Imaging Neuroscience
● MIT Press
Preprints posted in the last 30 days, ranked by how well they match Imaging Neuroscience's content profile, based on 242 papers previously published here. The average preprint has a 0.14% match score for this journal, so anything above that is already an above-average fit.
Hsu, T.-Y.; Chou, K.-P.; Liu, Y.-J.; Duncan, N. W.
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Inscapes is a low demand abstract animation used as an alternative to eyes open rest in neuroimaging studies, particularly with pediatric and clinical populations prone to head motion. Although prior work has established that functional connectivity patterns during Inscapes closely resemble those during rest, no study has examined whether the two conditions differ in aperiodic neural activity, a broadband feature of the power spectrum linked to excitation/inhibition balance. Here we used magnetoencephalography (MEG) in 54 healthy adults to compare spectrally parameterised aperiodic and periodic measures between eyes open rest and Inscapes viewing (visual component only, without audio). At the sensor level, both the aperiodic exponent and offset were significantly higher during rest than during Inscapes across widespread frontoparietal and occipital distributions in both magnetometers and gradiometers. Source level analyses at both the parcellation and vertex levels largely supported these patterns. The pericalcarine cortex was a notable exception, where both aperiodic measures were higher during Inscapes than during rest, indicating a regionally specific reversal in primary visual cortex. These results demonstrate that Inscapes and eyes open rest produce distinct aperiodic spectral profiles, indicating that the two conditions are not interchangeable for analyses involving broadband spectral dynamics or excitation/inhibition balance estimation.
da Silva Castanheira, J.; Landry, M.; Fleming, S. M.
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Brain activity comprises both rhythmic (periodic) and arrhythmic (aperiodic) components. These signal elements vary across healthy aging, and disease, and may make distinct contributions to conscious perception. Despite pioneering techniques to parameterize rhythmic and arrhythmic neural components based on power spectra, the methodology for quantifying rhythmic activity remains in its infancy. Previous work has relied on parametric estimates of rhythmic power extracted from specparam, or estimates of rhythmic power obtained after detrending neural spectra. Variation in analytical choices for isolating brain rhythms from background arrhythmic activity makes interpreting findings across studies difficult. Whether these current approaches can accurately recover the independent contribution of these neural signal elements remains to be established. Here, using simulation and parameter recovery approaches, we show that power estimates obtained from detrended spectra conflate these two neurophysiological components, yielding spurious correlations between spectral model parameters. In contrast, modelled rhythmic power obtained from specparam, which detrends the power spectra and parametrizes brain rhythms, independently recovers the rhythmic and arrhythmic components in simulated neural time series, minimising spurious relationships. We validate these methods using resting-state recordings from a large cohort. Based on our findings, we recommend modelled rhythmic power estimates from specparam for the robust independent quantification of rhythmic and arrhythmic signal components for cognitive neuroscience.
Bhalerao, G. V.; Markiewicz, P.; Turnbull, J.; Thomas, D. L.; De Vita, E.; Parkes, L.; Thompson, G.; MacKewn, J.; Krokos, G.; Wimberley, C.; Hallett, W.; Su, L.; Malhotra, P.; Hoggard, N.; Taylor, J.-P.; Brooks, D.; Ritchie, C.; Wardlaw, J.; Matthews, P.; Aigbirho, F.; O'Brien, J.; Hammers, A.; Herholz, K.; Barkhof, F.; Miller, K.; Matthews, J.; Smith, S.; Griffanti, L.
