Brain and Behavior

Background and purpose: People after mild traumatic brain injury (mTBI) show persistent deficits in reactive balance. Cortical processes engaged during preparation and execution of balance reactions are reflected in distinct cortical activity signatures that can be measured with electroencephalography (EEG). The purpose of this study was to 1) compare preparatory cortical beta activity and evoked cortical N1 responses during balance recovery in people with mTBI and controls, and 2) explore relationships between preparatory and evoked cortical activity. Methods: Participants (age 21-35 years) with symptomatic mTBI (n=5, 27 +/- 13 days post-injury) and controls (n=5) completed the instrumented and modified push & release tests of reactive balance. Cortical activity was recorded using encephalography (EEG). Main outcome measures were 1) preparatory sensorimotor cortical beta-bust power and duration prior to balance perturbation onset (-1s-0s), and 2) cortical N1 response amplitude and latency during the post-perturbation balance recovery (50-250ms). Results: People with mTBI exhibited lower preparatory beta-burst power compared to controls (p=0.044, g=1.18). During balance recovery, cortical N1 responses occurred earlier in people with mTBI compared to controls (p=0.045, g=3.28). Relationships between preparatory and evoked cortical activity were altered after mTBI compared to controls; people after mTBI with greater beta-burst power and longer duration elicited shorter N1 latencies (r's>0.77, p's<0.010). Discussion and conclusion: The results serve as preliminary, hypothesis-generating observations to guide future research directions investigating neural signatures of reactive balance deficits in people after mTBI. The preparatory brain state before reactive balance recovery should be explored as a potential target for post-mTBI balance rehabilitation.

Prehabilitation (PRH) is a preoperative process aimed at optimizing patients functional capacity to improve surgical outcomes and overall well-being. While its physical and cognitive benefits are increasingly documented, its emotional impact, particularly in neuro-oncology patients, remains less explored. This study assessed the psychological effects of a PRH program on 29 brain tumor patients. The primary outcome, emotional well-being, was measured using quality of life and emotional distress metrices. Secondary outcomes included perceived stress levels and control attitudes. Additionally, qualitative data from structured interviews provided further insights into the psychological effects of the intervention. The results indicated significant improvements in quality of life and reductions in emotional distress, particularly among women. While perceived stress levels remained stable, control attitudes showed an increase. Qualitative analysis further highlighted the positive changes in the control sense and identified additional factors, such as the importance of social support sources during the PRH process. Overall, these findings suggest that PRH interventions play a significant role in enhancing emotional well-being among neuro-oncological patients in the preoperative phase. These results underscore the importance of implementing comprehensive and personalized PRH approaches to optimize clinical status both before and after surgery, thereby promoting sustained psychological benefits in this population. This study is based on data collected at Institut Guttmann in Barcelona in the context of the Prehabilita project (ClinicalTrials.gov identifier: NCT05844605; registration date: 06/05/2023).

ObjectiveFinding indicators of early response to antidepressant treatment in EEG signals recorded from patients suffering from major depressive disorder. MethodsFunctional brain connectivity networks based on weighted imaginary coherence and weighted imaginary mean phase coherence were computed for 176 patients for 6 different EEG frequency bands. Cross-hemispheric connectivity (CH) and lateral asymmetry (LA) were estimated from these networks based on EEG signals recorded before the beginning of treatment (V is1) and one week after the start of the treatment (V is2). Repeated measures ANOVA was used to check for statistically significant changes in connectivity based on these measures at V is2 w.r.t. V is1. Post-hoc analysis was performed with multiple pairwise comparison tests to determine which group means were significantly different. ResultsIt was found that CHV is2 was significantly reduced w.r.t. CHV is1 in the {beta}1 [12.5 - 17.5 Hz] frequency band for the responders to treatment. Also, LAV is2 was significantly increased w.r.t. LAV is1 in the {beta}1 frequency band for the responders. No such significant changes were observed for the non-responders. Brain networks constructed using both weighted imaginary coherence and weighted imaginary mean phase coherence were found to exhibit these results. For the CH connectivity changes, binarized networks and for the LA connectivity changes, weighted networks were found to be more reliable. ConclusionsResponders were found to show a reduction in cross-hemispheric connectivity and an increase in lateral asymmetry, both in the {beta}1 band while no such change was observed for the non-responders. SignificanceDecrease in cross-hemispheric connectivity and increase in lateral asymmetry in the {beta}1 band may represent candidate neurophysiological indicators of early treatment response, but they require independent replication before any clinical application can be considered.

