Imaging Neuroscience

Optically pumped magnetometer magnetoencephalography (OPM-MEG) offers a wearable, movement-tolerant alternative to conventional cryogenic MEG, placing sensors closer to the scalp and, in principle, improving sensitivity to deep sources. This is advantageous for examining subcortical structures that are affected by ageing, disorders and disease, such as the hippocampus. However, it remains unclear whether well-established activity (such as the attenuation of theta oscillations during the imagination of novel scenes) can be recovered from the medial temporal lobe (MTL) with OPM-MEG, and whether an individual structural MRI is required. Here, fifteen adults completed a scene imagination task. Initially we applied a 12-parameter template warping coregistration pipeline to the full sample. Following source reconstruction, we recovered the expected attenuation of theta (4-8 Hz) power during scene imagination compared to a counting baseline, with a significant cluster of activity peaking in the left parahippocampal gyrus. The clusters centre of mass was localised to the left hippocampus (t = -3.55, p = 0.048, whole-brain FWE-corrected) and was mostly confined to the left medial temporal lobe. We further supported our findings by using an individual T1-weighted MRI reconstruction pipeline in six participants who had these scans available. The two approaches produced similar whole-brain topographies and localised the peak MTL theta effect to left hippocampus, with temporal-lobe conjunction centroids 3-mm apart. These findings provide evidence that the theta attenuation of the scene construction network can be recovered at the group level with OPM-MEG, without an individual MRI.

Quantitative magnetic resonance imaging (qMRI) supports both basic neuroscience and clinical research, providing the foundation for longitudinal studies of brain development, aging, and neurological disease. However, its validity rests on a little-studied assumption: that physical relocation of imaging hardware leaves underlying neuroimaging biomarkers intact. When research facilities expand or modernize, an entire scanner undergoes radical disruption--field ramp-down, physical transport, shielding reconstruction, and re-shimming. Whether qMRI metrics remain stable following such invasive procedures without introducing systematic biases is largely unquantified. Here, we systematically evaluated the impact of relocating a 3T clinical scanner over a distance of 30 km on a broad, multimodal suite of neuroimaging markers in healthy volunteers. To disentangle variance components, we benchmarked within- and cross-site stability using percent variation (PV; measurement precision), intraclass correlation coefficients (ICC; absolute reliability), and Spearman rank correlations (R2; spatial and order agreement). We show that scanner relocation introduces no greater variance than baseline within-site assessments. High-resolution brain structural morphometry from different sequences (multi-echo MPRAGE, compressed sensing MPR2RAGE) and quantitative relaxometry (compressed sensing MP2RAGE T1 mapping) demonstrated excellent stability (PV<1%, ICC=0.89-0.99, R2>0.93). Diffusion tensor (mean diffusivity: MD, fractional anisotropy: FA) and mean signal kurtosis (MSK) metrics from multi-shell diffusion MRI maintained low variability across white and deep gray matter (global cross-site ICC>0.90; global PV: MD<1.7%, MSK<1.2%, FA<3.8%; global R2: MSK>0.93; MD>0.90; FA>0.77), confirming relocation robustness for diffusion-derived microstructural markers. Resting-state functional networks displayed high cross-site reproducibility (ICC>0.90), while task-based fMRI activation peaks retained acceptable spatial and magnitude agreement (ICC=0.30-0.60) despite intrinsic physiological variability. In the absence of software or hardware upgrades, physical scanner relocation leaves qMRI biomarkers remarkably intact--providing the empirical foundation required to preserve data integrity across major facility transitions and multi-site longitudinal cohorts. Key points that summarize the paperO_LIHardware transitions do not compromise qMRI data integrity: Physical relocation of a 3T scanner (including field ramp-down, 30 km transport, and re-shimming) introduces no greater variance in quantitative MRI metrics than baseline within-site test-retest assessments. C_LIO_LIMultimodal biomarker robustness: Brain morphometry, T1 relaxometry, diffusion tensor and kurtosis, resting-state functional connectivity display comparable within- and cross-site stability reflected by different metrics (percent variation, intraclass correlation coefficient and Spearman correlation) C_LIO_LIEmpirical backing for longitudinal research: In the absence of hardware or software upgrades, multimodal qMRI biomarkers remain remarkably stable, reassuring researchers that long-term cohort studies and multi-site harmonization can survive major facility relocations. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/26363342v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@773d03org.highwire.dtl.DTLVardef@46a09borg.highwire.dtl.DTLVardef@da5bc0org.highwire.dtl.DTLVardef@1bdbf9d_HPS_FORMAT_FIGEXP M_FIG This study evaluates the impact of physically relocating a 3T MRI scanner on neuroimaging biomarkers. By comparing before and after relocation sessions on healthy volunteers, we conclude that the procedure does not introduce significant variability. Parameters for morphometry, T1 relaxometry, diffusion, and resting-state functional connectivity show high stability. Task-based fMRI showed greater within-site variability, but no increase in variability following relocation, consistent with the inherently higher variability of task-evoked responses.. The results confirm the integrity of qMRI data after infrastructure relocation, ensuring reliability for longitudinal studies. C_FIG

