NeuroImage: Reports

Background: Transcranial direct current stimulation (tDCS) is increasingly used as an adjunct to rehabilitation for young people with cerebral palsy (CP), yet considerable variability exists in clinical response. Individualised electric field modelling provides an opportunity to estimate the distribution of electrical fields generated by the stimulation delivered to the brain and explore potential relationships with functional outcomes. Methods: Structural MRI scans from nineteen participants (10-16 years) from a previously published randomised controlled trial (ISRCTN74235136) investigating the effects of tDCS combined with motor training, underwent participant-specific finite element modelling using SimNIBS. Electric field strength was quantified within anatomically defined motor regions of interest, including the primary motor cortex (M1), dorsal premotor cortex (PMd), supplementary motor area (SMA), and a combined motor network. Global grey matter electric field metrics and stimulation focality were also extracted. Results: Estimated electric field strength differed significantly across motor regions (p<0.001), with PMd receiving significantly greater stimulation than both M1 and SMA. Electric field strength within a control region (primary visual cortex) was significantly lower than within M1 (p<0.001). Despite inter-individual variability in regional and global electric field metrics, no significant associations were observed between estimated electric field strength or focality and changes in function following intervention. Conclusion: Individualised electric field modelling demonstrated that an M1-targeted tDCS montage preferentially stimulated PMd rather than M1 in young people with CP. These findings highlight the importance of subject-specific modelling when characterising current distribution and suggest that variability in electric field strength alone does not explain variability in behavioural response.

Background: Large language models have been proposed to improve patient comprehension of radiology reports. However, whether they improve objective understanding remains unproven. Purpose: To evaluate the effect of appending an LLM-generated lay summary to brain MRI reports on objective and subjective patient comprehension in a randomized controlled trial. Materials and Methods: In this randomized controlled trial, 2,727 adult participants from the ComPaRe e-cohort were randomly assigned to interpret six standardized brain MRI reports for headache, presented either in their native format (control; n = 1,401) or appended with a lay summary generated by an open-weights LLM (Mistral Small 3.2) (intervention; n = 1,326). The primary outcome was objective comprehension, defined as the rate of correct classification of whether the report provided a probable explanation for the headache, with ground truth established by four-radiologist consensus. Secondary outcomes included satisfaction, subjective comprehension, anxiety, and willingness to contact a healthcare professional. Generalized estimating equations accounted for repeated within-participant observations. Results: A total of 2,727 participants (mean age, 52 years +/- 15; 75.2% women) were evaluated. Objective comprehension did not differ between arms (58.3% vs 59.4%; odds ratio (OR) 0.97; 95% CI: 0.90-1.06; P = .54). The intervention significantly improved overall satisfaction (64.9% vs 36.7%; OR 3.26; 95% CI: 2.93-3.64; P < .001) and subjective comprehension (50.3% vs 24.0%; OR 3.17; 95% CI: 2.82-3.56; P < .001). High anxiety was modestly reduced (25.1% vs 26.6%; OR 0.92; P = .037). The effect on objective comprehension varied by report type (P for interaction < .001): summaries improved comprehension of symptom-explaining reports (42.4% vs 37.4%; P < .001) but reduced it for normal reports (72.5% vs 76.6%; P = .001). Conclusion: LLM-generated lay summaries appended to brain MRI reports improved patient satisfaction and subjective comprehension but did not improve objective comprehension, indicating a gap between perceived and actual understanding that should be addressed before clinical integration.

Background: Late preterm (LP) children (34 0/7 - 36 6/7 weeks of gestation) are at risk for neurocognitive challenges, yet the neuroanatomic and functional disruptions underlying these developmental differences remain poorly understood. Purpose or Hypothesis: Investigate (1) regional differences in cortical surface area and thalamic nuclei volume and (2) structural variations that may explain heterogeneity in neurocognitive functioning in LP versus full term (FT) school-aged children, using two complementary approaches: a vertex-wise analysis of cortical surface area and a region-of-interest volumetric analysis of thalamic nuclei. Study Type: Secondary analysis of a prospective observational cohort study. Population or Subjects: 48 LP and 72 FT children aged 6-13 years. Field Strength/Sequence: 3T; Sagittal T1-weighted MP-RAGE and axial T2-weighted 3D SPACE. Assessment: FreeSurfer 7.4.1 was used to parcellate cortical regions (Destrieux atlas) and segment thalamic nuclei (25 nuclei). Neurocognitive functioning was assessed across four domains: hyperactivity/inattention (Pediatric Behavior Scale), processing speed (WISC-IV), working memory (WISC-III), and visual-spatial perception (Benton JLO). Statistical Tests: Independent samples t-tests for group comparisons; vertex-wise GLMs for cortical surface analyses with false discovery rate (FDR) correction; and multiple linear regression for thalamic nuclei analyses with FDR-corrected q < 0.05. Results: Vertex-wise analyses revealed regional differences in cortical surface area between LP and FT children in both hemispheres, along with associations between surface area in several cortical regions and hyperactivity/inattention, working memory, and visual-spatial perception. In contrast, using an ROI approach, thalamic nuclei volumes did not differ between groups and were not associated with any neurocognitive domains. Conclusion: LP birth may be associated with subtle, region-specific bidirectional left and right hemispheric cortical surface area differences rather than widespread structural alterations in middle childhood, with regional macrostructural measures associated with individual differences in neurocognitive functioning.

