Multimodal MRI characterization of visual word recognition: an integrative view

228 p.The ventral occipito-temporal (vOT) association cortex contributes significantly to recognize different types of visual patterns. It is widely accepted that a subset of this circuitry, including the visual word form area (VWFA), becomes trained to perform the task of rapidly identifying word forms. An important open question is the computational role of this circuitry: To what extent is part of a bottom-up hierarchical processing of information on visual word recognition and/or is involved in processing top-down signals from higher-level language regions. This doctoral dissertation thesis proposal is aimed at characterizing the vOT reading circuitry using behavioral, functional, structural and quantitative MRI indexes, and linking its computations to the other two important regions within the language network: the posterior parietal cortex (pPC) and the inferior frontal gyrus (IFG). Results revealed that two distinct word-responsive areas can be segregated in the vOT: one responsible for visual feature extraction that is connected to the intraparietal sulcus via the vertical occipital fasciculus and a second one responsible for semantic processing that is connected to the angular gyrus via the posterior arcuate fasciculus and to the IFG via the anterior arcuate fasciculus. Importantly, reading behavior was predicted by functional activation in regions identified along the vOT, pPC and IFG, as well as by structural properties of the white matter fiber tracts linking them. The present work constitutes a critical step in the creation of a highly detailed characterization of the early stages of reading at the individual-subject level and to establish a baseline model and parameter range that might serve to clarify functional and structural differences between typical, poor and atypical readers.BCBL: basque center on cognition, brain and languag

Multimodal MRI characterization of visual word recognition: an integrative view

228 p.The ventral occipito-temporal (vOT) association cortex contributes significantly to recognize different types of visual patterns. It is widely accepted that a subset of this circuitry, including the visual word form area (VWFA), becomes trained to perform the task of rapidly identifying word forms. An important open question is the computational role of this circuitry: To what extent is part of a bottom-up hierarchical processing of information on visual word recognition and/or is involved in processing top-down signals from higher-level language regions. This doctoral dissertation thesis proposal is aimed at characterizing the vOT reading circuitry using behavioral, functional, structural and quantitative MRI indexes, and linking its computations to the other two important regions within the language network: the posterior parietal cortex (pPC) and the inferior frontal gyrus (IFG). Results revealed that two distinct word-responsive areas can be segregated in the vOT: one responsible for visual feature extraction that is connected to the intraparietal sulcus via the vertical occipital fasciculus and a second one responsible for semantic processing that is connected to the angular gyrus via the posterior arcuate fasciculus and to the IFG via the anterior arcuate fasciculus. Importantly, reading behavior was predicted by functional activation in regions identified along the vOT, pPC and IFG, as well as by structural properties of the white matter fiber tracts linking them. The present work constitutes a critical step in the creation of a highly detailed characterization of the early stages of reading at the individual-subject level and to establish a baseline model and parameter range that might serve to clarify functional and structural differences between typical, poor and atypical readers.BCBL: basque center on cognition, brain and languag

Population Receptive Field Shapes in Early Visual Cortex Are Nearly Circular

First published February 2, 2021.The visual field region where a stimulus evokes a neural response is called the receptive field (RF). Analytical tools combined with functional MRI (fMRI) can estimate the RF of the population of neurons within a voxel. Circular population RF (pRF) methods accurately specify the central position of the pRF and provide some information about the spatial extent (diameter) of the RF. A number of investigators developed methods to further estimate the shape of the pRF, for example, whether the shape is more circular or elliptical. There is a report that there are many pRFs with highly elliptical pRFs in early visual cortex (V1–V3; Silson et al., 2018). Large aspect ratios (.2) are difficult to reconcile with the spatial scale of orientation columns or visual field map properties in early visual cortex. We started to replicate the experiments and found that the software used in the publication does not accurately estimate RF shape: it produces elliptical fits to circular ground-truth data. We analyzed an independent data set with a different software package that was validated over a specific range of measurement conditions, to show that in early visual cortex the aspect ratios are ,2. Furthermore, current empirical and theoretical methods do not have enough precision to discriminate ellipses with aspect ratios of 1.5 from circles. Through simulation we identify methods for improving sensitivity that may estimate ellipses with smaller aspect ratios. The results we present are quantitatively consistent with prior assessments using other methodologies.This work was supported by the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie Grant 795807 (to G.L.-U.) and by National Institutes of Health Grants EY027401, EY027964, and MH111417 (to J.W.). We thank E. Silson, C. Baker, and R. Reynolds. We also thank R. Reynolds for help with the AFNI softwar