Negative cognitive biases in depression are more pronounced in females than in males. This sex difference emerges during adolescence, a sensitive developmental stage when chronic stress exposure increases the risk of depression in adulthood. The neurobiology linking adolescent stress to sex-specific cognitive bias and resting-state network reorganization in adults remain poorly understood. The study aimed to investigate the longitudinal effects of chronic restraint stress (CRS) during adolescence on cognitive bias and functional connectome in emerging adulthood. 28 Wistar rats (sex-balanced; aged five weeks on arrival) were trained on a judgment bias task with distinct tactile cues signalling differential rewards. Cognitive bias was quantified from responses to ambiguous probe trials. Following training, animals were randomly and equally assigned to CRS or control groups (sex-balanced). Offline resting-state functional MRI scans were conducted at adolescent baseline (pre-CRS) and again in adulthood (post-CRS), followed by probe trials to assess neural and behavioural changes. Following CRS, females showed a greater tendency to shift toward negative bias than males (ratio of odds ratio=3.67). Furthermore, CRS significantly reduced functional connectivity between the left cerebellar-auditory and hypothalamic-thalamic networks only in females. Repeated-measures correlation between cognitive bias and network connectivity were not statistically significant across sex-by-group strata, potentially due to offline imaging and small sample size. However, intra-individual association revealed sex-specific trends, with CRS females showing moderately positive correlations and CRS males exhibiting a weak negative association. The results could inform stratified connectome-based interventions targeting adolescent stress exposures to potentially reduce the risk of adult depression. Six keywords: Resting-State Functional MRI, Chronic Restraint Stress, Judgement Bias, Open Field Test, Sex Differences

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

Spinal cord injury (SCI) is associated with cardiovascular deficits that affect cerebral blood flow, cerebral perfusion, and cerebrovascular control. While several studies use neuroimaging techniques such as functional magnetic resonance imaging (fMRI) to understand neuroplasticity following SCI, more work needs to be done to evaluate the cerebrovascular changes following SCI. Understanding these effects using neuroimaging is essential as these deficits also affect neurovascular coupling and how we interpret neuroplasticity measured based on neuroimaging. Hence, we conducted a pilot study in twelve healthy males and thirteen males with thoracolumbar SCI using functional near-infrared spectroscopy (fNIRS) to understand the effects of breath-holding induced hypercapnia on the hemodynamics of the sensorimotor cortex and prefrontal cortex (PFC) after SCI. Participants performed 30 seconds of regular breathing alternated by 15 seconds of breath-holding for 5 minutes. Compared to controls, the SCI group presented with a greater initial decrease in oxy-hemoglobin concentration change and a delayed subsequent increase in oxy-hemoglobin concentration change in response to hypercapnia at p<. Additionally, the net increase in oxy-hemoglobin concentration change following BH in the PFC was negatively correlated with the level of injury at p=0.005, where higher levels of injury were associated with a smaller increase in oxy-hemoglobin concentration following hypercapnia. These findings confirm that a) SCI, including lower levels of injury (below T6) are associated with cerebrovascular changes that are quantifiable using fNIRS, and b) fNIRS could be a robust tool to understand the neuroplastic and cerebrovascular changes in people with SCI.