Abstract Background The neuropsychiatric sequelae (cognitive deficits, anxiety and depression) post-COVID-19 exist as part of the spectrum of the multisystemic long COVID. People with these symptoms have been shown to have worse functional outcomes. Hence, this significantly impacts the economy, primarily due to productivity losses. Yet, the precise underlying pathogenesis remains unknown, as do any diagnostic or prognostic biomarkers. Aim This study aims to identify functionally impacted brain regions in those with post-COVID-19 neurological sequelae and to evaluate how alterations in brain function relate to acute serum inflammatory mediators and brain injury biomarkers. Methods The study will utilise data from the COVID-19 Clinical Neuroscience Study (CNS), a large UK multicentre study conducted during the pandemic. This sub-study will be a secondary analysis of the COVID-19 CNS, a prospective observational study that compared COVID-19-positive participants with negative controls. Participants had an MRI, blood tested for acute serum inflammatory mediators and brain injury biomarkers, and neuropsychiatric assessment (cognitron test, PHQ-9 and GAD-7) post-acutely and at follow-up. The DPABI (Data Processing & Analysis for Brain Imaging) toolbox will be used for pre-processing and analysis of the neuroimaging data (resting state functional MRI) to obtain regional homogeneity (ReHo). The association between ReHO and neuropsychiatric symptoms, acute inflammatory mediators and brain injury biomarkers will be explored. Regression models would be used to determine the risk and protective factors for developing these symptoms. Conclusion It is anticipated that the study will provide new insights into the functional basis of post-acute COVID-19 neuropsychiatric manifestations and identify new diagnostic biomarkers. Key words: Regional Homogeneity, COVID-19, functional MRI, neuropsychiatry, biomarkers

Objective. Intermittent theta burst stimulation (iTBS) is a repetitive transcranial magnetic stimulation (rTMS) protocol used in clinical settings to alleviate symptoms of psychiatric disorders. Although the pulse parameters currently used in iTBS have remained unchanged since the first treatments, recent controllable TMS devices allow for the personalization of pulse shape and duration, opening the possibility of testing the efficacy of other pulse parameters in modulating corticospinal excitability (CSE). Methods. In a repeated-measures design, changes in CSE were induced by the administration of iTBS over the left primary motor cortex under three different conditions: long bidirectional pulse (L-Bi), long quasi-unidirectional pulse (L-QU), and a control short quasi-unidirectional pulse (S-QU). We assessed TMS-induced motor evoked potentials before and up to 70 minutes after iTBS. We hypothesized that L-QU pulses would induce greater facilitation than other conditions. Results. A mixed linear model showed that all conditions induced increased MEPs compared to baseline. However, the L-Bi pulse led to a larger and more sustained MEP increase than both unidirectional pulses, while the S-QU pulse appeared less effective in modulating CSE. We observed large within- and between-subject variability in responsiveness to the iTBS protocols. Conclusion. These results suggest that L-Bi pulses in iTBS protocols are more potent than unidirectional pulses in inducing CSE changes in the cortex of healthy adults. The individual variability in response to iTBS and the potential clinical relevance of these findings are discussed.

