In this study, we aimed to identify structural biomarkers linked to the severity and outcome of aphasia after a left-hemispheric stroke. We recruited 72 individuals with post-stroke aphasia and assessed their initial aphasia severity using the Aphasia Severity Rating Scale, alongside measures of naming ability and executive function. Aphasia outcome was determined for 56 out of 72 participants with available Aphasia Severity Rating Scale scores at discharge. We performed support-vector regression symptom mapping analyses at both cortical and white matter levels to examine the relationship between structural brain damage and our variables of interest (initial aphasia severity, naming, executive functions, and aphasia outcome). Our results revealed that (a) disconnections in white matter tracts within ventral and dorsal language pathways were associated with aphasia severity and naming deficits initially; and (b) disconnections in white matter tracts within executive networks (i.e., fronto-parietal, executive control, and salience networks) were related to executive dysfunction. This retrospective cohort study highlighted the crucial roles of white matter tracts within both dorsal (i.e., arcuate fasciculus, superior longitudinal fasciculus) and ventral (uncinate, inferior longitudinal, and middle longitudinal fasciculi) language streams in shaping the cognitive phenotypes of post-stroke aphasia patients, particularly concerning aphasia severity and naming impairment, by delineating distinct patterns of affected brain structures.
{"title":"Structural correlates of aphasia severity, cognitive impairment, and outcome after stroke","authors":"Célise Haldin , Hélène Lœvenbruck , Céline Piscicelli , Valérie Marcon , Shenhao Dai , Olivier Detante , Dominic Pérennou , Monica Baciu","doi":"10.1016/j.nicl.2026.103954","DOIUrl":"10.1016/j.nicl.2026.103954","url":null,"abstract":"<div><div>In this study, we aimed to identify structural biomarkers linked to the severity and outcome of aphasia after a left-hemispheric stroke. We recruited 72 individuals with post-stroke aphasia and assessed their initial aphasia severity using the Aphasia Severity Rating Scale, alongside measures of naming ability and executive function. Aphasia outcome was determined for 56 out of 72 participants with available Aphasia Severity Rating Scale scores at discharge. We performed support-vector regression symptom mapping analyses at both cortical and white matter levels to examine the relationship between structural brain damage and our variables of interest (initial aphasia severity, naming, executive functions, and aphasia outcome). Our results revealed that (a) disconnections in white matter tracts within ventral and dorsal language pathways were associated with aphasia severity and naming deficits initially; and (b) disconnections in white matter tracts within executive networks (i.e., fronto-parietal, executive control, and salience networks) were related to executive dysfunction. This retrospective cohort study highlighted the crucial roles of white matter tracts within both dorsal (i.e., arcuate fasciculus, superior longitudinal fasciculus) and ventral (uncinate, inferior longitudinal, and middle longitudinal fasciculi) language streams in shaping the cognitive phenotypes of post-stroke aphasia patients, particularly concerning aphasia severity and naming impairment, by delineating distinct patterns of affected brain structures.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103954"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077836","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 : 2026-01-01Epub Date: 2026-01-20DOI: 10.1016/j.nicl.2026.103952
Merle J. Marek , Dieter Wolke , Christian Sorg , Jil Wendt , Aurore Menegaux , Dennis Hedderich , Peter Bartmann , Micha Burkhardt , Andrea Hildebrandt , Axel Heep
This study investigates the long-term effects of very preterm (VPT) birth (<32 weeks of gestation) on cognitive control and structural brain network topology. Data were obtained from 61 very VPT and 79 full term (FT) individuals aged 26 years, who participated in the prospective Bavarian Longitudinal Study since birth (BLS, https://www.bayerische-entwicklungsstudie.de). Cognitive control ability was estimated through a multi-group confirmatory factor analysis, while the structural topology of the cognitive control brain network was analysed through diffusion-weighted magnetic resonance imaging, tractography, and graph-theoretic analysis. Brain-behaviour associations were further examined using structural equation modelling. Consistent with expectations, we observed significant group differences in cognitive control, especially in a latent speed of cognitive control factor, with FT individuals scoring 0.742 standard deviations higher than the VPT group (p = 0.001). This was statistically confirmed by a model comparison in the multi-group framework. Additionally, the VPT group exhibited lower structural network integration, as indicated by reduced global efficiency and average degree of the cognitive control brain network. Contrary to our hypothesis, we found no group differences in network segregation (average clustering coefficient), and structural network characteristics were not significantly associated with latent cognitive control. These findings indicate cognitive control deficits and reduced structural brain network integration in adulthood for VPT individuals and underscores the need for ongoing support and intervention to mitigate the lasting neurodevelopmental impacts of preterm birth.