Background and ObjectivesNormal appearing white matter (NAWM) may already harbor subtle microstructural alterations not yet visible on conventional MRI. Quantitative Multi-Parametric Mapping (qMPM) such as Magnetization Transfer saturation (MTsat), longitudinal relaxation rate (R1), and Proton Density (PD) offer new possibilities for analyzing NAWM which are sensitive to demyelination, axonal loss, and edema. We aimed to characterize these alterations within white matter hyperintensities (WMH) and the perilesional NAWM (pNAWM), to gain insights into the underlying process of lesion progression. We also investigated their association with cerebrovascular risk factors (CVRF) and long-term cognitive performance. MethodsThis investigation included the cerebral MRI data of 245 participants from the prospective Berlin Longterm Observation of Vascular Events (BeLOVE) study. Furthermore, 121 participants cognitive performance was evaluated at baseline and longitudinally at 2 years follow-up using Montreal Cognitive Assessment (MoCA). Regions of interest (ROIs) of WMH, pNAWM at 1, 2, 3 mm were assessed in comparison to the mirrored contralesional white matter (cWM). Linear mixed effects models were employed to demonstrate the pairwise comparisons between each region using estimated marginal means and the association of MPM metrics with CVRFs. Linear regression was used to assess the association with cognitive performance. ResultsIn 245 participants, (mean age 62 years, SD: 12 years; 29.8% females), MPM metrics demonstrated a clear spatial gradient of microstructural injury. MTsat and R1 values were lower in WMH compared to cWM ({beta} = -0.48 (-0.52 - -0.44) and {beta} = -0.07 (-0.08 - -0.06), p<0.001, respectively) and showed gradual recovery with increasing distance indicating a microstructural gradient in pNAWM. Conversely, PD values were higher in WMH and decreased peripherally ({beta} = 2.32 (2.05 - 2.61, p<0.001). No substantial associations were found between MPM parameters and CVRFs in our cohort. At baseline and 2-year follow-up, cognitive performance was associated with higher pNAWM R1 values, whereas MTsat were only moderately associated. DiscussionQuantitative MPM reliably detects microstructural alterations not only within WMH, but also in pNAWM, confirming the high sensitivity of qMPM to subtle tissue pathology and support its utility as a promising biomarker for longitudinal studies and monitoring therapeutic effects.

Stroke is the third leading cause of death and disability combined worldwide and often results in hemiparesis. Functional magnetic resonance imaging (fMRI) is a non-invasive technique used to investigate changes in brain activations during tasks aimed at restoring the lost motor function. Participants with chronic stroke and residual hemiparesis in the upper extremity were recruited for a clinical intervention that included neurofeedback training and fMRI sessions with motor-execution and motor-imagery tasks. The present study provides a baseline characterization of brain activations prior to neurofeedback training. Since lesion site and volume varied across participants, two fMRI preprocessing pipelines were applied. The first one was used for twelve participants with lesions restricted to a single hemisphere and for one participant with small secondary lesions in the contralesional hemisphere, whereas the second one was used for two participants with large bilateral lesions. These were followed by quality control measures and statistical analysis. First-level (i.e., single-participant) analysis returned the strongest and most extensive activation across participants during motor-execution tasks, with clusters identified in the ipsilesional parietal lobe, bilateral occipital lobes, and cerebellum after Family-Wise Error correction. Second-level (i.e., group-level) analysis involving participants who underwent the first fMRI preprocessing pipeline revealed a significant cluster in the cerebellum after False Discovery Rate correction. These results are consistent with previous studies involving participants with chronic stroke performing motor-tasks. Cerebellar recruitment observed consistently across participants could reflect compensatory mechanisms supporting motor control after stroke.

