Biology subjects

Saygin, Z. M.

Publications and source records attributed to Saygin, Z. M..

13 recordsLinked to original sources

bioRxiv2026

Literacy acquisition and functional connectivity drive the emergence and continued development of the VWFA

The visual word form area (VWFA) is a hallmark of literacy in the human brain. Alongside reading acquisition, the functional organization of the ventral temporal cortex (VTC) undergoes substantial changes. However, it remains unclear what factors uniquely drive the emergence and continued development of the VWFA, or more broadly shaping category selectivity across the VTC. Here, we combined cross-sectional and longitudinal data from children in early childhood (3-9 years) to investigate the development of visual language selectivity. We found that after controlling for age, literacy acquisition drove increases in word selectivity of the VWFA, but not the continued development of other early-developed category selectivity. Sensitivity to spoken higher-level language information within the VWFA was also associated with reading ability. By projecting the VWFA defined at the later time point onto each childs earlier time point, we also found that the pre-VWFA showed no preferential tuning to any particular visual category. Finally, longitudinal changes within the VWFA, both increased responses to visually presented words and decreased responses to auditory control conditions, were associated with changes in functional connectivity of VWFA to high-level language regions, even after controlling for initial activity levels. Together, the current study shows a unique role for literacy acquisition and experience-dependent connectivity changes in the emergence and functional specialization of the VWFA, providing empirical evidence for the revised neuronal recycling hypothesis and connectivity hypothesis of functional brain organization.

neuroscience↗

bioRxiv2026

A Tripartite Map of the Ventromedial Prefrontal Cortex

The ventromedial prefrontal cortex (VMPFC) has been repeatedly implicated in affect, valuation, and social cognition, yet how these diverse functions are organized within a single cortical territory has remained unresolved. Here, we integrate large-scale meta-analysis, individual-level task fMRI, artificial neural-network encoding models, and multimodal connectivity analyses to reveal the internal functional architecture of the human VMPFC. Across four complementary studies, we identify a robust tripartite organization along the anterior-posterior axis, comprising posterior affective, middle valuation, and anterior social functional motifs. Connectivity fingerprinting demonstrates that each motif is preferentially embedded within distinct large-scale brain networks, providing a mechanistic account of VMPFC functional specialization. This organization is reproducible at the level of individual subjects, generalizes to naturalistic stimuli, extends across development, and shows cross-species correspondence with non-human primates and multiple neurobiological markers. Together, these findings resolve a long-standing organizational question and establish a biologically grounded framework for interpreting VMPFC function.

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bioRxiv2025

The ventral visual stream for reading converges on the transmodal language network

Reading bridges sensation and cognition. To derive meaning from written words, visual input is first processed in unimodal (i.e., sensory-specific) visual streams and then engages a distributed language network (LANG) that includes classic perisylvian language areas and supports transmodal (i.e., sensory-nonspecific) functions. A reading-relevant region in the inferotemporal cortex (ITC), sometimes called the visual word form area (VWFA), has been the subject of controversy because it displays properties of both systems: it responds to meaningless written pseudowords, implying a unimodal visual function, but also responds to meaningful speech, implying a transmodal function. We investigated whether precision functional mapping could help clarify this regions role in reading. We characterized a stream of visual regions along the ITC that responded preferentially to visual orthographic forms (i.e., written pseudowords, consonant strings, and real words). Network mapping revealed that only the most anterior region of this "orthographic stream" was connected to the LANG network and accordingly showed responses to meaningful speech. Furthermore, this anterior region was more selective, responding preferentially to text-based stimuli, whereas the more posterior regions of the stream were additionally activated by perceptually similar images (i.e., number strings, foreign script). Our results support that connections to the LANG network may drive specialization along the orthographic stream for writing. This basal language network region may represent an interface between visual and transmodal language systems, thus serving as a critical nexus for reading.

neuroscience↗

bioRxiv2025

Functional Dissociation in the Developing Superior Temporal Lobe: Language and Theory of Mind

Language and theory of mind (ToM; the ability to infer others mental states) are both crucial for human communication and yet their developmental origins are unclear. Are their neural substrates distinct within the superior temporal lobe (STL) but with opposing lateralization, as in adults? Or do they emerge from common neural substrates during development, perhaps in homologous regions originally involved in more basic social processing? Here we investigate the development of this functional dissociation, and the dissociation of their underlying connectivity fingerprints in a large cohort of children (ages 4-9 years, n=58 sessions) and adults (n=29). We demonstrate for the first time that children show distinct patterns of neural specificity for language and ToM in STL, just like adults. Children show no evidence of developmental disentangling cross-sectionally or longitudinally. Finally, childrens connectivity fingerprints predicting future language or ToM activation are almost identical to concurrent fingerprints and are largely non-overlapping across domains. While linguistic and ToM processing undergo continued neural specialization to reach the mature adult-like state, they are distinct remarkably early in human development. Our results challenge the idea that language develops from neural processors common for social communication and instead support distinct neural origins of these mental domains.