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Harmonisation is widely used to mitigate site- and scanner-related batch variability in multisite neuroimaging studies and is particularly critical in longitudinal clinical trials, where detection of subtle biological or treatment-related changes depends on reliable measurement across scanners and timepoints. However, the effectiveness of harmonisation in small, heterogeneous clinical datasets remains insufficiently understood, particularly in relation to subject-level variability and consistency across acquisition settings, and its impact on both removal of technical variability and preservation of biological variation in pooled multisite analyses. We systematically evaluated a range of image-based and statistical harmonisation methods using a clinically realistic multisite, multiscanner structural T1-weighted (T1w) MRI test-retest dataset comprising three controlled acquisition scenarios: repeatability, intra-scanner reproducibility and inter-scanner reproducibility. Methods were applied under different batch specifications (site, scanner, or both) and performance was assessed within each scenario and in pooled data using a multi-metric framework capturing both technical and biological variability in volumetric imaging-derived phenotypes (IDPs) relevant to aging and dementia research. Across IDPs, before harmonisation variability was lowest in the repeatability scenario (median variability=0.6 to 2.7%, rank consistency {rho} [≥]0.9), with modest increases under intra-scanner reproducibility (0.5 to 3.2%, {rho}=0.5 to 1.0) and substantially greater variability under inter-scanner reproducibility conditions (1.7 to 19.2%, {rho} =-0.1 to 0.9). These results offer important information to consider for multisite study design, including sample size calculation in clinical trials. Harmonisation performance was strongly context dependent, with clearer benefits emerged in inter-scanner scenarios where both variability reduction and improvements in subject-level consistency were observed. In pooled data, approaches that explicitly modelled site as batch and accounted for repeated-measure structure showed greater consistency across IDPs in batch effect mitigation and more accurately reflected underlying biological variation. Our evaluation metrics enabled disentangling the removal of global batch effect while highlighting residual variability at the phenotype-specific or multivariate levels. These findings demonstrate that harmonisation cannot be treated as a one-size-fits-all solution and must be interpreted relative to the acquisition context, dataset structure, and downstream analytic goals. Multi-metric evaluation under realistic clinical constraints is essential to support reliable and translatable neuroimaging inference by ensuring appropriate correction of batch effects while preserving longitudinal biological signals and sensitivity to clinically meaningful change in multisite studies.
Fiene, M.; Siems, M.; Kammerer, T.; Schneider, T. R.; Engel, A. K.
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BackgroundIntrinsic functional coupling at multiple temporal scales is a hallmark of human brain dynamics. Among these coupling modes, slow co-fluctuations of oscillatory amplitudes, termed amplitude coupling, are thought to represent a key organizing principle of the large-scale functional architecture, constraining and gating network activity. Yet, despite extensive correlational evidence, direct causal access to amplitude coupling remains limited, restricting insight into its functional relevance. ObjectivesHere, we investigated whether dual-site amplitude-modulated transcranial alternating current stimulation (AM-tACS) can selectively modulate interhemispheric amplitude coupling in human resting-state networks. MethodsTwenty-eight participants received AM-tACS with a carrier frequency in the beta-band whose amplitude was modulated by low-frequency, scale-free dynamics. By applying dual-site AM-tACS either coherently or incoherently across bilateral parieto-occipital cortices, we tested whether stimulation could systematically enhance or disrupt amplitude co-fluctuations in the electrophysiological aftereffect. ResultsIncoherent AM-tACS significantly reduced interhemispheric amplitude coupling between targeted parieto-occipital cortices, with the strongest effects observed in the stimulated beta-band carrier frequency range. This modulation occurred independently of changes in local power or inter-areal phase coupling, indicating a selective effect of AM-tACS on amplitude-based connectivity. Moreover, reductions in amplitude coupling were correlated with the induced electric field strength, suggesting a dose-dependent relationship between stimulation intensity and coupling modulation. ConclusionsOur findings demonstrate that dual-site AM-tACS can causally and selectively modulate amplitude coupling in the human brain. By establishing causal control over lasting amplitude coupling dynamics, this work provides a methodological foundation for future investigations into the functional and behavioral relevance of amplitude coupling in both healthy and pathological brain states. HighlightsO_LIDual-site AM-tACS selectively modulates amplitude coupling in humans C_LIO_LIAM-tACS was designed to mimic natural, scale-free amplitude fluctuations C_LIO_LIStimulation effects are spatially confined to interactions between target regions C_LIO_LIE-field strength predicts the change in amplitude coupling, suggesting a dose-response relationship C_LIO_LIAmplitude coupling modulations are not mediated by band-limited power changes C_LI
