Characterizing Spatiotemporal Population Receptive Fields in Human Visual Cortex with fMRI.

The use of fMRI and computational modeling has advanced understanding of spatial characteristics of population receptive fields (pRFs) in human visual cortex. However, we know relatively little about the spatiotemporal characteristics of pRFs because neurons' temporal properties are one to two orders of magnitude faster than fMRI BOLD responses. Here, we developed an image-computable framework to estimate spatiotemporal pRFs from fMRI data. First, we developed a simulation software that predicts fMRI responses to a time-varying visual input given a spatiotemporal pRF model and solves the model parameters. The simulator revealed that ground-truth spatiotemporal parameters can be accurately recovered at the millisecond resolution from synthesized fMRI responses. Then, using fMRI and a novel stimulus paradigm, we mapped spatiotemporal pRFs in individual voxels across human visual cortex in 10 participants (both females and males). We find that a compressive spatiotemporal (CST) pRF model better explains fMRI responses than a conventional spatial pRF model across visual areas spanning the dorsal, lateral, and ventral streams. Further, we find three organizational principles of spatiotemporal pRFs: (1) from early to later areas within a visual stream, spatial and temporal windows of pRFs progressively increase in size and show greater compressive nonlinearities, (2) later visual areas show diverging spatial and temporal windows across streams, and (3) within early visual areas (V1-V3), both spatial and temporal windows systematically increase with eccentricity. Together, this computational framework and empirical results open exciting new possibilities for modeling and measuring fine-grained spatiotemporal dynamics of neural responses using fMRI.

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

Animal 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.SIGNIFICANCE STATEMENT Reciprocal MD-PFC interactions are critical for complex human cognition and learning. Reliably tracing, measuring and characterizing MD-PFC white matter tracts using high-resolution noninvasive methods is key to assess individual variation of these systems in humans. Here, we propose a high-resolution tractography protocol that reliably reconstructs 39 area-specific MD-PFC white matter tracts per hemisphere and quantifies structural information from diffusion MRI data. This protocol revealed a detailed mapping of thalamocortical and corticothalamic MD-PFC tracts in four different PFC territories (dorsal, medial, orbital/frontal pole, inferior frontal) showing structural connections resembling those observed in tracing studies with macaques. Furthermore, our automated protocol revealed high test-retest reproducibility and is made publicly available, constituting a step forward in mapping human MD-PFC circuits in clinical and academic research.

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

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 (https://freesurfer.net/fswiki/ThalamicNucleiDTI).

Population Receptive Field Shapes in Early Visual Cortex Are Nearly Circular.

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.SIGNIFICANCE STATEMENT We evaluated whether the shape of many population receptive fields (RFs) in early visual cortex is elliptical and differs substantially from circular. We evaluated two tools for estimating elliptical models of the pRF; one tool was valid over the measured compliance range. Using the validated tool, we found no evidence that confidently rejects circular fits to the pRF in visual field maps V1, V2, and V3. The new measurements and analyses are consistent with prior theoretical and experimental assessments in the literature.

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

The "primary" or "first-order relay" nuclei of the thalamus feed the cerebral cortex with information about ongoing 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 thalamocortical 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 nucleus (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 diffusion 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.

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

Neuroimaging 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.

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

The 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.

The human connectome project for disordered emotional states: Protocol and rationale for a research domain criteria study of brain connectivity in young adult anxiety and depression.