{"title":"Structural network topology and cognitive control in very preterm born young adults","authors":"Merle J. Marek , Dieter Wolke , Christian Sorg , Jil Wendt , Aurore Menegaux , Dennis Hedderich , Peter Bartmann , Micha Burkhardt , Andrea Hildebrandt , Axel Heep","doi":"10.1016/j.nicl.2026.103952","DOIUrl":"10.1016/j.nicl.2026.103952","url":null,"abstract":"<div><div>This study investigates the long-term effects of very preterm (VPT) birth (<32 weeks of gestation) on cognitive control and structural brain network topology. Data were obtained from 61 very VPT and 79 full term (FT) individuals aged 26 years, who participated in the prospective Bavarian Longitudinal Study since birth (BLS, <span><span>https://www.bayerische-entwicklungsstudie.de</span><svg><path></path></svg></span>). Cognitive control ability was estimated through a multi-group confirmatory factor analysis, while the structural topology of the cognitive control brain network was analysed through diffusion-weighted magnetic resonance imaging, tractography, and graph-theoretic analysis. Brain-behaviour associations were further examined using structural equation modelling. Consistent with expectations, we observed significant group differences in cognitive control, especially in a latent <em>speed of cognitive control</em> factor, with FT individuals scoring 0.742 standard deviations higher than the VPT group (<em>p</em> = 0.001). This was statistically confirmed by a model comparison in the multi-group framework. Additionally, the VPT group exhibited lower structural network integration, as indicated by reduced global efficiency and average degree of the cognitive control brain network. Contrary to our hypothesis, we found no group differences in network segregation (average clustering coefficient), and structural network characteristics were not significantly associated with latent cognitive control. These findings indicate cognitive control deficits and reduced structural brain network integration in adulthood for VPT individuals and underscores the need for ongoing support and intervention to mitigate the lasting neurodevelopmental impacts of preterm birth.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103952"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037894","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 : 2026-01-01Epub Date: 2026-02-12DOI: 10.1016/j.nicl.2026.103960
Nicolas Gninenko , Pascal Senn , Sven Haller , Dimitri Van De Ville
Chronic subjective tinnitus is the most common form of tinnitus and refers to an internal persistent phantom auditory perception. Evidence from neuroimaging studies has established tinnitus and its associated distress as a brain network disorder, with multiple brain regions displaying dysregulated activity or connectivity extending way beyond the auditory pathway. Hyperactivity in the auditory cortex has been associated with perceived tinnitus loudness, and somatosensory-auditory interactions have recently been involved in promising treatment avenues through their disruption using non-invasive or bimodal neuromodulation techniques, albeit with low mechanistic evidence.
In this study, we evaluated the neural effects of prolonged downregulation of bilateral auditory cortex activity mediated by real-time fMRI neurofeedback in individuals with moderate to severe (Tinnitus Handicap Inventory [THI] scores ≥ 48) chronic tinnitus. Twenty-one participants (aged 49 ± 11.4 years old, 16 males, 5 females) completed 15 fMRI neurofeedback sessions over 3–4 months each, as part of a randomized clinical trial (ClinicalTrials.gov: NCT05737888) comparing neurofeedback interventions over the current standard of care, cognitive behavioral therapy (CBT). We performed whole-brain general linear modeling analyses to delineate regulated brain areas, accounting for age, gender, and THI scores at baseline. Task-modulated functional connectivity analyses were carried out using psychophysiological interactions to unveil associated connectivity patterns emerging during cognitively demanding tinnitus defocalization.
Most participants succeeded at reducing the average activity of their auditory cortex throughout the training. Whole brain analyses additionally revealed a strong downregulation of parietal operculum 3 (OP3), a region previously reported to be activated in the right hemisphere during experimentally induced transient phantom percepts. In accordance with the hypothesis that OP3 may mediate the integration of multisensory inputs in tinnitus, we have shown that both left and right auditory cortices decrease their connectivity with OP3 during closed-loop auditory downregulation. Moreover, we observed a reduced connectivity of bilateral OP3 with a functional multisensory integration network that was previously found to be engaged by the primary and secondary auditory cortices during audio-tactile integration.
