Biology subjects

Gabrieli, J. D. E.

Publications and source records attributed to Gabrieli, J. D. E..

15 recordsLinked to original sources

bioRxiv2026

Neurodiversity in the brain: More variable localization of face regions in autism

A fundamental principle in human neuroscience is that the brain is organized into distinct functional regions specialized for particular processes. These functional regions develop early and are shaped by sensory experiences. Strikingly, the precise location of these functional regions is relatively consistent across individuals, with specific regions found in stereotyped locations with respect to the macroanatomy (e.g., particular sulci and gyri). An important question is how flexible this functional neuroanatomy is, particularly in neurodevelopmental disorders like autism which are characterized by atypical brain development and behavior. Here, we investigated this question by focusing on the organization of the face-processing network -- a well-characterized system of regions that are reliably localized across neurotypical individuals, including, famously, the fusiform face area. Using precision fMRI, we identified subject-specific face-sensitive regions in the brains of autistic and neurotypical adults, and assessed their topographical alignment across individuals. Face regions in autism were globally and highly variably displaced - located farther from their expected locations in the brain relative to much more homogenous localization in neurotypical adults. Autistic individuals whose face regions were more displaced had greater sociocommunicative challenges. In contrast, the spatial organization of object-sensitive regions was not affected. These findings suggest that the spatial organization of the face network is atypical in autism, with behaviorally meaningful increased variability in the precise location of face-sensitive areas, and highlights the importance of individualized approaches in neuroimaging. Significance StatementThe human brain is organized into specialized functional regions positioned in remarkably consistent locations across individuals. It is unclear how altered neurodevelopment affects this organization. Using precision fMRI, we found that autism was characterized by globally and highly variably displaced face-sensitive functional brain regions. Atypical spatial organization of these regions was associated with greater sociocommunicative difficulties. In contrast, the spatial organization of object-sensitive regions did not differ in autism. These findings reveal that functional neuroanatomy in autism is altered in category-specific ways, with direct relevance to core sociocommunicative features of the condition. This work underscores the importance of individualized brain mapping in neuroimaging and may shed light on inconsistent findings in previous group-level neuroimaging studies.

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bioRxiv2025

Limited generalizability of dynamic fMRI correlates of adolescent rumination

Rumination, or perseverative negative self-referential thinking, is a hallmark of depression. In adults, a dynamic resting-state fMRI model of trait rumination was recently identified through predictive modelling. In adolescents, a development period during which rumination and depression increase, the neurobiological correlates of ruminative thinking are less clear. In the current preregistered study, we examine dynamic connectivity correlates of self-reported rumination in the largest sample of adolescents to date (n = 443, containing clinical and non-clinical individuals). Notably, the adult model failed to generalize to our sample. In addition, linear models trained on default-mode network (DMN) connectivity, as well as whole-brain connectome models, failed to generalize to held-out data. In an exploratory random forest analysis, we found significant prediction performance of a model where increased variability between DMN-cerebellum, DMN-dorsal attention network, and DMN-DMN connections was nominally associated with higher rumination. However, the model did not generalize to an external sample with lower rumination scores and a distinct scanner protocol. Our findings illustrate the difficulty of characterizing the neurodevelopment of risk factors for depression.

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bioRxiv2025

Incorporating special interests to investigate the language system in autism: A feasibility pilot fMRI study

Most autistic individuals have sustained, focused interests in particular topics or activities. In some cases, these special interests have been shown to motivate communicative behaviors, a domain in which many autistic individuals experience challenges. We conducted a pilot study with 15 autistic children (ages 8.18 - 13.27 years, mean(SD)= 11.17(1.62), 3 female/11 male/1 nonbinary), comparing brain responses elicited by short narratives tailored to individuals special interests to responses elicited by generic, non-tailored narratives. Using functional magnetic resonance imaging (fMRI), we found that autistic children did not show typical language responses to generic narratives. However, they did show heightened responses to the narratives that incorporated their special interests relative to the generic narratives in language regions and in regions associated with reward and self-reference. Brain responses for personalized narratives were also more consistent across children than responses for the generic narratives. These results suggest that personalizing stimuli by incorporating special interests might be a promising approach for neuroimaging in autistic participants. LAY SUMMARYIn a pilot sample of autistic children, we found that listening to short narratives tailored to each childs special interest elicited higher responses in the brain than listening to non-personalized narratives. Brain responses across children were also more similar for the special interest narratives. Thus, personalizing stimuli to special interests may be a promising approach for neuroimaging studies of autism.

