Everyday Cognition (ECog) questionnaire, relates to three AD biomarkers: amyloid burden, glucose hypometabolism, and cortical atrophy. We included 785 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), spanning cognitively normal (CN), mild cognitive impairment (MCI), and AD dementia. All biomarkers were assessed at baseline across the same 86 cortical regions, enabling anatomically harmonized, cross-modality comparisons. Linear mixed models incorporating all three biomarkers revealed no significant associations in CN. In MCI, declining awareness was associated with widespread cortical amyloid deposition (significant in 80/86 regions), sparing some limbic areas. Atrophy in 11 regions—including limbic, lateral temporal, and occipital cortices—also predicted awareness decline (all p < 0.044). In AD, no significant associations were found between amyloid and awareness, suggesting a plateau effect at advanced stages. In both MCI and AD, lower baseline glucose metabolism in the left posterior cingulate cortex (PCC) was associated with poorer awareness (MCI: β ± SE = − 0.14 ± 0.04, p = 0.006; AD: β ± SE = − 0.24 ± 0.07, p = 0.042). No significant biomarker-time interactions were found in AD, suggesting relatively stable awareness levels at advanced disease stages. These findings indicate that anosognosia in AD is linked to distinct biomarker and regional profiles that vary by disease phase. Multimodal analysis across harmonized regions reveals the left PCC as a robust metabolic correlate of awareness, underscoring its potential as a key target in understanding and monitoring self-awareness impairment in neurodegenerative disease.
{"title":"Multimodal neural correlates of cognitive awareness in aging and Alzheimer’s disease","authors":"Federica Cacciamani , Marion Houot , Sophie Tezenas du Montcel , Elina Thibeau-Sutre , Patrizia Vannini , Raffaella Lara Migliaccio","doi":"10.1016/j.nicl.2025.103922","DOIUrl":"10.1016/j.nicl.2025.103922","url":null,"abstract":"<div><div>Impaired cognitive awareness—anosognosia—is a core symptom of Alzheimer’s disease (AD), yet its neural correlates remain poorly defined. This study examined how cognitive awareness, measured both cross-sectionally and longitudinally via subject-informant discrepancy on the Everyday Cognition (ECog) questionnaire, relates to three AD biomarkers: amyloid burden, glucose hypometabolism, and cortical atrophy. We included 785 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), spanning cognitively normal (CN), mild cognitive impairment (MCI), and AD dementia. All biomarkers were assessed at baseline across the same 86 cortical regions, enabling anatomically harmonized, cross-modality comparisons. Linear mixed models incorporating all three biomarkers revealed no significant associations in CN. In MCI, declining awareness was associated with widespread cortical amyloid deposition (significant in 80/86 regions), sparing some limbic areas. Atrophy in 11 regions—including limbic, lateral temporal, and occipital cortices—also predicted awareness decline (all p < 0.044). In AD, no significant associations were found between amyloid and awareness, suggesting a plateau effect at advanced stages. In both MCI and AD, lower baseline glucose metabolism in the left posterior cingulate cortex (PCC) was associated with poorer awareness (MCI: β ± SE = − 0.14 ± 0.04, p = 0.006; AD: β ± SE = − 0.24 ± 0.07, p = 0.042). No significant biomarker-time interactions were found in AD, suggesting relatively stable awareness levels at advanced disease stages. These findings indicate that anosognosia in AD is linked to distinct biomarker and regional profiles that vary by disease phase. Multimodal analysis across harmonized regions reveals the left PCC as a robust metabolic correlate of awareness, underscoring its potential as a key target in understanding and monitoring self-awareness impairment in neurodegenerative disease.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103922"},"PeriodicalIF":3.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.nicl.2025.103917
Le Jiao , Yuanyuan Tao , Dawei Zhang , Qingmei Chen , Liying Han , Gengrun Tian , Chunlei Shan , Hongjun Zhu
Background
While 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting contralesional primary motor cortex (M1) shows promise for stroke recovery, individual response variability remains a critical challenge. Emerging evidence suggests that interhemispheric activation patterns may mediate rTMS efficacy. We investigated whether pretreatment spatial features of contralesional activation, measured by functional near-infrared spectroscopy (fNIRS), could predict response to 1 Hz rTMS.