Meisler, S. L.; Cieslak, M.; Bagautdinova, J.; Hendrickson, T. J.; Pandhi, T.; Chen, A. A.; Hillman, N.; Radhakrishnan, H.; Salo, T.; Feczko, E.; Weldon, K. B.; McCollum, r.; Fayzullobekova, B.; Moore, L. A.; Sisk, L.; Davatzikos, C.; Huang, H.; Avelar-Pereira, B.; Caffarra, S.; Chang, K.; Cook, P. A.; Flook, E. A.; Gomez, T.; Grotheer, M.; Hagen, M. P.; Huque, Z. M.; Karipidis, I. I.; Keller, A. S.; Kruper, J.; Luo, A. C.; Macedo, B.; Mehta, K.; Mitchell, J. L.; Pines, A. R.; Pritschet, L.; Rauland, A.; Roy, E.; Sevchik, B. L.; Shafiei, G.; Singleton, S. P.; Stone, H. L.; Sun, K. Y.; Sydnor,
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The Adolescent Brain Cognitive Development (ABCD) Study is the largest U.S.-based neuroimaging initiative of adolescent brain maturation. Diffusion MRI (dMRI) provides unique insights into white matter organization, yet applying advanced processing pipelines and managing technical variability across scanning environments remains challenging at scale. To address these issues, we present ABCD-BIDS Community Collection (ABCC) release 3.1.0, including a curated resource of more than 24,000 fully processed ABCD dMRI datasets. ABCC provides fully processed images, nuanced image quality metrics, advanced microstructural measures, and person-specific bundle tractography. Evaluating these rich data revealed that measures of diffusion restriction and non-Gaussianity--in particular the intracellular volume fraction from NODDI and return-to-origin probability from MAP-MRI--were highly sensitive to neurodevelopment and robust to variation in image quality. Additionally, harmonization of microstructural features markedly improved the cross-vendor generalizability of developmental effects. Together, ABCC accelerates reproducible, rigorous research on adolescent white matter development.
Sullivan-Toole, H.; Parr, A. C.; Heller, C.; Tervo-Clemmens, B.; McCollum, r.; Ojha, A.; Feczko, E. J.; Lee, E.; Foran, W.; Calabro, F. J.; Luna, B.; Larsen, B.
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Dopaminergic (DA) function and basal ganglia neurobiology are central to reward learning, motivation, and cognitive control, and dysregulation of these systems contributes to neuropsychiatric conditions that emerge during development. Adolescence is marked by profound reorganization of DAergic basal ganglia circuitry, yet direct in vivo assessment of the DA system remains limited in youth. Brain tissue iron is a developmentally sensitive marker of DA-related neurobiology that can be measured non-invasively via magnetic resonance imaging (MRI). Iron is an essential co-factor for DA synthesis and a foundational metabolic resource that supports cellular metabolism, myelination, and energetic demands of the basal ganglia. T2*-weighted echo-planar imaging (EPI), collected during functional MRI (fMRI), is sensitive to magnetic susceptibility of non-heme brain iron. Leveraging this property, we demonstrate the validity and broad applicability of an iron-sensitive metric that can be derived from conventional single-echo fMRI: {Delta}R2*. In a longitudinal developmental dataset (N = 151; age range 12-31), {Delta}R2* showed high reliability, strong longitudinal stability, and validity via robust convergence with established quantitative relaxometry-based iron measures (R2* and R2). Critically, {Delta}R2* can be retrospectively estimated from extant fMRI data and derived in large-scale consortium data repositories, demonstrated here in the Adolescent Brain and Cognitive Development (ABCD) baseline cohort (N = 8,366; ages 9-11). We show that {Delta}R2* captures known age-related increases in basal ganglia iron, highlighting neurodevelopmental sensitivity at population-scale. Together, these findings establish {Delta}R2* as a reliable, widely accessible marker of basal ganglia iron, enabling scalable investigation of lifespan trajectories and neuropsychiatric risk in existing and future datasets.
Galea, S.; Seychell, B. C.; Galdi, P.; Hunter, T.; Bajada, C. J.
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Functional magnetic resonance imaging (fMRI) quality assurance has traditionally relied on static, geometrically regular phantoms that cannot generate the dynamic signal changes fMRI analysis pipelines are designed to detect. Here we present the Signal Generating (SiGn) anthropomorphic brain phantom, a 3D-printed cortical model derived from an individual participants structural MRI, filled with tissue-mimicking agar gels and coupled to a hemin-based infusion system that produces controlled, time-varying T *-weighted signal changes. We validated the phantom across two scanning sessions on a 3 T Siemens MAGNETOM Vida scanner, demonstrating that hemin infusion produced spatially localised activation detectable by standard general linear model analyses. Because the phantoms geometry is derived from real participant anatomy, its functional data can be coregistered and spatially normalised to standard brain templates through the same pipeline applied to human data, enabling end-to-end assessment of how each preprocessing step affects a known ground-truth signal. To support adoption and reproducibility, we openly release the full resource at https://doi.org/10.60809/drum.31411158, including 3D-printable STL model files, tissue-mimicking gel recipes, the BIDS-formatted dataset, preprocessing and analysis scripts, and a containerised reproducibility workflow; the corresponding archival container image is also deposited on Zenodo at https://doi.org/10.5281/zenodo.19495290. This framework is intended to lower the barrier for other groups to fabricate, scan, and analyse an equivalent device on their own hardware, adapt it to specific research questions, and iteratively improve the design, thereby supporting more rigorous and transparent fMRI quality assurance practices across the neuroimaging community.
