Neuroimage. Reports最新文献

{"title":"Cerebral plasticity after hypoglosso-facial anastomosis in facial palsy: a magnetoencephalography study","authors":"Rémi Hervochon ,&nbsp;Deborah Ziri ,&nbsp;Guillaume Dupuch ,&nbsp;Maximilien Chaumon ,&nbsp;Claire Foirest ,&nbsp;Denis Schwartz ,&nbsp;Christophe Gitton ,&nbsp;Nathalie George ,&nbsp;Frédéric Tankere","doi":"10.1016/j.ynirp.2025.100294","DOIUrl":"10.1016/j.ynirp.2025.100294","url":null,"abstract":"<div><h3>Background</h3><div>Hypoglosso-facial anastomosis (HFA) consists in suturing the proximal part of the hypoglossal nerve with the distal part of the facial nerve in patients with facial palsy. Axonal regrowth through the anastomosis makes it possible to restore facial motor skills, which become spontaneous after physiotherapy. This suggests cerebral plasticity.</div></div><div><h3>Objective</h3><div>We used magnetoencephalography (MEG) in a pilot study to test this hypothesis.</div></div><div><h3>Methods</h3><div>Twenty-one healthy volunteers (CTRL) and 12 patients after HFA performed 5 motor tasks with MEG and electromyographic recordings: eyelid closure, smile, tongue protraction, mastication and thumb flexion. For each task, we picked the location of the maximum source activity within the precentral gyrus. We calculated the distances between this location and the vertex for each task and a somatotopy index.</div></div><div><h3>Results</h3><div>There was an interaction between the participant’s group and the task (F(4,124) = 4.07, p = 0.0039). In CTRL, the maximum source location was statistically different between smile and tongue tasks and between eyelid and tongue tasks (p &lt; 0.001). No such difference was observed in HFA (p = 1.000). 90.5 % of CTRL and 41.7 % of HFA showed a normal somatotopy (p = 0.0046).</div></div><div><h3>Conclusions</h3><div>In CTRL, the organization of the cortical motor areas was similar to that of Penfield’s motor Homunculus. In contrast, in HFA, eyelid closure, tongue protraction and smile areas were not significantly distinct. This supports the hypothesis of cerebral plasticity after HFA.</div><div>The Ethical Committee of Paris Idf VI approved the study (CPP Ouest 6-CPP975-HPS2).</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 4","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcortical resting state functional connectivity as a neural marker of first onset internalizing disorder in high-risk youth","authors":"McKinley Pawlak ,&nbsp;Signe Bray ,&nbsp;Ford Burles ,&nbsp;Daniel C. Kopala-Sibley","doi":"10.1016/j.ynirp.2025.100291","DOIUrl":"10.1016/j.ynirp.2025.100291","url":null,"abstract":"<div><h3>Background</h3><div>Research has linked individual differences in resting state functional connectivity (RSFC) of subcortical brain regions to internalizing disorders, but little research has examined if these changes are pre-morbid risk factors. This study examined individual differences in subcortical RSFC as risk factors for the first lifetime onset of an internalizing disorder in youth at familial risk.</div></div><div><h3>Methods</h3><div>Participants (n = 93) were adolescents with a parental history of internalizing disorders, but with no such history themselves. Youth completed resting state fMRI scans, as well as the MINI-Kid and the Youth Self Report internalizing symptoms scale at baseline. The MINI-Kid was completed again at 9 or 18-month follow-up to assess onset of internalizing disorders. Seed-to-whole brain analyses consisted of a multiple regression models controlling for sex, age, in scanner motion, and baseline symptoms.</div></div><div><h3>Results</h3><div>First onsets at follow-up were associated with increased baseline RSFC between the left caudate and the bilateral SMA (pFDR = .002), and between the right nucleus accumbens and the right superior parietal lobule (pFDR = .0003).</div></div><div><h3>Conclusion</h3><div>Altered RSFC of subcortical regions may represent a pre-morbid risk factor for developing a first onset of an internalizing disorder. Results may have implications for understanding the neural bases of internalizing disorders and for early identification and prevention efforts.