Objectives: Non-invasive brain stimulation (NIBS) holds significant promise for treating neurological and neuropsychiatric conditions, yet translation into routine clinical practice remains limited. We aimed to explore stakeholder perceptions of NIBS and barriers to its clinical adoption. Methods: We conducted focus-group interviews with 33 participants across three key stakeholder groups in the UK: (1) people with lived experience of brain injury, depression, or dementia; (2) healthcare professionals; and (3) researchers. Reflexive thematic analysis was used to identify themes in the data. Findings: Seven key themes emerged spanning preferences, hope and disappointment, communication, accessibility, infrastructure, ethical/regulatory uncertainty, and the evidence base. Across groups, NIBS was viewed positively and with cautious optimism, but substantial barriers were highlighted, including limited public and clinical awareness, challenges in demonstrating cost-effectiveness, infrastructure constraints, and difficulties navigating regulatory and translational pathways. Participants emphasised the importance of clear communication, improved education, and stronger interdisciplinary collaboration to support adoption. Notably, stakeholders prioritised evidence of clinical efficacy and usability over detailed mechanistic understanding. Conclusions: These findings provide actionable insights into the translational gap in NIBS and highlight priorities for facilitating its integration into clinical care.

Background and Objective: For their acceptance as endpoints in clinical trials, biomarkers and clinical outcome assessment (COA) measures should show reliability by being reproducible (precise) and responsive to change. We evaluated precision and responsiveness of MRI-derived brain volume metrics and various COAs in ceroid-lipofuscinosis, neuronal-3 (CLN3) disease. Methods: This longitudinal observational study (NCT03307304) included 44 individuals with CLN3-related disease (ages 0.5-29.1 years, 48% female). Brain volumetric measures were computed using SynthSeg-v2.0 from T1-weighted 3D MPRAGE images acquired at 3T (Median [Q1, Q3] total MRI follow-up duration from baseline: 2.04 [0.00, 3.69] years). Compartmental tissue volumes were normalized to a model-adjusted total intracranial volume and scaled to the tissue-specific volume fraction expected in healthy adolescent brains to extract measures of brain atrophy. COAs included the Vineland Adaptive Behavior Scales, verbal IQ, and the Unified Batten Disease Rating Scale (UBDRS). Analysis of linear mixed-effects models included only CLN3 participants with syndromic presentation, having three or more visits per measurement to estimate slope, its relative standard error (RSE), and the minimum inter-visit interval (Tmin) for statistically significant progression for each participant. Tmin to detect progression in 75% of the population (Tmin,75%) was computed for each metric. Results: Among brain volumetric measures, brain parenchyma volume (BPV) and gray matter volume (GMV) were the most precise and responsive metrics. BPV showed an overall intra-individual decline with age of -1.32%/year (95% CI: -1.64% to -0.99%), low RSE of 12.5%, and short Tmin,75% of 0.85 years (95% CI: 0.47-1.24). Amongst COAs, the UBDRS Clinical Global Impression (CGI) score was the most precise and responsive with an overall intra-individual increase of 1.26 units/year (95% CI: 1.03-1.49), RSE of 24.10%, and Tmin,75% of 2.56 years (95% CI: 1.73-3.46), though with lower precision (RSE higher) and lower responsiveness (Tmin,75% longer) than BPV. Discussion: MRI-derived metrics, in particular BPV and GMV, detected change in brain atrophy with high precision and responsiveness suggesting that they would be informative for evaluating potential neuroprotective therapies in CLN3 disease. These findings support incorporating MRI-derived volumetric measurements alongside clinical assessments in future clinical trials in CLN3.

Transcranial magnetic stimulation (TMS) is widely used in both clinical and research settings to study and treat neurological and neuropsychiatric disorders, yet its underlying neural mechanisms remain unclear; particularly how stimulation influences both local and distant regional activity in relation to behavior. In this study, we combined single-pulse TMS with concurrent whole-head functional near-infrared spectroscopy (fNIRS) to examine hemodynamic and behavioral responses during a working memory task, with a focus on behavioral variability. Single TMS pulses were delivered to the left dorsolateral prefrontal cortex (DLPFC) while healthy participants rested; additionally, single pulses were delivered online to the left DLPFC while participants performed the working memory task. Across all participants, we observed a reliable load-dependent increase in hemodynamic activity associated with task. However, behavioral responses to TMS varied during the task. When participants were stratified into subgroups based on performance, a distinct topographic pattern emerged. During the task, TMS systematically modulated hemodynamic responses in regions including DLPFC, superior medial gyrus, precuneus, and parietal lobule, which are areas belonging to the default mode network. Moreover, the hemodynamic response during the single pulse alone sessions without any task was also found to be associated with the behavioral responses in a coherent pattern involving DLPFC, precuneus and parietal lobules. These findings suggest that variable behavioral outcomes during online TMS task are linked to distinct hemodynamic responses in a topographic pattern of local and distant regional areas.

