Biology subjects

Mitchell, J. L.

Publications and source records attributed to Mitchell, J. L..

9 recordsLinked to original sources

bioRxiv2026

Functional connectivity scaffolds the emergence of the visual word form area

Complex cognitive tasks, like reading, require coordinated computations across distant cortical regions. Connectivity among regions is therefore key for understanding the neurobiological basis of behavior. It remains an open question whether connectivity serves as an innate organizational blueprint that guides functional specialization, or if it evolves with learning. Here, we address this fundamental question through the prism of learning to read: We measured functional connectivity at five timepoints over a year in children with dyslexia who participated in an intensive reading intervention. We found that specific patterns of functional connectivity of the reading circuitry were in place prior to the intervention, and remained stable over time. Further, functional connectivity before the intervention predicted the location of text-selective regions a year later, showing that connectivity precedes and predicts functional specialization that emerge with learning. These findings support a view of functional connectivity as a stable organizational principle of high-level cortex.

neuroscience↗

bioRxiv2026

Anatomy of the Visual Word Form Area in Dyslexia

The Visual Word Form Area (VWFA), located in ventral occipitotemporal cortex, plays a critical role in skilled reading. Researchers have theorized that the VWFA develops in its specific anatomical location due to the convergence of major white matter tracts and proximity to functionally similar regions. This suggests that precise anatomical positioning may be crucial for optimal VWFA function. Previous research has identified several functional differences in this region between typical and struggling readers (i.e. dyslexia): struggling readers show weaker text-selective responses and often exhibit a smaller or even absent VWFA. However, it remains unexplored whether the precise anatomical location of this region also differs between typical and struggling readers. We tested whether VWFA anatomy differs between children with and without dyslexia (N=87). Participants completed a functional localizer, which we used to manually define the VWFA in each individual's native anatomy. We examined whether: (1) VWFA anatomical location relates to reading ability, (2) children with dyslexia show greater variability in VWFA location compared to typical readers, and (3) VWFA location with respect to white matter tracts relates to reading ability. Results reveal that, despite being smaller in children with dyslexia, there is no relationship between VWFA location and reading ability. Specifically, individual VWFA location relative to anatomy, relative to other's VWFAs, and relative to white matter tracts, is not related to reading ability. These findings suggest that while the VWFA's general anatomy may be facilitated by development, its precise location remains stable and unrelated to reading proficiency.

neuroscience↗

bioRxiv2026

Highly replicable multisite patterns of adolescent white matter maturation

The Adolescent Brain Cognitive Development (ABCD) Study is the largest U.S.-based neuroimaging initiative of adolescent brain maturation. Diffusion MRI (dMRI) provides unique insights into white matter organization, yet applying advanced processing pipelines and managing technical variability across scanning environments remains challenging at scale. To address these issues, we present ABCD-BIDS Community Collection (ABCC) release 3.1.0, including a curated resource of more than 24,000 fully processed ABCD dMRI datasets. ABCC provides fully processed images, nuanced image quality metrics, advanced microstructural measures, and person-specific bundle tractography. Evaluating these rich data revealed that measures of diffusion restriction and non-Gaussianity--in particular the intracellular volume fraction from NODDI and return-to-origin probability from MAP-MRI--were highly sensitive to neurodevelopment and robust to variation in image quality. Additionally, harmonization of microstructural features markedly improved the cross-vendor generalizability of developmental effects. Together, ABCC accelerates reproducible, rigorous research on adolescent white matter development.

neuroscience↗

bioRxiv2025

Visual Word Form Area demonstrates individual and task-agnostic consistency but inter-individual variability

Ventral Occipital Temporal Cortex (VOTC) contains a mosaic of categorically-selective functional regions that respond to visual stimuli. Within left VOTC lies the Visual Word Form Area (VWFA) - a text-selective region that develops as individuals learn to read. While there is consistency in the general location of text-selective responses - within the posterior occipitotemporal sulcus (OTS) - there is substantial variability across individuals in the size and precise anatomical location. Moreover, debate continues regarding whether VWFA a) encodes the visual features of text, versus b) is driven by the task of reading. Using functional magnetic resonance imaging, we scanned adults and children as they completed two tasks while viewing text, pseudo fonts, faces, objects, limbs: (1) a fixation task where participants ignored stimuli while making psychophysical judgements on a fixation dot, and (2) a one-back task, where they attend to stimuli to detect repeats. We found a consistent VWFA location could be identified on each individuals cortical surface using either task. At the same time, the one-back task evoked a larger territory of text-selective response (leading to a larger ROI) than the fixation task. However, when averaged in template space, text-selective cortex could not be identified due to variability in the relative locations of text-, face-, object-, and limb-selective cortex. Thus, despite task-agnostic consistency in individual VWFA, text-selective responses are masked when averaged in template space due to variability in the exact configuration of category-selective regions. Furthermore, these effects were present in both children and adults.

