Biology subjects

Grotheer, M.

Publications and source records attributed to Grotheer, M..

13 recordsLinked to original sources

bioRxiv2026

Preliterate symbolic language processing sets the neural stage for learning to read

Formal writing is evolutionarily recent, yet the brains of literate adults contain regions - the OTS-words subregions - that respond more strongly to written text than other stimuli. We tested a novel solution to this multi-disciplinary paradox: Does symbolic language processing, which emerged early in human history, lay the neural foundation for reading? In a longitudinal fMRI study, we followed 17 children through their first year of literacy training and related neural responses to text, symbolic language processing, and emerging reading skills over time. We found that middle OTS-words is engaged in symbolic language processing before children learn to read, and that this early engagement predicts later text selectivity and reading ability. These findings suggest that literacy builds on a pre-existing neural scaffold linking vision and language.

neuroscience↗

bioRxiv2026

Highly replicable multisite patterns of adolescent white matter maturation

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.

neuroscience↗

bioRxiv2025

A fast and child-friendly localizer for the identification of ITG-math based on its preference for mathematical processing

The visual number form areas (here referred to as ITG-math) have gained recent attention as a neural substrate of mathematical cognition. Yet, the function of these regions remains debated with some research suggesting selectivity for digits and others suggesting a visual stimulus-independent role in mathematical processing. Here we addressed this debate by exploring the impact of different tasks and stimuli on neural responses in ITG-math. Participants were presented with digits and UFOs, while performing a 1-back task either on stimulus numerosity or on stimulus color. We collected two sessions of this experiment from 17 healthy adults and could identify voxels with higher responses in the numerosity than the color task in 92% of the participants, whereas contrasting digits with UFOs lead to selective responses in only 35% of the participants. Accordingly, in independent data, ITG-math showed a task preference, but no stimulus preference. Multivariate analyses further revealed task encoding, and a combination of task and stimulus encoding, in the left and right ITG-math, respectively. Our work hence supports the notion that the role of ITG-math in mathematical cognition goes beyond the encoding of digits.

neuroscience↗

bioRxiv2025

Cortical and white matter T1w/T2w development proceed in concert during early infancy

The infant brain undergoes rapid myelination that is critical for healthy brain function. This development has been characterized for gray and white matter independently, but the link between gray and white matter myelination remains unexplored. To close this knowledge gap, we evaluated two complementary myelin-sensitive imaging metrics: Large-scale (N=273) T1w/T2w and quantitative (N=21) R1 data. Automated software was employed to identify 26 white matter bundles and map their cortical terminations, before evaluating T1w/T2w and R1 development shortly after birth. Here we show that for both metrics mean values as well as developmental slopes are correlated across tissues. The synchrony of brain T1w/T2w is impacted by gestational age and prematurity, whereas inter-individual differences in this synchrony predict motor outcomes at 17 - 25 months of age. As T1w/T2w and R1 are associated with myelin content, our results reveal an intricate relationship between gray and white matter myelination.

neuroscience↗

bioRxiv2024

White matter connections of human ventral temporal cortex are organized by cytoarchitecture, eccentricity, and category-selectivity from birth

Category-selective regions in ventral temporal cortex (VTC) have a consistent anatomical organization, which is hypothesized to be scaffolded by white matter connections. However, it is unknown how white matter connections are organized from birth. Here, we scanned newborn to 6-month-old infants and adults to determine the organization of the white matter connections of VTC. We find that white matter connections are organized by cytoarchitecture, eccentricity, and category from birth. Connectivity profiles of functional regions in the same cytoarchitectonic area are similar from birth and develop in parallel, with decreases in endpoint connectivity to lateral occipital, and parietal, and somatosensory cortex, and increases to lateral prefrontal cortex. Additionally, connections between VTC and early visual cortex are organized topographically by eccentricity bands and predict eccentricity biases in VTC. These data show that there are both innate organizing principles of white matter connections of VTC, and the capacity for white matter connections to change over development.

neuroscience↗

bioRxiv2023

Both mOTS-words and pOTS-words prefer emoji stimuli over text stimuli during a reading task

