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.

Human visual cortex is organized along two genetically opposed hierarchical gradients with unique developmental and evolutionary origins.

Human visual cortex is organized with striking consistency across individuals. While recent findings demonstrate an unexpected coupling between functional and cytoarchitectonic regions relative to the folding of human visual cortex, a unifying principle linking these anatomical and functional features of the cortex remains elusive. To fill this gap in knowledge, we combined independent and ground truth measurements of cytoarchitectonic regions and genetic tissue characterization within human occipitotemporal cortex. Using a data-driven approach, we examined whether differential gene expression among cytoarchitectonic areas could contribute to the arealization of occipitotemporal cortex into a hierarchy based on transcriptomics. This approach revealed two opposing gene expression gradients: one that contains a series of genes with expression magnitudes that ascend from posterior (e.g., areas human occipital [hOc]1, hOc2, hOc3, etc.) to anterior cytoarchitectonic areas (e.g., areas fusiform gyrus [FG]1-FG4) and another that contains a separate series of genes that show a descending gradient from posterior to anterior areas. Using data from the living human brain, we show that each of these gradients correlates strongly with variations in measures related to either thickness or myelination of cortex, respectively. We further reveal that these genetic gradients emerge along unique trajectories in human development: the ascending gradient is present at 10-12 gestational weeks, while the descending gradient emerges later (19-24 gestational weeks). Interestingly, it is not until early childhood (before 5 years of age) that the two expression gradients achieve their adult-like mean expression values. Additional analyses in nonhuman primates (NHPs) reveal that homologous genes do not generate the same ascending and descending expression gradients as in humans. We discuss these findings relative to previously proposed hierarchies based on functional and cytoarchitectonic features of visual cortex. Altogether, these findings bridge macroscopic features of human cytoarchitectonic areas in visual cortex with microscopic features of cellular organization and genetic expression, which, despite the complexity of this multiscale correspondence, can be described by a sparse subset (approximately 200) of genes. These findings help pinpoint the genes contributing to healthy cortical development and explicate the cortical biology distinguishing humans from other primates, as well as establishing essential groundwork for understanding future work linking genetic mutations with the function and development of the human brain.

Sulcal Depth in the Medial Ventral Temporal Cortex Predicts the Location of a Place-Selective Region in Macaques, Children, and Adults.

The evolution and development of anatomical-functional relationships in the cerebral cortex is of major interest in neuroscience. Here, we leveraged the fact that a functional region selective for visual scenes is located within a sulcus in the medial ventral temporal cortex (VTC) in both humans and macaques to examine the relationship between sulcal depth and place selectivity in the medial VTC across species and age groups. To do so, we acquired anatomical and functional magnetic resonance imaging scans in 9 macaques, 26 human children, and 28 human adults. Our results revealed a strong structural-functional coupling between sulcal depth and place selectivity across age groups and species in which selectivity was strongest near the deepest sulcal point (the sulcal pit). Interestingly, this coupling between sulcal depth and place selectivity strengthens from childhood to adulthood in humans. Morphological analyses suggest that the stabilization of sulcal-functional coupling in adulthood may be due to sulcal deepening and areal expansion with age as well as developmental differences in cortical curvature at the pial, but not the white matter surfaces. Our results implicate sulcal features as functional landmarks in high-level visual cortex and highlight that sulcal-functional relationships in the medial VTC are preserved between macaques and humans despite differences in cortical folding.

Neural adaptation to faces reveals racial outgroup homogeneity effects in early perception.

A hallmark of intergroup biases is the tendency to individuate members of one's own group but process members of other groups categorically. While the consequences of these biases for stereotyping and discrimination are well-documented, their early perceptual underpinnings remain less understood. Here, we investigated the neural mechanisms of this effect by testing whether high-level visual cortex is differentially tuned in its sensitivity to variation in own-race versus other-race faces. Using a functional MRI adaptation paradigm, we measured White participants' habituation to blocks of White and Black faces that parametrically varied in their groupwise similarity. Participants showed a greater tendency to individuate own-race faces in perception, showing both greater release from adaptation to unique identities and increased sensitivity in the adaptation response to physical difference among faces. These group differences emerge in the tuning of early face-selective cortex and mirror behavioral differences in the memory and perception of own- versus other-race faces. Our results suggest that biases for other-race faces emerge at some of the earliest stages of sensory perception.