Intracranial EEG (iEEG) affords a unique opportunity to assess human neural activity with millisecond temporal resolution and millimeter spatial precision. However, group-level statistical analyses remain challenging due to sparse and heterogeneous electrode coverage, anatomical variability, and the difficulty of integrating spatiotemporal responses across individuals. Most iEEG studies therefore define brain regions of interest for the group analysis, sacrificing a spatial resolution strength of iEEG and excluding data outside those regions of interest. Here, we present a spatiotemporal analysis and mapping with permutation-based linear mixed-effects models (STAMP-LME), a cortical-mapping framework for population-level iEEG analysis independent of predefined cortical regions of interest. STAMP-LME is a complete processing pipeline spanning electrode localization, mapping to a standardized surface of the cortical mantle, including medial, orbitofrontal, and insular regions, and statistical inference at the cortical level. Electrode-level data from each participant is mapped to a standardized cortical surface using weights that account for electrode-to-cortex distance and confidence in cortical sampling. Brain signals are then combined with a spatial smoothing kernel and entered into LME models at each vertex-node and time point. Data-derived null distributions are generated through controlled permutations and used for spatiotemporal inference with threshold-free cluster enhancement (TFCE) or false-discovery-rate (FDR) correction. We validated STAMP-LME using simulations with known cortical ground truth while varying effect size, interparticipant source-location variability, electrode coverage, and spatial smoothing. The framework reliably detected simulated effects and recovered their spatiotemporal distribution while maintaining low localization error and limiting false-positive detections across different sampling conditions. We then applied the method to intracranial recordings from nine individuals performing an auditory oddball task. The empirical analysis revealed distributed auditory cortical responses consistent with conventional channel-level analyses, while providing more fine-grained group-level activation maps across sampled cortical regions. STAMP-LME provides a flexible, open-source framework for data-driven population-level cortical iEEG analysis that preserves the spatiotemporal strengths of intracranial recordings while accounting for sparse and heterogeneous electrode coverage. The structured workflow enables reproducible and anatomically precise group-level inference on a standardized cortical surface and facilitates comparison with surface-based fMRI and source-localized M/EEG results, therefore providing a practical tool for cognitive and clinical neuroscience research.

Resting-state connectivity can predict task-evoked fMRI activation, but correspondence with an individual task map may partly reflect a shared population pattern. We evaluated the Variational Resting-state-to-Task Prediction TransformeR (VRPTR), a three-dimensional encoder-decoder combining a compressed Transformer bottleneck, variational latent sampling, and multiscale skip connections. Models were trained in 360 healthy adults from the WU-Minn Human Connectome Project and evaluated in 40 held-out participants from the same dataset for the story-versus-math language contrast. VRPTR achieved mean voxel-map Pearson r=0.642 and Dice AUC=0.519, exceeding compact volumetric BrainSurfCNN-like and SWIFUN-like comparators by {Delta}r=0.0376 and 0.0335, respectively. A template fixed from the 360 training maps yielded residual correlation 0.364; VRPTR improved correlation but not mean absolute or root mean squared error over this template. A matched factorial ablation associated Transformer processing with improved map correlation ({Delta}r=0.0168); the variational main effect did not survive multiple-comparison correction. Component swaps indicated that subject-specific activation patterns depended more on multiscale skip features than on the bottleneck representation. Latent sampling produced a modest association between posterior standard deviation and voxelwise absolute error (mean Spearman {rho}=0.091). Raw 95% intervals covered only 4.7% of observed values. Five-fold calibration within the held-out cohort increased coverage to 94.8%, and spatially varying uncertainty modestly improved probabilistic scores over a constant-width model. Uncertainty also increased under input degradation. These findings support the contribution of Transformer processing to language-map prediction and distinguish it from subject-specific spatial conditioning and relative uncertainty estimation. Independent validation of calibrated uncertainty and evaluation in clinical cohorts remain necessary.