These findings support the hypothesis of OP3 having a key role in multisensory integration stemming from altered somatosensory-auditory crosstalk in chronic tinnitus. Targeted neuromodulation to desynchronize the connectivity between OP3 and the auditory cortex could further inform our understanding of the mechanisms behind recent successful bimodal interventions for reducing tinnitus.
{"title":"Altered parietal multisensory integration in chronic tinnitus during closed-loop real-time fMRI auditory downregulation","authors":"Nicolas Gninenko , Pascal Senn , Sven Haller , Dimitri Van De Ville","doi":"10.1016/j.nicl.2026.103960","DOIUrl":"10.1016/j.nicl.2026.103960","url":null,"abstract":"<div><div>Chronic subjective tinnitus is the most common form of tinnitus and refers to an internal persistent phantom auditory perception. Evidence from neuroimaging studies has established tinnitus and its associated distress as a brain network disorder, with multiple brain regions displaying dysregulated activity or connectivity extending way beyond the auditory pathway. Hyperactivity in the auditory cortex has been associated with perceived tinnitus loudness, and somatosensory-auditory interactions have recently been involved in promising treatment avenues through their disruption using non-invasive or bimodal neuromodulation techniques, albeit with low mechanistic evidence.</div><div>In this study, we evaluated the neural effects of prolonged downregulation of bilateral auditory cortex activity mediated by real-time fMRI neurofeedback in individuals with moderate to severe (Tinnitus Handicap Inventory [THI] scores ≥ 48) chronic tinnitus. Twenty-one participants (aged 49 ± 11.4 years old, 16 males, 5 females) completed 15 fMRI neurofeedback sessions over 3–4 months each, as part of a randomized clinical trial (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>: NCT05737888) comparing neurofeedback interventions over the current standard of care, cognitive behavioral therapy (CBT). We performed whole-brain general linear modeling analyses to delineate regulated brain areas, accounting for age, gender, and THI scores at baseline. Task-modulated functional connectivity analyses were carried out using psychophysiological interactions to unveil associated connectivity patterns emerging during cognitively demanding tinnitus defocalization.</div><div>Most participants succeeded at reducing the average activity of their auditory cortex throughout the training. Whole brain analyses additionally revealed a strong downregulation of parietal operculum 3 (OP3), a region previously reported to be activated in the right hemisphere during experimentally induced transient phantom percepts. In accordance with the hypothesis that OP3 may mediate the integration of multisensory inputs in tinnitus, we have shown that both left and right auditory cortices decrease their connectivity with OP3 during closed-loop auditory downregulation. Moreover, we observed a reduced connectivity of bilateral OP3 with a functional multisensory integration network that was previously found to be engaged by the primary and secondary auditory cortices during audio-tactile integration.</div><div>These findings support the hypothesis of OP3 having a key role in multisensory integration stemming from altered somatosensory-auditory crosstalk in chronic tinnitus. Targeted neuromodulation to desynchronize the connectivity between OP3 and the auditory cortex could further inform our understanding of the mechanisms behind recent successful bimodal interventions for reducing tinnitus.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103960"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208483","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}
Functional Neurological Disorder (FND) presents with disabling and heterogeneous motor, sensory, and cognitive symptoms despite the absence of gross structural pathology. A key question is whether symptoms reflect disruptions in the intrinsic organization of brain networks. Electroencephalography (EEG) offers a high temporal resolution view of ongoing dynamics, making it a powerful means to probe such mechanisms.
Methods
We applied a seven-class microstate decomposition to resting-state EEG from 39 patients with FND and 47 matched healthy controls to characterize the temporal dynamics of brain activity. Microstate were labelled A-G according to established topographies. Symptom severity was assessed with the Simplified-Functional Movement Disorder Rating Scale, and correlations were tested. Logistic regression was used to assess group discrimination, with accuracy quantified by the area under the curve.