Apparent thinning of human visual cortex during childhood is associated with myelination.

Human cortex appears to thin during childhood development. However, the underlying microstructural mechanisms are unknown. Using functional magnetic resonance imaging (fMRI), quantitative MRI (qMRI), and diffusion MRI (dMRI) in children and adults, we tested what quantitative changes occur to gray and white matter in ventral temporal cortex (VTC) from childhood to adulthood, and how these changes relate to cortical thinning. T1 relaxation time from qMRI and mean diffusivity (MD) from dMRI provide independent and complementary measurements of microstructural properties of gray and white matter tissue. In face- and character-selective regions in lateral VTC, T1 and MD decreased from age 5 to adulthood in mid and deep cortex, as well as in their adjacent white matter. T1 reduction also occurred longitudinally in children's brain regions. T1 and MD decreases 1) were consistent with tissue growth related to myelination, which we verified with adult histological myelin stains, and 2) were correlated with apparent cortical thinning. In contrast, in place-selective cortex in medial VTC, we found no development of T1 or MD after age 5, and thickness was related to cortical morphology. These findings suggest that lateral VTC likely becomes more myelinated from childhood to adulthood, affecting the contrast of MR images and, in turn, the apparent gray-white boundary. These findings are important because they suggest that VTC does not thin during childhood but instead gets more myelinated. Our data have broad ramifications for understanding both typical and atypical brain development using advanced in vivo quantitative measurements and clinical conditions implicating myelin.

Learning to Read Increases the Informativeness of Distributed Ventral Temporal Responses.

Becoming a proficient reader requires substantial learning over many years. However, it is unknown how learning to read affects development of distributed visual representations across human ventral temporal cortex (VTC). Using fMRI and a data-driven, computational approach, we quantified the development of distributed VTC responses to characters (pseudowords and numbers) versus other domains in children, preteens, and adults. Results reveal anatomical- and hemisphere-specific development. With development, distributed responses to words and characters became more distinctive and informative in lateral but not medial VTC, and in the left but not right hemisphere. While the development of voxels with both positive and negative preference to words affected distributed information, only development of voxels with positive preference to words (i.e., word-selective) was correlated with reading ability. These data show that developmental increases in informativeness of distributed left lateral VTC responses are related to proficient reading and have important implications for both developmental theories and for elucidating neural mechanisms of reading disabilities.

Development of population receptive fields in the lateral visual stream improves spatial coding amid stable structural-functional coupling.

Human visual cortex encompasses more than a dozen visual field maps across three major processing streams. One of these streams is the lateral visual stream, which extends from V1 to lateral-occipital (LO) and temporal-occipital (TO) visual field maps and plays a prominent role in shape as well as motion perception. However, it is unknown if and how population receptive fields (pRFs) in the lateral visual stream develop from childhood to adulthood, and what impact this development may have on spatial coding. Here, we used functional magnetic resonance imaging and pRF modeling in school-age children and adults to investigate the development of the lateral visual stream. Our data reveal four main findings: 1) The topographic organization of eccentricity and polar angle maps of the lateral stream is stable after age five. 2) In both age groups there is a reliable relationship between eccentricity map transitions and cortical folding: the middle occipital gyrus predicts the transition between the peripheral representation of LO and TO maps. 3) pRFs in LO and TO maps undergo differential development from childhood to adulthood, resulting in increasing coverage of the central visual field in LO and of the peripheral visual field in TO. 4) Model-based decoding shows that the consequence of pRF and visual field coverage development is improved spatial decoding from LO and TO distributed responses in adults vs. children. Together, these results explicate both the development and topography of the lateral visual stream. Our data show that the general structural-functional organization is laid out early in development, but fine-scale properties, such as pRF distribution across the visual field and consequently, spatial precision, become fine-tuned across childhood development. These findings advance understanding of the development of the human visual system from childhood to adulthood and provide an essential foundation for understanding developmental deficits.

Defining the most probable location of the parahippocampal place area using cortex-based alignment and cross-validation.