The visual word form area in the occipitotemporal sulcus (OTS), here referred to as OTS-words, responds more strongly to text than other visual stimuli and is crucial for reading. We hypothesized, that this text preference may be driven by a preference for reading tasks, as in most prior fMRI studies only the text stimuli were readable. Hence, we performed three fMRI experiments (N=15) and systematically varied the participant s task and the stimulus, investigating mOTS-words and pOTS-words subregions. In experiment 1, we contrasted text stimuli with non-readable visual stimuli (faces, limbs, houses, objects). Experiment 2 utilized an fMRI adaptation paradigm, presenting compound words in text or emoji formats. In experiment 3, participants performed a reading or a color task on compound words in text or emoji format. Using experiment 1 data, we identified mOTS-words and pOTS-words by contrasting texts with non-readable stimuli. In experiment 2, pOTS-words, but not mOTS-words, showed fMRI adaptation for compound words in both text and emoji formats. In experiment 3, surprisingly, both subregions showed higher responses to compound words in emoji than text format. Moreover, mOTS-words showed higher responses during the reading than the color task and a task-stimulus interaction. Multivariate analyses revealed that distributed responses in pOTS-words encode the visual stimulus, while responses in mOTS-words encode both stimulus and task. Together, our findings suggest that the function of the OTS-words subregions goes beyond the specific visual processing of text and that these regions are flexibly recruited whenever semantic meaning needs to be assigned to visual input. Significance StatementReading skills are essential in modern society and supported by a brain region in the occipitotemporal sulcus (OTS-words) that is critical for fluent reading. Here we evaluated if responses in OTS-words are driven by the activity of reading or simply by seeing text or other readable symbols (emojis). We found that OTS-words can be divided into two sub-regions which both prefer readable emojis over text, whereas the anterior sub-region also prefers reading over other tasks. These results suggest that OTS-words is flexibly recruited to encode any readable visual stimulus, not just text. By demonstrating OTS-words flexibility, this work reconciles previous contradictory findings on this regions functional properties and inspires future research on OTS-words, including its emergence during literacy acquisition.

neuroscience↗

bioRxiv2023

Human white matter myelination rate slows down at birth

The formation of myelin, the fatty sheath that insulates nerve fibers, is critical for healthy brain function. A fundamental open question is what is the impact of being born on myelin growth. To address this question, we evaluated a large (n=300) cross-sectional sample of newborns from the Developing Human Connectome Project (dHCP). First, we developed new software for the automated identification of 20 white matter bundles in individuals that is well-suited for large samples. Next, we fit linear models that quantify T1w/T2w, a myelin-sensitive imaging contrast, increases along bundles. We found faster growth of T1w/T2w along the lengths of all bundles before birth than right after birth. Further, in a separate longitudinal sample of preterm infants (N=34), we found lower T1w/T2w at term-equivalent age than in full-term peers. By applying the linear models fit on the cross-section sample to the longitudinal sample of preterm infants, we find that their delay in T1w/T2w growth is well explained by the amount of time preterm infants spend developing in utero and ex utero. These results suggest that being born slows the rate of myelin growths. This reduction in the rate of myelin growth at birth, in turn, explains lower myelin content in individuals born preterm, and could account for long-term cognitive, neurological, and developmental consequences of preterm birth. We hypothesize that closely matching the environment of infants born preterm to what they would have experienced in the womb may reduce delays in myelin growth and hence improve developmental outcomes.

neuroscience↗

bioRxiv2022

White matter connections of high-level visual areas predict cytoarchitecture better than category-selectivity

Ventral temporal cortex (VTC) consists of high-level visual regions that are arranged in consistent anatomical locations across individuals. This consistency has led to several hypotheses about the factors that constrain the functional organization of VTC. A prevailing theory is that white matter connections influence the organization of VTC, however, the nature of this constraint is unclear. Here, we test two hypotheses: (1) white matter tracts are specific for each category or (2) white matter tracts are specific to cytoarchitectonic areas of VTC. To test these hypotheses, we used diffusion magnetic resonance imaging (dMRI) to identify white matter tracts and functional magnetic resonance imaging (fMRI) to identify category-selective regions in VTC in children and adults. We find that in childhood, white matter connections are linked to cytoarchitecture rather than category-selectivity. In adulthood, however, white matter connections are linked to both cytoarchitecture and category-selectivity. These results suggest a rethinking of the view that category-selective regions in VTC have category-specific white matter connections early in development. Instead, these findings suggest that the neural hardware underlying the processing of categorical stimuli may be more domain-general than previously thought, particularly in childhood.

neuroscience↗

bioRxiv2021

Catch me if you can: Least myelinated white matter develops fastest during early infancy

Development of myelin, a fatty sheath that insulates nerve fibers, is critical for brain function. Myelination during infancy has been studied with histology, but postmortem data cannot evaluate the longitudinal trajectory of white matter development. Here, we obtained longitudinal diffusion MRI and quantitative MRI measures of R1 in 0, 3 and 6 months-old human infants, and (ii) developed an automated method to identify white matter bundles and quantify their properties in each infants brain. We find that R1 increases from newborns to 6-months-olds in all bundles. R1 development is nonuniform: there is faster development in white matter that is less mature in newborns, and along inferior-to-superior as well as anterior-to-posterior spatial gradients. As R1 is linearly related to myelin fraction in white matter bundles, these findings open new avenues to elucidate typical and atypical white matter myelination in early infancy, which has important implications for early identification of neurodevelopmental disorders.

neuroscience↗

bioRxiv2021

Myelin contributes to microstructural growth in human sensory cortex during early infancy.

