Brain Imaging and Behavior

Low statistical power remains a persistent concern in functional magnetic resonance imaging (fMRI) research, largely due to small sample sizes. Although prior work has documented gradual increases in sample size over time, it remains unclear whether structural factors in the publication process are associated with study design characteristics such as sample size. This review addresses this gap by analyzing a large sample of fMRI studies to assess how institutional prestige, journal impact factor, and journal review practices are associated with sample size. We analyzed articles published in 2021-2024 reporting new fMRI data collection in adult humans and including a measure of memory. We found studies with specialized populations, such as patient populations, had smaller sample sizes, as did studies with task-based designs compared to resting-state designs. We also found larger sample sizes were associated with journals with a double-blind review process. Institutional prestige was positively associated with sample size such that more highly ranked institutions tended to have larger samples, but there was no interaction between review type (single-vs. double-blind) and prestige, indicating this difference is not likely due to reviewer bias. Journal impact factor was not associated with sample size, however institutional prestige score predicted journal impact factor. These results suggest structural factors at the institutional level likely have a stronger influence on published study sample size than reviewer practices or biases.

Background: Persistent neurological and cognitive symptoms following SARS-CoV-2 infection point to long-term alterations in brain structure and function. The thalamus, orbitofrontal cortex, and limbic networks are particularly susceptible to inflammatory and neurovascular stressors. However, the relationship between cortical, white-matter, and thalamocortical alterations in post-COVID syndrome remains unclear. Methods: 76 COVID-19 recovered participants (CRPs) and 51 healthy controls (HCs) underwent multimodal MRI comprising T1-weighted structural, diffusion, and resting-state functional acquisitions. Grey-matter morphology was assessed using voxel-based morphometry (VBM), white-matter microstructure using tract-based spatial statistics (TBSS), and thalamocortical functional connectivity (TC-FC) using seed-based analyses from major thalamic nuclei. Results were evaluated both across the groups (HC vs. CRP) and after stratifying CRPs by hospitalisation status (HC vs. Non-hospitalized patients (NHPs) vs. Hospitalized patients (HPs)). Results: No group-level grey-matter differences were observed between HCs and CRPs; however, HPs showed localized volume loss in the orbitofrontal and frontal-pole cortices (pFWE < 0.05). TBSS revealed widespread microstructural abnormalities, including reduced fractional anisotropy and mean diffusivity across association and commissural tracts (pcorr < 0.05), with regional increases in mode of anisotropy indicating selective loss of crossing fibres (pcorr < 0.05). Resting-state analyses revealed increased TC-FC from the mediodorsal thalamic nucleus to anterior cingulate, parietal, and occipital cortices (pcorr < 0.05), while differences in pulvinar and ventrolateral nuclei were not significant (pcorr > 0.05). Conclusions: Our findings indicate that COVID-19 recovery is associated with enduring alterations in fronto-limbic and thalamo-cortical circuits, most prominently in individuals with severe infection. Convergent structural and functional changes involving the orbitofrontal cortex and mediodorsal thalamus suggest network-specific reorganisation that may underpin persistent cognitive and affective symptoms of post-COVID syndrome.

IntroductionCoronary artery disease (CAD) increases the risk of cerebrovascular events, yet early brain injury in this population remains poorly characterized. White matter hyperintensities (WMHs), a biomarker of cerebrovascular lesions, are prevalent in CAD and are linked to risk of stroke. Beyond total burden, spatial distribution of WMHs carries pathological significance and is critical for understanding CAD-related injury. While clinical outcomes including coronary revascularization procedure and myocardial infarction influence CAD prognosis, their impact on WMH burden remains unclear. MethodsThis study investigated regional WMH burden in CAD and its relationship with clinical characteristics. 82 adults over 50 years participated, including 44 individuals with CAD and 38 controls. WMHs were segmented from fluid attenuated inversion recovery and T1-weighted MRI and categorized as total, periventricular, deep, and superficial regions. History of myocardial infarction and coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI)), was obtained from medical files. ResultsIndividuals with CAD exhibited higher total, periventricular, and deep WMH volumes than controls. Participants who underwent CABG had higher superficial WMH volumes than those with PCI, suggesting greater disease severity influences WMH burden. ConclusionCAD is characterized by a distinct pattern of cerebrovascular vulnerability, with revascularization procedures influencing WMH burden