The parahippocampal place area (PPA) is a widely studied high-level visual region in the human brain involved in place and scene processing. The goal of the present study was to identify the most probable location of place-selective voxels in medial ventral temporal cortex. To achieve this goal, we first used cortex-based alignment (CBA) to create a probabilistic place-selective region of interest (ROI) from one group of 12 participants. We then tested how well this ROI could predict place selectivity in each hemisphere within a new group of 12 participants. Our results reveal that a probabilistic ROI (pROI) generated from one group of 12 participants accurately predicts the location and functional selectivity in individual brains from a new group of 12 participants, despite between subject variability in the exact location of place-selective voxels relative to the folding of parahippocampal cortex. Additionally, the prediction accuracy of our pROI is significantly higher than that achieved by volume-based Talairach alignment. Comparing the location of the pROI of the PPA relative to published data from over 500 participants, including data from the Human Connectome Project, shows a striking convergence of the predicted location of the PPA and the cortical location of voxels exhibiting the highest place selectivity across studies using various methods and stimuli. Specifically, the most predictive anatomical location of voxels exhibiting the highest place selectivity in medial ventral temporal cortex is the junction of the collateral and anterior lingual sulci. Methodologically, we make this pROI freely available (vpnl.stanford.edu/PlaceSelectivity), which provides a means to accurately identify a functional region from anatomical MRI data when fMRI data are not available (for example, in patient populations). Theoretically, we consider different anatomical and functional factors that may contribute to the consistent anatomical location of place selectivity relative to the folding of high-level visual cortex.

Development of Neural Sensitivity to Face Identity Correlates with Perceptual Discriminability.

Face perception is subserved by a series of face-selective regions in the human ventral stream, which undergo prolonged development from childhood to adulthood. However, it is unknown how neural development of these regions relates to the development of face-perception abilities. Here, we used functional magnetic resonance imaging (fMRI) to measure brain responses of ventral occipitotemporal regions in children (ages, 5-12 years) and adults (ages, 19-34 years) when they viewed faces that parametrically varied in dissimilarity. Since similar faces generate lower responses than dissimilar faces due to fMRI adaptation, this design objectively evaluates neural sensitivity to face identity across development. Additionally, a subset of subjects participated in a behavioral experiment to assess perceptual discriminability of face identity. Our data reveal three main findings: (1) neural sensitivity to face identity increases with age in face-selective but not object-selective regions; (2) the amplitude of responses to faces increases with age in both face-selective and object-selective regions; and (3) perceptual discriminability of face identity is correlated with the neural sensitivity to face identity of face-selective regions. In contrast, perceptual discriminability is not correlated with the amplitude of response in face-selective regions or of responses of object-selective regions. These data suggest that developmental increases in neural sensitivity to face identity in face-selective regions improve perceptual discriminability of faces. Our findings significantly advance the understanding of the neural mechanisms of development of face perception and open new avenues for using fMRI adaptation to study the neural development of high-level visual and cognitive functions more broadly. SIGNIFICANCE STATEMENT: Face perception, which is critical for daily social interactions, develops from childhood to adulthood. However, it is unknown what developmental changes in the brain lead to improved performance. Using fMRI in children and adults, we find that from childhood to adulthood, neural sensitivity to changes in face identity increases in face-selective regions. Critically, subjects' perceptual discriminability among faces is linked to neural sensitivity: participants with higher neural sensitivity in face-selective regions demonstrate higher perceptual discriminability. Thus, our results suggest that developmental increases in face-selective regions' sensitivity to face identity improve perceptual discrimination of faces. These findings significantly advance understanding of the neural mechanisms underlying the development of face perception and have important implications for assessing both typical and atypical development.

The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex.

UNLABELLED: Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage. SIGNIFICANCE STATEMENT: Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks.

Comparing retinotopic maps of children and adults reveals a late-stage change in how V1 samples the visual field.