Clements, R. G.; Geranmayeh, F.; Parkinson, N. V.; Bright, M. G.
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Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in response to a vasoactive stimulus, is an important measure of cerebrovascular health. Accurate CVR estimation requires accounting for the time required for the vasoactive stimulus to reach each brain region and the time it takes for local arterioles to modulate cerebral blood flow. The temporal search range used to calculate this spatially varying offset can substantially impact CVR estimates, and the appropriate search range may vary across populations, acquisition protocols, and even brain regions. Here, we present an iterative approach for automatically determining the appropriate maximum shift, using breath-hold fMRI data acquired in a cohort of stroke survivors. This approach selectively expands the delay search range only for voxels with estimated delays at the boundary (i.e., near the minimum or maximum shift) until the estimated delay is no longer constrained or a predefined value is reached. In the context of stroke, this approach significantly increased the number of voxels with statistically significant CVR among those initially at the boundary. It also resulted in CVR polarity reversals in voxels originally at the early-response boundary and amplified negative CVR values in voxels originally at the late-response boundary, suggesting that using an iterative maximum shift can critically impact CVR interpretation. This approach is broadly applicable beyond stroke, but careful parameter tuning is required, as illustrated by our demonstration of the parameter tuning process for a participant with Moyamoya disease. Together, these findings suggest that iterative delay correction allows for improved CVR assessments in clinical populations.
Anand, S.; Yeh, F.-c.; Venkadesh, S.
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Multi-site diffusion MRI studies face scanner-induced variability that can obscure biological signal. Harmonization methods such as ComBat have been developed to address this, but have been evaluated primarily on diffusion scalar metrics. Whether scanner reproducibility differs across fundamentally distinct tract-derived representations has not been systematically compared. Here, we compared the reproducibility of three metric families (diffusion, shape, and connectivity) across 36 association tracts using the MASiVar dataset (5 subjects, 4 scanners, 27 sessions). We assessed intraclass correlation coefficients (ICC) and multivariate subject discrimination at baseline, under dimensionality reduction, and after ComBat harmonization. At baseline, shape metrics showed the highest reproducibility (median ICC 0.69), followed by connectivity (0.49) and diffusion (0.34). Shape and connectivity achieved comparable subject discrimination (both 1.75), significantly exceeding diffusion (1.23). ComBat harmonization improved all families but harmonized diffusion (0.58) remained below unharmonized shape (0.69), indicating that metric family selection remains consequential even after harmonization. Under low-dimensional representation, connectivity showed the largest gains (ICC 0.86, subject discrimination 3.0), exceeding other families at any dimensionality. Analysis of principal component loadings identified a small number of cortical regions per tract (median 6) that capture 95% of the reproducible connectivity signal, providing a per-tract reference for selecting the most informative regions in future multi-site studies. These findings indicate that the choice of which tract-derived metrics to analyze in multi-site studies deserves at least as much consideration as how to harmonize them.
Huang, C.; Shi, N.; Wang, Y.; Gao, X.
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The visual receptive field (RF) characterizes the spatiotemporal properties of the visual pathway and serves as a fundamental unit for information encoding. While RFs have been extensively studied across various neural modalities, such as functional Magnetic Resonance Imaging (fMRI), Electrocorticography (ECoG), and Magnetoencephalography (MEG), their investigation via Electroencephalography (EEG) remains limited. In this study, we introduce a stimulation paradigm that combines white noise image sequences with a letter detection task to elicit central visual field EEG responses. Using the aligned/shuffled reverse correlation, we estimate RFs across different resolutions and demonstrate that the resulting RFs exhibit rich spatiotemporal characteristics. To validate the reliability of the estimated RFs, we constructed a visual EEG reconstruction model, which achieved good performance in a classification task. The same RF estimation method was subsequently applied to high-density EEG recordings to investigate the information gain afforded by high-density configurations in visual space. This work fills a gap in the study of visual RFs regarding the EEG modality and may inform the paradigm design of visual brain-computer interfaces.
