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Yeatman, J. D.

Publications and source records attributed to Yeatman, J. D..

At least 19 recordsLinked to original sources

Functional connectivity scaffolds the emergence of the visual word form area

Complex cognitive tasks, like reading, require coordinated computations across distant cortical regions. Connectivity among regions is therefore key for understanding the neurobiological basis of behavior. It remains an open question whether connectivity serves as an innate organizational blueprint that guides functional specialization, or if it evolves with learning. Here, we address this fundamental question through the prism of learning to read: We measured functional connectivity at five timepoints over a year in children with dyslexia who participated in an intensive reading intervention. We found that specific patterns of functional connectivity of the reading circuitry were in place prior to the intervention, and remained stable over time. Further, functional connectivity before the intervention predicted the location of text-selective regions a year later, showing that connectivity precedes and predicts functional specialization that emerge with learning. These findings support a view of functional connectivity as a stable organizational principle of high-level cortex.

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Anatomy of the Visual Word Form Area in Dyslexia

The Visual Word Form Area (VWFA), located in ventral occipitotemporal cortex, plays a critical role in skilled reading. Researchers have theorized that the VWFA develops in its specific anatomical location due to the convergence of major white matter tracts and proximity to functionally similar regions. This suggests that precise anatomical positioning may be crucial for optimal VWFA function. Previous research has identified several functional differences in this region between typical and struggling readers (i.e. dyslexia): struggling readers show weaker text-selective responses and often exhibit a smaller or even absent VWFA. However, it remains unexplored whether the precise anatomical location of this region also differs between typical and struggling readers. We tested whether VWFA anatomy differs between children with and without dyslexia (N=87). Participants completed a functional localizer, which we used to manually define the VWFA in each individual's native anatomy. We examined whether: (1) VWFA anatomical location relates to reading ability, (2) children with dyslexia show greater variability in VWFA location compared to typical readers, and (3) VWFA location with respect to white matter tracts relates to reading ability. Results reveal that, despite being smaller in children with dyslexia, there is no relationship between VWFA location and reading ability. Specifically, individual VWFA location relative to anatomy, relative to other's VWFAs, and relative to white matter tracts, is not related to reading ability. These findings suggest that while the VWFA's general anatomy may be facilitated by development, its precise location remains stable and unrelated to reading proficiency.

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Sulcal anatomy of ventral temporal cortex and reading development

Individual differences in cognitive abilities have been linked to variability in cortical folding, a stable neuroanatomical scaffold largely established in utero. In the domain of reading, recent findings in small groups of typical readers suggest that a sulcal interruption (superficial annectant gyrus, gyral gap) in the left posterior occipital temporal sulcus (lhpOTS) predicts better reading skills, posing the lhpOTS as a potential early biomarker of reading difficulties. However, it remains unknown whether this relationship found in typical readers generalizes to the dyslexic population and whether the lhpOTS can serve as a biomarker for dyslexia or predict response to targeted instruction.To fill these gaps, we examine the patterns of the lhpOTS in 209 children, including children with dyslexia, from four independently-collected samples. In typical readers, we find that the relationship between the lhpOTS and reading skills is robust, replicating across binary and continuous quantifications of the sulcal interruption. However, lhpOTS patterns neither distinguish dyslexic children from typical readers nor do they predict response to intervention. Instead, targeted reading intervention drives long-term gains in reading skills that are equivalent irrespective of VOTC anatomy. Together, these findings distinguish neuroanatomical correlates of skilled reading from determinants of reading impairment and learning capacity and emphasize the importance of the educational environment in supporting reading acquisition for children with dyslexia. SIGNIFICANCE STATEMENTEarly predictors of dyslexia are important for understanding the etiology of reading difficulties and informing early intervention. One candidate biomarker for dyslexia is the left posterior occipital temporal sulcus (lhpOTS), a neuroanatomical feature established before birth. In typical readers, the presence of an interruption in the lhpOTS has been linked to better reading skills. Here, we examine this neuroanatomical feature in 209 children with and without dyslexia. While the lhpOTS reliably relates to reading skill in typical readers, it neither differentiates dyslexic from typical readers nor predicts response to intensive reading intervention. These results show that brain anatomy reflects reading proficiency but does not constrain learning and highlights the power of targeted intervention to support reading development.