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 4","pages":"Article 100291"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Test-retest reliability of template-defined vs. manual tracing processing streams in neuromelanin-sensitive magnetic resonance imaging analysis","authors":"Tyler A. Lesh ,&nbsp;Jason Smucny ,&nbsp;Joshua P. Rhilinger ,&nbsp;Sarvenaz Pakzad ,&nbsp;Guillermo Horga ,&nbsp;Cameron S. Carter","doi":"10.1016/j.ynirp.2025.100290","DOIUrl":"10.1016/j.ynirp.2025.100290","url":null,"abstract":"<div><div>Neuromelanin (NM) magnetic resonance imaging (MRI) is a relatively new, noninvasive method used as a proxy measure of midbrain dopamine function. Previous studies in schizophrenia have found evidence of enhanced signal in patients that are associated with positive psychotic symptoms. However, there are limited data available comparing methods of computing signal in substantia nigra (SN). We sought to examine the reliability and validity of manual tracing vs template-defined methods to help guide the field in identifying optimal approaches in NM imaging. NM-MRI was performed on 22 participants (18 with early psychosis (EP) and 4 healthy controls (HCs)) scanned twice over a 1–14 week period. Mean SN NM signal was calculated using template-defined and manual tracing methods to define SN ROIs. Intraclass correlation coefficients (ICCs) based on absolute agreement were calculated between test and retest. Correlations between NM signal for each method and symptoms in EP were also examined. ICCs for the template-defined were in the excellent range (.81–.85) and manual tracing methods were in the poor to fair range (−.14 to .56). The template-defined method showed a trend positive relationship with reality distortion symptoms (r = .45, <em>p</em> = .06) and the manual tracing method showed a significant positive relationship (r = .47, <em>p</em> = .05). Supplemental analyses highlighted the importance of thresholding and using the mode to compute CNR for identifying these relationships to symptomatology. While both methods showed clinical validity, the excellent reliability of the template-defined method suggests this technique is the preferred strategy for NM-MRI analysis.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 4","pages":"Article 100290"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered white matter connection from the locus coeruleus to the thalamus in Parkinson's disease","authors":"M.G. Wanders ,&nbsp;J.F.A. Jansen ,&nbsp;A.F. Wolters ,&nbsp;M. Heijmans ,&nbsp;Y. Temel ,&nbsp;M.L. Kuijf ,&nbsp;S.M.A. Michielse","doi":"10.1016/j.ynirp.2025.100292","DOIUrl":"10.1016/j.ynirp.2025.100292","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is the fastest growing neurodegenerative movement disorder. It is characterized by both motor and non-motor, including neuropsychiatric disturbances such as depression and anxiety. The locus coeruleus (LC), a small nucleus in the brainstem, plays a key role in these symptoms and has white matter connections to the thalamus. This study aims to investigate this LC-thalamic tract in PD patients using ultra-high-field diffusion-weighted imaging (DWI) and to examine its relationship with non-motor symptoms.</div></div><div><h3>Methods</h3><div>100 participants, including 69 early-stage PD and 31 healthy control (HC) participants were evaluated using several questionnaires and a 7T diffusion MRI scan. Tractography was performed to reconstruct the LC-thalamic white matter tract, and diffusion parameters (FA, MD, AD, RD) were analysed.</div></div><div><h3>Results</h3><div>PD patients showed significantly higher mean diffusivity (MD) and axial diffusivity (AD) in the white matter tissue compared to HC, indicating reduced white matter integrity.</div></div><div><h3>Discussion</h3><div>This study shows the feasibility to visualize the LC-thalamic tract with the use of 7T DWI data. The results provide evidence of the association between the integrity of the white matter tracts and early PD development, highlighting its potential as a target for therapeutic interventions. Further research is needed to elucidate the role of the LC and its white matter connections in the progression of PD and neuropsychiatric and other symptoms.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 4","pages":"Article 100292"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A transdiagnostic, multi-modal approach to understanding apathy: Methodological and analytical framework","authors":"Yunglin Gazes ,&nbsp;Hideo Suzuki ,&nbsp;Lee-Anne Morris ,&nbsp;Seonjoo Lee ,&nbsp;Zekai Jin ,&nbsp;Edward D. Huey ,&nbsp;Bryan B. Chen ,&nbsp;Campbell Le Heron ,&nbsp;Sarah R. Heibronner ,&nbsp;Nora Vanegas-Arroyave","doi":"10.1016/j.ynirp.2025.100289","DOIUrl":"10.1016/j.ynirp.2025.100289","url":null,"abstract":"<div><div>Apathy is characterized by loss of motivation and manifests as a reduction of goal-directed behavior. Apathy is highly prevalent across neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD), and is an important contributor to the disability and reduce quality