Human white matter myelinates faster in utero than ex utero.

The formation of myelin, the fatty sheath that insulates nerve fibers, is critical for healthy brain function. A fundamental open question is what impact being born has on myelin growth. To address this, we evaluated a large (n = 300) cross-sectional sample of newborns from the Developing Human Connectome Project (dHCP). First, we developed software for the automated identification of 20 white matter bundles in individual newborns that is well suited for large samples. Next, we fit linear models that quantify how T1w/T2w (a myelin-sensitive imaging contrast) changes over time at each point along the 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 than in full-term peers measured at the same age. 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 they spent developing in utero and ex utero. These results suggest that white matter myelinates faster in utero than ex utero. The reduced rate of myelin growth after 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.

Characterizing Spatiotemporal Population Receptive Fields in Human Visual Cortex with fMRI.

The use of fMRI and computational modeling has advanced understanding of spatial characteristics of population receptive fields (pRFs) in human visual cortex. However, we know relatively little about the spatiotemporal characteristics of pRFs because neurons' temporal properties are one to two orders of magnitude faster than fMRI BOLD responses. Here, we developed an image-computable framework to estimate spatiotemporal pRFs from fMRI data. First, we developed a simulation software that predicts fMRI responses to a time-varying visual input given a spatiotemporal pRF model and solves the model parameters. The simulator revealed that ground-truth spatiotemporal parameters can be accurately recovered at the millisecond resolution from synthesized fMRI responses. Then, using fMRI and a novel stimulus paradigm, we mapped spatiotemporal pRFs in individual voxels across human visual cortex in 10 participants (both females and males). We find that a compressive spatiotemporal (CST) pRF model better explains fMRI responses than a conventional spatial pRF model across visual areas spanning the dorsal, lateral, and ventral streams. Further, we find three organizational principles of spatiotemporal pRFs: (1) from early to later areas within a visual stream, spatial and temporal windows of pRFs progressively increase in size and show greater compressive nonlinearities, (2) later visual areas show diverging spatial and temporal windows across streams, and (3) within early visual areas (V1-V3), both spatial and temporal windows systematically increase with eccentricity. Together, this computational framework and empirical results open exciting new possibilities for modeling and measuring fine-grained spatiotemporal dynamics of neural responses using fMRI.

High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting.

PURPOSE: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. METHODS: We developed 3D visualization of short transverse relaxation time component (ViSTa)-MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors. RESULTS: The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in vivo results of 1 mm- and 0.66 mm-isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5-min whole-brain 1 mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. CONCLUSIONS: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1 and 0.66 mm isotropic resolution in 5 and 15 min, respectively. This advancement allows for quantitative investigations of myelination changes in 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.

Attention enhances category representations across the brain with strengthened residual correlations to ventral temporal cortex.

How does attention enhance neural representations of goal-relevant stimuli while suppressing representations of ignored stimuli across regions of the brain? While prior studies have shown that attention enhances visual responses, we lack a cohesive understanding of how selective attention modulates visual representations across the brain. Here, we used functional magnetic resonance imaging (fMRI) while participants performed a selective attention task on superimposed stimuli from multiple categories and used a data-driven approach to test how attention affects both decodability of category information and residual correlations (after regressing out stimulus-driven variance) with category-selective regions of ventral temporal cortex (VTC). Our data reveal three main findings. First, when two objects are simultaneously viewed, the category of the attended object can be decoded more readily than the category of the ignored object, with the greatest attentional enhancements observed in occipital and temporal lobes. Second, after accounting for the response to the stimulus, the correlation in the residual brain activity between a cortical region and a category-selective region of VTC was elevated when that region's preferred category was attended vs. ignored, and more so in the right occipital, parietal, and frontal cortices. Third, we found that the stronger the residual correlations between a given region of cortex and VTC, the better visual category information could be decoded from that region. These findings suggest that heightened residual correlations by selective attention may reflect the sharing of information between sensory regions and higher-order cortical regions to provide attentional enhancement of goal-relevant information.

A Probabilistic Functional Atlas of Human Occipito-Temporal Visual Cortex.

Human visual cortex contains many retinotopic and category-specific regions. These brain regions have been the focus of a large body of functional magnetic resonance imaging research, significantly expanding our understanding of visual processing. As studying these regions requires accurate localization of their cortical location, researchers perform functional localizer scans to identify these regions in each individual. However, it is not always possible to conduct these localizer scans. Here, we developed and validated a functional region of interest (ROI) atlas of early visual and category-selective regions in human ventral and lateral occipito-temporal cortex. Results show that for the majority of functionally defined ROIs, cortex-based alignment results in lower between-subject variability compared to nonlinear volumetric alignment. Furthermore, we demonstrate that 1) the atlas accurately predicts the location of an independent dataset of ventral temporal cortex ROIs and other atlases of place selectivity, motion selectivity, and retinotopy. Next, 2) we show that the majority of voxel within our atlas is responding mostly to the labeled category in a left-out subject cross-validation, demonstrating the utility of this atlas. The functional atlas is publicly available (download.brainvoyager.com/data/visfAtlas.zip) and can help identify the location of these regions in healthy subjects as well as populations (e.g., blind people, infants) in which functional localizers cannot be run.