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Neonatal brain-age models in full- and preterm infants

Prematurity affects brain development and increases risk for neurodevelopmental impairments. Yet reliable biomarkers for at-risk infants remain limited. The goals of this study are (1a) to construct a white matter neonatal brain-age model including full-term and preterm neonates from a large publicly-available data set, (1b) to evaluate the accuracy of this model for characterizing the preterm brain from the same data set; (2) to determine if a similar model can predict brain-age based on clinical MRI scans from high-risk neonates born preterm; and (3) to evaluate whether this predictive model provides information about the infants health beyond conventional clinical and demographic measures. We developed brain-age prediction models using diffusion magnetic resonance imaging-derived white matter features from two datasets: (1) the developing Human Connectome Project (dHCP; 368 healthy infants) and (2) a clinical sample collected at the Lucile Packard Childrens Hospital (LPCH; 162 high-risk preterm infants). White matter features demonstrated strong predictive performance in the dHCP dataset (within 3.9 days) and the LPCH clinical dataset (within 6.6 days). However, brain-age metrics (i.e., brain-age gap) showed no significant associations with health complications measured by a composite score of common prematurity complications. While tractometry-derived brain-age models accurately characterize brain maturation in the neonatal brain, their sensitivity to clinical complications in preterm infants appears limited. Global white matter maturation measures derived from clinical grade data may be insufficiently sensitive to capture the cumulative burden of prematurity-related morbidities, suggesting need for multimodal or longitudinal biomarkers. HIGHLIGHTSBrain-age models of neonatal dMRI data predict age within days. Brain-age models of preterm infants predict post-menstrual age within a week. Brain-age models are accurate with research and clinical dMRI data in preterm infants. Brain-age gap was not sensitive to health status in a clinical preterm sample. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/701337v1_ufig1.gif" ALT="Figure 1000"> View larger version (15K): org.highwire.dtl.DTLVardef@16f5c5dorg.highwire.dtl.DTLVardef@1918e0org.highwire.dtl.DTLVardef@1b0246eorg.highwire.dtl.DTLVardef@127f132_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Visual Word Form Area demonstrates individual and task-agnostic consistency but inter-individual variability

Ventral Occipital Temporal Cortex (VOTC) contains a mosaic of categorically-selective functional regions that respond to visual stimuli. Within left VOTC lies the Visual Word Form Area (VWFA) - a text-selective region that develops as individuals learn to read. While there is consistency in the general location of text-selective responses - within the posterior occipitotemporal sulcus (OTS) - there is substantial variability across individuals in the size and precise anatomical location. Moreover, debate continues regarding whether VWFA a) encodes the visual features of text, versus b) is driven by the task of reading. Using functional magnetic resonance imaging, we scanned adults and children as they completed two tasks while viewing text, pseudo fonts, faces, objects, limbs: (1) a fixation task where participants ignored stimuli while making psychophysical judgements on a fixation dot, and (2) a one-back task, where they attend to stimuli to detect repeats. We found a consistent VWFA location could be identified on each individuals cortical surface using either task. At the same time, the one-back task evoked a larger territory of text-selective response (leading to a larger ROI) than the fixation task. However, when averaged in template space, text-selective cortex could not be identified due to variability in the relative locations of text-, face-, object-, and limb-selective cortex. Thus, despite task-agnostic consistency in individual VWFA, text-selective responses are masked when averaged in template space due to variability in the exact configuration of category-selective regions. Furthermore, these effects were present in both children and adults.

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Two Axes of White Matter Development

Despite decades of neuroimaging research, how white matter develops along the length of major tracts in humans remains unknown. Here, we identify fundamental patterns of white matter maturation by examining developmental variation along major, long-range cortico-cortical tracts in youth ages 5-23 years using diffusion MRI from three large-scale, cross-sectional datasets (total N = 2,716). Across datasets, we delineate two replicable axes of human white matter development. First, we find a deep-to-superficial axis, in which superficial tract regions near the cortical surface exhibit greater age-related change than deep tract regions. Second, we demonstrate that the development of superficial tract regions aligns with the cortical hierarchy defined by the sensorimotor-association axis, with tract ends adjacent to sensorimotor cortices maturing earlier than those adjacent to association cortices. These results reveal developmental variation along tracts that conventional tract-average analyses have previously obscured, challenging the implicit assumption that white matter tracts mature uniformly along their length. Such developmental variation along tracts may have functional implications, including mitigating ephaptic coupling in densely packed deep tract regions and tuning neural synchrony through hierarchical development in superficial tract regions - ultimately refining neural transmission in youth.

