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High-frequency contralesional dorsal premotor cortex and low-frequency contralesional primary motor cortex rTMS in subacute stroke with severe upper limb impairment: comparable motor outcomes and differential regional degree centrality changes.

BACKGROUND: The contralesional dorsal premotor cortex has been proposed as a potential neuromodulatory target for patients with severe upper limb impairment due to subacute ischemic stroke. This proof-of-concept study aimed to compare behavioral outcomes and resting-state neuroimaging findings between high-frequency repetitive transcranial magnetic stimulation (rTMS) over the contralesional dorsal premotor cortex and guideline-supported low-frequency stimulation over the contralesional primary motor cortex. METHODS: In this randomized trial, 46 patients with severe upper limb impairment in the subacute stage after ischemic stroke were randomly assigned to receive either high-frequency rTMS over the contralesional dorsal premotor cortex or low-frequency rTMS over the contralesional primary motor cortex. Low-frequency stimulation over the contralesional primary motor cortex served as an evidence-supported active comparator for poststroke upper limb motor recovery. Stimulation was administered five times per week for two weeks using magnetic resonance imaging-guided neuronavigation. All participants received concurrent standard rehabilitation therapy. The primary outcome was the Fugl-Meyer Assessment for Upper Extremity. Secondary outcomes included the Arm Subscore of the Motricity Index, the Hong Kong version of the Functional Test for the Hemiplegic Upper Extremity, the Modified Barthel Index, and resting-state functional magnetic resonance imaging-derived degree centrality. RESULTS: Both groups showed significant improvements in the primary and secondary behavioral measures (p&#x202f;<&#x202f;0.01), with no significant between-group differences in the magnitude of change (p&#x202f;>&#x202f;0.05). In neuroimaging analyses, patients receiving high-frequency rTMS over the contralesional dorsal premotor cortex showed significantly greater degree centrality changes in the ipsilesional middle occipital gyrus, contralesional medial superior frontal gyrus, and contralesional middle frontal gyrus than those receiving low-frequency rTMS over the contralesional primary motor cortex (p&#x202f;<&#x202f;0.05). Within the high-frequency stimulation group, degree centrality changes in the ipsilesional middle occipital gyrus were positively correlated with improvements in the Fugl-Meyer Assessment for Upper Extremity (r&#x202f;=&#x202f;0.619, false discovery rate-corrected p&#x202f;=&#x202f;0.018). CONCLUSIONS: High-frequency rTMS over the contralesional dorsal premotor cortex produced behavioral improvements comparable to guideline-supported low-frequency rTMS over the contralesional primary motor cortex, without establishing superiority or formal non-inferiority. Exploratory neuroimaging analyses showed greater degree centrality changes in the ipsilesional middle occipital gyrus after high-frequency premotor stimulation, and these changes correlated with upper-limb motor improvement. These findings support further investigation of contralesional dorsal premotor cortex-targeted high-frequency rTMS for severe subacute post-stroke upper limb impairment. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR2000038049.

Humans

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p&#x2009;<&#x2009;0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p&#x2009;<&#x2009;0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans

Lateral Femoral Condyle Angle Is an Anatomic Risk Factor for Anterior Cruciate Ligament Primary Injury and Secondary Graft Rerupture.

