A practical guide for combining functional regions of interest and white matter bundles.

Diffusion-weighted imaging (DWI) is the primary method to investigate macro- and microstructure of neural white matter in vivo. DWI can be used to identify and characterize individual-specific white matter bundles, enabling precise analyses on hypothesis-driven connections in the brain and bridging the relationships between brain structure, function, and behavior. However, cortical endpoints of bundles may span larger areas than what a researcher is interested in, challenging presumptions that bundles are specifically tied to certain brain functions. Functional MRI (fMRI) can be integrated to further refine bundles such that they are restricted to functionally-defined cortical regions. Analyzing properties of these Functional Sub-Bundles (FSuB) increases precision and interpretability of results when studying neural connections supporting specific tasks. Several parameters of DWI and fMRI analyses, ranging from data acquisition to processing, can impact the efficacy of integrating functional and diffusion MRI. Here, we discuss the applications of the FSuB approach, suggest best practices for acquiring and processing neuroimaging data towards this end, and introduce the FSuB-Extractor, a flexible open-source software for creating FSuBs. We demonstrate our processing code and the FSuB-Extractor on an openly-available dataset, the Natural Scenes Dataset.

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 and used a data-driven approach 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 have important implications for theories of cortical functional development and open new possibilities for understanding typical and atypical white matter development.

Reading instruction causes changes in category-selective visual cortex.

Education sculpts specialized neural circuits for skills like reading that are critical to success in modern society but were not anticipated by the selective pressures of evolution. Does the emergence of brain regions that selectively process novel visual stimuli like words occur at the expense of cortical representations of other stimuli like faces and objects? "Neuronal Recycling" predicts that learning to read should enhance the response to words in ventral occipitotemporal cortex (VOTC) and decrease the response to other visual categories such as faces and objects. To test this hypothesis, and more broadly to understand the changes that are induced by the early stages of literacy instruction, we conducted a randomized controlled trial with pre-school children (five years of age). Children were randomly assigned to intervention programs focused on either reading skills or oral language skills and magnetoencephalography (MEG) data collected before and after the intervention was used to measure visual responses to images of text, faces, and objects. We found that being taught reading versus oral language skills induced different patterns of change in category-selective regions of visual cortex, but that there was not a clear tradeoff between the response to words versus other categories. Within a predefined region of VOTC corresponding to the visual word form area (VWFA) we found that the relative amplitude of responses to text, faces, and objects changed, but increases in the response to words were not linked to decreases in the response to faces or objects. How these changes play out over a longer timescale is still unknown but, based on these data, we can surmise that high-level visual cortex undergoes rapid changes as children enter school and begin establishing new skills like literacy.

The transition from vision to language: Distinct patterns of functional connectivity for subregions 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 text-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 also exhibit different patterns of functional connectivity. To this end, we capitalize on two complementary datasets: Using the Natural Scenes Dataset (NSD), we identify text-selective responses in high-quality 7T adult data (N = 8), and investigate functional connectivity patterns of VWFA-1 and VWFA-2 at the individual level. We then turn to the Healthy Brain Network (HBN) database to assess whether these patterns replicate in a large developmental sample (N = 224; age 6-20 years), and whether they relate to reading development. In both datasets, we find that VWFA-1 is primarily correlated with bilateral visual regions. In contrast, VWFA-2 is more strongly correlated with language regions in the frontal and lateral parietal lobes, particularly the bilateral inferior frontal gyrus. Critically, these patterns do not generalize to adjacent face-selective regions, suggesting a specific relationship between VWFA-2 and the frontal language network. No correlations were observed between functional connectivity and reading ability. Together, our findings support the distinction between subregions of the VWFA, and suggest that functional connectivity patterns in the ventral temporal cortex are consistent over a wide range of reading skills.

Rethinking cortical recycling in ventral temporal cortex.

High-level visual areas in ventral temporal cortex (VTC) support recognition of important categories, such as faces and words. Word-selective regions are left lateralized and emerge at the onset of reading instruction. Face-selective regions are right lateralized and have been documented in infancy. Prevailing theories suggest that face-selective regions become right lateralized due to competition with word-selective regions in the left hemisphere. However, recent longitudinal studies examining face- and word-selective responses in childhood do not provide support for this theory. Instead, there is evidence that word representations recycle cortex previously involved in processing other stimuli, such as limbs. These findings call for more longitudinal investigations of cortical recycling and a new era of work that links visual experience and behavior with neural responses.

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.

White matter connections of high-level visual areas predict cytoarchitecture better than category-selectivity in childhood, but not adulthood.

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 2 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 to identify white matter tracts and functional magnetic resonance imaging 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.

Establishing the functional relevancy of white matter connections in the visual system and beyond.

For over a century, researchers have examined the functional relevancy of white matter bundles. Consequently, many large-scale bundles spanning several centimeters have been associated in their entirety with specific brain functions, such as language or attention. However, these coarse structural-functional relationships are at odds with modern understanding of the fine-grained functional organization of human cortex, such as the mosaic of category-selective regions in ventral temporal cortex. Here, we review a multimodal approach that combines fMRI to define functional regions of interest within individual's brains with dMRI tractography to identify the white matter bundles of the same individual. Combining these data allows to determine which subsets of streamlines within a white matter bundle connect to specific functional regions in each individual. That is, this approach identifies the functionally defined white matter sub-bundles of the brain. We argue that this approach not only enhances the accuracy of interpreting the functional relevancy of white matter bundles, but also enables segmentation of these large-scale bundles into meaningful functional units, which can then be linked to behavior with enhanced precision. Importantly, this approach has the potential for making new discoveries of the fine-grained functional relevancy of white matter connections in the visual system and the brain more broadly, akin to the flurry of research that has identified functional regions in cortex.

Word selectivity in high-level visual cortex and reading skill.

Word-selective neural responses in human ventral occipito-temporal cortex (VOTC) emerge as children learn to read, creating a visual word form area (VWFA) in the literate brain. It has been suggested that the VWFA arises through competition between pre-existing selectivity for other stimulus categories, changing the topography of VOTC to support rapid word recognition. Here, we hypothesized that competition between words and objects would be resolved as children acquire reading skill. Using functional magnetic resonance imaging (fMRI), we examined the relationship between responses to words and objects in VOTC in two ways. First, we defined the VWFA using a words > objects contrast and found that only skilled readers had a region that responded more to words than objects. Second, we defined the VWFA using a words > faces contrast and examined selectivity for words over objects in this region. We found that word selectivity strongly correlated with reading skill, suggesting reading skill-dependent tuning for words. Furthermore, we found that low word selectivity in struggling readers was not due to a lack of response to words, but to a high response to objects. Our results suggest that the fine-tuning of word-selective responses in VOTC is a critical component of skilled reading.

Reading ability and phoneme categorization.

Dyslexia is associated with abnormal performance on many auditory psychophysics tasks, particularly those involving the categorization of speech sounds. However, it is debated whether those apparent auditory deficits arise from (a) reduced sensitivity to particular acoustic cues, (b) the difficulty of experimental tasks, or (c) unmodeled lapses of attention. Here we investigate the relationship between phoneme categorization and reading ability, with special attention to the nature of the cue encoding the phoneme contrast (static versus dynamic), differences in task paradigm difficulty, and methodological details of psychometric model fitting. We find a robust relationship between reading ability and categorization performance, show that task difficulty cannot fully explain that relationship, and provide evidence that the deficit is not restricted to dynamic cue contrasts, contrary to prior reports. Finally, we demonstrate that improved modeling of behavioral responses suggests that performance does differ between children with dyslexia and typical readers, but that the difference may be smaller than previously reported.