of life in these conditions. The treatment of apathy remains challenging due to a lack of specific therapies, largely attributed to an incomplete understanding of its cognitive and neuroanatomical underpinnings, crucial for developing targeted interventions. Apathy can be mechanistically studied through effort-based decision-making (EBDM) paradigms, where individuals choose between low- and high-effort tasks for varying reward magnitudes. Anatomically, apathy has been associated with alterations in brain regions previously implicated in EBDM. Using a novel transdiagnostic study design in individuals with AD and PD, we aim to: (1) evaluate the independent effects of reward and effort sensitivity as a mechanistic link between apathy and neurodegeneration of basal ganglia-frontal networks and, (2) in a subset of PD patients receiving deep brain stimulation (DBS) surgery, determine whether electrical manipulation of subthalamic nucleus and/or DBS connectivity, directly alter reward and effort information processing and, consequently, goal-directed behavior. Understanding how neurodegeneration—alone or in combination with neuromodulatory interventions—drives apathy, is essential for guiding clinical decision-making and therapeutic development. Given its prevalence across neurodegenerative disorders, apathy provides a unique framework for investigating shared and disease-specific neuroanatomical, functional, and behavioral mechanisms. In this protocol paper, we describe the rationale and methodology of our proposed multimodal approach, to investigate apathy in a transdiagnostic cohort of individuals with AD and PD.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 4","pages":"Article 100289"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building blocks of functional connectivity measures for aperiodic electrophysiological brain signals","authors":"Rikkert Hindriks ,&nbsp;Thomas O. Rot ,&nbsp;Michel J.A.M. van Putten ,&nbsp;Prejaas Tewarie","doi":"10.1016/j.ynirp.2025.100284","DOIUrl":"10.1016/j.ynirp.2025.100284","url":null,"abstract":"<div><div>A challenge in interpreting functional connectivity results in electroencephalography (EEG) data is volume conduction. A common way to mitigate spurious connectivity due to volume conduction is to use connectivity measures that are insensitive to volume conduction. Examples of such measures are the imaginary coherence, the lagged coherence, and the (weighted) phase-lag index. Their insensitivity to volume conduction stems from an invariant property and it is of both practical and theoretical interest to identify all measures with this property. In this study we derive a set of invariant connectivity measures that are fundamental in the sense that all others can be constructed from them by combination. These ”building blocks” of connectivity measures quantify the lack of invariance of multivariate EEG signals under permutation of the time-points. We use this result to construct a new connectivity measure for stationary aperiodic EEG signals, referred to as the <em>temporal irreversibility index</em> (TII) and illustrate its use by applying it to local field potentials recorded from primary visual cortex of a macaque monkey and to EEG data from comatose survivors of cardiac arrest. As far as we are aware, the TII is currently the only functional connectivity measure for aperiodic signals that is insensitive to volume conduction.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 4","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse and distributed haemodynamic effects of theta burst stimulation in the prefrontal cortex","authors":"Amy Miller,&nbsp;Melanie Burke","doi":"10.1016/j.ynirp.2025.100282","DOIUrl":"10.1016/j.ynirp.2025.100282","url":null,"abstract":"<div><h3>Background</h3><div>Theta Burst Stimulation (TBS) is a form of non-invasive brain stimulation that can induce neuroplastic changes in the underlying intracortical areas. It has significant potential in clinical and research settings for modulating cognitive and motor performance. Little is known about how TBS affects oxygenations levels within and across brain hemispheres during stimulation of the Dorsolateral Prefrontal Cortex (DLPFC). This study aimed to investigate blood oxygenation levels in the DLPFC during TBS, using concurrent functional Near-Infrared Spectroscopy (fNIRS).</div></div><div><h3>Methods</h3><div>44 young adults completed within-subjects 2 × 2 design with 4 conditions that included intermittent TBS (iTBS), and continuous TBS (cTBS) stimulation applied to the left and right DLPFC. FNIRS was recorded concurrently, with 12 optode channels spanning across the left, medial and right prefrontal cortex.