PURPOSE: To define the lateral femoral condylar angle (LFCA)-a parameter measuring condylar inclination-and assess its predictive capacity for primary and recurrent anterior cruciate ligament (ACL) injuries. METHODS: Patients aged 18 to 50&#x2009;years who underwent primary ACL reconstruction between 2017 and 2022 were screened. Those with graft rerupture were matched 1:1:1 by sex, age, body mass index, and meniscal status to ACL-intact controls and patients without graft failure during a minimum 48-month follow-up. LFCA was measured as the angle between the long axis of the distal femur and the axis of the lateral femoral condyle, alongside 38 established parameters using preoperative 3.0-T magnetic resonance imaging scans. Intergroup differences were assessed with one-way analysis of variance; multivariate regression and receiver operating characteristic analyses identified independent predictors and evaluated predictive performance. RESULTS: The study included 540 patients (180 per group: primary ACL injury, rerupture, controls). One-way analysis of variance revealed a significant gradient in LFCA across controls (81.3&#xb0;, 95% CI: 80.8-81.8&#xb0;), primary injuries (81.9&#xb0;, 95% CI: 81.5-82.3&#xb0;), and reruptures (84.2&#xb0;, 95% CI: 83.7-84.6&#xb0;) (P&#x2009;<&#x2009;.001). In multivariate models adjusted for baseline factors, LFCA independently predicted primary injury (odds ratio [OR]&#x2009;=&#x2009;1.27, 95% CI: 1.13-1.42, P&#x2009;<&#x2009;.001; area under the curve [AUC]&#x2009;=&#x2009;.576) and rerupture (OR&#x2009;=&#x2009;1.46, 95% CI: 1.21-1.76, P&#x2009;<&#x2009;.001; AUC&#x2009;=&#x2009;.704). Combined models incorporating LFCA with tibial slopes, notch angle, and notch height achieved an AUC of .847 for primary injury prediction, whereas models with LFCA, lateral condylar flexion curvature radius, slope asymmetry, and tibial AP distance reached an AUC of .817 for rerupture. LFCA alone with lateral condylar flexion curvature radius yielded an AUC of .777 for rerupture prediction. Sex-stratified analyses confirmed LFCA predicted rerupture in both male patients (OR&#x2009;=&#x2009;1.44, 95% CI: 1.19-1.75) and female patients&#xa0;(OR&#x2009;=&#x2009;1.49, 95% CI: 1.16-1.92), and primary injury in male patients&#xa0;(OR&#x2009;=&#x2009;1.30, 95% CI: 1.15-1.48). CONCLUSIONS: LFCA is an independent predictor of ACL injury, showing particular strength in identifying Asian patients at high risk for graft rerupture. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Humans

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n&#x2009;=&#x2009;38) or sham stimulation (n&#x2009;=&#x2009;36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0&#x2009;mA, 20&#x2009;min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74&#x2009;&#xb1;&#x2009;2.76 vs. sham: 2.69&#x2009;&#xb1;&#x2009;2.69; t&#x2009;=&#x2009;4.799, p&#x2009;<&#x2009;0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p&#x2009;<&#x2009;0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p&#x2009;<&#x2009;0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans

Changes in ACL T2* Metrics Over the Course of the Female Menstrual Cycle: A New Biomarker for the ACL Injury Risk?

BACKGROUND: Sex-based disparities in the anterior cruciate ligament (ACL) injury risk may be partly explained by cyclic variations in sex hormones that drive systemic shifts in tissue osmoregulation. Ultrashort echo time (UTE) T2* magnetic resonance imaging provides a noninvasive, quantitative means of evaluating the water content and collagen orientation in tissue. HYPOTHESIS: Eumenorrheic female participants will exhibit significant ACL T2* changes across the cycle, while anovulatory control participants will demonstrate no significant changes over time. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 25 women with no prior knee injuries were enrolled: 10 premenopausal, eumenorrheic participants and 15 anovulatory control participants (6 postmenopausal and 9 premenopausal using oral contraceptives). Bilateral knee magnetic resonance imaging was performed at 4 time points evenly spaced over 1 month, with the first visit within 24 hours of menses onset. Ovulation status was confirmed using commercially available ovulation predictor kits. Three-dimensional UTE sequences (11 echoes; 0.03-25 ms) were acquired to evaluate bicomponent ACL T2* metrics. Linear mixed-effects models assessed temporal differences in long and short T2* values, and the Cohen d quantified effect size. RESULTS: Eumenorrheic participants demonstrated significantly shorter preovulatory long T2* values compared with postovulatory values (mean difference, 1.0 ms [95% CI, 0.2-1.9 ms]; P = .015; Cohen d = 0.51). No significant temporal differences were observed for any T2* metric in anovulatory controls. CONCLUSION: Eumenorrheic female participants exhibited significant preovulatory to postovulatory changes in ACL T2* metrics, while anovulatory controls demonstrated no significant changes over time. These findings suggest that ACL T2* metrics are sensitive to cyclic fluctuations in female sex hormones across the menstrual cycle.

Humans

Continuous theta-burst stimulation over the right DLPFC modulates central executive network connectivity in depression: exploratory analysis of a randomized clinical trial.