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Small or absent Visual Word Form Area is a trait of dyslexia

Understanding the balance between plastic and persistent traits in the dyslexic brain is critical for developing effective interventions. This longitudinal intervention study examines the Visual Word Form Area in dyslexic and typical readers, exploring how this key component of the brains reading circuitry changes with learning. We find that children with dyslexia show significant differences in Visual Word Form Area presence, size, and tuning properties compared to typical readers. While reading intervention improves reading skills and increases Visual Word Form Area size, disparities persist a year later, suggesting that Visual Word Form Area abnormalities are enduring traits of dyslexia. Our results reveal long-term neural and behavioral changes, while also elucidating stable differences in the functional architecture of the dyslexic brain. This work provides comprehensive insights into the potential and limitations of short-term learning-induced plasticity in human visual cortex.

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Development of the Left Arcuate Fasciculus is Linked to Learning Gains in Reading, but not Math

Past studies leveraging cross-sectional data have raised questions surrounding the relationship between diffusion properties of the white matter and academic skills. Some studies have suggested that white matter properties serve as static predictors of academic skills, whereas other studies have observed no such relationship. On the other hand, longitudinal studies have suggested that within-individual changes in the white matter are linked to learning gains over time. In the present study, we look to replicate and extend the previous longitudinal results linking longitudinal changes in the white matter properties of the left arcuate fasciculus to individual differences in reading development. To do so, we analyzed diffusion MRI data, along with reading and mathematics scores in a longitudinal sample of 340 students as they progressed from 1st grade into 4th grade. Longitudinal growth models revealed that year-to-year within-individual changes in reading scores, but not math, were related to the development of the left arcuate fasciculus. These findings provide further evidence linking the dynamics of white matter development and learning in a unique sample and highlight the importance of longitudinal designs.

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Anatomically distinct regions in the inferior frontal cortex are modulated by task and reading skill

Inferior frontal cortex (IFC) is a critical region for reading and language. This part of the cortex is highly heterogeneous in its structural and functional organization and shows high variability across individuals. Despite decades of research, the relationship between specific IFC regions and reading skill remains unclear. To shed light on the function of IFC in reading, we aim to (1) characterize the functional landscape of text-selective responses in the IFC, while accounting for interindividual variability; and (2) examine how text-selective regions in the IFC relate to reading proficiency. To this end, children with a wide range of reading ability (N=66; age 7-14 years, 34 female, 32 male) completed functional MRI scans while performing two tasks on text and non-text visual stimuli. Importantly, both tasks do not explicitly require reading, and can be performed on all visual stimuli. This design allows us to tease apart stimulus-driven responses from task-driven responses and examine where in the IFC task and stimulus interact. We were able to identify three anatomically-distinct, text-selective clusters of activation in the IFC, in the inferior frontal sulcus (IFS), and dorsal and ventral precentral gyrus (PrG). These three regions showed a strong task effect that was highly specific to text. Furthermore, text-selectivity in the IFS and dorsal PrG was associated with reading proficiency, such that better readers showed higher selectivity to text. These findings suggest that text-selective regions in the IFC are sensitive to both stimulus and task, and highlight the importance of this region for proficient reading. Significance statementThe inferior frontal cortex (IFC) is a critical region for language processing, yet despite decades of research, its relationship with reading skill remains unclear. In a group of children with a wide range of reading skills, we were able to identify three anatomically distinct text-selective clusters of activation in the IFC. These regions showed a strong task effect that was highly selective to text. Text-selectivity was positively correlated with reading proficiency, such that better readers showed higher selectivity to text, even in tasks that did not require reading. These findings suggest that multiple text-selective regions within IFC are sensitive to both stimulus and task, and highlight the critical role of IFC for reading proficiency.