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.

Ultra-high-resolution fMRI of Human Ventral Temporal Cortex Reveals Differential Representation of Categories and Domains.

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans.SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.

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

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

Combined Neural Tuning in Human Ventral Temporal Cortex Resolves the Perceptual Ambiguity of Morphed 2D Images.

We have an amazing ability to categorize objects in the world around us. Nevertheless, how cortical regions in human ventral temporal cortex (VTC), which is critical for categorization, support this behavioral ability, is largely unknown. Here, we examined the relationship between neural responses and behavioral performance during the categorization of morphed silhouettes of faces and hands, which are animate categories processed in cortically adjacent regions in VTC. Our results reveal that the combination of neural responses from VTC face- and body-selective regions more accurately explains behavioral categorization than neural responses from either region alone. Furthermore, we built a model that predicts a person's behavioral performance using estimated parameters of brain-behavior relationships from a different group of people. Moreover, we show that this brain-behavior model generalizes to adjacent face- and body-selective regions in lateral occipitotemporal cortex. Thus, while face- and body-selective regions are located within functionally distinct domain-specific networks, cortically adjacent regions from both networks likely integrate neural responses to resolve competing and perceptually ambiguous information from both categories.

Diverse Temporal Dynamics of Repetition Suppression Revealed by Intracranial Recordings in the Human Ventral Temporal Cortex.

Repeated stimulus presentations commonly produce decreased neural responses-a phenomenon known as repetition suppression (RS) or adaptation-in ventral temporal cortex (VTC) of humans and nonhuman primates. However, the temporal features of RS in human VTC are not well understood. To fill this gap in knowledge, we utilized the precise spatial localization and high temporal resolution of electrocorticography (ECoG) from nine human subjects implanted with intracranial electrodes in the VTC. The subjects viewed nonrepeated and repeated images of faces with long-lagged intervals and many intervening stimuli between repeats. We report three main findings: 1) robust RS occurs in VTC for activity in high-frequency broadband (HFB), but not lower-frequency bands; 2) RS of the HFB signal is associated with lower peak magnitude (PM), lower total responses, and earlier peak responses; and 3) RS effects occur early within initial stages of stimulus processing and persist for the entire stimulus duration. We discuss these findings in the context of early and late components of visual perception, as well as theoretical models of repetition suppression.

X-Chromosome Insufficiency Alters Receptive Fields across the Human Early Visual Cortex.

Here, we investigated processing by receptive fields, a fundamental property of neurons in the visual system, using fMRI and population receptive field (pRF) mapping in 20 human females with monosomic Turner syndrome (TS) (mean age, 10.3 ± 2.0 years) versus 22 age- and sex-matched controls (mean age, 10.4 ± 1.9 years). TS, caused by X-chromosome haploinsufficiency in females, is associated with well-recognized effects on visuospatial processing, parieto-occipital cortical anatomy, and parietal lobe function. However, it is unknown whether these effects are related to altered brain structure and function in early visual areas (V1-V3) versus downstream parietal cortical regions. Results show that girls with TS have the following: (1) smaller volume of V1-V3, (2) lower average pRF eccentricity in early visual areas, and (3) sparser pRF coverage in the periphery of the visual field. Further, we examined whether the lower volume of early visual areas, defined using retinotopic mapping, in TS is due to smaller surface area or thinner cortex. Results show that girls with TS had a general reduction in surface area relative to controls in bilateral V1 and V2. Our data suggest the possibility that the smaller cortical surface area of early visual areas in girls with TS may be associated with a lower number of neurons, which in turn, leads to lesser coverage of the peripheral visual field compared to controls. These results indicate that X-chromosome haploinsufficiency associated with TS affects the functional neuroanatomy of early visual areas, and suggest that investigating pRFs in TS may shed insights into their atypical visuospatial processing.SIGNIFICANCE STATEMENT Turner syndrome is caused by the absence of one of the two X-chromosomes in females. Using functional neuroimaging and population receptive field mapping, we find that chromosome dosage variation (X-monosomy) associated with Turner syndrome affects the functional neuroanatomy of the visual cortex. Specifically, girls with Turner syndrome have smaller early visual areas that provide lesser coverage of the peripheral visual field compared with healthy controls. Our observations provide compelling evidence that the X-chromosome affects not only parietal cortex, as described in previous studies, but also affects early visual areas. These findings suggest a paradigm change in understanding the effect of X-monosomy on the development of visuospatial abilities in humans.