</div></div><div><h3>Results</h3><div>Findings focused on corrected significant effects that revealed clear neurovascular coupling during stimulation. Right hemisphere iTBS stimulation on the DLPFC resulted in excitation within and between hemispheres as expected, however left hemisphere stimulation decreased oxygenation levels both ipsilaterally and contralaterally. CTBS on the right and left hemisphere revealed reductions in HbO as expected in support of previous literature and potential LTD-like effects.</div></div><div><h3>Conclusion</h3><div>This is the first study to show the extent and dispersion of blood-oxygenation changes in the ipsilateral and contralateral hemispheres during excitatory and inhibitory TBS applied to the DLPFC. The findings demonstrate that TMS stimulation may originate from more global and interhemispheric effects, but that iTBS on the left-DLPFC induces decreases in oxygenated haemoglobin (HbO) providing the potential links for beneficial effects in cognition.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 3","pages":"Article 100282"},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADHD diagnostics and severity assessment using topological manifold learning of resting-state functional magnetic resonance imaging (rs-fMRI)","authors":"Yan Xue ,&nbsp;Yuxiang Zhou ,&nbsp;Xiaoxu Na ,&nbsp;Xiawei Ou ,&nbsp;Yongming Liu","doi":"10.1016/j.ynirp.2025.100283","DOIUrl":"10.1016/j.ynirp.2025.100283","url":null,"abstract":"<div><div>Non-intrusive neuroimaging technology offers fast and robust diagnostic tools for neuro-disorder disease diagnosis, such as Attention-Deficit/Hyperactivity Disorder (ADHD). Resting-state functional magnetic imaging (rs-fMRI) has been demonstrated to have great potential for such applications due to its unique capability and convenience in providing spatial-temporal brain imaging. One critical challenge of using rs-fMRI data is the high dimensionality for both spatial and temporal domains. Thus, direct use of rs-fMRI data for the diagnosis will usually perform poorly due to the “curse of dimensionality.” This paper proposes a novel nonlinear dimension reduction technique for rs-fMRI data for easy downstream analysis, such as diagnostics, regression, and visualization. The proposed method integrates the Curvature Augmented Manifold Embedding and Learning (CAMEL) algorithm with key rs-fMRI features, such as Amplitude of Low-Frequency Fluctuations (ALFF), Regional Homogeneity (ReHo), and Functional Connectivity (FC). The ADHD diagnosis problem is formulated as a classification problem in the reduced latent space and is validated with 551 data points from an open fMRI database. Compared to available literature models and results, 13 %–26 % improvement in diagnostic accuracy is observed. Additionally, the proposed methodology also supports individualized ADHA severity assessment by regression analysis in the latent space and provides a potential tool for personalized treatment. Finally, an ADHD sensitivity map is developed, highlighting brain regions associated with ADHD scores and providing interpretable insights into ADHD's neural underpinnings.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 3","pages":"Article 100283"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal short-chain fatty acid turnover is not associated with resting state functional connectivity in mesolimbic dopaminergic network in healthy adults","authors":"Madelief Wijdeveld ,&nbsp;Anouk Schrantee ,&nbsp;Júlia Tolra Azor ,&nbsp;Francesca van Baarzel ,&nbsp;Eelco van Duinkerken ,&nbsp;Max Nieuwdorp ,&nbsp;Richard G. Ijzerman","doi":"10.1016/j.ynirp.2025.100285","DOIUrl":"10.1016/j.ynirp.2025.100285","url":null,"abstract":"<div><div>People with obesity tend to have altered functional connectivity of reward-related areas in the brain, contributing to overeating and weight gain. The gut-brain axis may function as a mediating factor, with gut-derived short-chain fatty acids (SCFAs) as possible intermediates in the relationship between microbiota and functional connectivity. We investigated the influence of SCFA turnover on resting state functional connectivity in healthy individuals with extremely high and extremely low levels of intestinal SCFA turnover. In this study, we included individuals with low or high intestinal SCFA turnover (estimated by fecal concentration of the butyryl-coenzyme A (CoA)-transferase (ButCoA) gene). Resting state functional magnetic resonance imaging (rs-fMRI) was used to assess functional connectivity of eight regions of interest (ROIs) either directly involved in the mesolimbic dopaminergic network (amygdala, hippocampus, caudate nucleus, putamen and nucleus accumbens) or primary projection regions of this network (middle frontal gyrus, superior frontal gyrus, insula). Functional connectivity was assessed using connectivity strength and eigenvector centrality. No differences in connectivity strength or eigenvector centrality were observed between the high and the low ButCoA group in any of our ROIs, suggesting SCFA turnover is not associated with resting state functional connectivity of central reward-related areas. Although previous studies provide evidence for an association between gut microbiota and resting state functional connectivity of reward-related areas, our findings do not support the hypothesis that this relationship is mediated by SCFAs. This suggests the existence of alternative mechanisms via which the intestinal microbiota may affect appetite, beyond local SCFA production.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 3","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI signatures associated with active ischemia and disease severity in cerebral small vessel disease","authors":"Peter Kang ,&nbsp;Matthew R. Brier ,&nbsp;Chunwei Ying ,&nbsp;Andria L. Ford ,&nbsp;Hongyu An ,&nbsp;Jin-Moo Lee","doi":"10.1016/j.ynirp.2025.100281","DOIUrl":"10.1016/j.ynirp.2025.100281","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Cerebral small vessel disease, a leading cause of stroke and cognitive impairment, manifests on neuroimaging with white matter hyperintensities (WMH) and disrupted microstructure in normal-appearing white matter. WMH, by definition have high T2 FLAIR signal; however, both T2 FLAIR and T1 signal in WMH are highly variable. We hypothesized that signal intensity parameters would differ in cerebral small vessel disease compared to healthy controls and that signal heterogeneity would be associated with more severe ischemia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this case-control cross-sectional study, participants with cerebral small vessel disease (n = 27) and controls (n = 35) underwent T1-weighted and T2 FLAIR MRI for signal intensity quantification as well as pseudocontinuous arterial spin labeling and asymmetric spin echo to measure cerebral blood flow, and oxygen extraction fraction, respectively, and diffusion tensor imaging to assess white matter microstructure. Following signal intensity normalization, we quantified white matter T1 and T2 FLAIR mean and heterogeneity and correlated them to biomarkers of disease severity and physiology (cerebral blood flow and oxygen extraction fraction) in order to understand how signal variability relates to tissue hypoxia-ischemia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The cerebral small vessel disease group had increased T2 FLAIR intensity (&lt;em&gt;P&lt;/em&gt; = 0.006) and heterogeneity (&lt;em&gt;P&lt;/em&gt; = 0.017) in normal-appearing white matter compared to controls. Within those with WMH, normal-appearing white matter T2 FLAIR intensity (&lt;em&gt;P&lt;/em&gt; = 0.0016) and heterogeneity (&lt;em&gt;P&lt;/em&gt; = 0.00036) showed significant relationships with lesion burden. Focal voxel-wise analyses within individual WMH demonstrated that T1 and T2 FLAIR signal intensities were highly variable within lesions, with greater variability in larger lesions. Moreover, the combination of regionally high T2 FLAIR and low T1 intensities was associated with elevated oxygen extraction, suggesting active underlying ischemia. Cluster analysis of lesion signal properties revealed a cluster of lesions that had low T1 intensity, high T2 FLAIR intensity, elevated oxygen extraction and mean diffusivity, representing a specific group of lesions characterized by ischemic physiology.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;div&gt;In conclusion, we found evidence that T1 and T2 FLAIR signal is heterogeneous in cerebral small vessel disease and is associated with disease severity. Within WMH, focal T1 hypointensity and variability, as well as T2 FLAIR hyperintensity and variability is associated with ischemia, but not infarction, particularly in larger lesions, suggesting that these patterns of MRI signal follow both disease severity and aberrant physiology. Finally, WMH clustered by structural properties align with specific physiologic patterns suggesting that imaging appearance may reveal underlying ischemic vulnerability. Although these ","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"5 3","pages":"Article 100281"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}