Imaging Neuroscience

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.

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.

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.

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.

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.

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.

Understanding how the brain processes the everyday world is fundamental, yet laboratory paradigms exclude self-generated movement, unscripted events, and a continuously evolving multisensory environment. Wearable neuroimaging enables real-world measurement, but linking neural activity to uncontrolled sensory information remains challenging. Here, we extend a feature-based framework from naturalistic movie viewing to everyday behavior using wearable whole-head high-density fNIRS and participant-specific audiovisual recordings during movies and outdoor walking with no explicit task or scripted audiovisual sequence. Luminance- and sound-related cortical maps showed significant spatial correspondence, particularly in visual and auditory regions, whereas face-related correspondence was weaker. Luminance- and face-related maps were reproducible within individuals across repeated walks. Additional exploratory analysis demonstrated, to our knowledge, the first out-of-sample encoding of continuous environmental features during unconstrained real-world fNIRS, predicting cortical activity during held-out walking periods. Together, these findings establish a feature-based framework for linking cortical activity to naturally unfolding sensory experience in everyday behavior.

Submillimeter functional magnetic resonance imaging (fMRI) based on blood-oxygenation-level-dependent (BOLD) signal enables the study of brain function at the submillimeter level, uncovering insights into fine-scale organisations like cortical layers and columns. However, its inherently low contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) often limit its reliability and applicability. Noise Reduction with Distribution Corrected Principal Components Analysis (NORDIC PCA) is a locally low-rank denoising algorithm that reduces thermal noise levels in BOLD fMRI in a local patch manner. However, local patches often contain a mixture of signals from multiple tissues that negatively affects the low-rank structure of the patches, which limits the denoising capabilities of the algorithm. We propose an alternative approach for patch formation by gathering similar non-local voxels, dubbed voxel-matching (VM) NORDIC. The results on submillimeter-resolution BOLD fMRI data indicate that VM-NORDIC effectively promotes the low rank of the patches by boosting signal redundancy, allowing for more efficient noise attenuation. Moreover, the method barely affects spatial smoothness due to the non-local voxel selection based on time-series similarity. In particular, VM-NORDIC outperforms standard NORDIC with default local patching (Standard-NORDIC) in terms of temporal SNR (tSNR) (~9-90% larger than Standard-NORDIC; ~23-250% larger than the original) and spatial smoothness estimates (~20% of the smoothness induced by Standard-NORDIC). These improvements are fundamental to improving the validity and precision of fMRI studies at submillimeter resolutions.

Flow is a subjective state where tasks feel effortless and rewarding. It has been linked to distinct neural signatures, yet dynamics of these signals remain poorly understood. Here, we investigated spectral dynamics of brain activity in flow. We recorded electroencephalogram (EEG) data at positions AF7, AF8, TP9, and TP10 using a lightweight wearable device worn by ten adult participants while they completed a go-signal task and two stop-signal tasks. Task difficulty was continuously adjusted to induce either a sense of flow or frustration. Time-resolved spectral power and interregional coherence were extracted with continuous wavelet and wavelet coherence transforms; subjective flow was assessed after each block with the short-form Flow-State Scale. Subjective ratings confirmed that the flow and frustration conditions diverged in perception of flow. In the flow block, errors on stop trials coincided with pre-stimulus reductions in right temporoparietal gamma power and frontal beta and gamma power, alongside diminished frontotemporal gamma coherence. Comparison of flow and frustration revealed higher temporal beta power during frustration, consistent with greater cognitive load. Flow may involve finely balanced beta and gamma dynamics, and brief collapses of these rhythms may predict task errors. Spectral dynamics are actionable features for closed-loop engagement monitoring applications.

Mobile EEG can link neuroimaging to natural behavior, but effects recorded during movement, and sport in particular, are difficult to interpret because neural activity overlaps with signals from movement, muscle activity, and cable movement artifacts. We analyzed the OpenNeuro Real World Table Tennis dataset to test whether peri-hit spectral activity could be analyzed and how it differed between human-opponent and ball-machine play. Data from 25 participants comprising EEG, noise-layers, EMG and motion recordings was analyzed with pre-hit, impact, and post-hit windows. EEG power bands were residualized using trial-level root mean square from noise-layer, EMG, and motion/miscellaneous channels. Spectral parameterization modeled spectra as an aperiodic component plus periodic peaks. The principal short-window model was resolution-aware; sensitivity analyses reduced model complexity, used a 2.0-s peri-hit subwindow (-1.0 to +1.0 s), or disabled periodic fitting. Results showed residualized alpha and beta power was lower during ball-machine play, including pre-hit posterior alpha power. The clearest context difference was a higher ball-machine aperiodic exponent over posterior and parietal sensors, corresponding to a steeper broadband spectral slope. Posterior post-hit means were 0.451 and 0.606 for human-opponent and ball-machine play, respectively. A focal parietal effect persisted across specifications. The results support artifact-informed, resolution-aware spectral analysis as an effective approach for detecting robust spectral differences between naturalistic visuomotor contexts and suggest that EEG may provide useful information about the processes engaged by different practice environments, without establishing a single cognitive or physiological mechanism or demonstrating a training outcome.