Adult visual performance differs with angular location -it is better for stimuli along the horizontal than vertical, and lower than upper vertical meridian of the visual field. These perceptual asymmetries are paralleled by asymmetries in cortical surface area in primary visual cortex (V1). Children, unlike adults, have similar visual performance at the lower and upper vertical meridian. Do children have similar V1 surface area representing the upper and lower vertical meridian? Using MRI, we measure the surface area of retinotopic maps (V1-V3) in children and adults. Many features of the maps are similar between groups, including greater V1 surface area for the horizontal than vertical meridian. However, unlike adults, children have a similar amount of V1 surface area representing the lower and upper vertical meridian. These data reveal a late-stage change in V1 organization that may relate to the emergence of the visual performance asymmetry along the vertical meridian by adulthood.

Longitudinal development of category representations in ventral temporal cortex predicts word and face recognition.

Regions in ventral temporal cortex that are involved in visual recognition of categories like words and faces undergo differential development during childhood. However, categories are also represented in distributed responses across high-level visual cortex. How distributed category representations develop and if this development relates to behavioral changes in recognition remains largely unknown. Here, we used functional magnetic resonance imaging to longitudinally measure the development of distributed responses across ventral temporal cortex to 10 categories in school-age children over several years. Our results reveal both strengthening and weakening of category representations with age, which was mainly driven by changes across category-selective voxels. Representations became particularly more distinct for words in the left hemisphere and for faces bilaterally. Critically, distinctiveness for words and faces across category-selective voxels in left and right lateral ventral temporal cortex, respectively, predicted individual children's word and face recognition performance. These results suggest that the development of distributed representations in ventral temporal cortex has behavioral ramifications and advance our understanding of prolonged cortical development during childhood.

A multifaceted gradient in human cerebellum of structural and functional development.

The organization of the basic tissue and functional properties of the cerebellum across development is unknown. Combining several large datasets, we demonstrate in the human cerebellum a static tissue gradient in adults that mirrors a similar growth-rate gradient across development. Quantitative tissue metrics corroborate unique densities of certain lipids and proteins among lobules, and cerebellar structural development closely follows cerebellar functional properties through childhood.

The relationship between transcription and eccentricity in human V1.

Gene expression gradients radiating from regions of primary sensory cortices have recently been described and are thought to underlie the large-scale organization of the human cerebral cortex. However, the role of transcription in the functional layout of a single region within the adult brain has yet to be clarified, likely owing to the difficulty of identifying a brain region anatomically consistent enough across individuals with dense enough tissue sampling. Overcoming these hurdles in human primary visual cortex (V1), we show a relationship between differential gene expression and the cortical layout of eccentricity in human V1. Interestingly, these genes are unique from those previously identified that contribute to the positioning of cortical areas in the visual processing hierarchy. Enrichment analyses show that a subset of the identified genes encode for structures related to inhibitory interneurons, ion channels, as well as cellular projections, and are expressed more in foveal compared to peripheral portions of human V1. These findings predict that tissue density should be higher in foveal compared to peripheral V1. Using a histological pipeline, we validate this prediction using Nissl-stained sections of postmortem occipital cortex. We discuss these findings relative to previous studies in non-human primates, as well as in the context of an organizational pattern in which the adult human brain employs transcription gradients at multiple spatial scales: across the cerebral cortex, across areas within processing hierarchies, and within single cortical areas.

Differential spatial computations in ventral and lateral face-selective regions are scaffolded by structural connections.

Face-processing occurs across ventral and lateral visual streams, which are involved in static and dynamic face perception, respectively. However, the nature of spatial computations across streams is unknown. Using functional MRI and population receptive field (pRF) mapping, we measured pRFs in face-selective regions. Results reveal that spatial computations by pRFs in ventral face-selective regions are concentrated around the center of gaze (fovea), but spatial computations in lateral face-selective regions extend peripherally. Diffusion MRI reveals that these differences are mirrored by a preponderance of white matter connections between ventral face-selective regions and foveal early visual cortex (EVC), while connections with lateral regions are distributed more uniformly across EVC eccentricities. These findings suggest a rethinking of spatial computations in face-selective regions, showing that they vary across ventral and lateral streams, and further propose that spatial computations in high-level regions are scaffolded by the fine-grain pattern of white matter connections from EVC.

Cortical recycling in high-level visual cortex during childhood development.