Methods
In this nested unmatched case-control study, 60 patients with upper limb motor impairment received 1 Hz rTMS over contralesional M1 hand area plus conventional rehabilitation for 4 weeks. Responders were defined by a ≥5-point improvement on the Upper Extremity Fugl-Meyer (UEFM) assessment. Cortical activation during affected wrist extension was recorded using fNIRS, and the Euclidean distance from the peak activation channel to the M1 hand area (“activation distance”) was computed. An additional non-rTMS cohort (n=30) receiving only conventional rehabilitation was included to evaluate specificity.
Results
In the rTMS cohort, responders (n=32) exhibited significantly shorter pretreatment activation distances than non-responders (n=28) (25.80±8.82 mm vs. 34.07±7.81 mm; p<0.001). Activation distance independently predicted treatment response after adjusting for baseline UEFM, time since stroke and age (adjusted OR=0.40 per 10 mm increase; 95% CI: 0.17–0.83; p=0.014). A cutoff of ≤25 mm optimally discriminated responders (response rate 86% vs. 34% for >25 mm). No association was found in the non-rTMS cohort, confirming specificity to rTMS response.
Conclusion
Pretreatment contralesional activation proximity to M1—assessed via fNIRS—predicts response to inhibitory rTMS, supporting its use as a biomarker for personalized neuromodulation therapy in stroke rehabilitation.
背景：虽然针对对侧初级运动皮层（M1）的1hz重复经颅磁刺激（rTMS）显示出中风恢复的希望，但个体反应的可变性仍然是一个关键的挑战。新出现的证据表明，半球间激活模式可能介导rTMS的疗效。我们研究了用功能近红外光谱（fNIRS）测量的对侧激活的预处理空间特征是否可以预测对1hz rTMS的反应。方法60例上肢运动障碍患者在对照M1手区接受1 Hz rTMS治疗，外加常规康复治疗4周。反应者的定义是上肢Fugl-Meyer （ufm）评估改善≥5分。使用近红外光谱（fNIRS）记录受影响的手腕伸展期间的皮质激活，并计算从激活峰通道到M1手区的欧几里得距离（“激活距离”）。另外一个仅接受常规康复治疗的非rtms队列（n=30）被纳入以评估特异性。结果在rTMS队列中，应答者（n=32）的预处理激活距离明显短于应答者（n=28）（25.80±8.82 mm vs. 34.07±7.81 mm; p<0.001）。在调整基线UEFM、卒中后时间和年龄后，激活距离独立预测治疗反应（每增加10 mm调整OR=0.40; 95% CI: 0.17-0.83; p=0.014）。≤25毫米的临界值最能区分应答者（应答率为86%，而≤25毫米的应答率为34%）。在非rTMS队列中未发现关联，证实了rTMS应答的特异性。结论通过fnirs评估的接近m1的预处理对照激活可预测对抑制性rTMS的反应，支持其作为脑卒中康复个性化神经调节治疗的生物标志物。
{"title":"Pretreatment spatial signature of contralesional cortical activation predicts therapeutic response to 1 Hz rTMS in post-stroke upper limb motor Recovery: A fNIRS-based biomarker study","authors":"Le Jiao , Yuanyuan Tao , Dawei Zhang , Qingmei Chen , Liying Han , Gengrun Tian , Chunlei Shan , Hongjun Zhu","doi":"10.1016/j.nicl.2025.103917","DOIUrl":"10.1016/j.nicl.2025.103917","url":null,"abstract":"<div><h3>Background</h3><div>While 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting contralesional primary motor cortex (M1) shows promise for stroke recovery, individual response variability remains a critical challenge. Emerging evidence suggests that interhemispheric activation patterns may mediate rTMS efficacy. We investigated whether pretreatment spatial features of contralesional activation, measured by functional near-infrared spectroscopy (fNIRS), could predict response to 1 Hz rTMS.</div></div><div><h3>Methods</h3><div>In this nested unmatched case-control study, 60 patients with upper limb motor impairment received 1 Hz rTMS over contralesional M1 hand area plus conventional rehabilitation for 4 weeks. Responders were defined by a ≥5-point improvement on the Upper Extremity Fugl-Meyer (UEFM) assessment. Cortical activation during affected wrist extension was recorded using fNIRS, and the Euclidean distance from the peak activation channel to the M1 hand area (“activation distance”) was computed. An additional non-rTMS cohort (n=30) receiving only conventional rehabilitation was included to evaluate specificity.</div></div><div><h3>Results</h3><div>In the rTMS cohort, responders (n=32) exhibited significantly shorter pretreatment activation distances than non-responders (n=28) (25.80±8.82 mm vs. 34.07±7.81 mm; p<0.001). Activation distance independently predicted treatment response after adjusting for baseline UEFM, time since stroke and age (adjusted OR=0.40 per 10 mm increase; 95% CI: 0.17–0.83; p=0.014). A cutoff of ≤25 mm optimally discriminated responders (response rate 86% vs. 34% for >25 mm). No association was found in the non-rTMS cohort, confirming specificity to rTMS response.</div></div><div><h3>Conclusion</h3><div>Pretreatment contralesional activation proximity to M1—assessed via fNIRS—predicts response to inhibitory rTMS, supporting its use as a biomarker for personalized neuromodulation therapy in stroke rehabilitation.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103917"},"PeriodicalIF":3.6,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-30DOI: 10.1016/j.nicl.2025.103919