Mapping brain connections is paramount in neuroscience. Lacking has been a method that can systematically map mesoscale (<1mm) connections in the brain in vivo at brainwide scale. Mesoscale mapping is particularly important for NHPs in which information is represented in submillimeter clusters (e.g. cortical columns, striosomes, thalamic rods). Here, we present a method called INS-fMRI, which comprises optical stimulation of single sites in the brain using pulsed Infrared Neural Stimulation (INS), coupled with mapping of functionally connected sites in the brain using ultrahigh field fMRI. It is the only method available for mapping mesoscale connections rapidly (multiple networks mapped within single MRI sessions), systematically (allowing comparison of networks within single individuals), in vivo (no animal sacrifice needed), at whole brain scale, and without viral transfection. This method has broad applicability to a wide range of neuroscience questions. It can be used at any brain site, on different animal models, and on different MRI platforms. The ability to probe circuits repeatedly within single individuals also opens doors for studying changes in mesoscale circuits over time (e.g. for development, aging, disease studies). In addition, as this method circumvents the need for viral transfection, there is exciting potential for human clinical application.

Objective. Frontal-midline theta (FM-theta; 4-8 Hz) oscillations are thought to support cognition. Brief trains of transcranial magnetic stimulation (TMS) can probe these oscillations with high temporal precision but have rarely changed theta power. One possible reason is that prior studies ignored the instantaneous phase of the oscillation, which strongly shapes the cortical response to TMS. We tested whether brief TMS trains triggered at specific FM-theta phases in real time directionally modulate post-train FM-theta power. Approach. Six healthy adults received TMS over dorsomedial prefrontal cortex (Fz) with concurrent electroencephalography during a whole-report working memory task. A beamformer and real-time phase-estimation pipeline triggered four-pulse 6 Hz trains (110% of resting motor threshold) at FM-theta peaks (0 degrees) or troughs (180 degrees), randomized trial by trial. Post-train spectral power was decomposed into total, induced (non-phase-locked) and evoked (phase-locked) components. Main results. Trough-triggered trains transiently increased post-train FM-theta power relative to peak-triggered trains; task performance did not differ. Cluster-based permutation tests showed trough-peak differences in total (4.6-7.1 Hz) and induced (5.0-7.8 Hz) power ~50-440 ms after the train, suggesting amplification of the oscillation . No evoked effect was detected. The total-power effect was robust at the subject level (Cohen's dz = 1.32, p = 0.023). Within-train theta power did not differ between conditions, suggesting a cortical origin. Significance. To our knowledge, this is the first study to lock brief rhythmic TMS trains to the real-time phase of an ongoing oscillation, and to show phase-dependent modulation of FM-theta power after individual trains on timescales relevant to behavior. Open-loop brief-train protocols may have missed such effects by mixing faciliatory and suppressive phases. Phase-locked brief trains offer a precise tool for testing the causal role of oscillations in cognition.

Neuroimaging studies that pool data across clinical sites often suffer from site effects --- variability in imaging measures that arises from technical heterogeneity across sites as opposed to true biological signal. While numerous harmonization methods have been proposed to remove site effects from imaging features, less attention has been placed on how to incorporate harmonization models into common machine-learning pipelines. We demonstrate that current approaches for integration either suffer from data leakage, fail to fully remove site effects from the target data, or attenuate true biological associations during the harmonization process. To address these issues, we propose Multiple Imputation for Removing Technical Heterogeneity (MIRTH), which uses imputed outcomes to harmonize the test data. We benchmark MIRTH's performance using both simulated and real-world volumetric data from the Alzheimer's Disease Neuroimaging Initiative and the Baltimore Longitudinal Study of Aging, demonstrating that MIRTH can achieve high predictive accuracy while avoiding inflated performance when the outcome is imbalanced across clinical sites.