Introduction: Glioblastoma multiforme (GBM) remains the most lethal primary brain tumor with median survival of 14-15 months. Current prognostic markers inadequately stratify patient outcomes. PINK1 (PTEN-induced putative kinase 1), a mitochondrial kinase regulating mitophagy and cellular stress responses, has emerged as a promising prognostic candidate. Our preliminary analysis of 20 GBM cases demonstrated significant PINK1 expression with correlation to aggressive phenotypes (Turizo Smith et al., 2025). This multicenter study aims to prospectively validate PINK1 as a prognostic biomarker for survival and functional outcomes in a Latin American cohort. Methods and analysis: PINK1-GBM Colombia is a multicenter, observational cohort study across four tertiary hospitals in Bogota, Colombia (Hospital de Kennedy, Hospital El Tunal, Hospital Santa Clara and Hospital Universitario de la Samaritana). We will enroll at least 26-50 adults (18+ years) with newly diagnosed IDH-wild type GBM undergoing surgical resection. PINK1 expression will be quantified by immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue using standardized protocols. Primary outcomes: overall survival (OS) and progression-free survival (PFS). Secondary outcomes: functional status trajectories (KPS/ECOG). Follow-up extends 24 months with clinical, imaging (RANO 2.0), and telephone assessments. Survival analyses will employ Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models adjusted for established prognostic factors. Ethics and dissemination: Approved by Universidad Nacional de Colombia Ethics Committee (Acta 001, February 5, 2026; Ref: 2.FM.1.002-CE-002-26), Subred Sur Occidente (P-AP-19-2025, July 11, 2025), and Subred Centro Oriente (CEI 067/2025, October 24, 2025). Conducted per Declaration of Helsinki and Colombian Resolution 8430/1993. Results will be disseminated via peer-reviewed publication, international conferences, and thesis submission.

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.

Traumatic brain injury (TBI) remains a global health challenge with mechanisms that are still insufficiently understood. While neuroimaging has been used to probe microstructural alterations and their association with head kinematics, findings remain heterogeneous. Finite element (FE) head modelling offers a more robust alternative, demonstrating a superior correlation with observed microstructural changes compared to traditional impact exposure metrics. However, most existing FE models are derived from single-subject scans or generic atlases, which often fail to represent specific study cohorts and introduce significant output variability. This study presents a reproducible computational framework that generates a cohort-specific template brain from MRI scans of adolescent male rugby players to produce a representative FE head model. The model was validated against cadaveric head experiments, demonstrating strong agreement with observed nodal displacements. Furthermore, simulations comparing the template-based model to subject-specific FE models with the identical impact conditions revealed significant differences in brain response. These results underscore the critical necessity of subject-specific modelling for the personalised characterisation of brain biomechanics. Our framework utilizes open-access tools, ensuring full reproducibility for research groups seeking to develop population-, sex-, or ethnicity-specific models. By providing a more accurate representation of cohort-average and individual brain responses, this work contributes to the improved mapping of mechanical strain to clinical findings and neurological alterations. TRANSPARENCY, RIGOR, AND REPRODUCIBILITY SUMMARYThis study is part of an ongoing longitudinal study in New Zealand. All procedures conducted in this study are in accordance with the ethics approval from the New Zealand Health and Disability Ethics Committee (20/NTB/14). All participants aged 16 and older provided informed consent, while participants under 16 provided assent with parental consent. For this study, general exclusion criteria included contraindication to MRI, neurological/psychiatric conditions, and dental braces affecting imaging quality. A total of 78 male high school rugby players (aged 14-18 years old) participated in this study. Inclusion criteria required no mTBI within the past six months prior to start of study, no history of mTBI incident with loss of consciousness, no neurological disorders, no history of drug or excessive alcohol use and no diagnosis of dementia or delirium. Each scan included a multi-parametric MRI scan (i.e. structural, diffusion, functional MRI), and a cognitive and symptom assessment. More details of the parameters and tests used are reported in the manuscript. To record head acceleration exposure across the whole season, an instrumented mouthguard was provided for each rugby player. A control group (14-18 years old) composed of non-collision sport, male athletes, was recruited and scanned at a single timepoint following the same protocol as the rugby players. The same inclusion and exclusion criteria were applied for the control group, with the addition of no self-reported mTBI history or participation in collision sports within the past two years. The primary aim of this study is to establish a computational framework that enables the creation of an average brain from MRI scans of subjects and to develop an FE model. Moreso, this FE model will incorporate fibre dispersion parameter from diffusion MRI and be validated against human head cadaveric experiments reported in the literature. This study is among the few to present a complete framework from MRI to finite element modelling using open-access tools, making it reproducible.