Through the Human Connectome Project (HCP) our understanding of the functional connectome of the healthy brain has been dramatically accelerated. Given the pressing public health need, we must increase our understanding of how connectome dysfunctions give rise to disordered mental states. Mental disorders arising from high levels of negative emotion or from the loss of positive emotional experience affect over 400 million people globally. Such states of disordered emotion cut across multiple diagnostic categories of mood and anxiety disorders and are compounded by accompanying disruptions in cognitive function. Not surprisingly, these forms of psychopathology are the leading cause of disability worldwide. The Research Domain Criteria (RDoC) initiative spearheaded by NIMH offers a framework for characterizing the relations among connectome dysfunctions, anchored in neural circuits and phenotypic profiles of behavior and self-reported symptoms. Here, we report on our Connectomes Related to Human Disease protocol for integrating an RDoC framework with HCP protocols to characterize connectome dysfunctions in disordered emotional states, and present quality control data from a representative sample of participants. We focus on three RDoC domains and constructs most relevant to depression and anxiety: 1) loss and acute threat within the Negative Valence System (NVS) domain; 2) reward valuation and responsiveness within the Positive Valence System (PVS) domain; and 3) working memory and cognitive control within the Cognitive System (CS) domain. For 29 healthy controls, we present preliminary imaging data: functional magnetic resonance imaging collected in the resting state and in tasks matching our constructs of interest ("Emotion", "Gambling" and "Continuous Performance" tasks), as well as diffusion-weighted imaging. All functional scans demonstrated good signal-to-noise ratio. Established neural networks were robustly identified in the resting state condition by independent component analysis. Processing of negative emotional faces significantly activated the bilateral dorsolateral prefrontal and occipital cortices, fusiform gyrus and amygdalae. Reward elicited a response in the bilateral dorsolateral prefrontal, parietal and occipital cortices, and in the striatum. Working memory was associated with activation in the dorsolateral prefrontal, parietal, motor, temporal and insular cortices, in the striatum and cerebellum. Diffusion tractography showed consistent profiles of fractional anisotropy along known white matter tracts. We also show that results are comparable to those in a matched sample from the HCP Healthy Young Adult data release. These preliminary data provide the foundation for acquisition of 250 subjects who are experiencing disordered emotional states. When complete, these data will be used to develop a neurobiological model that maps connectome dysfunctions to specific behaviors and symptoms.

Replication and generalization in applied neuroimaging.

There is much interest in translating neuroimaging findings into meaningful clinical diagnostics. The goal of scientific discoveries differs from clinical diagnostics. Scientific discoveries must replicate under a specific set of conditions; to translate to the clinic we must show that findings using purpose-built scientific instruments will be observable in clinical populations and instruments. Here we describe and evaluate data and computational methods designed to translate a scientific observation to a clinical setting. Using diffusion weighted imaging (DWI), Wahl et al. (2010) observed that across subjects the mean fractional anisotropy (FA) of homologous pairs of tracts is highly correlated. We hypothesize that this is a fundamental biological trait that should be present in most healthy participants, and deviations from this assessment may be a useful diagnostic metric. Using this metric as an illustration of our methods, we analyzed six pairs of homologous white matter tracts in nine different DWI datasets with 44 subjects each. Considering the original FA measurement as a baseline, we show that the new metric is between 2 and 4 times more precise when used in a clinical context. Our framework to translate research findings into clinical practice can be applied, in principle, to other neuroimaging results.

A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology.

The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimaging community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test-retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer.

Automated segmentation of the human hippocampus along its longitudinal axis.

The human hippocampal formation is a crucial brain structure for memory and cognitive function that is closely related to other subcortical and cortical brain regions. Recent neuroimaging studies have revealed differences along the hippocampal longitudinal axis in terms of structure, connectivity, and function, stressing the importance of improving the reliability of the available segmentation methods that are typically used to divide the hippocampus into its anterior and posterior parts. However, current segmentation conventions present two main sources of variability related to manual operations intended to correct in-scanner head position across subjects and the selection of dividing planes along the longitudinal axis. Here, our aim was twofold: (1) to characterize inter- and intra-rater variability associated with these manual operations and compare manual (landmark based) and automatic (percentage based) hippocampal anterior-posterior segmentation procedures; and (2) to propose and test automated rotation methods based on approximating the hippocampal longitudinal axis to a straight line (estimated with principal component analysis, PCA) or a quadratic Bézier curve (fitted with numerical methods); as well as an automated anterior-posterior hippocampal segmentation procedure based on the percentage-based method. Our results reveal that automated rotation and segmentation procedures, used in combination or independently, minimize inconsistencies generated by the accumulation of manual operations while providing higher statistical power to detect well-known effects. A Matlab-based implementation of these procedures is made publicly available to the research community. Hum Brain Mapp 37:3353-3367, 2016. © 2016 Wiley Periodicals, Inc.

Developmental evaluation of atypical auditory sampling in dyslexia: Functional and structural evidence.

Whether phonological deficits in developmental dyslexia are associated with impaired neural sampling of auditory information at either syllabic- or phonemic-rates is still under debate. In addition, whereas neuroanatomical alterations in auditory regions have been documented in dyslexic readers, whether and how these structural anomalies are linked to auditory sampling and reading deficits remains poorly understood. In this study, we measured auditory neural synchronization at different frequencies corresponding to relevant phonological spectral components of speech in children and adults with and without dyslexia, using magnetoencephalography. Furthermore, structural MRI was used to estimate cortical thickness of the auditory cortex of participants. Dyslexics showed atypical brain synchronization at both syllabic (slow) and phonemic (fast) rates. Interestingly, while a left hemispheric asymmetry in cortical thickness was functionally related to a stronger left hemispheric lateralization of neural synchronization to stimuli presented at the phonemic rate in skilled readers, the same anatomical index in dyslexics was related to a stronger right hemispheric dominance for neural synchronization to syllabic-rate auditory stimuli. These data suggest that the acoustic sampling deficit in development dyslexia might be linked to an atypical specialization of the auditory cortex to both low and high frequency amplitude modulations.