Results
Compared to controls, patients with FND exhibit significantly reduced duration of microstate G, associated with sensorimotor integration. This alteration correlated negatively with symptom severity scores and moderately discriminated groups. Transition probabilities analyses uncovered distinct patterns among microstates A, B and C, suggesting both an exaggerated shift from arousal-related to visual imagery networks and resistance to engage in self-referential processing.
Conclusions
Our findings provide the first direct evidence of disrupted resting-state microstate organization across a heterogeneous FND cohort.
{"title":"Altered microstate dynamics in Functional Neurological Disorder","authors":"Irene Lozzi , Cristina Concetti , Natascha Stoffel , Michael Mouthon , Miriam Braga , Michele Tinazzi , Mirta Fiorio , Selma Aybek","doi":"10.1016/j.nicl.2026.103969","DOIUrl":"10.1016/j.nicl.2026.103969","url":null,"abstract":"<div><h3>Background</h3><div>Functional Neurological Disorder (FND) presents with disabling and heterogeneous motor, sensory, and cognitive symptoms despite the absence of gross structural pathology. A key question is whether symptoms reflect disruptions in the intrinsic organization of brain networks. Electroencephalography (EEG) offers a high temporal resolution view of ongoing dynamics, making it a powerful means to probe such mechanisms.</div></div><div><h3>Methods</h3><div>We applied a seven-class microstate decomposition to resting-state EEG from 39 patients with FND and 47 matched healthy controls to characterize the temporal dynamics of brain activity. Microstate were labelled A-G according to established topographies. Symptom severity was assessed with the Simplified-Functional Movement Disorder Rating Scale, and correlations were tested. Logistic regression was used to assess group discrimination, with accuracy quantified by the area under the curve.</div></div><div><h3>Results</h3><div>Compared to controls, patients with FND exhibit significantly reduced duration of microstate G, associated with sensorimotor integration. This alteration correlated negatively with symptom severity scores and moderately discriminated groups. Transition probabilities analyses uncovered distinct patterns among microstates A, B and C, suggesting both an exaggerated shift from arousal-related to visual imagery networks and resistance to engage in self-referential processing.</div></div><div><h3>Conclusions</h3><div>Our findings provide the first direct evidence of disrupted resting-state microstate organization across a heterogeneous FND cohort.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103969"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311924","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 : 2026-01-01Epub Date: 2026-02-18DOI: 10.1016/j.nicl.2026.103973
Skyler Deutsch , Juhi Mehta , Lee B. Reid , Andrea Fuentes , Sarah Wang , John Kornak , Philip A. Starr , Jill L. Ostrem , Doris D. Wang , Ian O. Bledsoe , Melanie A. Morrison
Background
Patients implanted with modern deep brain stimulation (DBS) hardware can now undergo functional magnetic resonance imaging (fMRI), leading to its increased used to study DBS’ mechanisms and predict optimal therapy settings. To accurately interpret fMRI data and realize its clinical potential for DBS, a better understanding of reliability is needed.
Methods
Sixteen patients with Parkinson’s disease (PD) and DBS targeting the subthalamic nucleus or pallidum underwent 3T test–retest resting-state fMRI with and without concurrent stimulation. Effects of stimulation and device-metal artifacts on reliability of fMRI brain connectivity and moment-to-moment brain variability were explored, plus factors influencing between-subject variations in reliability such as motion.
Results
The brain variability fMRI metric yielded higher intra-class correlation coefficients than the connectivity metric (range across whole brain, motor, limbic, and cognitive networks: 0.36–0.85 and 0.68–0.99, respectively). Average network connectivity appeared less reproducible when DBS was ON versus OFF during fMRI, and fMRI metric reliability for brain areas affected by metal artifacts was significantly higher (brain variability) or lower (connectivity) than unaffected areas (puncorrected < 0.05). Motion and DBS target best explained between-subject variations.
Conclusion
DBS hardware and active stimulation may alter fMRI reliability. To develop clinically useful fMRI biomarkers for DBS and aid assessments of reproducibility across studies, the reliability of single study results need reporting.