Knudsen, L.; Lazarova, Y.; Moeller, S.; Nothnagel, N.; Faes, L. K.; Yacoub, E.; Ugurbil, K.; Vizioli, L.
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The human neocortex is organized into six laminae forming the structural basis for feedforward and feedback connections across the brain, yet their functional contributions have remained largely inaccessible for non-invasive imaging methods. Leveraging the ultrahigh field of a 10.5 Tesla scanner, we acquired anatomical and functional MRI data at 0.37mm ([~]0.05 {micro}L) and 0.35mm ([~]0.04 {micro}L) isotropic resolution, respectively, approaching the scale of individual cortical layers in humans. Using the Stria of Gennari as an in-vivo anatomical landmark, we extend our previous finding that feedforward visual activation in layer IV of the primary visual cortex during visual stimulation was resolved in laminar BOLD profiles. These laminar features were reproducible across sessions and were not clearly visible with more typical 0.8 mm resolutions at 7T, underscoring the benefits of further increases in magnetic field strength and resolution. This imaging domain, however, comes with increasing challenges of distortion, alignment, and cortical depth estimation, which must be addressed and mitigated to realize its benefits. In this paper we discuss the promises and challenges of this new regime of high resolutions. Our findings showcase the potential of ultrahigh field, ultrahigh resolution human fMRI to bridge the gap with invasive imaging of cortical layers.
Sitti, G.; Pitti, L.; Candia-Rivera, D.
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Growing evidence indicates that brain continuously interacts with other physiological systems through neural and non-neural pathways. The brain-heart and brain-gut axes play a central role in homeostasis, allostasis and behaviour, but also in cognitive aspects including emotion and decision-making. Disruptions in these axes have been linked to a wide range of cardiovascular, neurological, and psychiatric disorders. Despite this evidence, triadic crosstalk between the brain, heart, and gut remains largely unexplored. Brain activity, cardiac autonomic fluctuations, and gastric rhythms all exhibit slow temporal components in resting state, suggesting that brain-heart-gut electrophysiological interactions may occur over timescales from the infra-slow (0.01-0.1 Hz) physiological range. Using non-invasive electrophysiological recordings from 28 healthy participants at rest, we extracted time-varying power dynamics describing the activity of the three organs: brain alpha power, cardiac sympathetic and parasympathetic indices, and the power of the gastric rhythm. Statistical associations among these organs were quantified using the maximal information coefficient across the extended temporal delay range. Physiological interactions were confirmed using surrogate-based testing, which allowed us to construct the network topology of interactions between the three organs. Our findings show that triadic brain-heart-gut interactions form a multi-directional network at infra-slow timescales, shaping resting state activity. This study offers one of the first insights into the physiology of brain-heart-gut interplay, providing a methodological baseline for the development of more comprehensive biomarkers based on network dynamics capable of linking pathological conditions to dysregulation across multiple organ systems. Abstract figure legend O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/718683v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@6600d1org.highwire.dtl.DTLVardef@bfd404org.highwire.dtl.DTLVardef@1f85612org.highwire.dtl.DTLVardef@dac616_HPS_FORMAT_FIGEXP M_FIG C_FIG Simultaneous resting-state electroencephalographic (EEG), electrocardiographic (ECG), and electrogastrographic (EGG) recordings were processed to extract time-resolved physiological markers for each organ: EEG alpha-band power for the brain, cardiac sympathetic and parasympathetic indices (CSI, CPI) for the heart, and EGG power for the gastrointestinal tract. Coupling between time series was then quantified, and statistical significance was assessed using a surrogate-based method. Significant couplings were subsequently integrated to construct a large-scale network representation, summarizing the strength, temporal delays, and directionality of the predominant electrophysiological interactions among the three organs. Key points summaryO_LIFirst in-human, non-invasive investigation of parallel brain-heart-gut electrophysiological interactions in awake, healthy individuals. C_LIO_LIWe analysed simultaneous electroencephalographic (EEG), electrocardiographic (ECG) and electrogastrographic (EGG) recordings and quantified strength and temporal scale of the derived time-series associations, to construct a large-scale network of interactions. C_LIO_LIWe found that brain-heart-gut interactions extend into the infra-slow (0.01 - 0.1 Hz) range, indicating that spontaneous fluctuations in the electrophysiological activity of one organ at rest are typically followed by corresponding changes in the other two. C_LIO_LIWe found a consistent brain-heart-gut network topology across participants, with multidirectional interactions and bodily dynamics converging toward midline central-posterior brain regions. C_LIO_LIThese findings provide one of the first endeavours in understanding the physiology of brain-heart-gut interactions, and a methodology with strong biomarker development potential. C_LI
Leong, T. I.; Li, A.; Ang, J. H.; Reynolds, B. L.; Leong, C. T.; Choi, C. U.; Sereno, M. I.; Li, D.; Lei, V. L. C.; Huang, R.-S.