Objective: This computational modeling study quantified the influence of sex and race-related cranial anatomy on predicted brain-wide current flow during electroconvulsive therapy (ECT) across conventional (bifrontal (BF), bitemporal/bilateral (BL), right unilateral (RUL)) and experimental (focal electrically administered seizure therapy (FEAST) and frontomedial (FM)) electrode montages. The objective was to determine whether race-associated variability meaningfully contributes to differences in ECT stimulation metrics across montages. Methods: Finite element head models of Chinese, Black, and Caucasian subjects were developed using high-resolution magnetic resonance imaging and analyzed using the Realistic vOlumetric- Approach-based Stimulator for Transcranial electric stimulation (ROAST) pipeline (N = 150 total; n = 50 per cohort, comprising 25 M and 25 F, age range: 20-30 years). Five ECT montages were simulated under a constant-current condition (900mA). Stimulation strength (Ebrain/Eth) was quantified as 90th percentile of brain-wide E-field magnitude (Ebrain) relative to neuronal activation threshold (Eth = 0.25 V/cm) quantified stimulation strength. Overall focality was evaluated as a percentage of brain volume stimulated above the neural activation threshold (Ebrain [&ge;] Eth), while laterality was quantified as the median right-to-left hemispheric E-field magnitude ratio. The effects of race, sex, and montage on stimulation strength, focality, and hemispheric laterality were statistically analyzed. Results: Substantial race- and sex-related differences observed in cranial anatomy resulted in systematic variation in predicted ECT-induced E-field intensity. Brain-wide E-field magnitude varied by both race and montage, with the largest fields generally observed in Caucasian head models and during BL stimulation. Montage exerted the strongest effect on stimulation strength (Ebrain/Eth) with BL and FEAST producing the highest stimulation strengths, followed by RUL and FM, while BF produced the lowest. Caucasian subjects generally predicted higher stimulation strengths than Black and Chinese subjects, whereas females predicted modestly higher stimulation strengths than males. Laterality was primarily determined by montage, with FEAST producing the greatest hemispheric asymmetry, followed by RUL. Chinese subjects demonstrated higher laterality ratios than both Black and Caucasian subjects. BL, RUL, and FEAST stimulated substantially larger brain volumes above neural activation threshold (less focal stimulation) than BF. Lower focality was observed in Caucasian subjects relative to Black and Chinese subjects, and in females relative to males. Conclusions: Electrode montage was the primary determinant of predicted ECT stimulation strength, focality, and laterality. Race-related anatomical differences and, to a lesser extent, sex-related differences systematically altered stimulation patterns, supporting consideration of individualized anatomy in ECT dosing and treatment optimization.

Introduction The superior longitudinal fasciculus (SLF) is a major association fiber bundle implicated in cognition, visuospatial attention, language, and motor control, and its impairment is linked to several neurological and neuropsychiatric disorders. This proof-of-concept study was performed with three main objectives in healthy adults. First, to fuse whole brain spectroscopic (WBSI) and diffusion MRI (dMRI) derived parametric maps along the SLF I and II segments to quantify their spatial concordance, second, to evaluate regional metabolite concentrations and microstructural properties along these trajectories and finally, to determine the relationships between the WBSI and dMRI parameters within these segments. Methods Ten healthy adults (4F, 6M; mean age 31.4 {+/-} 7.53 years) underwent 3T MRI including multi-shell high angular resolution diffusion imaging and WBSI. After preprocessing and non-linear co-registration, WBSI-derived white matter metabolite maps and neurite orientation dispersion and density imaging (NODDI) / diffusion tensor imaging (DTI) derived parametric maps were spatially aligned and projected along the centroid of reconstructed SLF I and II segments divided into 20 discrete, anatomically contiguous sections. Results A strong spatial alignment between WBSI and dMRI imaging modalities was confirmed by mutual information and Pearson's correlation analyses. Intra-subject repeatability, as assessed from a single participant scanned three times, demonstrated high tract reconstruction reliability (mean Dice similarity coefficients >0.79; track density-weighted Dice >0.97) and acceptable intra-subject coefficients of variation. Inter-subject coefficients of variation were within acceptable ranges ({approx}3-17%) for most parameters, with free water fraction (fiso) exhibiting relatively higher variability. Single and multivariate regression analyses revealed significant associations between WBSI and dMRI tract profiles: choline/creatine (Cho/Cr) and choline/ N-acetyl aspartate (Cho/NAA) ratios showed positive linear associations with intra-cellular volume fraction (ficvf) and fractional anisotropy (FA), and negative associations with mean diffusivity (MD) along bilateral SLF I, with ficvf and MD identified as the strongest combined predictors of metabolite ratios. Conclusion Co-localization/fusion of WBSI and NODDI/DTI data into one framework offers a reliable, user-independent way for mapping regional metabolite and microstructural alterations along the path of SLF. Moving forward, this image processing pipeline has the potential to enhance diagnosis and clinical assessment of neurological disorders linked to SLF damage.