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bioRxiv2023

Demystifying the Visual Word Form Area: Precision fMRI of Visual, Linguistic, and Attentional Properties of Ventral Temporal Cortex

The functional nature of the visual word form area (VWFA), a region in left ventrotemporal cortex (VTC), remains debated after over two decades of investigation. Here we use precision fMRI to comprehensively examine the VWFAs responses to numerous visual and nonvisual stimuli. We find that the VWFA is a distinct region that while showing moderate activation to non-word visual stimuli, its response to words towers above other conditions. Interestingly, the VWFA is also the only VTC region uniquely engaged in auditory language processing, in contrast with the ubiquitous attentional effect within the VTC. However, this language selectivity is dwarfed by its visual responses. This suggests the VWFA primarily functions as a visual look-up orthographic dictionary. Searching within the entire VTC further reveals an additional language cluster in anterior fusiform preferring general visual semantics. Our detailed examination of the VWFA in direct comparison to other VTC regions clarifies the long-standing controversies about its functionality.

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bioRxiv2022

Individual variability in performance reflects selectivity of the multiple demand network among children and adults.

Executive function (EF) is essential for human cognition, allowing individuals to effectively engage in cognitively demanding tasks. In adults, EF is subserved by a set of frontoparietal brain regions (termed the multiple demand (MD) network) which show robust responses to a wide variety of cognitively demanding tasks (i.e., domain-general) and reflect cognitive effort exerted on the task. But while essential, children initially show poor EF skills with prolonged development of these skills. Do children recruit the same network as adults? Is it functionally and connectionally distinct from adjacent language cortex as it is in adults? And is this activation or connectivity dependent on age or on the individuals EF task performance? We scanned 44 adults and 37 children ages 4-12 years for two separate tasks (MD spatial working memory task and passive language task) and a resting-state fMRI scan. Because motion is a concern in child samples, we asked a subset of adult subjects to participate in additional "wiggly" scans of the MD task and to move slightly during those scans. We defined subject-specific functional regions of interest (ss-fROIs) and found bilateral activation of the MD network in children. In both children and adults, these ss-fROIs are not recruited for linguistic processing and are also connectionally distinct from language ss-fROIs. MD activation in children was lower than that observed in adults, but it was unrelated to motion as evidenced by motion-matched comparisons between children and adult groups and by repeated measures comparisons within the adult group. Right-lateralized ss-fROIs showed increasing load-based MD responses that were robustly associated with performance, demonstrated both cross-sectionally and in a subset of children scanned longitudinally about one year apart. These data suggest that even in young children the MD network is selective to cognitive demand, is distinct from adjacent cortex, and increases in its selectivity as a child improves their EF skills, independently of age. Overall, these findings show that neural structures subserving domain-general EF emerge early and are sensitive to ability in both children and adults. This research advances our understanding of how high-level human cognition emerges and can inform interventions targeting cognitive control. Significance statementThis study provides evidence that young children already show differentiated brain network organization between regions that process cognitive demand and language. These data support the hypothesis that children recruit a similar network as adults to process cognitive demand, and despite immature characteristics, childrens selectivity looks more adult-like as their executive function ability increases. Mapping early stages of network organization furthers our understanding of the functional architecture underlying domain-general executive function. Determining typical variability underlying cognitive processing across developmental periods helps establish a threshold for executive dysfunction. Early markers of risk are necessary for effective early identification, prevention, and intervention efforts for individuals struggling with deficits in processing cognitive demand.

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bioRxiv2022

The language network is selective and distinct from other cognition in both function and connectivity in early childhood