Inter-individual variability in adult brain aging can obscure early pathological alterations and is only partly represented by population-average or scalar brain-aging measures. We combined Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) with normative modeling (NM) to derive spatially resolved, molecularly informed deviation scores for dopamine transporter (DAT)-, norepinephrine transporter (NET)-, and serotonin transporter (SERT)-enriched resting-state functional connectivity (FC). We first evaluated whether these normative models could be transferred to independently processed external data through local calibration and then explored whether the resulting deviation profiles differed with cerebral amyloid burden in cognitively unimpaired older adults. Hierarchical Bayesian regression (HBR) models with a SHASHb likelihood were estimated separately for 204 cortical molecular-enriched FC features in 4,152 healthy adults (18.0--89.8 years) from seven publicly available neuroimaging datasets and evaluated in a held-out healthy test set. Pretrained models were locally adapted to three AMYPAD-PNHS acquisition batches using cognitively unimpaired, amyloid-negative participants (global Clinical Dementia Rating [CDR] = 0; Centiloid [CL] [lt] 10). The independent primary comparison contrasted participants with intermediate amyloid burden (10 [&le;] CL [lt] 30; n = 111) and amyloid-positive participants (CL [&ge;] 30; n = 66); secondary analyses tested linear associations with continuous CL within participants with CL [&ge;] 10. Of 204 normative reference models, 199 (97.5%) met the predefined diagnostic criteria; median held-out explained variance (EXPV) was 0.174. Of 612 feature-by-batch transfers, 541 (88.4%) met the strict transfer-diagnostic criteria. In the primary false discovery rate (FDR)-controlled regional analysis, DAT-enriched right caudal middle frontal cortex showed lower locally standardized deviation scores in the intermediate-amyloid-burden group than in the amyloid-positive group (adjusted difference = -0.582, q = 0.016). DAT extreme-deviation burden was also greater in the intermediate-amyloid-burden group (difference = 0.032, q = 0.044). The right frontal effect was reproduced with model-native scores across the three acquisition batches (pooled standardized effect = -0.698, q = 0.010). No NET- or SERT-enriched regional difference between these two groups survived FDR correction, and no regional or subject-level linear association with continuous CL values survived FDR correction in the CL [&ge;] 10 group. Normative modeling can provide spatially resolved reference distributions of molecular-enriched FC that are deployable in independently processed external data when local adaptation, calibration, and feature-level transfer diagnostics are incorporated. The AMYPAD-PNHS application identified modest, spatially selective, and molecular-system-specific categorical differences during a cognitively unimpaired stage of amyloid accumulation, while continuous analyses within CL [&ge;] 10 did not support a linear association. These findings support a methodological basis for distributed application of molecular-enriched normative models and motivate independent and longitudinal evaluation of their biological relevance.

Diffusion-weighted MRI, beyond the commonly used diffusion tensor framework, offers a unique window into tissue microstructure in vivo, yet its clinical adoption has remained limited. Major barriers include the complexity of diffusion MRI sequence design, lengthy acquisition protocols, and the challenges associated with robust estimation of high-dimensional microstructural model parameters. Here, we address these limitations by combining optimised diffusion encoding with state-of-the-art simulation-based inference, establishing a clinically feasible framework for multi-compartment diffusion modelling. We validate the approach through i) in-depth in silico experiments and ii) in vivo studies made up of both human and rodent data. The resulting microstructural metrics are robust, reproducible across healthy individuals and show significant spatial associations with brain-wide expression patterns of cell-specific genes. Requiring less than 10 minutes of acquisition time, this framework substantially lowers the barriers to advanced microstructural imaging, a prerequisite step toward its eventual evaluation for the diagnosis, stratification, and monitoring of brain disorders.