BackgroundThe balance between excitatory and inhibitory neuronal signalling (E/I balance), proposed as a key mechanism controlling neuronal activity, is disrupted in many neurodevelopmental conditions. One such condition is Neurofibromatosis Type 1, a monogenic neurodevelopmental disorder characterised by increased inhibitory tone. While previous research suggests that E/I balance may be altered in infancy, it is unknown whether E/I balance remains altered during adolescence in NF1. Here we investigated this question using the aperiodic exponent of the resting electroencephalogram (EEG) power spectrum, a proposed electrophysiological index of E/I balance. MethodThe aperiodic exponent of the EEG power spectrum ( 1/f) was estimated for 16 adolescents with NF1 diagnosis aged 11-16, and 16 age- and sex-matched neurotypical controls. General linear models (GLM) were fit to estimate effects of NF1 diagnosis, age and their interaction on aperiodic exponent. We also estimated the peak dominant frequency and power in oscillatory activity of the EEG signal and fitted the same structure of GLM models. Cognitive assessments across domains of memory, executive function and attention were also analysed with GLM to examine brain-cognition associations. ResultsThe NF1 group had higher aperiodic exponent compared to neurotypical controls, but the aperiodic exponent was not associated with cognitive performance. After accounting for aperiodic activity, the NF1 group also had lower dominant oscillatory frequency than the control group. There was no significant interaction between NF1 diagnosis and age on PAF. There were no group differences in peak alpha power. ConclusionsWe demonstrate for the first time that the alterations to aperiodic activity in NF1 are consistent with the proposed mechanism of increased inhibitory tone. These findings show the potential of this paradigm for future pharmacological and brain stimulation trials investigating treatment-related changes in cortical function.

Neurological and cardiovascular disorders frequently coexist, yet targeted dual-system interventions remain underinvestigated. Transcranial magnetic stimulation (TMS), including intermittent and continuous theta-burst stimulation (iTBS/cTBS), non-invasively modulates primary motor cortex (M1) excitability. Concurrently, ketone monoesters (KME) show neuroprotective potential and alter cardiovascular hemodynamics. In a randomized, double-blind, placebo-controlled crossover study, 44 healthy young adults were stratified to receive iTBS or cTBS (n = 22/group). Participants completed two sessions separated by 1 week, consuming either a KME or placebo beverage, followed by TBS 1-hour post-ingestion. Motor evoked potentials (MEPs) from the right first dorsal interosseous muscle were tracked for 30 minutes post-stimulation. Blood pressure was measured every 3-5 minutes, heart rate was monitored continuously, and venous blood was sampled for glucose, beta-hydroxybutyrate (BHB), pro-BDNF, mature BDNF (mBDNF), and the BDNF rs6265 polymorphism. We found that KME significantly elevated blood BHB and heart rate while decreasing blood glucose and diastolic blood pressure. KME did not alter resting motor threshold, baseline MEP amplitude, or MEP latency. Factorial analysis showed no significant modification of post-TBS MEP time courses by KME. In exploratory within-condition analyses, placebo-cTBS induced significant late increases in MEP amplitude, whereas KME-cTBS showed a blunted post-stimulation response. Serum mBDNF and pro-BDNF concentrations remained unchanged. In conclusion, combining KME and TBS is feasible, well-tolerated, and may exert concurrent neurological and cardiovascular effects. This work opens the door to a novel metabolic-neuromodulatory avenue that merits confirmation in larger cohorts and establishment of clinical relevance in patients with comorbid neurological and cardiovascular disorders.