ObjectivesNeuropsychiatric symptoms (NPS) are prevalent in individuals of cognitive impairement (CI). However, the similarities and disparatenesses in whole-brain dynamics between individuals of CI and NPS are controversy. Electroencephalography (EEG) microstates reflect the whole-brain dynamics. This study aimed to investigate the differential EEG microstates parameters between CI and NPS and to construct related diagnostic model. Methods/designThis study was a cross-sectional study. Clinical and EEG data were collected, and an EEG microstate analysis were performed. The Least absolute shrinkage and selection operation (LASSO) regression model was used to identify significant differential EEG microstates parameters between CI and NPS and to construct a diagnostic model. The model performance was tested by the receiver operating characteristic curve (ROC). ResultsThis study enrolled 78 participants. A total of 36 EEG microstates parameters were identified and included in the differential analysis. In the LASSO regression model, 4 significant differential EEG microstates parameters were selected, including the duration of class C, TPAB, TPBA, and TPDC. The ROC results showed that the diagnostic model for distinguishing NPS patients from CI patients achieved an area under the curve (AUC) of 0.905(95% CI: 0.784-1.000), with a sensitivity of 100.0% and a specificity of 76.9%. ConclusionsThe diagnostic model based on EEG microstate parameters showed a good performance for differentiating NPS patients from CI patients.

BackgroundCognitive restructuring, the process of identifying and challenging negative thoughts, is a key technique for treating depressive and anxiety disorders. Although neuroimaging studies have characterised the brain systems supporting cognitive restructuring in healthy individuals, it remains unclear how these systems are altered in depression and anxiety, or whether each disorder is associated with distinct neural dysfunction. MethodsSeventy-three clinical participants with depressive or anxiety disorders and 70 healthy controls completed a cognitive restructuring paradigm during 7 Tesla functional magnetic resonance imaging (fMRI). The task required participants to either repeat a series of negative statements or challenge them using Socratic questioning. Group-level fMRI analyses examined the effects of depressive and anxiety symptom severity on brain activation, while dynamic causal modelling characterized the directional neural influences between implicated regions. ResultsDuring challenging compared to repeating statements, greater depressive symptoms were associated with reduced dorsolateral prefrontal cortex (dlPFC) activation. Conversely, greater anxiety symptoms were associated with greater dlPFC activation. Effective connectivity results revealed that depressive symptoms were associated with greater inhibition from the ventrolateral prefrontal cortex (vlPFC) to the ventromedial prefrontal cortex, whereas anxiety symptoms were associated with greater excitation from the dlPFC to amygdala and greater inhibition from the vlPFC to amygdala. ConclusionsWhile clinical participants modified negative beliefs as effectively as healthy controls, depressive and anxiety symptoms were associated with dissociable neural signatures during restructuring. This suggests that cognitive behavioral therapy may engage partially distinct mechanisms depending on symptom profile, a possibility that warrants longitudinal investigation of treatment response.

Neurobiological models of emotion have proposed the existence of multiple direct subcortical pathways in humans, often referred to as "low roads", linking the thalamus to the amygdala and implicated in affective function. Among these, pulvinar-amygdala structural connectivity has been associated with individual differences in anxiety and anxiety-related conditions. However, whether distinct thalamo-amygdala pathways across thalamic subnuclei differentially relate to anxiety remains unknown. Using diffusion MRI in 34 healthy participants, we reconstructed four candidate subcortical "low roads" bilaterally from the medial geniculate body (MGB), as well as the medial, inferior and lateral pulvinar to the basolateral amygdala (BLA). We then tested whether their structural connectivity strength was associated with individual differences in state and trait anxiety. Linear regression analyses revealed that fiber density in three left thalamo-amygdala pathways predicted state, but not trait, anxiety. Importantly, our results showed a functional dissociation across pathways. While fiber density in MGB-BLA and medial pulvinar-BLA pathways was negatively related to state anxiety, the inferior pulvinar-BLA tract showed the opposite association. These findings support differentiated contributions across thalamo-amygdala pathways in humans to state anxiety. The results highlight these subcortical pathways as potentially relevant neurobiological substrates for understanding anxiety and affective function. Key pointsO_LIFiber density of three left thalamo-amygdala pathways explained 24.1% of the variance in state anxiety across 34 healthy individuals C_LIO_LIFiber density in the left medial geniculate body and left medial pulvinar-amygdala pathways was negatively associated with state anxiety C_LIO_LIFiber density in the left inferior pulvinar-amygdala pathway was positively associated with state anxiety C_LI