Is language distinct from other cognition during development? Does neural machinery for language emerge from general-purpose neural mechanisms, becoming tuned for language after years of experience and maturation? Answering these questions will shed light on the origins of domain-specificity in the brain. We address these questions using precision fMRI and found young children (35 months-9 years) show domain-specific, left-lateralized language activation, and the language network is not responsive to domain-general cognitive load. Additionally, the cortically adjacent multiple demand network is selective to cognitive load, but not to language. These networks show higher within vs. between-network functional connectivity. This connectivity is stable across ages (examined cross-sectionally and longitudinally), whereas language responses increase with age and across-time within subject, reflecting a domain-specific developmental change. Overall, these findings suggest that domain-specificity, even for uniquely human cognition like language, develops early and distinctly from mechanisms that presumably support other human cognition. Significance StatementThis study provides evidence of a double dissociation between neural processors for language and domain-general cognition (specifically, cognitive load) in young children. These results refute previous claims that linguistic function emerges from domain-general mechanisms supporting non-linguistic, higher-order cognition, and with both cross-sectional and longitudinal analyses, show that the continued development of linguistic specialization is also unrelated to domain-general mechanisms that support cognitive flexibility and executive function. This work emphasizes the importance of single-subject fMRI analyses with multiple tasks to explicitly dissociate cognitive constructs, and the importance of longitudinal research for scientific rigor, even in toddlers and preschoolers who are difficult to image with fMRI.

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bioRxiv2021

Intact reading ability in spite of a spatially distributed visual word form 'area' in an individual born without the left superior temporal lobe

The visual word form area (VWFA) is an experience-dependent region in the left ventral temporal cortex (VTC) of literate adults that responds selectively to visual words. Why does it emerge in this stereotyped location? Past research shows the VWFA is preferentially connected to the left-lateralized frontotemporal language network. However, it remains unclear whether the presence of a typical language network and its connections with VTC are critical for the VWFAs emergence, and whether alternative functional architectures may support reading ability. We explored these questions in an individual (EG) born without the left superior temporal lobe but exhibiting normal reading ability. We recorded fMRI activation to visual words, objects, faces, and scrambled words in EG and neurotypical controls. We did not observe word selectivity either in EGs right homotope of the VWFA (rVWFA)--the most expected location given that EGs language network is right-lateralized--or in her spared left VWFA (lVWFA), despite typical face selectivity in both the right and left fusiform face area (rFFA, lFFA). We replicated these results across scanning sessions (5 years apart). Moreover, in contrast with the idea that the VWFA is simply part of the language network that responds to general linguistic information, no part of EGs VTC showed selectivity to higher-level linguistic processing. Interestingly, multivariate pattern analyses revealed sets of voxels in EGs rVWFA and lVWFA that showed 1) higher within- than between-category correlations for words (e.g., Words-Words>Words-Faces), and 2) higher within-category correlations for words than other categories (e.g., Words-Words>Faces-Faces). These results suggest that a typical left-hemisphere language network may be necessary for the emergence of focal word selectivity within the VTC, and that orthographic processing can be supported by a distributed neural code.

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bioRxiv2021

Innate Organization of the Human Brain

The adult brain is organized into distinct functional networks, forming the basis of information processing and determining individual differences in behavior. Is this network organization genetically determined and present at birth? And what is the individual variability in this organization in neonates? Here, we use unsupervised learning to uncover intrinsic functional brain organization using resting-state connectivity from a large cohort of neonates (Developing Human Connectome Project). We identified a set of symmetric, hierarchical, and replicable networks: sensorimotor, visual, default mode, ventral attention, and high-level vision. We quantified individual variability across neonates, and found the most individual variability in the ventral attention networks. Crucially, the variability of these networks were not driven by SNR differences or differences from adult networks (Yeo et al., 2011). Finally, differential gene expression provided a potential explanation for the emergence of these distinct networks and identified potential genes of interest for future developmental and individual variability research. Overall, we found neonatal connectomes (even at the voxel-level) can reveal broad individual- specific information processing units. The presence of individual differences in neonates and the framework for personalized parcellations demonstrated here has the potential to improve prediction of behavior and future outcomes from neonatal and infant brain data.

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bioRxiv2020

Adults vs. neonates: Differentiation of functional connectivity between the basolateral amygdala and occipitotemporal cortex

The amygdala, a subcortical structure known for social and emotional processing, consists of multiple subnuclei with unique functions and connectivity patterns. Tracer studies in adult macaques have shown that the basolateral subnuclei differentially connect to parts of visual cortex, with stronger connections to anterior regions and weaker connections to posterior regions; infant macaques show robust connectivity even with posterior visual regions. Do these developmental differences also exist in the human amygdala, and are there specific functional regions that undergo the most pronounced developmental changes in their connections with the amygdala? To address these questions, we explored the functional connectivity (from resting-state fMRI data) of the basolateral amygdala to occipitotemporal cortex in human neonates scanned within one week of life and compared the connectivity patterns to those observed in young adults. Specifically, we calculated amygdala connectivity to anterior-posterior gradients of the anatomically-defined occipitotemporal cortex, and also to putative occipitotemporal functional parcels, including primary and high-level visual and auditory cortices (V1, A1, face, scene, object, body, high-level auditory regions). Results showed a decreasing gradient of functional connectivity to the occipitotemporal cortex in adults - similar to the gradient seen in macaque tracer studies - but no such gradient was observed in neonates. Further, adults had stronger connections to high-level functional regions associated with face, body, and object processing, and weaker connections to primary sensory regions (i.e., A1, V1), whereas neonates showed the same amount of connectivity to primary and high-level sensory regions. Overall, these results show that functional connectivity between the amygdala and occipitotemporal cortex is not yet differentiated in neonates, suggesting a role of maturation and experience in shaping these connections later in life.