Individualized resting-state functional magnetic resonance imaging (rs-fMRI) is increasingly used to guide neuromodulation target selection. However, clinical scans are often short and noisy, and standard pipelines for functional network identification do not provide information about confidence of network assignment. With limited data, unstable network assignments can misdirect stimulation toward off-target regions, making it critical to know which assignments can be trusted. We developed Precision Confidence Mapping (PCM), a bootstrap-based framework that makes this uncertainty explicit and actionable. PCM repeatedly resamples the time series and reruns network detection to estimate how consistently each vertex is assigned to a given network. The resulting confidence maps can be thresholded to exclude less stable regions. We evaluated PCM across scan durations from 5 to 70 minutes using positive predictive value (PPV) as the primary measure of network-assignment precision. PPV quantified the proportion of vertices assigned to a network that received the same label in an independent within-subject 70 minute reference map. Confidence thresholding markedly improved PPV across functional networks, with the largest gains for short scan durations. Compared with standard network assignment, PCM significantly increased agreement with this independent reference. Within-subject agreement remained greater than between-subject agreement, indicating that thresholding preserved individual-specific network topography. These precision gains came with modest reductions in reference-network coverage, particularly at shorter scan durations. This tradeoff may be acceptable for neuromodulation applications that prioritize minimizing off-network assignments. By adding a reliability layer to individualized mapping, PCM supports more cautious and precise neuromodulation targeting under real-world clinical scan constraints.

Background: Whole-brain segmentation of neonatal low-field MRI is needed for regional volumetric analysis, but established segmentation systems are designed around different field strengths, contrasts, and age ranges. Methods: We first applied complete end-to-end pipelines, including FreeSurfer, FSL-based processing, Infant FreeSurfer, FastSurfer, BrainSuite, SPM12/CAT12, iBEAT v2, the dHCP structural pipeline, and M-CRIB-S, directly to 0.35T neonatal T2-weighted images. Because those systems did not produce a complete 47-region output, we next tested released end-to-end AI segmentation models, including SynthSeg, FastSurfer, FastSurferVINN, and QuickNAT. These were highly sensitive to input format, contrast, voxel geometry, and the high-field training domain. We then decomposed the task into skull stripping, registration, super-resolution, atlas propagation, and tissue refinement and tested the available components individually. Results: No complete end-to-end pipeline or released AI model delivered a usable 47-region segmentation in direct application. Stage-wise testing showed that preprocessing, reconstruction, registration, atlas propagation, and expectation-maximization each solved only part of the problem. Their final assembly produced complete 47-region outputs across the neonatal cohort. Conclusions: Direct application of established pipelines was insufficient for 0.35T neonatal T2-weighted MRI. A stage-wise combination of compatible components provided the workable solution.

Large-scale neuroimaging datasets are increasingly used to map relationships between brain structure, function, and behavior across the human lifespan. Routinely, analyses exclude participants who moved too much during imaging. While this decision is framed as quality control, it is increasingly recognized that head motion is not randomly distributed across individuals within a study, and so motion-based exclusion may preferentially remove people with particular characteristics relevant to the scientific goals of the study. Here we survey head motion and how it relates to participant characteristics across six large, publicly available datasets spanning nearly the entire human lifespan, namely the Human Connectome Project (HCP) Young Adult, HCP in Development, HCP in Aging, Adolescent Brain Cognitive DevelopmentSM Study, UK Biobank, and Spatial Topology project. These six datasets comprise more than 50,000 unique participants and 300,000 scans. We further benchmark our findings against motion distributions aggregated by MRIQC across more than 1.5 million scans. Under commonly applied strict exclusion thresholds, large fractions of participants would be removed (exceeding 80 % in the UK Biobank task data), and these removals were demographically structured, disproportionately excluding younger and older participants, those with higher BMI, and those with motion-associated clinical conditions. Respiratory pseudo-motion inflated estimates of head motion in adult cohorts, and applying notch filtering to remove respiratory frequencies from these estimates meaningfully reduced exclusion rates. Exclusion also carried downstream consequences. Strict thresholds reduced statistical power, inflated study costs, and altered the apparent predictability of behavioral phenotypes by removing a non-random, behaviorally distinct subgroup. These findings demonstrate that motion exclusion thresholds are not neutral quality-control decisions but structured selection mechanisms that reshape the composition of neuroimaging samples. We recommend that studies report the demographic characteristics of excluded participants, prefer data-driven censoring methods over fixed motion cutoffs, and clarify the target population while considering appropriate weighting techniques.