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bioRxiv2024

Connectome predictive modeling of trait mindfulness

IntroductionTrait mindfulness refers to ones disposition or tendency to pay attention to their experiences in the present moment, in a non-judgmental and accepting way. Trait mindfulness has been robustly associated with positive mental health outcomes, but its neural underpinnings are poorly understood. Prior resting-state fMRI studies have associated trait mindfulness with within- and between-network connectivity of the default-mode (DMN), fronto-parietal (FPN), and salience networks. However, it is unclear how generalizable the findings are, how they relate to different components of trait mindfulness, and how other networks and brain areas may be involved. MethodsTo address these gaps, we conducted the largest resting-state fMRI study of trait mindfulness to-date, consisting of a pre-registered connectome predictive modeling analysis in 367 adults across three samples collected at different sites. ResultsIn the model-training dataset, we did not find connections that predicted overall trait mindfulness, but we identified neural models of two mindfulness subscales, Acting with Awareness and Non-judging. Models included both positive networks (sets of pairwise connections that positively predicted mindfulness with increasing connectivity) and negative networks, which showed the inverse relationship. The Acting with Awareness and Non-judging positive network models showed distinct network representations involving FPN and DMN, respectively. The negative network models, which overlapped significantly across subscales, involved connections across the whole brain with prominent involvement of somatomotor, visual and DMN networks. Only the negative networks generalized to predict subscale scores out-of-sample, and not across both test datasets. Predictions from both models were also negatively correlated with predictions from a well-established mind-wandering connectome model. ConclusionsWe present preliminary neural evidence for a generalizable connectivity models of trait mindfulness based on specific affective and cognitive facets. However, the incomplete generalization of the models across all sites and scanners, limited stability of the models, as well as the substantial overlap between the models, underscores the difficulty of finding robust brain markers of mindfulness facets.

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bioRxiv2024

Dynamic functional connectivity correlates of trait mindfulness in early adolescence

BackgroundTrait mindfulness, the tendency to attend to present-moment experiences without judgement, is negatively correlated with adolescent anxiety and depression. Understanding the neural mechanisms underlying trait mindfulness may inform the neural basis of psychiatric disorders. However, few studies have identified brain connectivity states that correlate with trait mindfulness in adolescence, nor have they assessed the reliability of such states. MethodsTo address this gap in knowledge, we rigorously assessed the reliability of brain states across 2 functional magnetic resonance imaging (fMRI) scan from 106 adolescents aged 12 to 15 (50% female). We performed both static and dynamic functional connectivity analyses and evaluated the test-retest reliability of how much time adolescents spent in each state. For the reliable states, we assessed associations with self-reported trait mindfulness. ResultsHigher trait mindfulness correlated with lower anxiety and depression symptoms. Static functional connectivity (ICCs from 0.31-0.53) was unrelated to trait mindfulness. Among the dynamic brains states we identified, most were unreliable within individuals across scans. However, one state, an hyperconnected state of elevated positive connectivity between networks, showed good reliability (ICC=0.65). We found that the amount of time that adolescents spent in this hyperconnected state positively correlated with trait mindfulness. ConclusionsBy applying dynamic functional connectivity analysis on over 100 resting-state fMRI scans, we identified a highly reliable brain state that correlated with trait mindfulness. The brain state may reflect a state of mindfulness, or awareness and arousal more generally, which may be more pronounced in those who are higher in trait mindfulness.