Multisite functional Magnetic Resonance Imaging (fMRI) studies are rapidly becoming the norm to allow the acquisition of large samples required to perform advanced statistical techniques, e.g. machine learning. However, acquiring data at multiple sites includes methodological and technical challenges due to the difference in the facilities of each site, such as scanner manufacturer and model. These new challenges add to the already well-known challenges of fMRI data, including scanner-related noise, participant movement, and physiological confounds. To ensure the optimal quality of data, a balance needs to be achieved between standardizing data preprocessing across sites and optimizing within-site data preprocessing. To define the optimal preprocessing pipeline including standard steps and additional denoising technique for our multisite dataset, we first tested 3 commonly used preprocessing pipelines, i.e. fMRIPrep, FSL, and CONN. These pipelines all include standard steps, e.g. motion correction, temporal filter, etc. In a second step, to further improve signal quality, we tested the efficiency of 3 additional denoising techniques on the output of the data preprocessed with the previously defined pipeline. These techniques included aCompCor, FSL FIX and ICA-AROMA. Signal quality was quantified as temporal signal-to-noise ratio (tSNR) across and within sites. Our results show that the performance of the preprocessing pipeline and denoising technique varies between sites. FSL yielded the highest tSNR at two sites and fMRIPrep at the third, revealing a significant site x pipeline interaction. An FSL-based pipeline with minimal adjustment to accommodate site-specific parameters and followed by denoising using a single FSL FIX classifier, which was custom-trained across sites, achieved the highest quality of signal in our data and yielded the greatest consistency in improved data quality across sites. Because of the potential of this pipeline to adequately identify and address site-specific noise, while remaining constant across sites, we selected it as optimal preprocessing pipeline for our dataset.

Background: Choroid plexus (CP) volume is an emerging magnetic resonance imaging (MRI) biomarker in various disorders of the central nervous system (CNS). However, clinical translation is hindered by methodological heterogeneity and inconsistent anatomical coverage. Double inversion recovery (DIR) - a sequence providing dual-tissue suppression - is a promising candidate to improve CP segmentation. Methods: The dataset included 93 scans across healthy subjects and individuals with multiple sclerosis (MS), divided into a training set (n = 63), an internal test set (n = 20), and an external test set (n = 10). First, relative CP signal intensity and tissue contrast ratios on DIR were compared against fluid-attenuated inversion recovery (FLAIR) and T1-weighted (T1w) sequences (pre- and post-contrast). Reproducibility of manual CP segmentations was assessed via intraclass correlation coefficients (ICCs). Subsequently, we developed a 3D nnU-Net model for CP segmentation based on manually labeled DIR masks. Model performance was evaluated against manual segmentation using spatial overlap and volumetric error metrics. Finally, we compared our DIR-based model against three publicly available T1w- or FLAIR-based tools by assessing slice-wise volume distributions and voxel-wise density maps. Results: DIR demonstrated the highest CP signal intensity and most consistent tissue contrast among evaluated MRI sequences (p < 0.001). Intra- and inter-rater agreement for manual CP segmentations was robust (ICC = 0.92 and 0.83, respectively). The trained nnU-Net achieved high internal accuracy (Dice = 0.82) independent of scanner, diagnosis, or absolute CP volume, and generalized well to the external test set (Dice = 0.75). Compared to public T1w- and FLAIR-based models, DIR-based approaches (nnU-Net and manual) yielded significantly larger CP volumes (p < 0.01). Axial volume distribution analysis attributed this difference to a distinct bimodal profile in DIR segmentations, more fully capturing the CP inside the temporal horn of the lateral ventricle (p < 0.001 against T1w- and FLAIR-based models). Conclusions: By leveraging the superior tissue contrast of DIR, our nnU-Net model achieves highly accurate CP segmentation that generalizes across scanners and captures the inferior extent of the C-shaped structure often missed by conventional models. This may improve standardization of CP volumetry and allow for more reliable studies in CNS disorders.

Purpose: To develop and evaluate an anatomy-aware deep learning framework for enhancement of neonatal 64mT T2-weighted MRI that improves anatomical visibility while preserving native ultra-low-field contrast and enabling quantitative structural analysis. Methods: A multitask network, jointly performing image enhancement and tissue segmentation, was trained on 75 and evaluated on 20 paired neonatal 64mT/3T MRI datasets spanning a broad range of gestational ages and pathologies. To preserve native 64mT contrast, 3T images were locally harmonized before training. The framework also generated quality-control maps and regional volumetric measurements. Volumetric agreement was further assessed in 40 paired term-born control datasets. Results: Enhanced 64mT images showed improved image quality metrics and better delineation of cortical, deep gray matter, ventricular, white matter, and posterior fossa structures while maintaining native contrast characteristics. Tissue segmentations demonstrated good agreement with reference 3T labels. Volumetric measurements showed excellent correspondence with 3T across major tissue compartments, with only small systematic regional biases. Conclusions: Anatomy-aware enhancement enables automated tissue segmentation and volumetric analysis directly from neonatal 64mT MRI while preserving native image contrast. These findings support the feasibility of quantitative neonatal neuroimaging at ultra-low field.