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects and is associated with alterations in functional connectivity (FC), but the neural correlates remain unclear. This exploratory sham-controlled trial investigated the effect of continuous theta-burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on FC in major depressive disorder (MDD). Seventy MDD patients were randomized to receive two-week treatment of personalized cTBS or sham stimulation. Resting-state fMRI was performed at baseline and post-treatment. Ultimately, 31 patients in the active cTBS group and 28 patients in the sham group passed imaging quality control and were included in the final analysis. To identify the FC that may have been influenced by cTBS treatment, two complementary FC analyses were conducted: (1) voxel-wise degree centrality (DC) followed by seed-based FC, and (2) an individual FC analysis based on the stimulation targets. Furthermore, correlations between FC changes and clinical symptoms improvement were examined. Both groups exhibited reductions of depression scores, with greater improvement in the active group. Compared to the sham group, active cTBS showed increased DC in the precuneus and elevated FC between the precuneus (within the para-cingulate network) and the right inferior parietal lobule (IPL) and DLPFC. Further stimulation target-based analysis revealed increased FC between stimulation targets and both the precuneus and visual regions following treatment. Our findings reveal neural changes associated with cTBS over the right DLPFC in MDD, notably involving the precuneus and its connectivity with the right IPL/DLPFC, suggesting alterations within the central executive network. TRIAL REGISTRATION: chictr.org.cn; ChiCTR2300068273.

Humans

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans

Subtle cortical thinning in the temporal pole in middle-aged APOE-&#x3b5;4 and PICALM (rs3851179) AA/AG carriers without dementia.

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N&#x202f;=&#x202f;69) participants (34 females, 35 males; age: 55.45&#x202f;&#xb1;&#x202f;3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+&#x202f;P+&#x202f;(APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

Humans

Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.

BACKGROUND: With the increasing prevalence of depression, there is an urgent clinical need for early screening in depression. The retina offers a promising window for early screening in depression due to its rapid, non-invasive, objective, eye-brain correlated characteristics, but previous research has yielded conflicting alterations in retinal microstructure in depression. METHODS: We screened retinal optical coherence tomography and brain magnetic resonance imaging data in the UK Biobank to enroll 23,225 participants for retinal study of depression occurrence, and 1475 participants for the eye-brain association study. We also used genetic data (ID: ebi-a-GCST90014267 and ukb-d-20,448) from the Integrative Epidemiology Unit Open Genome-Wide Association Study for Mendelian randomization analysis. We used Cox regression to assess the association between retinal microstructure and depression risk, Mendelian randomization to infer causality, and mediation analysis to explore retina-brain pathway association. RESULTS: The Cox regression analysis showed that retinal ganglion cell-inner plexiform layer (GCIPL) thickness remained a significant predictor of depression. The Mendelian randomization analysis indicated a positive statistical association between GCIPL thickness and depression. Moreover, there was a significant positive correlation (all p&#xa0;<&#xa0;0.001) between the volume of specific depression-related brain regions and the GCIPL thickness. Adjusting for age, sex, and head size, the mediation analysis provided preliminary evidence for a potential anatomical pathway linking retinal GCIPL thickness to depression-related brain regions through primary visual cortex and secondary visual cortex volumes. CONCLUSION: Thickened retinal GCIPL is a potential early phenotype of depression and has a potential association pathway with depression-related brain regions using a radiogenomics approach.

Humans

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N&#xa0;=&#xa0;41) from a randomized controlled trial who underwent ultra-high-field 7&#xa0;T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging

Effectiveness of psychologically informed physical therapy, tendon-specific exercise program and routine physical therapy in prolonged unilateral shoulder pain and symptom correlations with imaging: a single-center, randomized, parallel-group, three-arm study (RESPECT).

BACKGROUND: Shoulder complaints are one of the most common musculoskeletal ailments. Patient-specific characteristics such as obesity, depression and physical labor are established risk factors, whereas imaging findings are common and associations between specific imaging findings and symptomatology is limited. General exercises are considered useful in treatment whereas evidence for specific tendon exercises is lacking. Biopsychosocial model is also recommended, but has not been extensively studied concerning shoulder symptoms. This article describes the study protocol designed to evaluate the effectiveness and the cost-effectiveness of routine and specific physical therapy (PT) interventions. Imaging is performed for descriptive, longitudinal and imaging-symptom correlation studies. METHODS: The Rehabilitation of Shoulder Pain: Evaluation and Clinical Trial (RESPECT) is a randomized three-arm parallel-group study involving 300 participants aged 20 to 60&#xa0;years with prolonged unilateral shoulder pain. Participants will receive either routine PT, physiotherapist-guided tendon-specific exercise program or psychologically informed PT. Bilateral shoulder radiographs, ultrasound and magnetic resonance imaging will be done at the baseline and at 12 and 36&#xa0;months. Electronic surveys will be completed at the baseline and at 3, 6, 12 and 36&#xa0;months. The primary outcome will be patient-specific functional scale (PSFS) at 12&#xa0;months, analyzed using analysis of covariance (ANCOVA), adjusted for baseline PSFS. DISCUSSION: RESPECT will provide systematic and controlled data regarding different PT interventions in prolonged shoulder symptoms, which is currently limited. Being one of the most common sources of musculoskeletal pain, improved management could reduce symptom-related burden and prolonged functional impairment at individual and population level. CLINICALTRIALS: gov; Registration number NCT07235969; Registered November 18th, 2025; Version: 1.0.

