Neural correlates of phonological, orthographic and semantic reading processing in dyslexia

Developmental dyslexia is one of the most prevalent learning disabilities, thought to be associated with dysfunction in the neural systems underlying typical reading acquisition. Neuroimaging research has shown that readers with dyslexia exhibit regional hypoactivation in left hemisphere reading nodes, relative to control counterparts. This evidence, however, comes from studies that have focused only on isolated aspects of reading. The present study aims to characterize left hemisphere regional hypoactivation in readers with dyslexia for the main processes involved in successful reading: phonological, orthographic and semantic. Forty-one participants performed a demanding reading task during MRI scanning. Results showed that readers with dyslexia exhibited hypoactivation associated with phonological processing in parietal regions; with orthographic processing in parietal regions, Broca's area, ventral occipitotemporal cortex and thalamus; and with semantic processing in angular gyrus and hippocampus. Stronger functional connectivity was observed for readers with dyslexia than for control readers 1) between the thalamus and the inferior parietal cortex/ventral occipitotemporal cortex during pseudoword reading; and, 2) between the hippocampus and the pars opercularis during word reading. These findings constitute the strongest evidence to date for the interplay between regional hypoactivation and functional connectivity in the main processes supporting reading in dyslexia. Keywords: Dyslexia, Reading, Hypoactivation, Functional connectivity, Thalamus, Hippocampu

Neural correlates of phonological, orthographic and semantic reading processing in dyslexia

Available online 10 August 2018Developmental dyslexia is one of the most prevalent learning disabilities, thought to be associated with dysfunction in the neural systems underlying typical reading acquisition. Neuroimaging research has shown that readers with dyslexia exhibit regional hypoactivation in left hemisphere reading nodes, relative to control counterparts. This evidence, however, comes from studies that have focused only on isolated aspects of reading. The present study aims to characterize left hemisphere regional hypoactivation in readers with dyslexia for the main processes involved in successful reading: phonological, orthographic and semantic. Forty-one participants performed a demanding reading task during MRI scanning. Results showed that readers with dyslexia exhibited hypoactivation associated with phonological processing in parietal regions; with orthographic processing in parietal regions, Broca's area, ventral occipitotemporal cortex and thalamus; and with semantic processing in angular gyrus and hippocampus. Stronger functional connectivity was observed for readers with dyslexia than for control readers 1) between the thalamus and the inferior parietal cortex/ventral occipitotemporal cortex during pseudoword reading; and, 2) between the hippocampus and the pars opercularis during word reading. These findings constitute the strongest evidence to date for the interplay between regional hypoactivation and functional connectivity in the main processes supporting reading in dyslexia.Supported by grants (RYC-2014-15440, PSI2015-65696) from the Spanish Ministry of Economy and Competitiveness (MINECO), a grant (PI2016-12) from the Basque Government and a grant (Exp. 65/15) from the Programa Red guipuzcoana de Ciencia, Tecnología e Innovación from the Diputación Foral de Gipuzkoa (P.M.P-A.); a predoctoral grant from the Department of Education, Universities and Research from the Basque Government (M.O.); grant (PSI2015-64174P) from the MINECO (F.C.); grants (PSI2015-67353-R) from the MINECO and (ERC-2011-ADG-295362) from the European Research Council (M.C.). BCBL acknowledges funding from Ayuda Centro de Excelencia Severo OchoaSEV-2015-0490 from the MINECO

Accurate Bayesian segmentation of thalamic nuclei using diffusion MRI and an improved histological atlas