Converging evidence for functional and structural segregation within the left ventral occipitotemporal cortex in reading

Published online September 17, 2018The ventral occipitotemporal cortex (vOTC) is crucial for recognizing visual patterns, and previous evidence suggests that there may be different subregions within the vOTC involved in the rapid identification of word forms. Here, we characterize vOTC reading circuitry using a multimodal approach combining functional, structural, and quantitative MRI and behavioral data. Two main word-responsive vOTC areas emerged: a posterior area involved in visual feature extraction, structurally connected to the intraparietal sulcus via the vertical occipital fasciculus; and an anterior area involved in integrating information with other regions of the language network, structurally connected to the angular gyrus via the posterior arcuate fasciculus. Furthermore, functional activation in these vOTC regions predicted reading behavior outside of the scanner. Differences in the microarchitectonic properties of gray-matter cells in these segregated areas were also observed, in line with earlier cytoarchitectonic evidence. These findings advance our understanding of the vOTC circuitry by linking functional responses to anatomical structure, revealing the pathways of distinct reading-related processes.This work was supported by European Molecular Biology Organization (EMBO, Short-Term Fellowship 158-2015) and Marie Sklodowska-Curie (H2020-MSCA-IF-2017-795807-ReCiModel) grants (to G.L.-U.); Spanish Ministry of Economy and Competitiveness (MINECO, PSI2015- 67353-R, SEV-2015-0490) and European Research Council (ERC, ERC-2011- ADG-295362) grants (to M.C.); and MINECO (RYC-2014-15440, PSI2012- 32093, SEV-2015-0490) and Departamento de Desarrollo Económico y Competitividad, Gobierno Vasco (PI2016-12) grants (to P.M.P.-A.)

Separate lanes for adding and reading in the white matter highways of the human brain

Published: 15 August 2019 Es OAMath and reading involve distributed brain networks and have both shared (e.g. encoding of visual stimuli) and dissociated (e.g. quantity processing) cognitive components. Yet, to date, the shared vs. dissociated gray and white matter substrates of the math and reading networks are unknown. Here, we define these networks and evaluate the structural properties of their fascicles using functional MRI, diffusion MRI, and quantitative MRI. Our results reveal that there are distinct gray matter regions which are preferentially engaged in either math (adding) or reading, and that the superior longitudinal and arcuate fascicles are shared across the math and reading networks. Strikingly, within these fascicles, reading- and math-related tracts are segregated into parallel sub-bundles and show structural differences related to myelination. These findings open a new avenue of research that examines the contribution of sub-bundles within fascicles to specific behaviors.This research was supported by the National Institute of Health (NIH; 1R01EY023915), by the Deutsche Forschungsgemeinschaft (DFG; GR 4850/1–1) and by an Innovation Grant from the Stanford Center for Cognitive and Neurobiological Imaging (CNI)

A validation framework for neuroimaging software: The case of population receptive fields

Published: June 25, 2020Neuroimaging software methods are complex, making it a near certainty that some implementations will contain errors. Modern computational techniques (i.e., public code and data repositories, continuous integration, containerization) enable the reproducibility of the analyses and reduce coding errors, but they do not guarantee the scientific validity of the results. It is difficult, nay impossible, for researchers to check the accuracy of software by reading the source code; ground truth test datasets are needed. Computational reproducibility means providing software so that for the same input anyone obtains the same result, right or wrong. Computational validity means obtaining the right result for the ground-truth test data. We describe a framework for validating and sharing software implementations, and we illustrate its usage with an example application: population receptive field (pRF) methods for functional MRI data. The framework is composed of three main components implemented with containerization methods to guarantee computational reproducibility. In our example pRF application, those components are: (1) synthesis of fMRI time series from ground-truth pRF parameters, (2) implementation of four public pRF analysis tools and standardization of inputs and outputs, and (3) report creation to compare the results with the ground truth parameters. The framework was useful in identifying realistic conditions that lead to imperfect parameter recovery in all four pRF implementations, that would remain undetected using classic validation methods. We provide means to mitigate these problems in future experiments. A computational validation framework supports scientific rigor and creativity, as opposed to the oft-repeated suggestion that investigators rely upon a few agreed upon packages. We hope that the framework will be helpful to validate other critical neuroimaging algorithms, as having a validation framework helps (1) developers to build new software, (2) research scientists to verify the software’s accuracy, and (3) reviewers to evaluate the methods used in publications and grants.Supported by a Marie Sklodowska-Curie (https://ec.europa.eu/programmes/horizon2020/ en/h2020-section/marie-sklodowska-curie-actions) grant to G.L.-U. (H2020-MSCA-IF-2017-795807- ReCiModel) and National Institutes of Health (https://www.nih.gov/) grants supporting N.C.B. and J.W. (EY027401, EY027964, MH111417). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Reproducible protocol to obtain and measure first-order relay human thalamic white-matter tracts