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex-vivo investigations, the in-vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra-high field structural MRI at 7 Tesla to investigate the depth-dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth-dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer-specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrates the feasibility of describing the three layered myelin architecture of CA1 in vivo, and provides information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.

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.

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) frequently co-occur in Veterans, producing overlapping symptoms and shared autonomic dysregulation. Heart rate variability (HRV) offers a noninvasive measure of autonomic function. Univariate HRV analyses often fail to capture complex, multivariate patterns associated with comorbidity. This study applied machine learning to HRV features extracted from MEG-derived electrocardiogram (M-ECG) signals to differentiate Veterans with TBI alone (TBI-alone; n = 42) from those with comorbid PTSD (TBI+PTSD; n = 40). Time-domain, frequency-domain, geometric, and nonlinear HRV metrics were analyzed using nested cross-validated Random Forest and XGBoost classifiers, with Boruta-based feature selection and SHapley Additive exPlanations for model interpretability. Both classifiers achieved above-chance discrimination (Random Forest AUC = 0.663; XGBoost AUC = 0.635). Multivariate models identified distributed autonomic signatures in TBI+PTSD, including altered sympathovagal balance, increased low-frequency proportion, and greater heart rate complexity. In contrast, univariate HRV differences were subtle and did not survive correction for multiple comparisons. These findings demonstrate how using multivariate machine learning HRV analysis could help with detecting comorbidity-specific autonomic patterns, suggesting that HRV-derived signatures may serve as exploratory biomarkers for risk assessment and targeted interventions in Veterans with TBI and PTSD.

An inflammatory subtype of major depressive disorder (MDD) is associated with treatment resistance pointing to an unmet need for adjunctive treatments. To evaluate treatment-related changes in brain inflammation, diffusion basis spectrum imaging (DBSI) is a promising non-radiation-based technique for longitudinal designs which has been verified with histopathology. However, its use as an endpoint in clinical trials is dependent on its individual-level reliability to robustly track changes. Here, we evaluated two DBSI runs acquired in 94 participants (including 43 participants with MDD) on the same day about 1.5 h apart to assess short-term test-retest reliability. Fiber fraction (reflecting axonal/dendrite density) and hindered fraction (reflecting edema) showed moderate to high test-retest reliability in both gray and white matter regions, whereas restricted fraction (reflecting cellularity) showed lower values in gray and white matter. Group-level reliability was similar in participants with MDD, except for lower reliability of hindered fraction in gray matter. Re-identification rates of individual brain maps were higher using voxel-level white matter signatures compared to gray matter regions of interest (ROIs) (p<.001). Crucially, participants with MDD showed reduced fiber fraction (tmax=4.68, k=38) and elevated hindered fraction (tmax=4.74, k=32) in the cingulate bundle, consistent with increased white matter inflammation, while gray matter ROI-based classification failed to identify cases. We conclude that DBSI is a promising technique to track inflammatory signatures in MDD, particularly in white matter tracts. Since several frontal and subcortical gray matter ROIs showed insufficient reliability, their assessment would require multiple DBSI runs to provide robust estimates.