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Functional magnetic resonance imaging (fMRI) has been widely utilized to explore the neural mechanisms underlying speech processing. However, the intertwining of perception and production that exists in real-world scenarios remains underexplored due to challenges such as gradient noise and head motion artifacts from speaking. Previous research has often employed sparse-sampling designs, pausing image acquisition intermittently to present auditory stimuli or record overt speech. While this approach mitigates some challenges, it cannot capture continuous brain activity during speech processing and does not separate the mixed hemodynamic responses to external and self-generated speech occurring in succession. We overcame these limitations and continuously scanned thirty-one participants as they listened to and recited English sentences. Through independent component analysis (ICA), we decomposed each functional scan into spatially independent components (ICs), identifying task-related ICs in the superior temporal cortex, inferior frontal gyrus, and orofacial sensorimotor cortex. These ICs demonstrated time-resolved hemodynamic responses corresponding to distinct stages of speech perception, planning, and production. A linear subtraction between the IC time courses from the listening-reciting (perception-to-production) and listening (perception-only) tasks further revealed a secondary hemodynamic response to self-generated speech in the superior temporal cortex. Furthermore, we established precise temporal relationships between overt speech output and the peak, rise, and fall of hemodynamic responses for each independent component. Together, we present a methodological framework that can inform future fMRI studies on naturalistic tasks involving the perception of external auditory stimuli and monitoring of self-generated sounds.
Johansson, J.; Palonen, S.; Egorova, K.; Tuisku, J.; Harju, H.; Kärpijoki, H.; Maaniitty, T.; Saraste, A.; Saari, T.; Tuomola, N.; Rinne, J.; Nuutila, P.; Latva-Rasku, A.; Virtanen, K. A.; Knuuti, J.; Nummenmaa, L.
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BackgroundQuantitative cerebral blood flow (CBF) measured with [15O]water positron emission tomography (PET) is the reference standard for quantifying brain perfusion. However, clinical interpretation of individual CBF measurements is limited by the absence of large normative datasets accounting for physiological variability across the adult lifespan. Long-axial field-of-view PET enables high-sensitivity quantitative [15O]water perfusion imaging without arterial blood sampling, allowing normative characterization of cerebral perfusion at unprecedented scale. The aim of this study was to establish normative and covariate-adjusted models of cerebral blood flow across the adult lifespan using total-body [15O]water PET. MethodsQuantitative CBF measurements were obtained in 302 neurologically healthy adults (age 21-86 years) using total-body [15O]water PET. Linear mixed-effects models were used to evaluate the effects of age, sex, body mass index (BMI), and blood hemoglobin concentration on CBF and to generate normative prediction models across the adult lifespan. Between-subject and within-subject variability were estimated from repeated scans in a subset of participants (n=51). ResultsMean grey matter CBF was 46.1 mL/(min*dL), with substantial inter-individual variability but high within-subject reproducibility (intraclass correlation coefficients 0.78-0.89). Advancing age was associated with a decline in CBF of approximately 7% per decade (p_FDR < 10-12). Higher BMI was associated with lower CBF (approximately -6% per 10 kg/m2; p_FDR < 0.01). Women exhibited higher CBF than men (approximately 7.5%), but this difference was largely explained by lower blood hemoglobin concentration in women. Covariate-adjusted models were used to generate normative predictions and prediction intervals describing expected CBF across adulthood. ConclusionThis study establishes a normative database of quantitative cerebral blood flow across the adult lifespan using high-sensitivity [15O]water PET. Age, BMI, and hemoglobin are major determinants of inter-individual variability in CBF. The resulting generative models provide a quantitative reference framework for interpreting cerebral perfusion measurements and may enable automated detection of abnormal brain perfusion in clinical PET imaging.
