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.

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.

White matter myelination during early infancy is linked to spatial gradients and myelin content at birth.

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 longitudinal relaxation rate (R1) of white matter in 0, 3 and 6 months-old human infants, and developed an automated method to identify white matter bundles and quantify their properties in each infant's 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 development rate increases 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.

Infants' cortex undergoes microstructural growth coupled with myelination during development.

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 birth  to six months of age  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 prominent 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 light on the rate, sequence, and biological mechanisms of developing cortical systems during early infancy. Importantly, our findings propose a hypothesis that cortical myelination is a key factor in cortical development during early infancy, which has important implications for diagnosis of neurodevelopmental disorders and delays in infants.

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.

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.

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.

Stimulation of the Posterior Cingulate Cortex Impairs Episodic Memory Encoding.

Neuroimaging experiments implicate the posterior cingulate cortex (PCC) in episodic memory processing, making it a potential target for responsive neuromodulation strategies outside of the hippocampal network. However, causal evidence for the role that PCC plays in memory encoding is lacking. In human female and male participants (N = 17) undergoing seizure mapping, we investigated functional properties of the PCC using deep brain stimulation (DBS) and stereotactic electroencephalography. We used a verbal free recall paradigm in which the PCC was stimulated during presentation of half of the study lists, whereas no stimulation was applied during presentation of the remaining lists. We investigated whether stimulation affected memory and modulated hippocampal activity. Results revealed four main findings. First, stimulation during episodic memory encoding impaired subsequent free recall, predominantly for items presented early in the study lists. Second, PCC stimulation increased hippocampal gamma-band power. Third, stimulation-induced hippocampal gamma power predicted the magnitude of memory impairment. Fourth, functional connectivity between the hippocampus and PCC predicted the strength of the stimulation effect on memory. Our findings offer causal evidence implicating the PCC in episodic memory encoding. Importantly, the results indicate that stimulation targeted outside of the temporal lobe can modulate hippocampal activity and impact behavior. Furthermore, measures of connectivity between brain regions within a functional network can be informative in predicting behavioral effects of stimulation. Our findings have significant implications for developing therapies to treat memory disorders and cognitive impairment using DBS.SIGNIFICANCE STATEMENT Cognitive impairment and memory loss are critical public health challenges. Deep brain stimulation (DBS) is a promising tool for developing strategies to ameliorate memory disorders by targeting brain regions involved in mnemonic processing. Using DBS, our study sheds light on the lesser-known role of the posterior cingulate cortex (PCC) in memory encoding. Stimulating the PCC during encoding impairs subsequent recall memory. The degree of impairment is predicted by stimulation-induced hippocampal gamma oscillations and functional connectivity between PCC and hippocampus. Our findings provide the first causal evidence implicating PCC in memory encoding and highlight the PCC as a favorable target for neuromodulation strategies using a priori connectivity measures to predict stimulation effects. This has significant implications for developing therapies for memory diseases.

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.

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.

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.

On object selectivity and the anatomy of the human fusiform gyrus.

pFs is a functionally-defined region in the human brain that is involved in recognizing objects. A recent trend refers to pFs as the posterior fusiform sulcus, which is a neuroanatomical structure that does not exist. Here, we correct this mistake. To achieve this goal, we first recount the original definitions of pFs and then review the identification of sulci within and surrounding the fusiform gyrus (FG) including the mid-fusiform sulcus (MFS), which is a tertiary sulcus within the FG. We highlight that tertiary sulci, such as the MFS, are often absent from brain atlases, which complicates the accurate localization of functional regions, as well as the understanding of structural-functional relationships in ventral temporal cortex (VTC). When considering the location of object-selective pFs from previously published data relative to the sulci surrounding the FG, as well as the MFS, we illustrate that (1) pFs spans several macroanatomical structures, which is consistent with the original definitions of pFs (Grill-Spector et al., 1999, 2000), and (2) the topological relationship between pFs and MFS has both stable and variable features. To prevent future confusion regarding the anatomical location of functional regions within VTC, as well as to complement tools that automatically identify sulci surrounding the FG, we provide a method to automatically identify the MFS in individual brains using FreeSurfer. Finally, we highlight the benefits of using cortical surface reconstructions in large datasets to identify and quantify tertiary sulci compared to classic dissection methods because the latter often fail to differentiate tertiary sulci from shallow surface indentations produced by veins and arteries. Altogether, we propose that the inclusion of definitions and labels for tertiary sulci in neuroanatomical atlases and neuroimaging software packages will enhance understanding of functional-structural relationships throughout the human brain.