(1) Background: Brain cancer is the ninth leading cause of cancer death in the US, with approximately 76,000 newly diagnosed cases annually. Studies show that at time of diagnosis, up to six-months post-treatment, 50%-80% of brain cancer survivors (BCS) report cognitive dysfunction. Mild cognitive impairment (MCI) has gained increasing attention as a persistent disability experienced by up to 75% of all BCS, which affects memory, concentration, executive function, etc. Studies show cognitive training with computerized gaming as improving cognitive function for patients with stroke, dementia, and Parkinsons. It is of significant clinical interest to develop innovative interventions that reduce MCI. Aim: To improve cognitive performance of BCS suffering with MCI by evaluating the feasibility, acceptability and effect of a Virtual Reality Cognitive Rehabilitation Training (VR-CRT) platform during four weeks of cognitive training. (2) Methods: We employed a quasi-experimental pretest/posttest non-randomized/non-blinded single-arm design for 4 weeks, with an experimental group (n=6, after attrition) using VR-CRT. Participants were selected based on convenience sampling using the electronic medical record to identify qualified patients, guided by inclusion/exclusion criteria. Feasibility was defined by retention as >80%, with usability testing using the System Usability Scale (SUS) and NASA-TLX surveys. The Hopkins Verbal Learning Test (HVLT), Controlled Oral Word Association (COWA) test, and Trail Making A-B (TM-A/B) test were used to measure cognitive performance, comparing baseline to post week-four. (3) Results: The feasibility criteria of >80% was met. All SUS and NASA scores were in the higher index, suggesting a high degree of usability, with low workload demand. For effect, the COWA findings showed a significant improvement (41.38%), with a paired sample T-Test confirming that the participants COWA scores improved significantly from pre- to post-intervention (p = 0.03), indicating enhanced verbal fluency and executive functioning after intervention. HVLT (combined) showed improvements of 18.75% for Form A and 11.32% for Form B, which also showed a significant improvement (p = .04) in the retention discrimination index from pre- to post-test. The TM-A/B test showed an improvement (25.97%), suggesting that the participants spent less time completing both parts A and B, but was not statistically significant. (4) Conclusion: This study fulfilled our aim to demonstrate modest to significant cognitive improvement using VR-CRT with brain cancer patients with MCI. Despite the small sample size, we believe the use of virtual reality will lead to important advances for patients with MCI, particularly the frontal lobe brain region, expressed in executive function.

BackgroundMultiple sclerosis (MS) is characterized by focal white matter (WM) lesions, but subtle damage also occurs in normal-appearing white matter (NAWM). We developed a method to generate quantitative T1 maps from MPRAGE (Magnetization Prepared Rapid Gradient Echo) images and evaluated its ability to detect NAWM abnormalities across different MS phenotypes. MethodsT1 maps were derived from MPRAGE using a theoretical signal model and compared with MP2RAGE (Magnetization Prepared 2 Rapid Gradient Echoes) T1 values in four healthy volunteers. The method was then applied to 87 MS patients, divided into clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and primary progressive MS (PPMS), with age- and sex-matched healthy controls. T1 was measured in NAWM and lesions. Histogram analysis provided mean T1, full width at half maximum (FWHM), and skewness. ResultsIn healthy volunteers, T1 values matched MP2RAGE. In controls matched to the MS cohort, T1 increased with age (r = 0.35, p < 0.05). CIS patients showed no significant differences in any metric. RRMS and PPMS patients showed unchanged mean NAWM T1 but significantly different distributions, with higher FWHM (p<0.05) and skewness (p<0.001). An increase in T1 values was observed in MS lesions compared to NAWM in all groups. ConclusionThis study confirms the feasibility of deriving quantitative T1 maps from standard MPRAGE, offering reliable information to facilitate MS monitoring without additional acquisitions.