Moderate-to-severe traumatic brain injury (msTBI) is recognized as a chronic and evolving neurological condition characterized by progressive structural brain changes and persistent cognitive impairment. While prior studies have demonstrated widespread atrophy following msTBI, less is known regarding the longitudinal trajectory of gray matter (GM) changes during recovery and post-rehabilitation. The current study used longitudinal voxel-based morphometry (VBM) to characterize GM volume changes over a period of 9 months, in individuals with msTBI relative to healthy controls (HC). Associations between regional GM volume and neuropsychological functioning were examined. Twenty-eight participants (14 msTBI, 14 HC) completed MRI and neuropsychological assessments across three timepoints spanning outpatient rehabilitation and follow-up. Longitudinal VBM analyses revealed significant group and time interactions within subcortical and limbic regions. Relative to HC, individuals with msTBI showed lower GM volume in these regions at baseline, with trajectories that converged toward HC values (right hippocampus) or increased relative to HC over the rehabilitation period (bilateral pulvinar), whereas the right amygdala and inferior cerebellar vermis remained persistently reduced. Significant longitudinal improvements in memory and psychomotor speed during the rehabilitation period were demonstrated in msTBI. Greater (preserved) GM volume within the right hippocampus, thalamus, and bilateral pulvinar was associated with better performance across measures of verbal memory, processing speed, executive functioning, and cognitive flexibility. These findings suggest that msTBI is associated with dynamic structural brain changes involving subcortical, limbic, and cerebellar networks, and that the rehabilitation period was accompanied by relative volumetric stabilization in these regions and by meaningful cognitive improvement.

A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual. Then, we employed systematic and local artificial perturbations across intensities, re-optimised each model to create a response GEC (GECr), and assessed the extent of brain reorganisation by quantifying the brain network reconfiguration index (NRI). Our results showed that the global brain NRI increases with psilocybin and decreases with escitalopram. Across sessions and interventions, higher global NRI was related with localised perturbations in brain areas orchestrating the brain's hierarchical dynamics. Traditional approaches complemented our investigation. Our findings suggest distinct neural changes following each treatment for MDD. The increase in brain reorganisation under perturbation following psilocybin is consistent with greater brain flexibility and changeability, whereas the decrease following escitalopram suggests more stabilised brain dynamics. Overall, perturbation-induced brain NRI may represent a useful approach for uncovering neural changes following different interventions for depression.

Background Chemotherapy-related cognitive impairment is a well-documented concern among cancer survivors, yet the neural mechanisms underlying deficits in cognitive control remain poorly understood. This study examined group differences in brain activation during a flanker task using functional MRI (fMRI) between chemotherapy-exposed participants and healthy controls. Methods Participants (21 survivors (24.9 years old; 71.4 % female; 15 years from diagnosis) and 21 healthy controls (26.7 years old; 61.9 % female) completed a flanker task during fMRI, with congruent and incongruent conditions. Reaction time, accuracy, and Flanker scores were collected. Whole-brain group comparisons were performed for congruent, incongruent, and incongruent > congruent contrasts. Associations between the incongruent > congruent contrast and cognitive performance were examined. Results Compared to controls, the Chemo group had longer reaction times in both congruent and incongruent conditions (p < .001) and lower NIH Flanker scores (p = .01), with no differences in accuracy. They showed reduced activation in the bilateral inferior frontal gyri, supplementary motor area, and bilateral caudate, but greater activation in the right inferior temporal and cerebellar regions. The incongruent > congruent contrast correlated with increased activation in the orbitofrontal cortex, inferior temporal gyri, and fusiform gyrus with cognitive performance. Conclusions Chemotherapy-exposed participants showed cognitive control deficits and altered neural activation during a flanker task, indicating disrupted recruitment of frontoparietal and subcortical regions key for conflict processing. These findings improve understanding of neural causes of chemotherapy-related cognitive impairment and may help identify at-risk survivors and guide personalized rehabilitation.