The human brain undergoes rapid developmental changes through early life, underpinning the emergence of function but also marking a period of vulnerability to a range of neurodevelopmental disorders. With dynamic changes to brain size, morphology, and imaging contrast, consistent and accurate computational neuroanatomy remains a challenge. Deep learning tools for segmentation, like SynthSeg, offer robustness to heterogeneously acquired MRI contrast but remain unproven in early development. Here, we aggregated a large cohort (26k) of MRI scans spanning infant to adult development, and evaluated SynthSeg performance. Automated quality control scores, visual inspection, and spatial overlap with expert-segmented MRI scans revealed poor quality output segmentations during development. In the infant period only 36% of scans (1094/3069) passed automated QC. Rescaling infant scans to adult brain sizes significantly improved spatial overlap, and cropping scans to match adult fields of view retrieved automated quality control. Evaluation of the SynthSeg rescale + crop pipeline demonstrated visible and quantitative improvements in segmentation throughout infancy and childhood. There were marked increases in successful segmentations in infant scans, with 91% of scans now passing QC (2803/3069). These findings facilitate computational analysis of typical and disrupted neurodevelopment and should be considered when training the next generation of computational tools.

Functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both rely on the phenomenon of neurovascular coupling (NVC) to probe brain activity through their sensitivity to cerebral blood oxygenation. However, the relationship between fNIRS chromophores (oxy- and deoxyhaemoglobin, HbO and HbR), and fMRI (Blood Oxygen Level Dependent and Arterial Spin Labeling, BOLD and ASL) measurements, and whether this relationship remains consistent across subjects and physiological conditions, has only been partially characterised.. We acquired concurrent continuous-wave fNIRS and gradient-echo (GE) and spin-echo (SE) BOLD-ASL fMRI in healthy adults (n = 10) during visual stimulation. By applying calibrated fMRI methodology, we examined the relationships between fNIRS-derived haemoglobin modulations and fMRI-derived modulations in macrovascular (GE-) and microvascular (SE-) BOLD signals, cerebral blood flow (CBF), and oxygen metabolism (CMRO2). Group-level results showed strong temporal cross-modal agreement, with HbO and HbR tightly mirroring all fMRI signal time-courses (|r| > 0.8). A quantitative analysis of trial-by-trial modulations revealed distinct state-dependent behaviours: HbO maintained a stable relationship with the fMRI-derived metrics across conditions, whereas cross-modal relationships between HbR and fMRI-derived metrics substantially strengthened at higher flow-metabolism coupling (FMC), the ratio of CBF to CMRO2 change, an index of the strength of NVC. Both HbO and HbR were more strongly associated with GE-BOLD than with SE-BOLD. These findings provide a rigorous physiological grounding for fNIRS signal interpretation, demonstrating its utility as a surrogate marker for specific haemodynamic and metabolic parameters.

Optically pumped magnetometers (OPMs) can be used for magnetoencephalography (MEG) with equivalent or improved signal to noise ratio, relative to cryogenic MEG, when sensors are placed close to the scalp. OPM-based MEG can also be used in mobile contexts if sensors are placed in lightweight, wearable arrays. Individually tailored, rigid helmets known as scannercasts are currently the only method capable of achieving on-scalp, mobile recordings with high precision. However, these scannercasts are expensive to produce, require structural imaging in advance of the experiment, and can incur lengthy downtime while sensors are transferred between scannercasts. Here, we introduce a solution to these challenges that retains the advantages of scannercasts. We provide detailed steps for constructing a modular, cap-based design, suitable for all head sizes. Using simulations, we compare the leadfield power of this array against an idealised array and a commercially available mobile solution. We then validate our proposed solution empirically, in five participants, and provide a complete data preparation and analysis pipeline. Our design expands the accessibility of OPM-based MEG, and increases participant throughput to levels comparable to other imaging modalities. Crucially, it removes the trade-off between signal quality, mobility and practicality, promoting the unique potential of OPM-based MEG as a tool for studying naturalistic behaviour, and clinical assessment with high precision.