Data availability: Data will be made available on request.Supplementary materials are available online at: https://www.sciencedirect.com/science/article/pii/S1053811923002744?via%3Dihub#sec0024 .Research data are available online at: https://www.sciencedirect.com/science/article/pii/S1053811923002744?via%3Dihub#ec-research-data .Copyright © 2023 The Author(s). The human thalamus is a highly connected brain structure, which is key for the control of numerous functions and is involved in several neurological disorders. Recently, neuroimaging studies have increasingly focused on the volume and connectivity of the specific nuclei comprising this structure, rather than looking at the thalamus as a whole. However, accurate identification of cytoarchitectonically designed histological nuclei on standard in vivo structural MRI is hampered by the lack of image contrast that can be used to distinguish nuclei from each other and from surrounding white matter tracts. While diffusion MRI may offer such contrast, it has lower resolution and lacks some boundaries visible in structural imaging. In this work, we present a Bayesian segmentation algorithm for the thalamus. This algorithm combines prior information from a probabilistic atlas with likelihood models for both structural and diffusion MRI, allowing segmentation of 25 thalamic labels per hemisphere informed by both modalities. We present an improved probabilistic atlas, incorporating thalamic nuclei identified from histology and 45 white matter tracts surrounding the thalamus identified in ultra-high gradient strength diffusion imaging. We present a family of likelihood models for diffusion tensor imaging, ensuring compatibility with the vast majority of neuroimaging datasets that include diffusion MRI data. The use of these diffusion likelihood models greatly improves identification of nuclear groups versus segmentation based solely on structural MRI. Dice comparison of 5 manually identifiable groups of nuclei to ground truth segmentations show improvements of up to 10 percentage points. Additionally, our chosen model shows a high degree of reliability, with median test-retest Dice scores above 0.85 for four out of five nuclei groups, whilst also offering improved detection of differential thalamic involvement in Alzheimer’s disease (AUROC 81.98%). The probabilistic atlas and segmentation tool will be made publicly available as part of the neuroimaging package FreeSurfer.This work was primarily funded by Alzheimers Research UK (ARUK-IRG2019A003). PGs work in this area was supported by NIH NIBIB NAC P41EB015902 AYs work in this area was supported by NIH grants R01 EB021265 and R56 MH121426. DCAs work in this area was supported by EPSRC grant EP/R006032/1 and Wellcome Trust award 221915/Z/20/Z. The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research Unit and the University College London Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. This project has received funding from the European Unions Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 765148, as well as from the National Institutes Of Health under project number R01NS112161. MB is supported by a Fellowship award from the Alzheimers Society, UK (AS-JF-19a-004-517). MBs work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimers Society and Alzheimers Research UK. JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). JEI is supported by the European Research Council (Starting Grant 677697, project BUNGEE-TOOLS) and the NIH (1RF1MH123195-01 and 1R01AG070988-01). The collection and sharing of the ADNI data was funded by the Alzheimer’s Disease Neuroimaging Initiative (National Institutes of Health Grant U01 AG024904) and Department of Defence (W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds for ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health. The grantee is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI is disseminated by the Laboratory for Neuro Imaging at the University of Southern California