Multi-echo functional magnetic resonance imaging (fMRI) acquires signals with distinct contrast profiles across echo times (TEs). Empirical evidence suggests that different TEs capture distinct signal contributions with varying sensitivity to BOLD and non-BOLD processes from long to short TEs (Stroman, 2002; Krishnamurthy, 2023; Dong, 2024). Previous literature has not yet examined how brain states extracted from temporal dynamic functional connectivity (dFNC) evolve across TEs. Here we present a methodological and empirical study of TE-dependent evolution of dynamic connectivity states, with a phenomenological two-component model for interpretation. Multiple echoes were acquired with an echo planar time-resolved imaging (EPTI) sequence. TE-specific components were extracted via atlas-based group ICA (Neuromark 1.0), and brain connectivity states were generated via windowed dFNC and spatial ICA clustering of windows. Within-subject and group-level states evolved across TEs in network organization and variance. States exhibited TE-dependent variance profiles, with distinct peak echo times; and group-level points of state transition were independently mapped to TE-dependent transitions in variance. We modified a bi-exponential model to simulate and model changes in the dFNC time-course across TEs. The bi-exponential model revealed high consistency with subject states (R2 fit=0.86, res. error=0.55, 86% model convergence rate), suggesting a two-component signal system contributing to dynamic TE-dependent connectivity changes in state. A significant correlation between relative model terms was estimated on a cell-wise basis across states (r(24) = -0.43, p=0.03, 95% CI [-0.70, -0.04]). This suggests that specific bi-exponential signal parameters (i.e., short FNC1,TE=0, long FNC2,TE=0, and long FNC2,decay) were associated with the observed TE-dependent variations in connectivity states across TEs. In sum, our analyses provide downstream implications for TE-aware state analysis dependent on connectivity magnitude (FNCTE=0) and rate of connectivity decay (FNCdecay), in a two-component signal model, with future implications for TE-dependent state biomarkers.

Functional ultrasound (fUS) imaging provides deep, wide-field access to brain function, but instrument cost and complex acquisition and analysis workflows restrict its wider adoption. Here we introduce @fUS, an agentic transcranial imaging platform with an open architecture that integrates purpose-built hardware with executable experimental skills and persistent structured memory. The system combines 128-channel, 16-bit acquisition at 125 MHz with GPU-based processing and enables functional imaging through the intact scalp and skull of mice, with approximately 100-m spatial resolution and 10-Hz temporal sampling, providing a basis for longitudinal studies without cranial-window surgery. Its agent connects scientific objectives to experimental design, direct instrument control and data analysis, retaining context across interactions and supporting inspectable workflows through text and hands-free voice control. Neuroscience trainees with limited engineering experience independently configured the system within 30 min. Agent-assisted exploration of whisker-stimulation datasets revealed low-frequency vascular changes beyond conventional response mapping, supported by complementary two-photon measurements of single-vessel diameter. By combining transcranial imaging with accessible instrument control and analysis, @fUS provides a foundation for wider adoption and larger, more diverse neuroscience datasets. More broadly, it offers a framework for scientific instruments in which measurement, computation and experimental reasoning are developed as parts of the same system.

Blind source separation (BSS) recovers latent sources from observed mixtures. In brain imaging, sources occur in two domains, spatial and temporal, so a criterion applied in one leaves the other unconstrained. Independent component analysis, the most used BSS tool, exploits diversity such as non-Gaussianity and sample dependence, but in one domain at a time. Methods that use both domains apply the same criterion to each and weight them against each other. We propose spatio-dynamical decomposition (SDD), scoring maps by non-Gaussianity and timecourses by dynamical independence: how much each source's dynamics depend on the others. We normalize each score by how much it can improve on the data, eliminating the need for a weight. Across simulations and 130 naturalistic fMRI runs, SDD recovers sources distinguished by either maps or dynamics and reproduces both across disjoint episodes, while baselines trade off the two; map and timescale together also better predict stimulus tracking, with the largest gain for SDD. Together, these results show that separation is strongest when spatial and temporal domains each carry their own criterion.

Communication is inherently interactive, yet most neuroimaging studies examine individuals in isolation. Here, we used functional near-infrared spectroscopy (fNIRS) hyperscanning to investigate interbrain synchrony (IBS) during naturalistic communication. In Study 1, 13 healthy familiar dyads completed Joint Singing, Joint Reading, and Picture Guessing tasks. IBS was quantified using wavelet transform coherence across bilateral frontal and temporoparietal regions. Joint Singing produced higher IBS than the other tasks in several regions, including the dorsolateral prefrontal cortex and temporoparietal junction, and selected effects were greater in true than pseudo-dyads. In Study 2, we applied the same paradigm to five individuals with chronic post-stroke aphasia interacting with trained speech-language pathologists. IBS could be estimated in all dyads after lesion-informed channel exclusion, although regional coverage varied with lesion location. These findings demonstrate that fNIRS hyperscanning can capture task-dependent interpersonal neural coupling during spoken interaction and can be extended to communication involving individuals with aphasia. This approach provides a foundation for studying how neural coordination between communication partners relates to functional communication and partner-supported interaction.