Background and Objectives Transient ischemic attack (TIA) diagnosis is challenging because it relies mainly on clinical assessment and exclusion of common differential. Functional MRI (fMRI) may provide a diagnostic biomarker by detecting transient brain dysfunction not visible on conventional imaging. This pilot study aimed to characterize acute motor-task BOLD activation in patients with suspected DWI-negative TIA and compare functional patterns between confirmed TIA and alternative diagnoses. Secondary objectives were to assess longitudinal changes in activation and connectivity at 3 months. Methods In this prospective single-center study, adults presenting within 24 h of transient anterior-circulation neurological symptoms underwent conventional MRI and additional motor-task fMRI. Patients with acute DWI lesions were excluded. Final diagnosis was established after 3-month follow-up. Whole-brain analyses, individualized motor cortex region-of-interest (ROI) analyses, and generalized psychophysiological interaction (gPPI) connectivity analyses were performed during the acute phase and at 3 months. Results Eight patients were enrolled; six had complete longitudinal imaging data and were included in the final analyses. Final diagnoses were TIA (n=2), migraine aura (n=2), functional neurological disorder (n=1), and hypoglycemia (n=1). Whole-brain and ROI analyses showed reduced bilateral motor-related BOLD responses during the acute phase in both TIA patients and in the patient with hypoglycemia. In contrast, patients with migraine and functional neurological disorder exhibited less marked longitudinal changes. In TIA patients, motor cortex activation increased at 3 months, tending to normalize toward values observed in non-TIA participants. Connectivity analyses revealed heterogeneous patterns, but the 2 TIA patients demonstrated increased longitudinal connectivity between the motor cortex contralateral to symptoms and other sensorimotor regions, including supplementary motor, premotor, parietal, and postcentral cortices. Discussion These preliminary findings suggest that TIA may be associated with transient bilateral reductions in motor-network activity. Functional abnormalities appeared to improve over time, supporting the hypothesis of reversible network dysfunction. Although limited by the very small sample size, this study provides the first longitudinal assessment of emergency task-based fMRI in rigorously defined TIA and supports further investigation of acute functional MRI as a potential biomarker of transient cerebral dysfunction.

Limited access to neuroimaging remains a major constraint on neurological care in many low-resource areas. We conducted a descriptive landscape analysis of neuroimaging access in Chad using hospital-reported data, publicly available healthcare and infrastructure data, and contextual information from clinicians and radiology personnel at major hospitals in N'Djamena. This analysis characterizes key constraints on neuroimaging access in Chad and highlights practical considerations for expanding imaging capacity in resource-limited settings. Chad has only one magnetic resonance imaging scanner for a population of approximately twenty-one million. The country's major hospitals and imaging workforce are concentrated in the capital, and the sole MRI system is an older 0.35 T scanner located at a private hospital. Access is further limited by scan cost, geographic centralization, unreliable electricity, limited technical support, and shortages of trained imaging personnel. Hospital data indicate a substantial burden of neurological conditions, particularly stroke and neurological infections, for which imaging can be important for diagnosis and management. We place these findings in the context of emerging lower-cost, compact, and mobile magnetic resonance imaging technologies. Such systems may reduce some infrastructure and siting requirements, but limitations related to image quality, maintenance, workforce capacity, and long-term sustainability remain important considerations.

Background Non-invasive modulation of deep brain structures remains a major challenge in human neuroscience and neurorehabilitation. Transcranial temporal interference stimulation (tTIS) has emerged as a promising approach for engaging subcortical regions, but its effects on striatal neurochemical markers and functional connectivity remain unclear. Objective To investigate whether 20-Hz tTIS designed to target the right striatum modulates GABA+ and glutamate-glutamine complex (Glx) levels and whether neurochemical changes are associated with changes in resting-state functional connectivity. Methods Thirty-four healthy right-handed participants were randomly assigned to the tTIS group (20-Hz beat frequency) or sham group (0-Hz frequency difference). Participants underwent proton magnetic resonance spectroscopy (1H-MRS) and resting-state fMRI before and after 30 min of stimulation. One participant in the tTIS group was excluded from the 1H-MRS analyses because of data corruption. Results The direct between-group difference in Glx change did not reach statistical significance, although the tTIS group showed a numerically greater reduction than the sham group (p = 0.066). Exploratory within-group analyses showed a significant decrease in striatal Glx in the tTIS group (p < 0.001), whereas the decrease in the sham group was not significant. No significant GABA+ changes were observed within or between groups. The association between striatal Glx change and functional connectivity change differed between groups in the sensorimotor cortex, right parahippocampal gyrus, and bilateral fusiform gyri. Conclusion These exploratory findings suggest that 20-Hz tTIS may be associated with striatal Glx modulation and group-dependent coupling between neurochemical and cortico-subcortical network changes.