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process

Tractography dissection variability

Funding Information: This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. KS, BL, CH were supported by the National Institutes of Health under award numbers R01EB017230, and T32EB001628, and in part by ViSE/VICTR VR3029 and the National Center for Research Resources, Grant UL1 RR024975-01. This work was also possible thanks to the support of the Institutional Research Chair in NeuroInformatics of Université de Sherbrooke, NSERC and Compute Canada (MD, FR). MP received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754462. The Wisconsin group acknowledges the support from a core grant to the Waisman Center from the National Institute of Child Health and Human Development (IDDRC U54 HD090256). NSF OAC-1916518, NSF IIS-1912270, NSF IIS-1636893, NSF BCS-1734853, NIH NIBIB 1R01EB029272-01, and a Microsoft Faculty Fellowship to F.P. LF acknowledges the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2025. SW is supported by a Medical Research Council PhD Studentship UK [MR/N013913/1]. The Nottingham group's processing was performed using the University of Nottingham's Augusta HPC service and the Precision Imaging Beacon Cluster. JPA, MA and SMS acknowledges the support of FCT - Fundação para a Ciência e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013). MM was funded by the Wellcome Trust through a Sir Henry Wellcome Postdoctoral Fellowship [213722/Z/18/Z]. EJC-R is supported by the Swiss National Science Foundation (SNSF, Ambizione grant PZ00P2 185814/1). CMWT is supported by a Sir Henry Wellcome Fellowship (215944/Z/19/Z) and a Veni grant from the Dutch Research Council (NWO) (17331). FC acknowledges the support of the National Health and Medical Research Council ofAustralia (APP1091593 and APP1117724) and the Australian Research Council (DP170101815). NSF OAC-1916518, NSF IIS-1912270, NSF IIS-1636893, NSF BCS-1734853, Microsoft Faculty Fellowship to F.P. D.B. was partially supported by NIH NIMH T32-MH103213 to William Hetrick (Indiana University). CL is partly supported by NIH grants P41 EB027061 and P30 NS076408 “Institutional Center Cores for Advanced Neuroimaging. JYMY received positional funding from the Royal Children's Hospital Foundation (RCH 1000). JYMY, JC, and CEK acknowledge the support of the Royal Children's Hospital Foundation, Murdoch Children's Research Institute, The University of Melbourne Department of Paediatrics, and the Victorian Government's Operational Infrastructure Support Program. C-HY is grateful to the Ministry of Science and Technology of Taiwan (MOST 109-2222-E-182-001-MY3) for the support. LC acknowledges support from CONACYT and UNAM. ARM acknowledges support from CONACYT. LJO, YR, and FZ were supported by NIH P41EB015902 and R01MH119222. AJG was supported by P41EB015898. NM was supported by R01MH119222, K24MH116366, and R01MH111917. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 785907 & 945539 (HBP SGA2 & SGA3), and from the ANR IFOPASUBA- 19-CE45-0022-01. PG, CR, NL and AV were partially supported by ANID-Basal FB0008 and ANID-FONDECYT 1190701 grants. We would like to acknowledge John C Gore, Hiromasa Takemura, Anastasia Yendiki, and Riccardo Galbusera for their helplful suggestions regarding the analysis, figures, and discussions. Funding Information: This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. KS, BL, CH were supported by the National Institutes of Health under award numbers R01EB017230, and T32EB001628, and in part by ViSE/VICTR VR3029 and the National Center for Research Resources, Grant UL1 RR024975-01. This work was also possible thanks to the support of the Institutional Research Chair in NeuroInformatics of Universit? de Sherbrooke, NSERC and Compute Canada (MD, FR). MP received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No 754462. The Wisconsin group acknowledges the support from a core grant to the Waisman Center from the National Institute of Child Health and Human Development (IDDRC U54 HD090256). NSF OAC-1916518, NSF IIS-1912270, NSF IIS-1636893, NSF BCS-1734853, NIH NIBIB 1R01EB029272-01, and a Microsoft Faculty Fellowship to F.P. LF acknowledges the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany?s Excellence Strategy ? EXC 2025. SW is supported by a Medical Research Council PhD Studentship UK [MR/N013913/1]. The Nottingham group's processing was performed using the University of Nottingham's Augusta HPC service and the Precision Imaging Beacon Cluster. JPA, MA and SMS acknowledges the support of FCT - Funda??o para a Ci?ncia e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013). MM was funded by the Wellcome Trust through a Sir Henry Wellcome Postdoctoral Fellowship [213722/Z/18/Z]. EJC-R is supported by the Swiss National Science Foundation (SNSF, Ambizione grant PZ00P2 185814/1). CMWT is supported by a Sir Henry Wellcome Fellowship (215944/Z/19/Z) and a Veni grant from the Dutch Research Council (NWO) (17331). FC acknowledges the support of the National Health and Medical Research Council of Australia (APP1091593 and APP1117724) and the Australian Research Council (DP170101815). NSF OAC-1916518, NSF IIS-1912270, NSF IIS-1636893, NSF BCS-1734853, Microsoft Faculty Fellowship to F.P. D.B. was partially supported by NIH NIMH T32-MH103213 to William Hetrick (Indiana University). CL is partly supported by NIH grants P41 EB027061 and P30 NS076408 ?Institutional Center Cores for Advanced Neuroimaging. JYMY received positional funding from the Royal Children's Hospital Foundation (RCH 1000). JYMY, JC, and CEK acknowledge the support of the Royal Children's Hospital Foundation, Murdoch Children's Research Institute, The University of Melbourne Department of Paediatrics, and the Victorian Government's Operational Infrastructure Support Program. C-HY is grateful to the Ministry of Science and Technology of Taiwan (MOST 109-2222-E-182-001-MY3) for the support. LC acknowledges support from CONACYT and UNAM. ARM acknowledges support from CONACYT. LJO, YR, and FZ were supported by NIH P41EB015902 and R01MH119222. AJG was supported by P41EB015898. NM was supported by R01MH119222, K24MH116366, and R01MH111917. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 785907 & 945539 (HBP SGA2 & SGA3), and from the ANR IFOPASUBA- 19-CE45-0022-01. PG, CR, NL and AV were partially supported by ANID-Basal FB0008 and ANID-FONDECYT 1190701 grants. We would like to acknowledge John C Gore, Hiromasa Takemura, Anastasia Yendiki, and Riccardo Galbusera for their helplful suggestions regarding the analysis, figures, and discussions. Publisher Copyright: © 2021White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols foreach fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.Peer reviewe