Population-graph models can use cohort-level context, complicating interpretation of strong multisite neuroimaging performance. We investigated which information pathways accounted for high transductive cohort discrimination in a site-aware heterogeneous population graph neural network for autism classification. Using a frozen ABIDE-I cohort (871 participants, 20 sites) and evaluation protocol, we applied controlled graph, feature, supervision, and architecture interventions to a clean-room re-implementation across C-PAC and NIAK preprocessing pipelines. Cohort out-of-fold AUC was approximately 0.94. A site-only graph retained similarly high discrimination (0.948 versus 0.941 for the full model), with no statistically significant difference detected. Removing same-site supervision under a site-wise intervention reduced AUC to 0.480, whereas a supervision-budget control retaining same-site supervision achieved 0.921. Among the alternative heads evaluated, the high cohort AUC was observed only with the sex-heterogeneous dual-channel head; a canonical topology-only Parisot-GCN did not reproduce it. A demographic classifier using site, sex, and their interaction achieved a best pooled AUC of 0.51. Under leave-one-site-out evaluation, AUC was 0.522 for C-PAC and 0.532 for NIAK, with confidence intervals including 0.5 and no clear evidence of unseen-site discrimination; an imaging-only reference achieved 0.653 and 0.588. Because leave-one-site-out evaluation jointly changes supervision availability, target-site topology, and training-domain composition, the decrease cannot be attributed to a single factor. These findings distinguish cohort-visible transductive performance from unseen-site generalization and motivate explicit site-only, no-graph, and site-held-out controls.

Brain metabolic connectivity is increasingly studied using positron emission tomography (PET), but multiple analytical approaches exist with unknown comparability. Here we compared metabolic connectivity approaches in 80 participants who underwent simultaneous dynamic PET with 18F-fluorodeoxyglucose and functional magnetic resonance imaging (fMRI) scans and cognitive testing. Six connectivity approaches were compared, including the traditional across-subject method (often labelled metabolic covariance) and five approaches that estimate individual-level connectivity: across-subject metabolic covariance with individual scores derived using leave one out (LOO); functional PET (fPET) within-subject correlations of regional timeseries; and three approaches that use distance-based measures to estimate individual-level connectivity based on within-region tracer distribution and kinetic compartment C1 and C2 time activity curves. fMRI connectivity was also calculated. Each method showed distinct topological, behavioural, structural and genetic signatures. fPET connectivity demonstrated the strongest cognitive associations and largest age-related declines, with unique predictive power for cognition independent of age. Tracer distribution showed strong age group discrimination although with mixed direction of age and cognitive effects. Metabolic covariance (LOO) and kinetic C2 showed no significant age group differences and their cognition associations reflected age-related variance. Gene expression associations implicated a shared core glycolytic-insulin machinery in all approaches, but the direction of the association with regional connectivity diverged across approaches and unique gene signatures further distinguished most methods. Collectively, these results indicate that the optimal connectivity approach depends on the research question. fPET connectivity with dynamic scans offers utility for cognition and ageing studies, tracer distribution for single-scan designs with careful interpretation of age and cognition relationships, kinetic approaches for novel biological insights into glucose kinetics and fMRI for multi-modal integration. Metabolic covariance (LOO) should be used with caution for brain-behaviour investigations. Researchers should weigh trade-offs between physiological specificity, analytical complexity, acquisition requirements and interpretability when selecting a metabolic connectivity approach.

Iron is essential for neurophysiological health. Prior work has shown that subcortical tissue iron levels are the highest among all brain regions but also change over the lifespan. Recent functional MRI (fMRI) studies have provided evidence that an fMRI-derived iron-sensitive signal may index relative iron concentration in subcortical regions. In this context, we aimed to characterize the lifespan trajectory of this fMRI-derived iron-sensitive signal (relative iron quantification) in 10 subcortical regions and 14 thalamic nuclei from 881 healthy participants aged 12 to 88 years, using resting-state fMRI. Regressions were run with age as a predictor, separately for males (N = 429) and females (N = 452). The main results show non-linear effects of age, with an overall increase in iron levels across most subcortical regions within each sex. Six of the 14 thalamic nuclei in male participants had similar slopes of their lifespan iron levels, showing some homogeneity. The thalamic nuclei of female participants showed less agreement in slopes. This study provides new insight into the typical trajectory of iron levels across all major subcortical regions throughout the lifespan.