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bioRxiv2024

Precision fMRI reveals that the language network exhibits adult-like left-hemispheric lateralization by 4 years of age

In adults, left hemisphere (LH) damage often leads to aphasia, but many cases of early damage leave linguistic processing intact, with a functional language system developing in the right hemisphere. To explain this early apparent equipotentiality of the two hemispheres for language, some have proposed that the language system is more bilateral during early development and becomes increasingly left-lateralized with age. We examined language lateralization using fMRI in two large developmental cohorts (total n=273 children aged 4-16 years; n=107 adults). Strong, adult-like LH lateralization (in response magnitude and activation volume) was evident by age 4, although other features of the LH language network showed protracted development, including the magnitude of language response and the strength of functional connectivity. Thus, although the RH can take over language function in some cases of early brain damage, this plasticity occurs in spite of adult-level LH bias present by age 4 years.

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bioRxiv2023

White Matter Microstructural Plasticity Associated with Educational Intervention in Reading Disability

Childrens reading progress typically slows during extended breaks in formal education, such as summer vacations. This stagnation can be especially concerning for children with reading difficulties or disabilities (RD), such as dyslexia, because of the potential to exacerbate the skills gap between them and their peers. Reading interventions can prevent skill loss and even lead to appreciable gains in reading ability during the summer. Longitudinal studies relating intervention response to brain changes can reveal educationally relevant insights into rapid learning-driven brain plasticity. The current work focused on reading outcomes and white matter connections, which enable communication among the brain regions required for proficient reading. We collected reading scores and diffusion-weighted images at the beginning and end of summer for 41 children with RDs who had completed either 1st or 2nd grade. Children were randomly assigned to either receive an intensive reading intervention (n = 26; Seeing Stars from Lindamood-Bell which emphasizes orthographic fluency) or be deferred to a wait-list group (n = 15), enabling us to analyze how white matter properties varied across a wide spectrum of skill development and regression trajectories. On average, the intervention group had larger gains in reading compared to the non-intervention group, who declined in reading scores. Improvements on a proximal measure of orthographic processing (but not other more distal reading measures) were associated with decreases in mean diffusivity within core reading brain circuitry (left arcuate fasciculus and left inferior longitudinal fasciculus) and increases in fractional anisotropy in the left corticospinal tract. Our findings suggest that responses to intensive reading instruction are related predominantly to white matter plasticity in tracts most associated with reading.

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bioRxiv2023

Personal interests amplify engagement of language regions in the brains of children with and without autism

Cognition is shaped by individual experiences and interests. However, to study cognition in the brain, researchers typically use generic stimuli that are the same across all individuals. Language, in particular, is animated and motivated by several highly personal factors that are typically not accounted for in neuroimaging study designs, such as "interest" in a topic. Due to its inherently personal and idiosyncratic nature, it is unknown how interest in a topic modulates language processing in the brain. We conducted functional magnetic resonance imaging (fMRI) in 20 children (ages 6.98-12.01 years, mean(SD)=9.35(1.52), 5 female/15 male) as they listened to personalized narratives about a topic of specific interest, as well as to non-personalized generic narratives. We found that personalized narratives about a topic of interest increased activation in canonical language areas, as well as in reward and self-reference regions. Strikingly, we found that activation patterns elicited by topics of personal interest were more consistent across children, despite their idiosyncratic nature, than activation patterns elicited by narratives about an identical generic topic. These results reinforce the critical role that personal interests play in language processing in the human brain, and demonstrate the feasibility of using a personalized neuroimaging approach to study the effects of individually-varying factors such as interest in the brain.

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bioRxiv2022

Fiber-Specific Structural Properties Relate to Reading Skills in Children

Recent studies suggest that the cross-sectional relationship between reading skills and white matter microstructure, as indexed by fractional anisotropy, is not as robust as previously thought. Fixel-based analyses yield fiber-specific micro- and macrostructural measures, overcoming several shortcomings of the traditional diffusion tensor model. We ran a whole-brain analysis investigating whether the product of fiber density and cross-section (FDC) related to single-word reading skills in a large, open, quality-controlled data set of 983 children and adolescents ages 6-18. We also compared FDC between participants with (n = 102) and without (n = 570) reading disabilities. We found that FDC positively related to reading skills throughout the brain, especially in left temporoparietal and cerebellar white matter, but did not differ between reading proficiency groups. Exploratory analyses revealed that among metrics from other diffusion models - DTI, DKI, and NODDI - only the orientation dispersion and neurite density indexes from NODDI were associated (inversely) with reading skills. The present findings further support the importance of left-hemisphere dorsal temporoparietal white matter tracts in reading. Additionally, these results suggest future DWI studies of reading and dyslexia should be designed to benefit from advanced diffusion models, include cerebellar coverage, and consider continuous analyses that account for individual differences in reading skill.