Wanjau, E.; Chourrout, M.; Maffei, C.; Balbastre, Y.; Keenlyside, A.; Brunet, J.; Sharma, A.; Huang, S. Y.; Tafforeau, P.; Fischl, B.; Yendiki, A.; Lee, P. D.; Walsh, C.
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Diffusion MRI (dMRI) allows us to image the human connectome non-invasively, yet it provides indirect estimates of axonal orientations based on the diffusion of water molecules in millimeter-scale voxels, hence struggling to resolve complex micrometer-scale fiber geometries. Invasive methods for imaging axonal orientations ex vivo, e.g. histology, are destructive and limited to small volumes, creating a critical need for a non-destructive modality for imaging microscopic fiber orientations in 3D. Here, we use Hierarchical Phase-Contrast Tomography (HiP-CT) to characterize white matter architecture at the microscale. Applying structure-tensor analysis to HiP-CT data, we compute fiber Orientation Distribution Functions and perform tractography analogous to dMRI. Across multiple brain regions, HiP-CT derived fiber architecture shows strong correspondence with that derived from dMRI while revealing substantially greater microstructural complexity. Despite its label-free nature, we demonstrate that vascular structures minimally confound HiP-CT orientation estimates. These results establish HiP-CT as a reference microscopic modality that can complement dMRI in multi-scale studies of white-matter organization.
Matsui, T.; Li, R.; Masaoka, K.; Jimura, K.
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Compared with model-based and phenomenological descriptions of the spatiotemporal dynamics of resting-brain activity, statistical characterizations of resting-state fMRI (rs-fMRI) data remain relatively underexplored. Some sophisticated analysis techniques, such as Mapper-based topological data analysis (TDA) and innovation-driven coactivation pattern analysis (iCAP), can distinguish real data from phase-randomized (PR) surrogates, suggesting that rs-fMRI data are not as simple as stationary Gaussian processes. However, the exact statistical properties that distinguish real rs-fMRI data from PR surrogates have not yet been determined. In this study, we conducted system identification analysis and surrogate data analysis to specify key statistical properties that allow TDA and iCAP to discriminate real rs-fMRI data from PR surrogates. We first analyzed rs-fMRI data concatenated across scans using autoregressive (AR) modeling and found that the scan-concatenated rs-fMRI data were weakly non-Gaussian. However, non-Gaussianity alone was insufficient to reproduce realistic TDA and iCAP results because of non-stationarity across scans. AR modeling of single-scan data revealed that rs-fMRI data were statistically indistinguishable from a Gaussian distribution within a single scan, although TDA and iCAP results still differed between the real data and PR surrogates. A new surrogate dataset designed to preserve non-stationarity successfully reproduced realistic TDA and iCAP results, suggesting that TDA and iCAP likely capture the non-stationarity of rs-fMRI data to distinguish it from PR surrogates. Together, these results indicate approximate Gaussianity and non-stationarity in rs-fMRI data, providing a data-driven and statistical characterization of resting-state brain activity that can serve as a quantitative reference for whole brain simulations and generative models.
Olsen, A. S.; Larsen, K.; McCulloch, D. E.-W.; Ganz, M.; Madsen, M. K.; Ozenne, B.; Knudsen, G. M.; Rehman, N. u.; Fisher, P. M.
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Psilocybin and other serotonergic drugs acutely alter human brain function and large-scale connectivity as measured with BOLD fMRI, but whether these effects are frequency-specific remains unknown. We applied multitaper spectral and cross-spectral analyses to resting-state fMRI data from 28 healthy volunteers scanned multiple times acutely following oral psilocybin administration (0.2 - 0.3 mg/kg), together with plasma psilocin measurements, to estimate psilocin associations with temporal frequency-specific activity and connectivity. Psilocybin produced a selective reduction in low-frequency spectral power (0.01 - 0.06Hz) and an increase in spectral entropy, with the strongest effects in transmodal networks. We also observed a reduction in low-frequency connectivity energy explained by the unimodal/transmodal axis. These findings demonstrate that psilocin induces spatially distributed, frequency-dependent alterations, suggesting that broadband fMRI analyses may obscure low-frequency dynamics. Frequency-resolved approaches may offer greater sensitivity for characterizing psychedelic effects on brain activity.