Early human cortical development involves rapid changes in cytoarchitecture that remain difficult to interrogate non-invasively. Biophysical diffusion MRI models provide a potential window onto this microstructure, including water exchange across cell membranes, but their assumptions are difficult to validate directly in developing human tissue. Human cortical organoids provide a tractable biological model in which diffusion measurements can be related to tissue architecture within the same specimen. We scanned six fixed cortical organoids at 9.4~T, three grown under a directed and three under an undirected differentiation protocol, at three diffusion times and b-values up to 7000~s/mm$^2$. Center-to-periphery profiles of DKI-derived diffusion metrics were reproducible across the directed organoids but more variable across the undirected organoids, while nuclear staining revealed greater variability in the internal architecture of the undirected organoids. Unexpectedly, mean diffusivity increased with diffusion time in more than 80% of tissue voxels in both batches, opposite to previous organoid measurements. Across 12,348 simulated two-compartment substrates, this increase was reproduced only with permeable membranes and an extracellular diffusivity substantially exceeding the apparent intracellular diffusivity, a regime that challenges assumptions commonly used in current gray-matter exchange models. These results support cortical organoids as biologically realistic platforms for probing early cortical microstructure and testing diffusion models under controlled conditions, while remaining amenable to post-MRI histological validation.

Transcranial magnetic stimulation (TMS) is commonly dosed by setting stimulation intensity as a fixed percentage of the resting motor threshold (RMT), although a motor-derived intensity may not produce comparable neural recruitment across non-motor targets. We present TIDE (Tractography-Informed Dose Estimation), an open-source, SimNIBS-based pipeline designed to derive individualised stimulation intensities for non-motor white-matter targets. TIDE combines individual RMT measurements, finite-element electric-field modelling and diffusion MRI tractography to rescale the stimulation intensity according to the geometry and stimulation efficiency of the pathway of interest. Specifically, it computes the activating function along subject-specific streamlines and estimates the stimulator output, expressed as a percentage of maximum stimulator output, required for the target pathway to reach the activation level produced in the corticospinal tract at RMT. In an independent dataset of 19 participants, in which stimulation had been dosed conventionally as a fixed percentage of RMT, the relative difference between delivered and TIDE-estimated intensity was associated with the magnitude of TMS-induced behavioural effects at two frontal aslant tract (FAT) stimulation sites, while the delivered intensity alone was not. TIDE therefore extends conventional E-field dosing from cortical field magnitude to subject-specific pathway geometry, providing a method to move beyond the assumption of homogeneous pathway engagement while accounting for inter-individual variability in pathway-specific stimulation efficiency.

Background: Ultra-low field (ULF) magnetic resonance imaging (MRI) offers accessible point-of-care neuroimaging, yet its capability to support multivariate network analyses remains understudied. Methods: We systematically evaluated the feasibility and reliability of Morphometric Similarity Networks (MSN) and Morphometric Inverse Divergence (MIND) networks derived from paired high-field (HF, 3T/1.5T) and ULF (64mT) scans in a primary cohort(N=23) and an independent replication cohort (N=19). We tested the impact of super-resolution processing, cortical parcellation granularity (Desikan-Killiany vs. Destrieux), and mesh resolution (fsnative vs. fsaverage5) on edge-level cross-scanner agreement (Lin's concordance correlation coefficient, CCC) and subject-level identifiability. Results: MIND networks demonstrated higher edge-level HF-ULF agreement (mean CCC = 0.95) and ULF reproducibility (mean CCC = 0.98) compared to MSNs (mean CCC = 0.86-0.87 and 0.91-0.94, respectively). In contrast, MSNs yielded higher subject-level differential identifiability across field strengths due to a broader distinction between within- and between-subject similarity. Reconstructing MIND networks on native high-resolution meshes (fsnative) maximised cross-scanner agreement, whereas coarser meshes and finer cortical parcellations enhanced individual network identifiability. Conclusions: Structural similarity networks can be reliably constructed from ULF MRI data. Optimal analytic choices depend on study objectives: MIND on native meshes maximises cross-scanner stability, whereas MSNs excel at preserving individual uniqueness, paving the way for globally scalable connectomic research.