Available online 13 August 2022The “primary ”or “first-order relay ”nuclei of the thalamus feed the cerebral cortex with information about on- going activity in the environment or the subcortical motor systems. Because of the small size of these nuclei and the high specificity of their input and output pathways, new imaging protocols are required to investigate thala- mocortical interactions in human perception, cognition and language. The goal of the present study was twofold: I) to develop a reconstruction protocol based on in vivo diffusion MRI to extract and measure the axonal fiber tracts that originate or terminate specifically in individual first-order relay nuclei; and, II) to test the reliability of this reconstruction protocol. In left and right hemispheres, we investigated the thalamocortical/corticothalamic axon bundles linking each of the first-order relay nuclei and their main cortical target areas, namely, the lateral geniculate nucleus (optic radiation), the medial geniculate nucleus (acoustic radiation), the ventral posterior nu- cleus (somatosensory radiation) and the ventral lateral nucleus (motor radiation). In addition, we examined the main subcortical input pathway to the ventral lateral posterior nucleus, which originates in the dentate nucleus of the cerebellum. Our protocol comprised three components: defining regions-of-interest; preprocessing diffu- sion data; and modeling white-matter tracts and tractometry. We then used computation and test-retest methods to check whether our protocol could reliably reconstruct these tracts of interest and their profiles. Our results demonstrated that the protocol had nearly perfect computational reproducibility and good-to-excellent test-retest reproducibility. This new protocol may be of interest for both basic human brain neuroscience and clinical studies and has been made publicly available to the scientific community.This work was supported by grants from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (grant agreement No. 713673 ), and from “la Caixa ”Foundation (grant No. 11660016 ) to M.L.; grants from the Span- ish Ministerio de Ciencia e Innovación ( IJC2020-042887-I ; PID2021- 123577NA-I00 ) to G.L.-U.; grants from the European Union ’s Horizon 2020 Research and Innovation Program, European Commission (grant agreement No. 945539 - HBP SGA3 ) and from the Ministerio de Ciencia e Innovación FLAG-ERA grant NeuronsReunited ( MICINN-AEI PCI2019-111900-2 ) to F.C.; and grants from the Ministerio de Ciencia e Innovación ( PGC2018-093408-B-I00 ; PID2021-123574NB-I00 ), Neuro- science projects from the Fundación Tatiana Pérez de Guzmán el Bueno , Basque Government ( PIBA-2021-1-0003 ), and a grant from “la Caixa ”Banking Foundation under the project code LCF/PR/HR19/52160002 to P.M.P.-A. BCBL acknowledges support by the Basque Government through the BERC 2022-2025 program and by the S panish State Re- search Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010-S

Data-science ready, multisite, human diffusion MRI whitematter- tract statistics

Published 30 November 2020The white matter tracts in the living human brain are critical for healthy function, and the diffusion MRI measured in these tracts is correlated with diverse behavioral measures. The technical skills required to analyze diffusion MRI data are complex: data acquisition requires MRI sequence development and acquisition expertise, analyzing raw-data into meaningful summary statistics requires computational neuroimaging and neuroanatomy expertise. The human white matter study field will advance faster if the tract summaries are available in plain data-science-ready format for non-diffusion MRI experts, such as statisticians, computer graphic researchers or data scientists in general. Here, we share a curated and processed dataset from three different MRI centers in a format that is data-science ready. The multisite data we share include measures of within and between MRI center variation in white-matter-tract diffusion measurements. Along with the dataset description and summary statistics, we describe the state-of-the-art computational system that guarantees reproducibility and provenance from the original scanner output.This work was supported by a Marie Sklodowska-Curie (H2020-MSCA-IF-2017-795807-ReCiModel) grant to G.L.-U. We thank the Simons Foundation Autism Research Initiative and Weston Havens foundation for support

High-Resolution Tractography Protocol to Investigate the Pathways between Human Mediodorsal Thalamic Nucleus and Prefrontal Cortex