ABSTRACT INTRODUCTION: Microscopic fractional anisotropy ({micro}FA), an emerging diffusion MRI metric, may be more sensitive than conventional metrics to gray matter microstructural changes in neurodegeneration. This pilot study compared {micro}FA, mean diffusivity (MD), and volume between genetic frontotemporal dementia (FTD) variant carriers and non-carriers in the insula, frontal pole, and medial orbitofrontal cortex (mOFC). METHODS: Carriers and familial non-carriers of FTD variants in C9orf72, GRN, or MAPT were scanned between October 2024-December 2025. Non-parametric aligned rank transform ANCOVAs were computed to analyze between-group differences in {micro}FA, MD, and volume while controlling for age. RESULTS: Carriers (n=12) exhibited lower insula {micro}FA than non-carriers (n=8): F(1,19)=5.89, 95% CI [-10.7,-0.75], p=0.027, 2p=0.26. No group-differences were observed in other metrics, including MD and volume. DISCUSSION: Reduced {micro}FA in the insula, a region vulnerable to early atrophy in FTD, may be more sensitive to early microstructural changes in genetic FTD than traditional diffusivity measures.

Background: Head and neck cancer (HNC) patients experience clinically significant anxiety and depression in 65-85% of cases during active treatment. Current supportive care lacks personalized, real-time non-pharmacological interventions. Skitii is a novel HRV-adaptive music therapy system that uses continuous RMSSD (root mean square of successive differences) monitoring via a Polar H10 chest sensor to select music in real-time, targeting parasympathetic recovery (RMSSD >=30ms). Methods: This is a prospective, open-label, randomized controlled trial (1:1 allocation) at Yenepoya Medical College Hospital, Mangalore, India. Adults aged 18-75 years with confirmed head and neck cancer (any subsite, Stage I-IV) undergoing radiotherapy and/or chemotherapy with baseline distress (HADS >=8 or NCCN Distress Thermometer >=4) will be enrolled. Participants are randomized to Skitii adaptive music therapy (20-minute sessions, 3 times daily, 3 weeks) or static music therapy control. Skitii uses a two-phase algorithm: Phase 1 (0-2.5 minutes) uses heart rate as a stress proxy for immediate music selection; Phase 2 (2.5-20 minutes) uses RMSSD to adapt music every 2.5 minutes when physiological state changes by >=20%. Primary endpoints are HADS-Anxiety score and resting RMSSD at Week 3. Sample size is 70 (35 per arm), powered at 80% to detect a 2.5-point HADS difference (SD=3.8, alpha=0.05, 15% dropout). Analysis is ANCOVA, intent-to-treat. Discussion: This is the first randomized controlled trial evaluating RMSSD-based adaptive music therapy in cancer patients. The active control design isolates the effect of the adaptive algorithm from music exposure alone. If positive, results will support a scalable, cost-effective supportive care intervention with objective physiological monitoring, and provide the clinical evidence base for CDSCO Class B medical device approval for Skitii in India, with future CE Mark and FDA applications planned. Trial Registration: Clinical Trials Registry - India CTRI CTRI/2025/11/116732

The proliferation of gambling advertising has intensified concerns regarding its influence on vulnerable populations, yet the neural mechanisms underlying cue-reactivity to these stimuli remain underexplored in ecologically valid settings. This study protocol proposes a novel methodological framework to investigate prefrontal cortical responses to gambling advertisements in individuals with varying degrees of gambling experience. Materials and methods: This cross-sectional study will recruit 44 participants, divided into a clinical group (individuals with high-frequency gambling or gambling disorder) and a matched control group. Neural activity will be recorded using fNIRS while participants view gambling-related, neutral, violent, and sexual stimuli. Secondary measures include validated scales for gambling severity (SOGS), impulsivity, sensation seeking, and alexithymia. Data analysis will primarily utilize inter-subject correlation (ISC) to quantify neural synchronization and multiband frequency decomposition to capture dynamic affective processing. Advanced preprocessing, including short-channel regression, will be applied to ensure signal robustness. Discussion: By combining portable neuroimaging with a data-driven ISC approach, this study aims to identify objective neural markers of gambling vulnerability. The findings will provide novel insights into the idiosyncratic processing of commercial stimuli, potentially informing public health policies and the development of more effective evidence-based regulations for gambling marketing.