Humans

Imaging&#x2011;based models for predicting cerebrovascular complications of carotid stenosis.

This is a protocol for a Cochrane review (prognosis). The objectives are as follows: Primary objective To systematically review and critically appraise multivariable prognostic models developed for adults (&#x2265;&#x202f;18&#x202f;years) with carotid stenosis in which imaging biomarkers (e.g. plaque characteristics derived from magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) constitute the core predictors. The primary focus is to evaluate the predictive performance of these models for cerebrovascular complications - specifically ipsilateral ischaemic stroke and transient ischaemic attack (TIA) - which are the clinical outcomes to be predicted. Where feasible, we will summarise and compare the models' discrimination (C&#x2011;statistic/area under the curve (AUC)) and calibration (calibration&#x2011;in&#x2011;the&#x2011;large, calibration slope, observed&#x2011;to&#x2011;expected ratio) across studies, and assess their potential for clinical application and external validation. For the purpose of defining symptomatic carotid stenosis as an eligibility criterion and subgroup variable, we will include studies that also considered retinal ischaemia (e.g. retinal embolism, amaurosis fugax) as a qualifying event. Secondary objectives To describe the combinations of imaging markers, modelling techniques, sample sizes, and variable&#x2011;selection strategies used in the development of the included models To evaluate the performance of these models for additional secondary clinical outcomes: plaque progression or regression, incident high&#x2011;risk imaging features, and the transition from asymptomatic to symptomatic disease To explore whether predictive performance differs according to imaging modality (MRI versus CT versus contrast&#x2011;enhanced ultrasound (CEUS)) or technical protocol (e.g. 3&#x202f;T versus 1.5&#x202f;T, spectral CT versus conventional CT) For studies that report both cerebrovascular and broader cardiovascular outcomes (major adverse cardiovascular events, myocardial infarction, etc.), we will only extract the performance metrics relating to cerebrovascular events for the primary analysis. Performance metrics for cardiovascular outcomes will be considered exploratory and will not form part of the main synthesis.

Humans

MRI-Negative Posterior Reversible Encephalopathy Syndrome: Comparison of Hypertensive Encephalopathy With and Without Vasogenic Edema.

OBJECTIVE: To explore whether posterior reversible encephalopathy syndrome (PRES) can present with negative magnetic resonance imaging (MRI) by comparing clinical features between cases of PRES with vasogenic edema and cases of hypertensive encephalopathy without MRI changes. PATIENTS AND METHODS: Patients diagnosed with hypertensive encephalopathy from August 1, 2008, to December 31, 2017, were identified retrospectively and matched by age (&#xb1;5 years) and sex in a 1:2 ratio to patients retrospectively identified as having PRES from January 1, 2002, to November 30, 2017. A review of MRI images and clinical information was performed. RESULTS: We identified 16 cases of hypertensive encephalopathy and 32 age- and sex-matched controls with PRES showing vasogenic edema on MRI. There were no statistically significant differences in the odds of presentation with headache (odds ratio [OR], 1.372; 95% CI, 0.458 to 4.106), encephalopathy (OR, 2.303; 95% CI, 0.433 to 12.236), visual disturbance (OR, 0.826; 95% CI, 0.185 to 3.697), or focal neurologic deficit (OR, 4.000; 95% CI, 0.767 to 20.872). Seizures were more common in patients with vasogenic edema (OR, 0.082; 95% CI, 0.010 to 0.664). There were no significant differences in odds of acute kidney injury (OR, 2.90; 95% CI, 0.679 to 12.449) or odds of having a history of malignancy (OR, 0.295; 95% CI, 0.076 to 1.152), transplantation (OR, 3.347; 95% CI, 0.594 to 18.880), or autoimmune disease (OR, 0.400; 95% CI, 0.104 to 1.532). Systolic blood pressure at presentation was higher in patients with hypertensive encephalopathy and negative MRI as compared with patients with PRES and vasogenic edema (OR, 1.03; 95% CI, 1.01 to 1.05). CONCLUSION: Most presenting symptoms and risk factors were not significantly different between cases of hypertensive encephalopathy with and without vasogenic edema, arguing that the diagnosis of PRES in the setting of acute severe hypertension may not depend on MRI confirmation.