Longhao Ma , Pan Wang , Dawei Wang , Hongxiang Yao , Bo Zhou , Yonghua Zhao , Zhengluan Liao , Yan Chen , Xi Zhang , Ying Han , Jie Lu , Kun Zhao , Yihe Zhang , Yong Liu , for the Alzheimer’s Disease Neuroimaging Initiative, for the Multi-Center Alzheimer’s Disease Imaging (MCADI) Consortium
Alterations in brain network centrality are key features of Alzheimer’s disease (AD) and may offer insights into the disruption of network organization underlying cognitive decline. We introduce a novel centrality metric, DomiRank, to characterize dominance-driven connectivity patterns in the human brain network, using a multi-center MRI dataset comprising 809 participants. Compared with conventional metrics, DomiRank centrality showed greater sensitivity in detecting AD-related network disruptions, particularly within the cingulate gyrus, precuneus, and subcortical hubs such as the basal ganglia—regions critical for cognition. Regional DomiRank alterations were significantly correlated with clinical cognitive scores, indicating their potential relevance to disease severity. Gene enrichment analysis revealed that areas with reduced DomiRank centrality were enriched for genes involved in synaptic signaling and neuronal communication, suggesting molecular mechanisms underlying network vulnerability. These findings highlight DomiRank centrality as a promising biomarker for characterizing network disorganization in AD, linking changes in brain connectivity with underlying molecular processes.
{"title":"Brain topology alteration in Alzheimer’s disease brain networks: A multi-center study","authors":"Longhao Ma , Pan Wang , Dawei Wang , Hongxiang Yao , Bo Zhou , Yonghua Zhao , Zhengluan Liao , Yan Chen , Xi Zhang , Ying Han , Jie Lu , Kun Zhao , Yihe Zhang , Yong Liu , for the Alzheimer’s Disease Neuroimaging Initiative, for the Multi-Center Alzheimer’s Disease Imaging (MCADI) Consortium","doi":"10.1016/j.nicl.2025.103919","DOIUrl":"10.1016/j.nicl.2025.103919","url":null,"abstract":"<div><div>Alterations in brain network centrality are key features of Alzheimer’s disease (AD) and may offer insights into the disruption of network organization underlying cognitive decline. We introduce a novel centrality metric, DomiRank, to characterize dominance-driven connectivity patterns in the human brain network, using a multi-center MRI dataset comprising 809 participants. Compared with conventional metrics, DomiRank centrality showed greater sensitivity in detecting AD-related network disruptions, particularly within the cingulate gyrus, precuneus, and subcortical hubs such as the basal ganglia—regions critical for cognition. Regional DomiRank alterations were significantly correlated with clinical cognitive scores, indicating their potential relevance to disease severity. Gene enrichment analysis revealed that areas with reduced DomiRank centrality were enriched for genes involved in synaptic signaling and neuronal communication, suggesting molecular mechanisms underlying network vulnerability. These findings highlight DomiRank centrality as a promising biomarker for characterizing network disorganization in AD, linking changes in brain connectivity with underlying molecular processes.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103919"},"PeriodicalIF":3.6,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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