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bioRxiv2019

The intrinsic neonatal hippocampal network: rsfMRI findings

Many adults cannot voluntarily recall memories before the ages of 3-5, a phenomenon referred to as "infantile amnesia" The development of the hippocampal network likely plays a significant part in the emergence of the ability to form long-lasting memories. In adults, the hippocampus has specialized and privileged connections with certain cortical networks, which presumably facilitate its involvement in memory encoding, consolidation, and retrieval. Is the hippocampus already specialized in these cortical connections at birth? And are the topographical principles of connectivity (e.g. long-axis specialization) present at birth? We analyzed resting-state hippocampal connectivity in neonates scanned within one week of birth (Developmental Human Connectome Project) and compared them to adults (Human Connectome Project). We explored the connections of the whole hippocampus and its long-axis specialization to seven canonical cortical networks. We found that the neonatal hippocampal networks show clear immaturity at birth: adults showed hippocampal connectivity that was unique for each cortical network, whereas neonates showed no differentiation in hippocampal connectivity across these networks. Further, neonates lacked long-axis specialization (i.e., along anterior-posterior axis) of the hippocampus in its differential connectivity patterns to the cortical networks. This immaturity in connectivity may contribute to immaturity in memory formation in the first years of life. "New and Noteworthy"While animal data, and anatomical and behavioral human data from young children suggest that the hippocampus is immature at birth, to date, there are no direct assessments of human hippocampal functional connectivity (FC) very early in life. Our study explores the FC of the hippocampus to the cortex at birth, allowing insight into the development of human memory systems.

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bioRxiv2019

Cortical selectivity driven by connectivity: Innate connectivity patterns of the visual word form area

What determines the functional organization of cortex? One hypothesis is that innate connectivity patterns set up a scaffold upon which functional specialization can later take place. We tested this hypothesis by asking whether the visual word form area (VWFA), an experience-driven region, was already connected to proto language networks in neonates scanned within one week of birth. With resting-state fMRI, we found that neonates showed adult-like functional connectivity, and observed that i) language regions connected more strongly with the putative VWFA than other adjacent ventral visual regions that also show foveal bias, and ii) the VWFA connected more strongly with frontotemporal language regions than with regions adjacent to these language regions. These data suggest that the location of the VWFA is earmarked at birth due to its connectivity with the language network, providing evidence that innate connectivity instructs the later refinement of cortex.

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bioRxiv2019

Developmental changes in connectivity between the amygdala subnuclei and occipitotemporal cortex

The amygdala, a subcortical structure known for social and emotional processing, can be subdivided into multiple nuclei with unique functions and connectivity patterns. Tracer studies in adult macaques have shown that the lateral and basal amygdala subnuclei decrease in connectivity to visual cortical areas moving from anterior to posterior, and that infants have similar adult-like projections plus additional connections that are refined with development. Can we delineate the connectivity between the amygdala subnuclei and occipitotemporal cortex in humans, and will it show similar developmental differences as macaques? If so, what functional regions may be contributing to this pattern of connectivity? To address these questions, we anatomically defined the lateral and basal amygdala subnuclei in 20 adult subjects, 27 kids (aged 7-8), and 15 neonates. We then defined the occipitotemporal region in each individuals native anatomy, and split this entire region into five equal sections from anterior to posterior. We also defined visual functional parcellations in the occipitotemporal cortex (e.g. FFA, PPA) and anatomically defined primary visual cortex (i.e., V1). Using Diffusion Weighted Imaging data, we ran probabilistic tractography with FSL between the amygdala subnuclei as seeds and the occipitotemporal cortical parcellations as targets. Results showed that like macaques, the mean connectivity across subjects to the occipitotemporal cortex significantly decreased on a gradient from anterior to posterior, and that connectivity in kids and neonates was adult-like but became more refined across development. Further, refinement of connectivity to mid and posterior occipitotemporal cortex was largely driven by anterior PPA, LO, and V1, with connectivity to higher order visual areas increasing with age. The functional maturation of these regions may contribute to the continued refinement of these connections, in line with Interactive Specialization hypotheses of brain development.

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