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

Diffusion 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.

Characterizing spatiotemporal population receptive fields in human visual cortex with fMRI.

The use of fMRI and computational modeling has advanced understanding of spatial characteristics of population receptive fields (pRFs) in human visual cortex. However, we know relatively little about the spatiotemporal characteristics of pRFs because neurons' temporal properties are one to two orders of magnitude faster than fMRI BOLD responses. Here, we developed an image-computable framework to estimate spatiotemporal pRFs from fMRI data. First, we developed a simulation software that predicts fMRI responses to a time varying visual input given a spatiotemporal pRF model and solves the model parameters. The simulator revealed that ground-truth spatiotemporal parameters can be accurately recovered at the millisecond resolution from synthesized fMRI responses. Then, using fMRI and a novel stimulus paradigm, we mapped spatiotemporal pRFs in individual voxels across human visual cortex in 10 participants. We find that a compressive spatiotemporal (CST) pRF model better explains fMRI responses than a conventional spatial pRF model across visual areas spanning the dorsal, lateral, and ventral streams. Further, we find three organizational principles of spatiotemporal pRFs: (i) from early to later areas within a visual stream, spatial and temporal integration windows of pRFs progressively increase in size and show greater compressive nonlinearities, (ii) later visual areas show diverging spatial and temporal integration windows across streams, and (iii) within early visual areas (V1-V3), both spatial and temporal integration windows systematically increase with eccentricity. Together, this computational framework and empirical results open exciting new possibilities for modeling and measuring fine-grained spatiotemporal dynamics of neural responses in the human brain using fMRI.

Intrasession and Intersession Reproducibility of Artificial Scotoma pRF Mapping Results at Ultra-High Fields.

Functional magnetic resonance imaging (fMRI) combined with population receptive field (pRF) mapping allows for associating positions on the visual cortex to areas on the visual field. Apart from applications in healthy subjects, this method can also be used to examine dysfunctions in patients suffering from partial visual field losses. While such objective measurement of visual deficits (scotoma) is of great importance for, e.g., longitudinal studies addressing treatment effects, it requires a thorough assessment of accuracy and reproducibility of the results obtained. In this study, we quantified the reproducibility of pRF mapping results within and across sessions in case of central visual field loss in a group of 15 human subjects. We simulated scotoma by masking a central area of 2° radius from stimulation to establish ground-truth conditions. This study was performed on a 7T ultra-high field MRI scanner for increased sensitivity. We found excellent intrasession and intersession reproducibility for the pRF center position (Spearman correlation coefficients for x, y: >0.95; eccentricity: >0.87; polar angle: >0.98), but only modest reproducibility for pRF size (Spearman correlation coefficients around 0.4). We further examined the scotoma detection performance using an automated method based on a reference dataset acquired with full-field stimulation. For the 2° artificial scotoma, the group-averaged scotoma sizes were estimated at between 1.92° and 2.19° for different sessions. We conclude that pRF mapping of visual field losses yields robust, reproducible measures of retinal function and suggest the use of pRF mapping as an objective method for monitoring visual deficits during therapeutic interventions or disease progression.

Data-science ready, multisite, human diffusion MRI white-matter-tract statistics.

The 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.

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

Math 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.

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.

Brain morphometry of Dravet syndrome.

The aim of this study was to identify differential global and local brain structural patterns in Dravet Syndrome (DS) patients as compared with a control subject group, using brain morphometry techniques which provide a quantitative whole-brain structural analysis that allows for specific patterns to be generalized across series of individuals. Nine patients with the diagnosis of DS that tested positive for mutation in the SCN1A gene and nine well-matched healthy controls were investigated using voxel brain morphometry (VBM), cortical thickness and cortical gyrification measurements. Global volume reductions of gray matter (GM) and white matter (WM) were related to DS. Local volume reductions corresponding to several white matter regions in brainstem, cerebellum, corpus callosum, corticospinal tracts and association fibers (left inferior fronto-occipital fasciculus and left uncinate fasciculus) were also found. Furthermore, DS showed a reduced cortical folding in the right precentral gyrus. The present findings describe DS-related brain structure abnormalities probably linked to the expression of the SCN1A mutation.