Development of cortical tissue during infancy is critical for the emergence of typical brain functions in cortex. However, how cortical microstructure develops during infancy remains unknown. We measured the longitudinal development of cortex from newborns to six-months-old infants using multimodal quantitative imaging of cortical microstructure. Here we show that infants cortex undergoes profound microstructural tissue growth during the first six months of human life. Comparison of postnatal to prenatal transcriptomic gene expression data demonstrates that myelination and synaptic processes are dominant contributors to this postnatal microstructural tissue growth. Using visual cortex as a model system, we find hierarchical microstructural growth: higher-level visual areas have less mature tissue at birth than earlier visual areas but grow at faster rates. This overturns the prevailing view that visual areas that are most mature at birth develop fastest. Together, in vivo, longitudinal, and quantitative measurements, which we validated with ex vivo transcriptomic data, shed new light on the rate, sequence, and specific biological mechanisms of developing cortical systems. Importantly, our findings propose a new hypothesis that cortical myelination is a key factor in cortical development during early infancy, which has significant implications for diagnosis of neurodevelopmental disorders and delays in infants.

neuroscience↗

bioRxiv2021

Evaluating the reliability of human brain white matter tractometry

The validity of research results depends on the reliability of analysis methods. In recent years, there have been concerns about the validity of research that uses diffusion-weighted MRI (dMRI) to understand human brain white matter connections in vivo, in part based on reliability of the analysis methods used in this field. We defined and assessed three dimensions of reliability in dMRI-based tractometry, an analysis technique that assesses the physical properties of white matter pathways: (1) reproducibility, (2) test-retest reliability and (3) robustness. To facilitate reproducibility, we provide software that automates tractometry (https://yeatmanlab.github.io/pyAFQ). In measurements from the Human Connectome Project, as well as clinical-grade measurements, we find that tractometry has high test-retest reliability that is comparable to most standardized clinical assessment tools. We find that tractometry is also robust: showing high reliability with different choices of analysis algorithms. Taken together, our results suggest that tractometry is a reliable approach to analysis of white matter connections. The overall approach taken here both demonstrates the specific trustworthiness of tractometry analysis and outlines what researchers can do to demonstrate the reliability of computational analysis pipelines in neuroimaging.

neuroscience↗

bioRxiv2020

White matter fascicles and cortical microstructure predict reading-related responses in human ventral temporal cortex

Reading-related responses in the lateral ventral temporal cortex (VTC) show a consistent spatial layout across individuals, which is puzzling, since reading skills are acquired during childhood. Here, we tested the hypothesis that white matter fascicles and gray matter microstructure predict the location of reading-related responses in lateral VTC. We obtained functional (fMRI), diffusion (dMRI), and quantitative (qMRI) magnetic resonance imaging data in 30 adults. fMRI was used to map reading-related responses by contrasting responses in a reading task with those in adding and color tasks; dMRI was used to identify the brains fascicles and to map their endpoints density in lateral VTC; qMRI was used to measure proton relaxation time (T1), which depends on cortical tissue microstructure. We fit linear models that predict reading-related responses in lateral VTC from endpoint density and T1 and used leave-one-subject-out cross-validation to assess prediction accuracy. Using a subset of our participants (N=10, feature selection set), we find that i) endpoint density of the arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), and vertical occipital fasciculus (VOF) are significant predictors of reading-related responses, and ii) cortical T1 of lateral VTC further improves the predictions of the fascicle model. Next, in the remaining 20 participants (validation set), we showed that a linear model that includes T1, AF, ILF and VOF significantly predicts i) the map of reading-related responses across lateral VTC and ii) the location of the visual word form area, a region critical for reading. Overall, our data-driven approach reveals that the AF, ILF, VOF and cortical microstructure have a consistent spatial relationship with an individuals reading-related responses in lateral VTC. HighlightsThe ILF, AF, and VOF predict the spatial layout of reading-related responses in VTC Gray matter microstructure improves the prediction of reading-related responses Fascicles and gray matter structure together predict the location of the VWFA

neuroscience↗

bioRxiv2018

Separate lanes for math and reading in the white matter highways of the human brain

Math and reading involve distributed brain networks and learning disabilities associated with these skills have a high rate of co-occurrence. However, it is unknown what are shared vs. dissociated white matter substrates of math and reading networks. Here we address this question using an innovative, multimodal approach applying functional MRI, diffusion MRI, and quantitative MRI to define these networks and evaluate structural properties of their fascicles. Results reveal that the superior longitudinal (SLF) and arcuate (AF) fascicles are shared between math and reading networks. Strikingly, within these fascicles, reading- and math-related tracts are segregated into parallel sub-bundles and show structural differences related to myelination. These novel findings: (i) open a new avenue of research enabling linkage of sub-bundles within fascicles to behavior and (ii) may explain both isolated and comorbid cases of math and reading disabilities, which may be associated with white matter abnormalities within sub-bundles or entire fascicles, respectively.

neuroscience↗