PurposeQuantitative interpretation of brain [{superscript 1}F]FDG-PET increasingly relies on comparisons with normative datasets. However, normative values may be influenced by technical and biological factors, limiting their generalizability. We investigated the effects of scanner manufacturer, reference region, age, and sex on regional [{superscript 1}F]FDG uptake in cognitively normal (CN) adults and generated covariate-adjusted normative reference data. MethodsA total of 449 CN participants from the Alzheimers Disease Neuroimaging Initiative (ADNI) were included. Regional SUVr were calculated using three reference regions (whole cerebellum, pons, cortical gray matter) and converted to Z-scores. Linear regression models were used to estimate standardized regression coefficients ({beta}), and 10-fold cross-validation was performed to quantify the out- of-sample predictive contribution of each covariate using incremental explained variance ({Delta}R{superscript 2}). ResultsScanner manufacturer introduced large, spatially structured biases. Compared with Siemens systems, GE and Philips scanners yielded lower Z-scores in frontal and medial temporal regions, with effect sizes approaching one standard deviation in selected regions ({beta} up to -0.85). Age showed region- specific associations with subcortical nuclei, medial temporal structures, and the posterior cingulate cortex, and was the strongest biological predictor in cross-validation ({Delta}R{superscript 2}{approx}0.11). Sex effects were negligible ({Delta}R{superscript 2}<0.001). Cortical gray matter normalization minimized biological and technical confounding, and the AD meta-ROI demonstrated high robustness across manufacturers and normalization strategies. ConclusionScanner manufacturer and age are the major sources of variance in brain [{superscript 1}F]FDG-PET quantification in CN subjects. Cortical gray matter provides the most stable reference region and supports harmonized, covariate-adjusted normative datasets for clinical and research applications.

Background and Objectives: Word-finding difficulty is common in healthy aging and in neurologic disorders, including temporal lobe epilepsy (TLE) and early Alzheimer disease. Standard language measures have limited sensitivity for detecting subtle or longitudinal changes in spontaneous speech. We examined whether natural language processing and acoustic analysis of spoken biographical recall could identify lexical and temporal speech features associated with language and memory performance in TLE. Methods: We conducted a cross-sectional observational study of spoken recall during a Famous Faces biographical memory task. Adults with TLE and healthy controls (HCs) viewed 20 famous faces and spontaneously recalled biographical details. Speech was transcribed and diarized using automated tools. Lexical measures included word counts and lexical index (ratio of rare to common words). Acoustic measures included utterance and pause duration and pause frequency. Features were compared between groups and correlated with neuropsychological measures, including Montreal Cognitive Assessment (MoCA), Boston Naming Test (BNT), delayed recall, education, and biographical recall accuracy Results: Eighty-one adults participated (51 TLE, 30 HCs). Lexical measures did not differ between groups. In TLE, lexical index correlated with BNT performance (rs=0.62) and MoCA score (rs=0.35). Compared with HCs, participants with TLE produced shorter utterances (5.54 {+/-} 2.50 vs. 6.59 {+/-} 2.63; Cohen's d=0.41, 95% CI -0.05 to 0.86, p=0.041), shorter pauses (0.61 {+/-} 0.21 vs 0.67 {+/-} 0.22, Cohen's d=0.29, 95% CI -0.16 to 0.74, p=0.043), and more frequent pauses (10.81 {+/-} 3.30 vs 9.29 {+/-} 3.59, Cohen's d=-0.45, 95% CI -0.90 to 0.01, p=0.036). Higher education was associated with longer utterances, longer pauses, and lower pause frequency, without evidence of a diagnosis-by-education interaction. Faster utterance rate was associated with better biographical recall in both groups, while higher pause rate was associated with worse recall in TLE. Discussion: Speech-derived lexical and temporal features from naturalistic recall capture clinically relevant variation in language and memory-related performance. Although lexical output did not distinguish TLE from HCs, lexical richness tracked naming and global cognition in TLE, while temporal speech features related to recall performance. These findings support the potential of automated speech analysis as a digital behavioral biomarker for word-finding difficulty in neurologic populations.