Humans

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans

Association of Early Knee Extension Range of Motion Deficits With Cartilage T2 Relaxation Following Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) injury significantly increases the risk for developing knee osteoarthritis (OA), yet the early contributors to cartilage degeneration remain poorly understood. While range of motion (ROM) deficits after ACL reconstruction (ACLR) are associated with long-term development of radiographic OA, the association between early ROM recovery and cartilage composition has not been established. HYPOTHESIS: Knee extension ROM deficits at 2 months after ACLR would be associated with worsening tibiofemoral and patellofemoral cartilage T2 relaxation times at 6 months. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 30 participants (15-35 years) were enrolled within 1 month of ACL injury and before ACLR. At 2 months post-ACLR, active knee extension ROM was measured in the supine position using a goniometer. An extension deficit was considered >3&#xb0; less extension in the injured knee compared to the uninjured side. Quantitative magnetic resonance imaging-based T2 relaxometry of the injured knee was performed preoperatively and at 6 months post-ACLR to measure percent change in mean T2 relaxation times in predefined tibial and femoral cartilage regions. Independent t tests were used to compare changes in T2 values between participants with and without an extension deficit. RESULTS: The mean age of the participants was 18.8 &#xb1; 3.9 years, and 63.3% were female. Fifteen (50.0%) participants exhibited an extension deficit at 2 months. Those with an extension deficit demonstrated a greater increase in T2 relaxation time in the anterior (mean difference, 10.21% [95% CI, 3.67%-16.76%]; P = .003) and weightbearing (mean difference, 6.14% [95% CI, 2.19%-10.09%]; P = .004) cartilage of the medial femoral condyle. No significant group differences were observed in other cartilage regions (all P > .05). CONCLUSION: Knee extension ROM deficits at 2 months post-ACLR are associated with early compositional changes in the medial femoral cartilage, indicating a potential relationship between limited extension and OA risk.

Humans

Imaging techniques for assessing the hand in systemic sclerosis: a systematic review.

BACKGROUND: Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease frequently associated with hand involvement, leading to significant functional impairment. Imaging techniques provide unique opportunities to visualize and quantify structural and functional abnormalities of the hand, supporting diagnosis, monitoring, and treatment evaluation. This systematic review summarizes the imaging techniques used in SSc. METHODS: A systematic search of PubMed and Embase was conducted. Eligible studies included original research articles in English that applied or evaluated imaging techniques of the hands in SSc, published after 2000. Ultrasound and nailfold capillaroscopy were excluded, given their established use. Screening was performed independently by two authors. Findings were synthesized by clinical manifestations, study quality was assessed using the QUADAS-2 tool. RESULTS: Sixty-one studies met the inclusion criteria. In total, 25 distinct imaging techniques were identified, enabling assessment of various hand structures, including vascular involvement, inflammation, fibrosis, calcifications, erosions, and bone marrow edema. Vascular imaging was most extensively studied, particularly in the context of Raynaud's phenomenon and digital ischemia, with multiple techniques demonstrating impaired perfusion and altered thermoregulatory responses. MRI consistently detected subclinical inflammatory and erosive changes of joints and soft tissues,. CT-based techniques provided detailed assessment of calcinosis cutis, while optical and photoacoustic methods showed promise for quantifying skin fibrosis. CONCLUSION: Imaging techniques provide valuable, complementary insights into hand involvement in SSc, often revealing subclinical disease. Despite promising results, limited standardization and longitudinal validation currently restrict clinical implementation. Future studies should focus on harmonizing protocols and validating against clinically meaningful outcomes.

Humans

Complement component C4 and neuroimaging in psychiatry: A systematic review.

INTRODUCTION: Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. METHODS: We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. RESULTS: From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. CONCLUSION: The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.

Humans