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.

Spatiotemporal changes in neural response patterns to faces varying in visual familiarity.

Increasing experience with a previously unfamiliar face improves human ability to recognize it in challenging and novel viewing conditions. Differential neural responses to familiar versus unfamiliar faces in multiple regions of the ventral-temporal and parietal cortex have been reported in previous work, but with limited attention to how behavioral and neural measures change with increasing familiarity. We examined changes in the spatial and temporal characteristics of neural response patterns elicited by faces that vary in their degree of visual familiarity. First, we developed a behavioral paradigm to familiarize participants to low-, medium-, and high-levels of familiarity with faces. Recognition of novel, naturalistic images of the learned individuals improved with increasing familiarity with faces. Next, a new set of participants learned faces using the behavioral paradigm, outside the fMRI scanner, and subsequently viewed blocks of whole-body images of the learned and novel people, inside the scanner. We found that the face-selective FFA and OFA, and a combination of the ventral-temporal areas (e.g., fusiform gyrus) and parietal areas (e.g., precuneus) contained patterns useful for classifying highly familiar versus unfamiliar faces. Classification along the temporal-sequence of the face blocks revealed an early separation of neural patterns elicited in response to highly familiar versus unfamiliar faces in the FFA and OFA, but not in other regions of interest. This indicates the potential for a rapid assessment of the "known versus unknown" status of faces in core face-selective regions of the brain. The present study provides a first look at the perceptual and neural correlates underlying experience gains with faces as they become familiar.

Dissociable neural patterns of facial identity across changes in viewpoint.

We examined the neural response patterns for facial identity independent of viewpoint and for viewpoint independent of identity. Neural activation patterns for identity and viewpoint were collected in an fMRI experiment. Faces appeared in identity-constant blocks, with variable viewpoint, and in viewpoint-constant blocks, with variable identity. Pattern-based classifiers were used to discriminate neural response patterns for all possible pairs of identities and viewpoints. To increase the likelihood of detecting distinct neural activation patterns for identity, we tested maximally dissimilar "face"-"antiface" pairs and normal face pairs. Neural response patterns for four of six identity pairs, including the "face"-"antiface" pairs, were discriminated at levels above chance. A behavioral experiment showed accord between perceptual and neural discrimination, indicating that the classifier tapped a high-level visual identity code. Neural activity patterns across a broad span of ventral temporal (VT) cortex, including fusiform gyrus and lateral occipital areas (LOC), were required for identity discrimination. For viewpoint, five of six viewpoint pairs were discriminated neurally. Viewpoint discrimination was most accurate with a broad span of VT cortex, but the neural and perceptual discrimination patterns differed. Less accurate discrimination of viewpoint, more consistent with human perception, was found in right posterior superior temporal sulcus, suggesting redundant viewpoint codes optimized for different functions. This study provides the first evidence that it is possible to dissociate neural activation patterns for identity and viewpoint independently.

Category-specific cortical activity precedes retrieval during memory search.

Here we describe a functional magnetic resonance imaging study of humans engaged in memory search during a free recall task. Patterns of cortical activity associated with the study of three categories of pictures (faces, locations, and objects) were identified by a pattern-classification algorithm. The algorithm was used to track the reappearance of these activity patterns during the recall period. The reappearance of a given category's activity pattern correlates with verbal recalls made from that category and precedes the recall event by several seconds. This result is consistent with the hypothesis that category-specific activity is cueing the memory system to retrieve studied items.

Place from time: Reconstructing position from a distributed representation of temporal context.

The temporal context model (TCM) [. A distributed representation of temporal context. Journal of Mathematical Psychology, 46(3), 269-299] was proposed to describe recency and associative effects observed in episodic recall. Episodic recall depends on an intact medial temporal lobe, a region of the brain that also supports a place code. Howard, Fotedar, Datey, and Hasselmo [. The temporal context model in spatial navigation and relational learning: Toward a common explanation of medial temporal lobe function across domains. Psychological Review, 112(1), 75-116] demonstrated that the leaky integrator that supports a gradually changing representation of temporal context in TCM is sufficient to describe properties of cells observed in ventromedial entorhinal cortex during spatial navigation if it is provided with input about the animal's current velocity. This representation of temporal context generates noisy place cells in the open field, unlike the clearly defined place cells observed in the hippocampus. Here we demonstrate that a reasonably accurate spatial representation can be extracted from temporal context with as few as eight cells, suggesting that the spatial precision observed in the place code in the hippocampus is not inconsistent with the input from a representation of temporal-spatial context in entorhinal cortex.