Pamplona, G. S. P.; Stettler, S.; Hebling Vieira, B.; Di Pietro, S. V.; Frei, N.; Lutz, C.; Karipidis, I. I.; Brem, S.
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Reading is a complex skill with a well-characterized neural basis. Multivariate fMRI analyses have deepened our neuroscientific understanding of literacy by linking neural patterns to behavioral traits. Although task-based fMRI often outperforms resting-state fMRI in predicting cognitive traits, few studies have applied it to continuous measures of childrens reading ability. To identify neural markers of literacy, we compared predictive performance across multiple fMRI tasks and reading-related measures. In this data-driven study, we predicted literacy skills in school-aged children (6.7-10.3 years) from eleven behavioral scores grouped into Reading (fluency and comprehension), Verbal (vocabulary knowledge and verbal intelligence), and Naming (object naming speed). Predictive performance was examined across four fMRI tasks completed by subgroups of children (n = 73-97): two active tasks - phonological-lexical decisions (PhonLex) and audiovisual character learning (Learn) - and two passive tasks - word and face viewing (Localizer) and character processing (CharProc). Individual activation contrast maps, categorized as simple (single condition) or subtractive (condition contrasts), were analyzed using a machine learning model with whole-brain predictors derived from principal component analysis. Results showed the highest predictive performance for Reading and Naming with PhonLex > Learn > Localizer = CharProc, and for Verbal with PhonLex = Learn > Localizer = CharProc. Simple contrasts generally outperformed subtractive contrasts in predicting behavioral scores. Key neural predictors, identified through whole-brain and region-of-interest analyses, included the left inferior frontal gyrus, supramarginal gyrus, ventral occipitotemporal cortex, insula, and default mode network regions. Together, these findings indicate that, for predicting literacy traits in children, active tasks and tasks that engage brain systems involved in multisensory learning tend to outperform both passive paradigms and simple subtractive task contrasts. This study provides a methodological benchmark for brain-based prediction of reading ability and highlights the value of activation heterogeneity across distributed regions as a potential marker for tracking literacy development over time.
Keshavarzi, M.; Feltham, G.; Richards, S.; Parvez, L.; Goswami, U.
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Neural tracking of slow temporal modulations in speech supports extraction of prosodic and syllabic structure critical for speech comprehension, yet whether these automatic cortical tracking mechanisms are altered in children with developmental language disorder (DLD) remains unclear. We recorded MEG while children with and without DLD listened to a story, and quantified source-level lagged speech-brain coherence and frequency-specific cortical functional connectivity across bilateral cortical regions. Children with DLD showed significantly reduced coherence in the 0.9-2.5 Hz range associated with prosodic information in the story, spanning bilateral auditory and speech-related cortex. In the 2.5-5 Hz range, linked to syllabic-rate modulations in the story, group differences were right-lateralised. No reliable differences were observed at higher modulation rates (5-9 Hz or 12-40 Hz). These coherence reductions were accompanied by altered functional connectivity between cortical regions across all frequency bands, indicating disrupted large-scale coordination within speech-processing networks in DLD.
Tang, J.; Huth, A. G.
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Voxelwise encoding models trained on functional MRI data can produce detailed maps of cortical organization. However, voxelwise encoding models must be trained on many hours of brain responses from each participant, limiting clinical applications. In this study, we introduce a cross-participant modeling framework for rapid cortical mapping. In this framework, voxelwise encoding models are trained on many hours of brain responses from previously scanned reference participants, and then transferred to a new participant by aligning brain responses using a small set of stimuli. We evaluated cross-participant encoding models on linguistic semantic mapping, non-linguistic semantic mapping, and auditory mapping. In each case we found that cross-participant encoding models had more accurate selectivity estimates and prediction performance than within-participant encoding models trained on the same amount of data from the new participant. We also found that cross-participant encoding models improved with the amount of data from each reference participant and the number of reference participants. These results demonstrate that cross-participant modeling can substantially reduce the amount of data required for accurate cortical mapping, which may facilitate new clinical applications of functional neuroimaging.