Differential sustained and transient temporal processing across visual streams.

How do high-level visual regions process the temporal aspects of our visual experience? While the temporal sensitivity of early visual cortex has been studied with fMRI in humans, temporal processing in high-level visual cortex is largely unknown. By modeling neural responses with millisecond precision in separate sustained and transient channels, and introducing a flexible encoding framework that captures differences in neural temporal integration time windows and response nonlinearities, we predict fMRI responses across visual cortex for stimuli ranging from 33 ms to 20 s. Using this innovative approach, we discovered that lateral category-selective regions respond to visual transients associated with stimulus onsets and offsets but not sustained visual information. Thus, lateral category-selective regions compute moment-to-moment visual transitions, but not stable features of the visual input. In contrast, ventral category-selective regions process both sustained and transient components of the visual input. Our model revealed that sustained channel responses to prolonged stimuli exhibit adaptation, whereas transient channel responses to stimulus offsets are surprisingly larger than for stimulus onsets. This large offset transient response may reflect a memory trace of the stimulus when it is no longer visible, whereas the onset transient response may reflect rapid processing of new items. Together, these findings reveal previously unconsidered, fundamental temporal mechanisms that distinguish visual streams in the human brain. Importantly, our results underscore the promise of modeling brain responses with millisecond precision to understand the underlying neural computations.

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.

Encoding model of temporal processing in human visual cortex.

How is temporal information processed in human visual cortex? Visual input is relayed to V1 through segregated transient and sustained channels in the retina and lateral geniculate nucleus (LGN). However, there is intense debate as to how sustained and transient temporal channels contribute to visual processing beyond V1. The prevailing view associates transient processing predominately with motion-sensitive regions and sustained processing with ventral stream regions, while the opposing view suggests that both temporal channels contribute to neural processing beyond V1. Using fMRI, we measured cortical responses to time-varying stimuli and then implemented a two temporal channel-encoding model to evaluate the contributions of each channel. Different from the general linear model of fMRI that predicts responses directly from the stimulus, the encoding approach first models neural responses to the stimulus from which fMRI responses are derived. This encoding approach not only predicts cortical responses to time-varying stimuli from milliseconds to seconds but also, reveals differential contributions of temporal channels across visual cortex. Consistent with the prevailing view, motion-sensitive regions and adjacent lateral occipitotemporal regions are dominated by transient responses. However, ventral occipitotemporal regions are driven by both sustained and transient channels, with transient responses exceeding the sustained. These findings propose a rethinking of temporal processing in the ventral stream and suggest that transient processing may contribute to rapid extraction of the content of the visual input. Importantly, our encoding approach has vast implications, because it can be applied with fMRI to decipher neural computations in millisecond resolution in any part of the brain.

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 architecture of the ventral temporal cortex and its role in categorization.

Visual categorization is thought to occur in the human ventral temporal cortex (VTC), but how this categorization is achieved is still largely unknown. In this Review, we consider the computations and representations that are necessary for categorization and examine how the microanatomical and macroanatomical layout of the VTC might optimize them to achieve rapid and flexible visual categorization. We propose that efficient categorization is achieved by organizing representations in a nested spatial hierarchy in the VTC. This spatial hierarchy serves as a neural infrastructure for the representational hierarchy of visual information in the VTC and thereby enables flexible access to category information at several levels of abstraction.

A preference for mathematical processing outweighs the selectivity for Arabic numbers in the inferior temporal gyrus.

A region in the posterior inferior temporal gyrus (ITG), referred to as the number form area (NFA, here ITG-numbers) has been implicated in the visual processing of Arabic numbers. However, it is unknown if this region is specifically involved in the visual encoding of Arabic numbers per se or in mathematical processing more broadly. Using functional magnetic resonance imaging (fMRI) during experiments that systematically vary tasks and stimuli, we find that mathematical processing, not preference to Arabic numbers, consistently drives both mean and distributed responses in the posterior ITG. While we replicated findings of higher responses in ITG-numbers to numbers than other visual stimuli during a 1-back task, this preference to numbers was abolished when participants engaged in mathematical processing. In contrast, an ITG region (ITG-math) that showed higher responses during an adding task vs. other tasks maintained this preference for mathematical processing across a wide range of stimuli including numbers, number/letter morphs, hands, and dice. Analysis of distributed responses across an anatomically-defined posterior ITG expanse further revealed that mathematical task but not Arabic number form can be successfully and consistently decoded from these distributed responses. Together, our findings suggest that the function of neuronal regions in the posterior ITG goes beyond the specific visual processing of Arabic numbers. We hypothesize that they ascribe numerical content to the visual input, irrespective of the format of the stimulus.