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Assessing white matter plasticity in a randomized controlled trial of early literacy training in preschoolers

Reading is a cognitive skill that requires our brain to go through a myriad of changes during learning. While many studies have described how reading acquisition shapes childrens brain function, less is known about the impact of reading on brain structure. Here we examined short-term causal effects of reading training on preschoolers behavior and white matter structure. Forty-eight English-speaking preschoolers (4y10m to 6y2m) participated in a randomized controlled trial where they were randomly assigned to two training programs: the Letter training program was focused on key skills for reading (e.g., decoding and letter knowledge), while the Language training program strengthened oral language comprehension skills without exposure to text. Longitudinal behavioral data showed that only the Letter Training group increased letter knowledge and decoding skills after the two-week training. Diffusion MRI measures (FA and MD) of eighteen white matter pathways (including the left arcuate and the left inferior longitudinal fasciculus) did not reveal any statistically significant changes for either group despite high degrees of scan-rescan reliability across sessions. These findings suggest that a two- week reading training program can cause changes in preschoolers letter knowledge and decoding abilities, without being accompanied by measurable changes in the diffusion properties of the major white matter pathways of the reading network. We conclude highlighting possible constraints (i.e., age, training onset and duration, cognitive profile) to reading-related white matter plasticity.

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Fast and reliable quantitative measures of white matter development with magnetic resonance fingerprinting

Developmental cognitive neuroscience aims to shed light on evolving relationships between brain structure and cognitive development. To this end, quantitative methods that reliably measure individual differences in brain tissue properties are fundamental. Standard qualitative MRI sequences are influenced by scan parameters and hardware-related biases, and also lack physical units, making the analysis of individual differences problematic. In contrast, quantitative MRI can measure physical properties of the tissue but with the cost of long scan durations and sensitivity to motion. This poses a critical limitation for studying young children. Here, we examine the reliability and validity of an efficient quantitative multiparameter mapping method - Magnetic Resonance Fingerprinting (MRF) - in children scanned longitudinally. We focus on T1 values in white matter, since quantitative T1 values are known to primarily reflect myelin content, a key factor in brain development. Forty-nine children aged 8-13y (mean 10.3y {+/-}1.4) completed two scanning sessions 2-4 months apart. In each session, two 2-minute 3D-MRF scans at 1mm isotropic resolution were collected to evaluate the effect of scan duration on image quality and scan-rescan reliability. A separate calibration scan was used to measure B0 inhomogeneity and correct for bias. We examined the impact of scan time and B0 inhomogeneity correction on scan-rescan reliability of values in white matter, by comparing single 2-min and combined two 2-min scans, with and without B0-correction. Whole-brain voxel-based reliability analysis showed that combining two 2-min MRF scans improved reliability (pearsons r=0.87) compared with a single 2-min scan (r=0.84), while B0-correction had no effect on reliability in white matter (r=0.86 and 0.83 4-min vs 2-min). Using diffusion tractography, we delineated MRF-derived T1 profiles along major white matter fiber tracts and found similar or higher reliability for T1 from MRF compared to diffusion parameters (based on a 10-minute dMRI scan). Lastly, we found that T1 values in multiple white matter tracts were significantly correlated with age. In sum, MRF-derived T1 values were highly reliable in a longitudinal sample of children and replicated known age effects. Reliability in white matter was improved by longer scan duration but was not affected by B0-correction, making it a quick and straightforward scan to collect. We propose that MRF provides a promising avenue for acquiring quantitative brain metrics in children and patient populations where scan time and motion are of particular concern.

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Educational Environment and White Matter Development in Early Adolescence

Coarse measures of socioeconomic status, such as parental income or parental education, have been linked to differences in white matter development. However, these measures do not provide insight into specific aspects of an individuals environment and how they relate to brain development. On the other hand, educational intervention studies have shown that changes in an individuals educational context can drive measurable changes in their white matter. These studies, however, rarely consider socioeconomic factors in their results. In the present study, we examined the unique effect of educational opportunity on white matter development, even when controlling other known socioeconomic factors. To explore this question, we leveraged the rich demographic and neuroimaging data available in the ABCD study, as well the unique data-crosswalk between ABCD and the Stanford Education Data Archive (SEDA). We find that educational opportunity is related to accelerated white matter development, even when accounting for other socioeconomic factors, and that this relationship is most pronounced in white matter tracts associated with academic skills. These results suggest that the school a child attends has a measurable impact on brain development for years to come.