{"title":"Test-retest reliability of resting-state functional magnetic resonance imaging during deep brain stimulation for Parkinson’s disease","authors":"Skyler Deutsch , Juhi Mehta , Lee B. Reid , Andrea Fuentes , Sarah Wang , John Kornak , Philip A. Starr , Jill L. Ostrem , Doris D. Wang , Ian O. Bledsoe , Melanie A. Morrison","doi":"10.1016/j.nicl.2026.103973","DOIUrl":"10.1016/j.nicl.2026.103973","url":null,"abstract":"<div><h3>Background</h3><div>Patients implanted with modern deep brain stimulation (DBS) hardware can now undergo functional magnetic resonance imaging (fMRI), leading to its increased used to study DBS’ mechanisms and predict optimal therapy settings. To accurately interpret fMRI data and realize its clinical potential for DBS, a better understanding of reliability is needed.</div></div><div><h3>Methods</h3><div>Sixteen patients with Parkinson’s disease (PD) and DBS targeting the subthalamic nucleus or pallidum underwent 3T test–retest resting-state fMRI with and without concurrent stimulation. Effects of stimulation and device-metal artifacts on reliability of fMRI brain connectivity and moment-to-moment brain variability were explored, plus factors influencing between-subject variations in reliability such as motion.</div></div><div><h3>Results</h3><div>The brain variability fMRI metric yielded higher intra-class correlation coefficients than the connectivity metric (range across whole brain, motor, limbic, and cognitive networks: 0.36–0.85 and 0.68–0.99, respectively). Average network connectivity appeared less reproducible when DBS was ON versus OFF during fMRI, and fMRI metric reliability for brain areas affected by metal artifacts was significantly higher (brain variability) or lower (connectivity) than unaffected areas (p<sub>uncorrected</sub> < 0.05). Motion and DBS target best explained between-subject variations.</div></div><div><h3>Conclusion</h3><div>DBS hardware and active stimulation may alter fMRI reliability<strong>.</strong> To develop clinically useful fMRI biomarkers for DBS and aid assessments of reproducibility across studies, the reliability of single study results need reporting.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103973"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147312021","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":"2026-01-01","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 : 2026-01-01Epub 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":"2026-01-01","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}
Pub Date : 2026-01-01Epub Date: 2025-12-24DOI: 10.1016/j.nicl.2025.103929
Timothy Piton , Una Smailovic , Vesna Jelic , Thomas Koenig , Paul G. Unschuld , Lucie Bréchet
Aim
EEG microstate analysis enables the exploration of the brain’s neuronal network activity associated with distinct mental states and cognitive functions in neurodegenerative conditions, such as Alzheimer’s disease (AD). Some studies indicated that AD and patients with mild cognitive impairments (MCI) show a reduced presence of microstate C, which is related to self-related memory functions and mind-wandering and involves brain areas of the default mode network (DMN). However, other studies reported an increased presence of microstate A, which is associated with auditory/language functions. Here, we aimed to systematically investigate alterations in the four canonical EEG microstates (A, B, C, and D) in MCI and AD patients compared to healthy older adults.
Methods
We performed a meta-analysis that compared microstate temporal parameters − mean duration, occurrence rate, and time coverage − among MCI and AD patients and healthy older adults. We included 12 experimental studies that examined resting-state, eyes-closed EEG microstate parameters in 1347 participants (448 MCI patients, 514 AD patients, and 385 healthy controls).
Results
We found that AD patients showed increased duration and time coverage of microstate A and increased duration of microstate B, while the occurrence of microstates C and D was reduced. MCI patients also exhibited increased duration, occurrence, and time coverage of microstate A, while all three parameters of microstate D were reduced compared to healthy controls.
Conclusion
These results suggest that MCI and AD patients suffer from disruption in their cognitive control, memory, and self-referential processes. They may compensate for these deficits by verbalizing and visualizing their inner thoughts to maintain cognitive engagement.