Functional magnetic resonance imaging (fMRI) is widely used to map brain systems that process affective stimuli and predict concurrent affective experiences in the scanner. However, the extent to which affect-related fMRI activity in the scanner predicts affective experiences in daily life remains unclear. This study examined whether a multivariate brain pattern previously validated to predict negative affect to emotional images during fMRI testing (the Picture-Induced Negative Emotion Signature; PINES) associates with daily negative affect measured over 7-10 days via daily diaries and ecological momentary assessment. Among 287 midlife adults, those exhibiting greater PINES pattern expression showed greater daily (end-of-day) and hourly negative affect. These findings were not explained by demographic factors and trait negative affect. A cross-validated whole-brain pattern of negative affect generalizes beyond the fMRI testing context to predict negative affect severity in daily life.

BackgroundInduced pluripotent stem cell (iPSC)-derived brain cells are widely utilized as in vitro models for several neuropsychiatric disorders, as they retain the donors genetic profile, offering a unique opportunity to study living human brain cells and perform controlled experimental manipulations. In this study, we conducted whole transcriptome sequencing of cortical networks (co-cultures of neurons and astrocytes) derived from 12 participants with bipolar disorder (BD) and 12 participants without a history of mental health disorders. We aimed to identify new molecular mechanisms underlying the pathophysiology of bipolar disorder. MethodsiPSCs were generated by reprogramming peripheral blood mononuclear cells using episomal vectors. They were then differentiated into neural progenitor cells and matured into cortical networks that express markers of neurons and astrocytes. Whole transcriptome data were obtained using the Illumina NovaSeq X sequencing platform. ResultsDifferential expression analysis was performed using DESeq2 in R, and the identified genes were used for gene set enrichment analysis, which identified 191 enriched pathways in BD. Of these, the toll-like signalling pathway, which is downregulated in BD, was further investigated. ConclusionOur results suggest a profound immune dysregulation in BD, particularly highlighting the immune systems role as a complex signalling network.

Prior studies in bilinguals have reported relationships between brain structure and the dimensions of (i) language proficiency or (ii) language balance (the discrepancy between a bilinguals two proficiencies), but rarely both, even though they are highly related. These studies were often conducted in late bilinguals and the analyses limited to regions of interest. Here, we tested for relationships between brain structure and these two dimensions in 46 early cultural Spanish-English bilinguals (mean age = 16.7 years) at the level of the whole brain for gray matter volume (GMV) and cortical thickness (CT). Results revealed a positive association between GMV and proficiency in the weaker language in the right angular gyrus (AG; BA 39) extending into the superior temporal gyrus (BA 22). More balanced bilingualism was also associated with more GMV in the AG (BA 39), in addition to less GMV in left postcentral gyrus (BA 1), right cerebellum lobule IX and right superior occipital gyrus (BA 18). However, these relationships between GMV and balance disappeared after controlling for language proficiency. No significant associations were observed for CT and these two dimensions of language. Our findings suggest that relationships between GMV and balance are driven by language proficiency, and that the relationship between GMV and language proficiency likely does not involve language-specific mechanisms, given the location of the association is in the right inferior parietal cortex. Together, this study separates the neuroanatomical bases of these two language dimensions and places them in brain regions outside those usually targeted in prior studies. HighlightsO_LINeuroanatomy was correlated with proficiencies in early Spanish-English bilinguals C_LIO_LIRight angular gyrus gray matter volume (GMV) was positively related to proficiency C_LIO_LIGMV was positively related to balance, but not after controlling for proficiency C_LIO_LIRelations with these language dimensions are located outside of language cortex C_LIO_LINo significant associations were observed for cortical thickness C_LI