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The transition from vision to language:distinct patterns of functional connectivity for sub-regions of the visual word form area

Reading entails transforming visual symbols to sound and meaning. This process depends on specialized circuitry in the visual cortex, the Visual Word Form Area (VWFA). Recent findings suggest that this word-selective cortex comprises at least two distinct subregions: the more posterior VWFA-1 is sensitive to visual features, while the more anterior VWFA-2 processes higher level language information. Here, we explore whether these two subregions exhibit different patterns of functional connectivity, and whether these patterns have relevance for reading development. We address these questions using two complementary datasets: Using the Natural Scenes Datasets (NSD; Allen et al, 2022) we identify word-selective responses in high-quality 7T individual adult data (N=8; 6 females), and investigate functional connectivity patterns of VWFA-1 and VWFA-2 at the individual level. We then turn to the Healthy Brain Network (HBN; Alexander et al., 2017) database to assess whether these patterns a) replicate in a large developmental sample (N=224; 98 females, age 5-21y), and b) are related to reading development. In both datasets, we find that VWFA-1 is more strongly correlated with bilateral visual regions including ventral occipitotemporal cortex and posterior parietal cortex. In contrast, VWFA-2 is more strongly correlated with language regions in the frontal and lateral parietal lobes, particularly bilateral inferior frontal gyrus (IFG). Critically, these patterns do not generalize to adjacent face-selective regions, suggesting a unique relationship between VWFA-2 and the frontal language network. While connectivity patterns increased with age, no correlations were observed between functional connectivity and reading ability. Together, our findings support the distinction between subregions of the VWFA, and portray the functional connectivity patterns of the reading circuitry as an intrinsic stable property of the brain.

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Incremental improvements in tractometry-based brain-age modeling with deep learning

Multivariate measurements of human brain white matter (WM) with diffusion MRI (dMRI) provide information about the role of WM in a variety of cognitive functions and in brain health. Statistical models take advantage of the regularities in these data to make inferences about individual differences. For example, dMRI data provide the basis for accurate brain-age models - models that predict the chronological age of participants from WM tissue properties. Deep learning (DL) models are powerful machine learning models, which have been shown to provide benefits in many multivariate analysis settings. We investigated whether DL would provide substantial improvements for brain-age models based on dMRI measurements of WM in a large sample of children and adolescents. We found that some DL models fit the data better than a linear baseline, but the differences are small. In particular, recurrent neural network architectures provide up to [~]6% improvement in accuracy. This suggests that information about WM development is mostly accessible with linear models, and does not require the additional invariance and non-linearity offered by DL models. However, in some applications this incremental improvement may prove critical. We provide open-source software that fits DL models to dMRI data (https://yeatmanlab.github.io/AFQ-Insight).

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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.

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Specific and non-linear effects of glaucoma on optic radiation tissue properties

Changes in sensory input with aging and disease affect brain tissue properties. To establish the link between glaucoma, the most prevalent cause of irreversible blindness, and changes in major brain connections, we characterized white matter tissue properties in diffusion MRI measurements in a large sample of subjects with glaucoma (N=905; age 49-80) and healthy controls (N=5,292; age 45-80) from the UK Biobank. Confounds due to group differences were mitigated by matching a sub-sample of controls to glaucoma subjects. A convolutional neural network (CNN) accurately classified whether a subject has glaucoma using information from the primary visual connection to cortex (the optic radiations, OR), but not from non-visual brain connections. On the other hand, regularized linear regression could not classify glaucoma, and the CNN did not generalize to classification of age-group or of age-related macular degeneration. This suggests a unique non-linear signature of glaucoma in OR tissue properties.

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Engaging in word recognition elicits highly specific modulations in visual cortex

A persons cognitive state determines how their brain responds to visual stimuli. The most common such effect is a response enhancement when stimuli are task-relevant and attended rather than ignored. In this fMRI study, we report a surprising twist on such attention effects in the visual word form area (VWFA), a region that plays a key role in reading. We presented participants with strings of letters and visually similar shapes which were either relevant for a specific task (lexical decision or gap localization) or ignored (during a fixation dot color task). In the VWFA, the enhancement of responses to attended stimuli occurred only for letter strings, whereas the shapes evoked smaller responses when attended than when ignored. The enhancement of VWFA activity was accompanied by strengthened functional connectivity with higher-level language regions. These task-dependent modulations of response magnitude and functional connectivity were specific to the VWFA and absent in the rest of visual cortex. We suggest that language regions send targeted excitatory feedback into the VWFA only when the observer is trying to read. This feedback enables the discrimination of familiar and nonsense words, and is distinct from generic effects of visual attention.

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Optic radiations representing different eccentricities age differently

The white matter pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ 1 on a large sample of diffusion MRI (dMRI) data from the UK Biobank dataset (UKBB; N=6021; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with adulthood aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.

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