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bioRxiv2021

A Large-Scale Investigation of White Matter Microstructural Associations with Reading Ability

Reading involves the functioning of a widely distributed brain network, and white matter tracts are responsible for transmitting information between constituent network nodes. Several studies have analyzed fiber bundle microstructural properties to shed insights into the neural basis of reading abilities and disabilities. Findings have been inconsistent, potentially due to small sample sizes and varying methodology. To address this, we analyzed a large data set of 686 children ages 5-18 using state-of-the-art neuroimaging acquisitions and processing techniques. We searched for associations between fractional anisotropy (FA) and single-word and single-nonword reading skills in children with diverse reading abilities across multiple tracts previously thought to contribute to reading. We also looked for group differences in tract FA between typically reading children and children with reading disabilities. FA of the white matter increased with age across all participants. There were no significant correlations between overall reading abilities and tract FAs across all children, and no significant group differences in tract FA between children with and without reading disabilities. There were associations between FA and nonword reading ability in older children (ages 9 and above). Higher FA in the right superior longitudinal fasciculus (SLF) and left inferior cerebellar peduncle (ICP) correlated with better nonword reading skills. These results suggest that letter-sound correspondence skills, as measured by nonword reading, are associated with greater white matter coherence among older children in these two tracts, as indexed by higher FA.

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bioRxiv2021

Electrophysiological correlates of perceptual prediction error are attenuated in dyslexia

A perceptual adaptation deficit often accompanies reading difficulty in dyslexia, manifesting in poor perceptual learning of consistent stimuli and reduced neurophysiological adaptation to stimulus repetition. However, it is not known how adaptation deficits relate to differences in feedforward or feedback processes in the brain. Here we used electroencephalography (EEG) to interrogate the feedforward and feedback contributions to neural adaptation as adults with and without dyslexia viewed pairs of faces and words in a paradigm that manipulated whether there was a high probability of stimulus repetition versus a high probability of stimulus change. We measured three neural dependent variables: expectation (the difference between prestimulus EEG power with and without the expectation of stimulus repetition), feedforward repetition (the difference between event-related potentials (ERPs) evoked by an expected change and an unexpected repetition), and feedback-mediated prediction error (the difference between ERPs evoked by an unexpected change and an expected repetition). Expectation significantly modulated prestimulus theta- and alpha-band EEG in both groups. Unexpected repetitions of words, but not faces, also led to significant feedforward repetition effects in the ERPs of both groups. However, neural prediction error when an unexpected change occurred instead of an expected repetition was significantly weaker in dyslexia than the control group for both faces and words. These results suggest that the neural and perceptual adaptation deficits observed in dyslexia reflect the failure to effectively integrate perceptual predictions with feedforward sensory processing. In addition to reducing perceptual efficiency, the attenuation of neural prediction error signals would also be deleterious to the wide range of perceptual and procedural learning abilities that are critical for developing accurate and fluent reading skills.

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bioRxiv2021

Generalizable prediction of stimulus-independent, task-unrelated thought from functional brain networks

Neural substrates of "mind wandering" have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering--stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling--dominated by default-frontoparietal control subnetwork interactions--that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of attention-deficit/hyperactivity disorder (ADHD) adults. In three additional resting-state fMRI studies (total n=1,115), including healthy and ADHD populations, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales, populations, and contexts.