Human ventral temporal cortex contains category-selective regions that respond preferentially to ecologically relevant categories such as faces, bodies, places and words and that are causally involved in the perception of these categories. How do these regions develop during childhood? We used functional magnetic resonance imaging to measure longitudinal development of category selectivity in school-age children over 1 to 5 years. We discovered that, from young childhood to the teens, face- and word-selective regions in ventral temporal cortex expand and become more category selective, but limb-selective regions shrink and lose their preference for limbs. Critically, as a child develops, increases in face and word selectivity are directly linked to decreases in limb selectivity, revealing that during childhood, limb selectivity in ventral temporal cortex is repurposed into word and face selectivity. These data provide evidence for cortical recycling during childhood development. This has important implications for understanding typical as well as atypical brain development and necessitates a rethinking of how cortical function develops during childhood.

Extensive childhood experience with Pokémon suggests eccentricity drives organization of visual cortex.

The functional organization of human high-level visual cortex, such as the face- and place-selective regions, is strikingly consistent across individuals. An unanswered question in neuroscience concerns which dimensions of visual information constrain the development and topography of this shared brain organization. To answer this question, we used functional magnetic resonance imaging to scan a unique group of adults who, as children, had extensive visual experience with Pokémon. These animal-like, pixelated characters are dissimilar from other ecological categories, such as faces and places, along critical dimensions (foveal bias, rectilinearity, size, animacy). We show not only that adults who have Pokémon experience demonstrate distinct distributed cortical responses to Pokémon, but also that the experienced retinal eccentricity during childhood can predict the locus of Pokémon responses in adulthood. These data demonstrate that inherent functional representations in the visual cortex-retinal eccentricity-combined with consistent viewing behaviour of particular stimuli during childhood result in a shared functional topography in adulthood.

The functional neuroanatomy of face perception: from brain measurements to deep neural networks.

A central goal in neuroscience is to understand how processing within the ventral visual stream enables rapid and robust perception and recognition. Recent neuroscientific discoveries have significantly advanced understanding of the function, structure and computations along the ventral visual stream that serve as the infrastructure supporting this behaviour. In parallel, significant advances in computational models, such as hierarchical deep neural networks (DNNs), have brought machine performance to a level that is commensurate with human performance. Here, we propose a new framework using the ventral face network as a model system to illustrate how increasing the neural accuracy of present DNNs may allow researchers to test the computational benefits of the functional architecture of the human brain. Thus, the review (i) considers specific neural implementational features of the ventral face network, (ii) describes similarities and differences between the functional architecture of the brain and DNNs, and (iii) provides a hypothesis for the computational value of implementational features within the brain that may improve DNN performance. Importantly, this new framework promotes the incorporation of neuroscientific findings into DNNs in order to test the computational benefits of fundamental organizational features of the visual system.

Development differentially sculpts receptive fields across early and high-level human visual cortex.

Receptive fields (RFs) processing information in restricted parts of the visual field are a key property of visual system neurons. However, how RFs develop in humans is unknown. Using fMRI and population receptive field (pRF) modeling in children and adults, we determine where and how pRFs develop across the ventral visual stream. Here we report that pRF properties in visual field maps, from the first visual area, V1, through the first ventro-occipital area, VO1, are adult-like by age 5. However, pRF properties in face-selective and character-selective regions develop into adulthood, increasing the foveal coverage bias for faces in the right hemisphere and words in the left hemisphere. Eye-tracking indicates that pRF changes are related to changing fixation patterns on words and faces across development. These findings suggest a link between face and word viewing behavior and the differential development of pRFs across visual cortex, potentially due to competition on foveal coverage.

The Functional Neuroanatomy of Human Face Perception.

Face perception is critical for normal social functioning and is mediated by a network of regions in the ventral visual stream. In this review, we describe recent neuroimaging findings regarding the macro- and microscopic anatomical features of the ventral face network, the characteristics of white matter connections, and basic computations performed by population receptive fields within face-selective regions composing this network. We emphasize the importance of the neural tissue properties and white matter connections of each region, as these anatomical properties may be tightly linked to the functional characteristics of the ventral face network. We end by considering how empirical investigations of the neural architecture of the face network may inform the development of computational models and shed light on how computations in the face network enable efficient face perception.