IntroductionThe thalamic nuclei play a crucial role in regulating information flow to the cortex and supports diverse cognitive functions. Although previous studies have linked thalamic structural and functional characteristics to cognition, these measures do not fully capture the thalamuss role in dynamic control, which is essential for complex cognitive processes. Moreover, it remains unclear how these different metrics relate to each other in the way they account for cognition. MethodsT1-weighted MRI, diffusion MRI, resting-state fMRI, and neuropsychological data were obtained from 419 unrelated participants in the Human Connectome Project. We measured grey matter volume, white matter integrity, and functional controllability of each thalamic nucleus to examine their associations with cognitive performance across domains identified through clustering analysis of the neuropsychological data. We also assessed the relationships among these structural and functional metrics and evaluated their individual and combined contributions in capturing covariance with performance in various cognitive domains. ResultsSignificant correlations were observed between thalamic grey matter volume and white matter integrity; however, thalamic functional controllability showed no significant association with either structural metric. White matter integrity demonstrated the strongest association with sequence working memory and language processing. In contrast, thalamic controllability metrics accounted more for performance in executive function, reasoning and encoding, visuospatial processing, and impulse control, outperforming the combination of grey and white matter structural metrics. ConclusionThis study highlights the critical role of the thalamus from a dynamic control perspective, demonstrating that thalamic structural and functional metrics provide complementary rather than redundant information related to cognitive performance. These findings underscore a promising new direction for understanding the complex and dynamic contributions of the thalamus to human cognition.

BackgroundThe developmental timing of trauma exposure may critically shape neurobiological outcomes, yet distinctions between childhood-onset trauma (CT) and adulthood-onset trauma (AT) remain poorly understood. AimThis study explores whether trauma onset timing is associated with distinct resting-state functional connectivity (rsFC) pattern using data-driven approach. MethodsSeventy-seven trauma-exposed individuals (Mage=36.74 years) with post-traumatic stress disorder (PTSD), PTSD with major depressive disorder (MDD), and trauma-exposed healthy controls (TEHC) underwent resting-state fMRI. Of these participants, 15 with CT only, 17 with both CT and AT, and 47 with AT only. RsFC was calculated across the amygdala, hippocampus, nucleus accumbens (NAcc), the salience (SN), default mode (DMN), and frontoparietal networks (FPN). K-means clustering identified subgroups based on rsFC, with robustness assessed via bootstrapping, cross-validation, and replication using Gaussian Mixture Modeling. The identified clusters were compared on trauma timing, type, cumulative exposure, and clinical measures. ResultsA two-cluster solution provided the most stable fit. The two generated clusters were significantly different in CT-only prevalence (p < 0.05; Cramers V = 0.26, 95% CI). The CT cluster was marked by hyperconnectivity between amygdala-FPN, DMN-SN, NAcc-SN, and hippocampus-FPN relative to the AT cluster. Individuals with both CT and AT were evenly distributed across clusters. Clusters did not differ in PTSD or comorbid diagnoses, trauma type, or cumulative exposure. ConclusionData-driven clustering revealed distinct neurobiological profiles differentiating CT and AT. CT was associated with hyperconnectivity across salience, reward, and regulatory circuits, supporting developmental timing as a determinant of brain network organization in trauma-exposed populations.

Post-stroke semantic aphasia is characterised by multimodal semantic deficits and reflects disruption of a distributed brain network spanning frontal and temporal regions. Connectivity gradients, which capture key dimensions of whole-brain variation in functional connectivity, offer a promising framework for understanding the global impact of stroke on brain function. This study investigated whether changes in connectivity gradients following stroke can explain semantic aphasia deficits. First, we evaluated whether lesion-location and lesion-load information from structural MRI could predict the gradient changes observed in resting-state fMRI, as a proof-of-principle analysis. Second, we tested whether simulated gradient changes predict the severity of semantic impairment. Results show that post-stroke gradient changes simulated from structural MRI are correlated with actual changes in resting-state fMRI, particularly for the principal gradient that separates unimodal and heteromodal regions. Semantic deficits were related to simulated connectivity changes along this gradient: left prefrontal areas involved in controlled semantic retrieval exhibited stronger connectivity to unimodal cortex in patients with more severe deficits. Semantic deficits also correlated with changes in the second gradient, which distinguishes visual and motor cortex. Particularly, the right parahippocampal gyrus, typically visually biased--showed reduced visual connectivity in more impaired patients. These results help explain controlled semantic retrieval deficits in semantic aphasia. More broadly, the findings suggest that functional connectivity gradients capture post-stroke reorganisation of global brain networks linked to cognitive impairment, and that these changes can be estimated from structural MRI alone, enhancing clinical utility of gradient-based approaches. HighlightsO_LIFunctional connectivity gradients explain the multimodal impairments in semantic aphasia from a dimensional perspective, using the unimodal-transmodal and motor-visual axes. C_LIO_LIPost-stroke functional changes are explored through alterations in connectivity gradient patterns. C_LIO_LICortical lesion information from structural MRI can be used to simulate changes in connectivity gradients, offering potential clinical relevance. C_LI