Introduction: A new method that corrects for time-dependent bias in standardized-uptake value ratios (SUVRs) was adapted and optimized for [11C]PiB (PiB) amyloid-beta (A{beta}) PET, across low-to-high A{beta} loads, relying only on PET data collected during the SUVR time-window. This modeling approach was evaluated in cross-sectional and longitudinal cohorts for earlier and shorter SUVR time-windows (30-45 min, 45-60 min) than commonly applied, to enable higher throughput imaging. Methods: The SUVR correction (SUVRc) approach was optimized and tested on separate cross-sectional (n=88), and longitudinal (36 participants, two time-points, 72 images) cohorts from the Harvard Aging Brain Study. The cross-sectional cohort spanned low, intermediate and high levels of cortical A{beta} pathology and the longitudinal images included two cohorts with low (5-10%) and high levels (~40%) of A{beta} change. SUVR and SUVRc were compared against SRTM DVR (0-60 min) to quantify A{beta} burden through Pearson's and Lin's correlations, difference plots and longitudinal change. Results: The mean regional bias in PiB SUVR (5-15%, depending on time-window and A{beta} burden) was significantly reduced to < 3% by SUVRc (corrected p < 0.05) in the cross-sectional cohorts for all time-windows, along with reductions in bias variability. SUVRc also showed higher Pearson's correlation (r) and Lin's concordance (LCC) with DVR across time-windows (r=0.98, LCC=0.99 at 30-45 min and 45-60 min) compared to uncorrected SUVR (r=0.96, LCC=0.95 at 30-45 min, r=0.97, LCC=0.92 at 45-60 min). Bland-Altman plots confirmed better agreement between SUVRc and DVR (mean bias at 30-45 min: 0.02 for SUVRc, 0.10 for SUVR; mean bias at 45-60 min: 0.01 for SUVRc, 0.17 for SUVR). Longitudinal DVR changes were more accurately represented by SUVRc, compared to uncorrected SUVR. Conclusions: SUVRc for [11C]PiB PET enables more accurate quantification of A{beta} burden than SUVR in cross-sectional and longitudinal studies (relative to SRTM DVR), while enabling imaging at earlier and shorter time-windows. The improved accuracy would be beneficial in better quantifying amyloid re-emergence post anti-amyloid therapy and could be used for kinetic harmonization across time-windows and radiotracers.

Upper-extremity motor control has been widely studied with hand-task functional magnetic resonance imaging (fMRI) in healthy and disease states. However, proximal-arm motor tasks, such as at the shoulder, are uncommon during fMRI due to practical limitations, though they are critical to a complete understanding of upper-extremity motor control. Previous fMRI studies of proximal upper-extremity control have generally used unconstrained movements or a single low force or torque condition, leaving unknown how distributed supraspinal brain activity scales with increasing proximal motor output. Here, we implemented a custom, MR-safe device to test supraspinal brain activity during three levels of isometric shoulder abduction in healthy individuals using a whole-brain fMRI acquisition. We conducted subject-specific analysis with repeated sampling of the controlled shoulder abduction task within each individual (i.e., "precision mapping"), as the exact localization of shoulder motor activity is relatively understudied. Our analysis showed spatial variability in subject-specific motor activation compared to group-level localization. We found that shoulder abduction had a significant effect on motor activity in the primary motor cortex, supplementary motor area, dorsal premotor area, thalamus, putamen, and cerebellum. Across repeated fMRI runs, amplitude of motor activity was consistent across all tested regions. Overall, these findings provide an individualized, whole-brain torque-response characterization of the proximal upper-extremity motor system and establish an approach for examining how distributed supraspinal motor networks are recruited as mechanical demand increases. These whole-brain, subject-specific methods can be a critical tool for probing motor dysfunction in clinical populations.