Published: November 15, 2023Animal studies have established that the mediodorsal nucleus (MD) of the thalamus is heavily and reciprocally connected with all areas of the prefrontal cortex (PFC). In humans, however, these connections are difficult to investigate. High-resolution imaging protocols capable of reliably tracing the axonal tracts linking the human MD with each of the PFC areas may thus be key to advance our understanding of the variation, development, and plastic changes of these important circuits, in health and disease. Here, we tested in adult female and male humans the reliability of a new reconstruction protocol based on in vivo diffusion MRI to trace, measure, and characterize the fiber tracts interconnecting the MD with 39 human PFC areas per hemisphere. Our protocol comprised the following three components: (1) defining regions of interest; (2) preprocessing diffusion data; and, (3) modeling white matter tracts and tractometry. This analysis revealed largely separate PFC territories of reciprocal MD–PFC tracts bearing striking resemblance with the topographic layout observed in macaque connection-tracing studies. We then examined whether our protocol could reliably reconstruct each of these MD–PFC tracts and their profiles across test and retest sessions. Results revealed that this protocol was able to trace and measure, in both left and right hemispheres, the trajectories of these 39 area-specific axon bundles with good-to-excellent test-retest reproducibility. This protocol, which has been made publicly available, may be relevant for cognitive neuroscience and clinical studies of normal and abnormal PFC function, development, and plasticity.L.M. was supported by Horizon 2020 the European Union’s research and innovation program under Marie Skłodowska-Curie Grant 713673 and from “la Caixa” Foundation (Grants 11660016 and 100010434 under Agreement HR18-00178-DYSTHAL). G.L-U. was supported by the Spanish Ministry of Science and Innovation (Grants IJC2020-042887-I and PID2021-123577NA-I00) and the Basque Government (Grant PIBA-2022-1- 0014). F.C. was supported by the Spanish Ministry of Science and Innovation (Grants MICINN-AEI PCI2019- 111900-2 and PID2020-115780GB-I00). P.M.P-A. was supported by the Spanish Ministry of Science and Innovation (Grant PID2021-123574NB-I00), the Basque Government (Grant PIBA-2021-1-0003), and the Red guipuzcoana de Ciencia, Tecnología e Innovación of the Diputación Foral de Gipuzkoa (Grant FA/OF 422/2022), and “la Caixa” Foundation (Grant 100010434 under Agreement HR18-00178-DYSTHAL). The Basque Center on Cognition, Brain and Language (BCBL) acknowledges funding from the Basque Government through the BERC 2022-2025 program and by the Spanish State Research Agency through BCBL Severo Ochoa Excellence Accreditation CEX2020-001010-S

Reproducible Tract Profiles 2 (RTP2) suite, from diffusion MRI acquisition to clinical practice and research

Published: 2023 Apr 12Diffusion MRI is a complex technique, where new discoveries and implementations occur at a fast pace. The expertise needed for data analyses and accurate and reproducible results is increasingly demanding and requires multidisciplinary collaborations. In the present work we introduce Reproducible Tract Profiles 2 (RTP2), a set of flexible and automated methods to analyze anatomical MRI and diffusion weighted imaging (DWI) data for reproducible tractography. RTP2 reads structural MRI data and processes them through a succession of serialized containerized analyses. We describe the DWI algorithms used to identify white-matter tracts and their summary metrics, the flexible architecture of the platform, and the tools to programmatically access and control the computations. The combination of these three components provides an easy-to-use automatized tool developed and tested over 20 years, to obtain usable and reliable state-of-the-art diffusion metrics at the individual and group levels for basic research and clinical practice.G. L-U. was supported by grants from the Spanish Ministry of Science and Innovation (IJC2020-042887-I and PID2021-123577NA-I00) and Basque Government (PIBA-2022-1-0014); M.L. was supported by grants from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (grant agreement No. 713673), and from “la Caixa” Foundation (grant No. 11660016); P.M.P.-A. was supported by grants from the Spanish Ministry of Science and Innovation (PID2021-123574NB-I00), from the Basque Government (PIBA-2021-1-0003), from the Red guipuzcoana de Ciencia, Tecnología e Innovación of the Diputación Foral de Gipuzkoa (FA/OF 422/2022), from “la Caixa” Foundation (ID 100010434) under the agreement HR18-00178-DYSTHAL. BCBL acknowledges support by the Basque Government through the BERC 2022–2025 program and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010-S