IntroductionThe anterior limb of the internal capsule (ALIC) is a major white matter highway connecting prefrontal cortical (PFC) regions to the thalamus, brainstem, and subthalamic nucleus. Structural and functional abnormalities within the ALIC circuit have been associated with many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and depression, and deep brain stimulation (DBS) may provide effective treatment to some of these patients. However, it remains unclear whether the well-characterized topographic organization of the ALIC observed in healthy individuals and preclinical models is preserved in treatment-resistant psychiatric populations. MethodsWe first used diffusion tractography to evaluate the topography of PFC and subcortical fibers through the ALIC in patients with treatment-resistant OCD (n=18) and depression (n=5). In depression patients, we also evaluated ALIC topography using cerebro-cerebral evoked potentials (CCEPs) elicited by single-pulse electrical stimulation (SPES) of DBS leads in the ALIC and recordings in the ventral PFC (vPFC). ResultsThe topographic organization of PFC and subcortical projections is preserved in the ALIC among treatment-resistant psychiatric patients, consistent with patterns observed in healthy individuals and preclinical models. CCEP recordings in the ventral PFC showed a ventral ALIC to medial vPFC/dorsal ALIC to lateral vPFC response pattern in the left hemisphere, but not in the right. ConclusionOur findings confirm that topographic patterns within the ALIC previously identified using preclinical models and healthy controls are preserved in treatment-resistant psychiatric patients. Furthermore, by linking white matter topography to stimulation effects, this work supports more precise and individualized neuromodulatory strategies for neuropsychiatric disorders.

Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a genetic disease characterized by spasticity and ataxia which reflects involvement of the corticospinal tracts (CST) and cerebellum. The primary involvement of the middle cerebellar peduncles (MCP) and transverse pontine fibers (TPF) at the crossing with the CST, and their role in the pathophysiology of the disease, is currently debated. Objectives: Advanced MRI techniques capable of isolating sub-voxel microstructural parameters can test the hypothesis that the MCP and TPF are abnormally large, compressing the CST at their crossing, and potentially impairing CST development. Methods: Tract macro- and micro-structural properties, including axon and tract caliber, axon density and geometry, and myelin content were estimated from diffusion-relaxometry and magnetization transfer imaging. These features were analyzed along segments of the CST, MCP, and TPF of 9 patients and 9 age-matched controls. Results: While the CST showed significant decreases in tract size, axon caliber, and myelination throughout its length compared to controls (p<0.01), the MCP and TPF were relatively unaffected. In our group, neither the MCP nor the pons were enlarged. The proximal MCP showed an increase in axon caliber. Conclusions: The increase in fractional anisotropy and axon density towards the center of the TPF could be driven by geometric confounds related to differences in the relative sizes of the CST and TPF compared to controls. This highlights the importance of investigating tract-specific microstructural profiles, particularly in regions of geometric complexity. The findings confirm the involvement of the CST, with a relatively limited involvement of the MCP and TPF.

Abstract: BACKGROUND: Perivascular spaces (PVS), visible on brain MRI, contribute to the brain clearance system and are associated with age and neurodegenerative disorders. While lower volumes of PVS in the forebrains white matter and basal ganglia have been also demonstrated in preterm-born neonates, the long-term trajectory of PVS after premature birth remains unclear. This study tests for altered PVS volumes in very preterm/very low birthweight-born (VP/VLBW) adults compared to full-term controls and explores potential associations with cognitive performance. METHODS: PVS were assessed on T2-weighted MRI from 97 VP/VLBW and 89 full-term (FT) subjects at 26 years from the prospective, population-based Bavarian Longitudinal Study. PVS volume and count was based on automated nnU-Net-based segmentation. Regional PVS volumes were normalized by corresponding regional parenchyma volumes. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale. MANCOVA was used for PVS group comparisons, Spearman rank correlations for testing PVS relationships with birth variables and cognitive scores. RESULTS: VP/VLBW-born adults showed significantly higher normalized PVS volumes in bilateral basal ganglia (p < 0.001, partial eta-squared = 0.096) and insula-related white matter (p = 0.001, partial eta-squared = 0.057). In the basal ganglia, higher PVS volumes were negatively correlated with gestational age (rho = -0.223, p = 0.030) and positively correlated with the Intensity of Neonatal Treatment Index (rho = 0.222, p = 0.030) in the VP/VLBW group. PVS volume was not associated with IQ scores. CONCLUSION: We demonstrate region-specific alterations of perivascular spaces in VP/VLBW-born adults. Data suggest that prematurity has lasting impact on the PVS.