neuroscience↗

bioRxiv2025

Small or absent Visual Word Form Area is a trait of dyslexia

Understanding the balance between plastic and persistent traits in the dyslexic brain is critical for developing effective interventions. This longitudinal intervention study examines the Visual Word Form Area in dyslexic and typical readers, exploring how this key component of the brains reading circuitry changes with learning. We find that children with dyslexia show significant differences in Visual Word Form Area presence, size, and tuning properties compared to typical readers. While reading intervention improves reading skills and increases Visual Word Form Area size, disparities persist a year later, suggesting that Visual Word Form Area abnormalities are enduring traits of dyslexia. Our results reveal long-term neural and behavioral changes, while also elucidating stable differences in the functional architecture of the dyslexic brain. This work provides comprehensive insights into the potential and limitations of short-term learning-induced plasticity in human visual cortex.

neuroscience↗

bioRxiv2024

Anatomically distinct regions in the inferior frontal cortex are modulated by task and reading skill

Inferior frontal cortex (IFC) is a critical region for reading and language. This part of the cortex is highly heterogeneous in its structural and functional organization and shows high variability across individuals. Despite decades of research, the relationship between specific IFC regions and reading skill remains unclear. To shed light on the function of IFC in reading, we aim to (1) characterize the functional landscape of text-selective responses in the IFC, while accounting for interindividual variability; and (2) examine how text-selective regions in the IFC relate to reading proficiency. To this end, children with a wide range of reading ability (N=66; age 7-14 years, 34 female, 32 male) completed functional MRI scans while performing two tasks on text and non-text visual stimuli. Importantly, both tasks do not explicitly require reading, and can be performed on all visual stimuli. This design allows us to tease apart stimulus-driven responses from task-driven responses and examine where in the IFC task and stimulus interact. We were able to identify three anatomically-distinct, text-selective clusters of activation in the IFC, in the inferior frontal sulcus (IFS), and dorsal and ventral precentral gyrus (PrG). These three regions showed a strong task effect that was highly specific to text. Furthermore, text-selectivity in the IFS and dorsal PrG was associated with reading proficiency, such that better readers showed higher selectivity to text. These findings suggest that text-selective regions in the IFC are sensitive to both stimulus and task, and highlight the importance of this region for proficient reading. Significance statementThe inferior frontal cortex (IFC) is a critical region for language processing, yet despite decades of research, its relationship with reading skill remains unclear. In a group of children with a wide range of reading skills, we were able to identify three anatomically distinct text-selective clusters of activation in the IFC. These regions showed a strong task effect that was highly selective to text. Text-selectivity was positively correlated with reading proficiency, such that better readers showed higher selectivity to text, even in tasks that did not require reading. These findings suggest that multiple text-selective regions within IFC are sensitive to both stimulus and task, and highlight the critical role of IFC for reading proficiency.

neuroscience↗

bioRxiv2023

Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation

Histone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where particular combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognise trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me3 during mitosis. We find that H3K4me3 hinders adjacent H3T3ph deposition in cells, and that the PHD domain of TAF3 can bind H3K4me3 in mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.

cell biology↗

bioRxiv2022

HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We analyzed productively and latently infected cells in blood and lymphoid tissue from individuals in acute infection. The phenotype of productively infected cells rapidly evolved with time and differed between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded/disseminated cells, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct T cells in blood and lymph nodes and latently infected cells are generated simultaneously. One-Sentence SummaryHIV initially infects phenotypically and clonotypically distinct T cells and establishes a latent reservoir concomitantly.

microbiology↗

bioRxiv2021

Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets

A subset of patients with COVID-19 become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill COVID-19 patients are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesised that platelets might be susceptible to activation by anti-SARS-CoV-2 antibodies and contribute to thrombosis. We found that immune complexes containing recombinant SARS-CoV-2 spike protein and anti-spike IgG enhanced platelet-mediated thrombosis on von Willebrand Factor in vitro, but only when the glycosylation state of the Fc domain was modified to correspond with the aberrant glycosylation previously identified in patients with severe COVID-19. Furthermore, we found that activation was dependent on FcyRIIA and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by therapeutic small molecules R406 (fostamatinib) and ibrutinib that inhibit tyrosine kinases syk and btk respectively or by the P2Y12 antagonist cangrelor.

immunology↗