{"title":"Cognitive adaptations for memory deficits in MCI and AD patients: A meta-analysis of EEG microstates","authors":"Timothy Piton , Una Smailovic , Vesna Jelic , Thomas Koenig , Paul G. Unschuld , Lucie Bréchet","doi":"10.1016/j.nicl.2025.103929","DOIUrl":"10.1016/j.nicl.2025.103929","url":null,"abstract":"<div><h3>Aim</h3><div>EEG microstate analysis enables the exploration of the brain’s neuronal network activity associated with distinct mental states and cognitive functions in neurodegenerative conditions, such as Alzheimer’s disease (AD). Some studies indicated that AD and patients with mild cognitive impairments (MCI) show a reduced presence of microstate C, which is related to self-related memory functions and mind-wandering and involves brain areas of the default mode network (DMN). However, other studies reported an increased presence of microstate A, which is associated with auditory/language functions. Here, we aimed to systematically investigate alterations in the four canonical EEG microstates (A, B, C, and D) in MCI and AD patients compared to healthy older adults.</div></div><div><h3>Methods</h3><div>We performed a meta-analysis that compared microstate temporal parameters − mean duration, occurrence rate, and time coverage − among MCI and AD patients and healthy older adults. We included 12 experimental studies that examined resting-state, eyes-closed EEG microstate parameters in 1347 participants (448 MCI patients, 514 AD patients, and 385 healthy controls).</div></div><div><h3>Results</h3><div>We found that<!--> <!-->AD patients showed increased duration and time coverage of microstate A and increased duration of microstate B, while the occurrence of microstates C and D was reduced. MCI patients also exhibited increased duration, occurrence, and time coverage of microstate A, while all three parameters of microstate D were reduced compared to healthy controls.</div></div><div><h3>Conclusion</h3><div>These results suggest that MCI and AD patients suffer from disruption in their cognitive control, memory, and self-referential processes. They may compensate for these deficits by verbalizing and visualizing their inner thoughts to maintain cognitive engagement.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103929"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913932","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 : 2026-01-01Epub Date: 2026-02-09DOI: 10.1016/j.nicl.2026.103959
Ava J. White , Jennifer L. Robinson , Alan E. Wilson , Meredith A. Reid
Major Depressive Disorder (MDD) diagnoses have drastically increased in the United States from 6.5% to 21–30% since 2019, burdening individuals and society alike. Despite considerable efforts to understand the pathogenesis of MDD, the heterogeneity of the disorder has made it difficult to delineate its underpinnings, highlighting the need for biomarker identification. This study assessed the concentrations of key neurometabolites in the anterior cingulate cortex (ACC) in people with MDD (average n = 496) compared to healthy controls (average n = 404). We conducted a systematic review that ultimately led to the inclusion of n = 43 proton magnetic resonance spectroscopy (1H-MRS) studies for meta-analysis. Average concentrations of eight neurometabolites were compared using a random effects model. We found that subjects with MDD had significantly decreased N-acetylaspartate (NAA; Hedges’ g = -0.16, 95% CI −0.299 to −0.030, p = 0.017), and gamma-aminobutyric acid (GABA; Hedges’ g = -0.26, 95% CI −0.434 to −0.082, p = 0.004), and increased levels of glutamine (Gln; Hedges’ g = 0.21, 95% CI 0.105 to 0.311, p < 0.001) in the ACC. Subgroup analyses suggested significantly increased NAA detected by magnets stronger than 1.5 Tesla only, glutamate (Glu) in the dorsal ACC only and significantly increased myo-inositol (mI) and choline (Cho) in exclusively unmedicated subjects. This study provides a summative picture of the neurometabolic profile of the ACC in people with MDD and provides a foundation for the development of biomarker-based diagnostic criteria and novel pharmacological treatments.