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bioRxiv2020

Neuroplasticity associated with conversational turn-taking following a family-based intervention

Childrens early language environments are associated with linguistic, cognitive, and academic development, as well as concurrent brain structure and function. This study investigated neurodevelopmental mechanisms linking language input to development by measuring neuroplasticity associated with an intervention designed to enhance language environments of families primarily from lower socioeconomic backgrounds. Families of 52 4-to-6 year-old children were randomly assigned to a 9-week, interactive, family-based intervention or no-contact control group. Children completed pre- and post-assessments of verbal and nonverbal cognition (n=52), structural magnetic resonance imaging (n=45), and home auditory recordings of language exposure (n=39). Families who completed the intervention exhibited greater increases in adult-child conversational turns, and changes in turn-taking mediated intervention effects on language and executive functioning measures. Collapsing across groups, turn-taking changes were also positively correlated with cortical thickening in left inferior frontal and supramarginal gyri, the latter of which mediated relationships between changes in turn-taking and childrens language development. This is the first study of longitudinal neuroplasticity in response to changes in childrens language environments, and findings suggest that conversational turns support language development through cortical growth in language and social processing regions. This has implications for early interventions to enhance childrens language environments to support neurocognitive development.

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bioRxiv2020

Distinct neural substrates of individual differences in components of reading comprehension in adults with or without dyslexia

Reading comprehension is a complex task that depends on multiple cognitive and linguistic processes. According to the updated Simple View of Reading framework, in adults, individual variation in reading comprehension can be largely explained by combined variance in three component abilities: (1) decoding accuracy, (2) fluency, and (3) language comprehension. Here we asked whether the neural correlates of the three components are different in adults with dyslexia as compared to typically-reading adults and whether the relative contribution of these correlates to reading comprehension is similar in the two groups. We employed a novel naturalistic fMRI reading task to identify the neural correlates of individual differences in the three components using whole-brain and literature-driven regions-of-interest approaches. Across all participants, as predicted by the simple view framework, we found distinct patterns of associations with linguistic and domain-general regions for the three components, and that the left-hemispheric neural correlates of language comprehension in the angular and posterior temporal gyri made the largest contributions to explaining out-of-scanner reading comprehension performance. These patterns differed between the two groups. In typical adult readers, better fluency was associated with greater activation of left occipitotemporal regions, better comprehension with lesser activation in prefrontal and posterior parietal regions, and there were no significant associations with decoding. In adults with dyslexia, better fluency was associated with greater activation of bilateral inferior parietal regions, better comprehension was associated with greater activation in some prefrontal clusters and lower in others, and better decoding skills were associated with lesser activation of bilateral prefrontal and posterior parietal regions. Extending the behavioral findings of skill-level differences in the relative contribution of the three components to reading comprehension, the relative contributions of the neural correlates to reading comprehension differed based on dyslexia status. These findings reveal some of the neural correlates of individual differences in the three components and the underlying mechanisms of reading comprehension deficits in adults with dyslexia.

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bioRxiv2019

Putative protective neural mechanisms in pre-readers with a family history of dyslexia who subsequently develop typical reading skills

Developmental dyslexia is a learning disability characterized by difficulties in word reading. While the prevalence in the general public is around 10-12%, an increased prevalence of 40-60% has been reported for children with a familial risk. Neural atypicalities in the reading network have been observed in children with (FHD+) compared to without (FHD-) a family history of dyslexia, even before reading onset. Despite the hereditary risk, about half of FHD+ children develop typical reading abilities (FHD+Typical) but the underlying neural characteristics and the developmental trajectories of these favorable reading outcomes remain unknown. Utilizing a retrospective, longitudinal approach, this is the first study to examine whether potential protective neural mechanisms are present before reading onset in FHD+Typical. Functional and structural brain characteristics were examined in 69 pre-readers who subsequently developed typical reading abilities (35 FHD+Typical/34 FHD-Typical) using MRI/fMRI. Searchlight-based multivariate pattern analyses identified distinct activation patterns during phonological processing between FHD+Typical and FHD-Typical in right inferior frontal (RIFG) and left temporo-parietal (LTPC) regions. Hypoactivation in LTPC was further demonstrated in FHD+Typical compared to FHD-Typical, suggesting that this previously reported neural characteristic of dyslexia is primarily associated with familial risk. Importantly, FHD+Typical pre-readers exhibited higher activation in RIFG than FHD-Typical, which was associated with increased interhemispheric functional and structural connectivity. These results suggest that putative protective neural mechanisms are already established in FHD+Typical pre-readers and may therefore support their successful reading development. Further studies are needed to investigate the functional significance and developmental trajectories of these neural mechanisms as well as their enabling factors, which has the potential to inform the design of early preventative/remediation strategies.

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