PurposePost-acute sequalae of SARS-CoV-2 (PASC) are associated with persistent neurological symptoms (neuroPASC). Perivascular spaces (PVS) in the brain may enlarge in the context of inflammation and vascular dysfunction, reflecting impaired glymphatic clearance, and have been linked to cognitive decline. SARS-CoV-2 may disrupt the blood-brain barrier and impair glymphatic function, contributing to PVS burden. This study used 7 Tesla MRI to segment and quantify PVS in neuroPASC participants and uninfected comparators and examined associations with cognitive performance. MethodsAdult participants (36 neuroPASC (44.3 {+/-} 12.7 years) and 33 comparators (38.4 {+/-} 13.0 years)) underwent a 7 Tesla MRI scan. White matter masks of the whole brain and four lobes were segmented, and semi-automated segmentation was used to quantify PVS count and volume. All participants completed cognitive testing including Trails A and B sequencing tasks; neuroPASC participants also self-reported brain fog, fatigue, anxiety, and depression. PVS count, PVS volume, and total white matter volume (WMV) between groups were compared and associations between PVS metrics and cognitive function were assessed controlling for age, sex, and intracranial volume and corrected for multiple comparisons. ResultsAmong neuroPASC participants, those reporting anxiety (p =0.009) and depression (p =0.01) had higher WMV than those without. Greater PVS burden was associated with worse cognitive performance in PASC, particularly processing speed (Trails A) and executive function (Trails B). Specifically, processing speed was negatively associated with whole-brain PVS count (p-FDR = 0.008, R2 = 0.27), frontal PVS count (p-FDR = 0.03, R2 = 0.25), and frontal PVS volume (p-FDR = 0.04, R2 = 0.23). Trails B was also negatively associated with whole-brain PVS count (p-FDR = 0.005, R2 = 0.26). In comparators, higher PVS burden (volume and count) across multiple lobes was associated with worse semantic fluency (Animal Naming). There were no other significant associations between PVS measures and neuropsychiatric tests among participants within any of the subgroups to report. ConclusionAlthough group-level differences in PVS were not observed, PVS burden was meaningfully negatively associated with cognitive performance in neuroPASC, with the strongest effects in frontal regions. These findings suggest that microvascular and glymphatic alterations may contribute to the characteristic processing speed and executive dysfunction seen in neuroPASC. Elevated WMV in those with anxiety and depression may reflect heightened inflammatory vulnerability. PVS may serve as a sensitive imaging marker of glymphatic dysfunction and neuroinflammation in neuroPASC, offering insight into the mechanisms underlying cognitive impairment and potential intervention targets.

Quantitative MRI enables the detection of subtle microstructural alterations in normal-appearing white matter (NAWM) associated with pathological conditions such as multiple sclerosis. Quantitative metrics including R1, R2, and the bSSFP asymmetry index (AI) were evaluated in the WM of 20 relapsing-remitting multiple sclerosis (RRMS) patients and 10 healthy controls (HC). A multi-parametric frame-work based on a phase-cycled balanced steady-state free precession (pc-bSSFP) sequence was used. Diffusion tensor imaging-derived measures, including fiber-to-field angle, number of fiber orientations, and fractional anisotropy, were incorporated to assess parameter anisotropy. Statistical analysis was performed using linear mixed-effects models to test for group, ROI, and group-by-ROI effects for each metric, with ROI-specific group comparisons derived from the model. Significant main effects of group, ROI, and group-by-ROI interaction were observed for both R1 and R2, whereas for AI only the ROI effect reached significance (group p= 0.462; group-by-ROI p = 0.786). Fourteen of sixteen ROIs demonstrated significantly lower R1 and R2 values in RRMS compared with HC. No ROI showed significant differences in AI. In conclusion, pc-bSSFP-based relaxometry reveals predominantly white matter alterations in RRMS, while enabling a comprehensive whole-brain assessment that also encompasses gray matter.