自2019年以来，美国的重度抑郁症（MDD）诊出率从6.5%急剧增加到21-30%，给个人和社会都带来了负担。尽管在理解重度抑郁症的发病机制方面做了大量的努力，但这种疾病的异质性使得很难描述其基础，这突出了对生物标志物鉴定的需求。本研究评估了重度抑郁症患者（平均n = 496）与健康对照组（平均n = 404）前扣带皮层（ACC）中关键神经代谢物的浓度。我们进行了一项系统综述，最终纳入了n = 43项质子磁共振波谱（1H-MRS）研究进行meta分析。采用随机效应模型比较8种神经代谢物的平均浓度。我们发现重度抑郁症患者的n -乙酰天冬氨酸（NAA; Hedges' g = -0.16, 95% CI -0.299至-0.030,p = 0.017）和γ -氨基丁酸（GABA; Hedges' g = -0.26, 95% CI -0.434至-0.082,p = 0.004）水平显著降低，谷氨酰胺（Gln; Hedges' g = 0.21, 95% CI 0.105至0.311,p = 0.017）水平显著升高
{"title":"Neurometabolics of the anterior cingulate cortex (ACC) in major depressive disorder (MDD): A systematic review and meta-analysis","authors":"Ava J. White , Jennifer L. Robinson , Alan E. Wilson , Meredith A. Reid","doi":"10.1016/j.nicl.2026.103959","DOIUrl":"10.1016/j.nicl.2026.103959","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) diagnoses have drastically increased in the United States from 6.5% to 21–30% since 2019, burdening individuals and society alike. Despite considerable efforts to understand the pathogenesis of MDD, the heterogeneity of the disorder has made it difficult to delineate its underpinnings, highlighting the need for biomarker identification. This study assessed the concentrations of key neurometabolites in the anterior cingulate cortex (ACC) in people with MDD (average n = 496) compared to healthy controls (average n = 404). We conducted a systematic review that ultimately led to the inclusion of n = 43 proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) studies for <em>meta</em>-analysis. Average concentrations of eight neurometabolites were compared using a random effects model. We found that subjects with MDD had significantly decreased N-acetylaspartate (NAA; Hedges’ <em>g</em> = -0.16, 95% CI −0.299 to −0.030, p = 0.017), and gamma-aminobutyric acid (GABA; Hedges’ <em>g</em> = -0.26, 95% CI −0.434 to −0.082, p = 0.004), and increased levels of glutamine (Gln; Hedges’ <em>g</em> = 0.21, 95% CI 0.105 to 0.311, p < 0.001) in the ACC. Subgroup analyses suggested significantly increased NAA detected by magnets stronger than 1.5 Tesla only, glutamate (Glu) in the dorsal ACC only and significantly increased myo-inositol (mI) and choline (Cho) in exclusively unmedicated subjects. This study provides a summative picture of the neurometabolic profile of the ACC in people with MDD and provides a foundation for the development of biomarker-based diagnostic criteria and novel pharmacological treatments.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103959"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183422","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 : 2026-01-01Epub Date: 2026-02-16DOI: 10.1016/j.nicl.2026.103971
Lars A. Ross , Sophie Molholm , John J. Foxe
Individuals on the Autism Spectrum do not benefit as much from visual articulatory cues when compared to neurotypicals, especially under noisy environmental conditions. We hypothesized that this deficit would vary with the severity of Autism related symptoms and assessed this relationship in a behavioral speech-in-noise task (n = 32) and a functional neuroimaging study (n = 37). We found that Calibrated Symptom Severity Scores (CSS) were associated with poorer audiovisual performance but not performance in the auditory-alone condition indicating that impairments are limited to multisensory (MS) information processing. These findings underscore the validity of MS deficits and their potential relevance to the broader symptomatology in Autism. We also found that CSS significantly correlated with hemodynamic responses to audiovisual stimulation. Here, higher symptom severity was associated with lower multisensory gain in dorsal speech and language regions. Subsequent exploratory analysis suggested that individuals with Autism may not engage speech motor regions in similar ways to typically developing (TD) individuals.
{"title":"Associations between symptom severity in autism and functional neuroimaging measures of audiovisual speech perception","authors":"Lars A. Ross , Sophie Molholm , John J. Foxe","doi":"10.1016/j.nicl.2026.103971","DOIUrl":"10.1016/j.nicl.2026.103971","url":null,"abstract":"<div><div>Individuals on the Autism Spectrum do not benefit as much from visual articulatory cues when compared to neurotypicals, especially under noisy environmental conditions. We hypothesized that this deficit would vary with the severity of Autism related symptoms and assessed this relationship in a behavioral speech-in-noise task (n = 32) and a functional neuroimaging study (n = 37). We found that Calibrated Symptom Severity Scores (CSS) were associated with poorer audiovisual performance but not performance in the auditory-alone condition indicating that impairments are limited to multisensory (MS) information processing. These findings underscore the validity of MS deficits and their potential relevance to the broader symptomatology in Autism. We also found that CSS significantly correlated with hemodynamic responses to audiovisual stimulation. Here, higher symptom severity was associated with lower multisensory gain in dorsal speech and language regions. Subsequent exploratory analysis suggested that individuals with Autism may not engage speech motor regions in similar ways to typically developing (TD) individuals.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103971"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776663","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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