brainlife.io: a decentralized and open-source cloud platform to support neuroscience research.

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

ezBIDS: Guided standardization of neuroimaging data interoperable with major data archives and platforms.

Data standardization promotes a common framework through which researchers can utilize others' data and is one of the leading methods neuroimaging researchers use to share and replicate findings. As of today, standardizing datasets requires technical expertise such as coding and knowledge of file formats. We present ezBIDS, a tool for converting neuroimaging data and associated metadata to the Brain Imaging Data Structure (BIDS) standard. ezBIDS contains four major features: (1) No installation or programming requirements. (2) Handling of both imaging and task events data and metadata. (3) Semi-automated inference and guidance for adherence to BIDS. (4) Multiple data management options: download BIDS data to local system, or transfer to OpenNeuro.org or to brainlife.io. In sum, ezBIDS requires neither coding proficiency nor knowledge of BIDS, and is the first BIDS tool to offer guided standardization, support for task events conversion, and interoperability with OpenNeuro.org and brainlife.io.

Development of human hippocampal subfield microstructure and relation to associative inference.

The hippocampus is a complex brain structure composed of subfields that each have distinct cellular organizations. While the volume of hippocampal subfields displays age-related changes that have been associated with inference and memory functions, the degree to which the cellular organization within each subfield is related to these functions throughout development is not well understood. We employed an explicit model testing approach to characterize the development of tissue microstructure and its relationship to performance on 2 inference tasks, one that required memory (memory-based inference) and one that required only perceptually available information (perception-based inference). We found that each subfield had a unique relationship with age in terms of its cellular organization. While the subiculum (SUB) displayed a linear relationship with age, the dentate gyrus (DG), cornu ammonis field 1 (CA1), and cornu ammonis subfields 2 and 3 (combined; CA2/3) displayed nonlinear trajectories that interacted with sex in CA2/3. We found that the DG was related to memory-based inference performance and that the SUB was related to perception-based inference; neither relationship interacted with age. Results are consistent with the idea that cellular organization within hippocampal subfields might undergo distinct developmental trajectories that support inference and memory performance throughout development.

brainlife.io: A decentralized and open source cloud platform to support neuroscience research.

Neuroscience research has expanded dramatically over the past 30 years by advancing standardization and tool development to support rigor and transparency. Consequently, the complexity of the data pipeline has also increased, hindering access to FAIR data analysis to portions of the worldwide research community. brainlife.io was developed to reduce these burdens and democratize modern neuroscience research across institutions and career levels. Using community software and hardware infrastructure, the platform provides open-source data standardization, management, visualization, and processing and simplifies the data pipeline. brainlife.io automatically tracks the provenance history of thousands of data objects, supporting simplicity, efficiency, and transparency in neuroscience research. Here brainlife.io's technology and data services are described and evaluated for validity, reliability, reproducibility, replicability, and scientific utility. Using data from 4 modalities and 3,200 participants, we demonstrate that brainlife.io's services produce outputs that adhere to best practices in modern neuroscience research.

Denoising diffusion weighted imaging data using convolutional neural networks.

Diffusion weighted imaging (DWI) with multiple, high b-values is critical for extracting tissue microstructure measurements; however, high b-value DWI images contain high noise levels that can overwhelm the signal of interest and bias microstructural measurements. Here, we propose a simple denoising method that can be applied to any dataset, provided a low-noise, single-subject dataset is acquired using the same DWI sequence. The denoising method uses a one-dimensional convolutional neural network (1D-CNN) and deep learning to learn from a low-noise dataset, voxel-by-voxel. The trained model can then be applied to high-noise datasets from other subjects. We validated the 1D-CNN denoising method by first demonstrating that 1D-CNN denoising resulted in DWI images that were more similar to the noise-free ground truth than comparable denoising methods, e.g., MP-PCA, using simulated DWI data. Using the same DWI acquisition but reconstructed with two common reconstruction methods, i.e. SENSE1 and sum-of-square, to generate a pair of low-noise and high-noise datasets, we then demonstrated that 1D-CNN denoising of high-noise DWI data collected from human subjects showed promising results in three domains: DWI images, diffusion metrics, and tractography. In particular, the denoised images were very similar to a low-noise reference image of that subject, more than the similarity between repeated low-noise images (i.e. computational reproducibility). Finally, we demonstrated the use of the 1D-CNN method in two practical examples to reduce noise from parallel imaging and simultaneous multi-slice acquisition. We conclude that the 1D-CNN denoising method is a simple, effective denoising method for DWI images that overcomes some of the limitations of current state-of-the-art denoising methods, such as the need for a large number of training subjects and the need to account for the rectified noise floor.

Protracted Neural Development of Dorsal Motor Systems During Handwriting and the Relation to Early Literacy Skills.

Handwriting is a complex visual-motor skill that affects early reading development. A large body of work has demonstrated that handwriting is supported by a widespread neural system comprising ventral-temporal, parietal, and frontal motor regions in adults. Recent work has demonstrated that this neural system is largely established by 8 years of age, suggesting that the development of this system occurs in young children who are still learning to read and write. We made use of a novel MRI-compatible writing tablet that allowed us to measure brain activation in 5-8-year-old children during handwriting. We compared activation during handwriting in children and adults to provide information concerning the developmental trajectory of the neural system that supports handwriting. We found that parietal and frontal motor involvement during handwriting in children is different from adults, suggesting that the neural system that supports handwriting changes over the course of development. Furthermore, we found that parietal and frontal motor activation correlated with a literacy composite score in our child sample, suggesting that the individual differences in the dorsal response during handwriting are related to individual differences in emerging literacy skills. Our results suggest that components of the widespread neural system supporting handwriting develop at different rates and provide insight into the mechanisms underlying the contributions of handwriting to early literacy development.

Ecological validity of experimental set-up affects parietal involvement during letter production.

Studies of symbol production using fMRI often use techniques that introduce an artificial pairing between motor production and visual perception. These techniques allow participants to see their own output by recording their pen trajectories using a touchscreen-only tablet and displaying these productions on a mirror placed above their head. We recently developed an MR-safe writing tablet with video display that allows participants to see their own hand and their own productions while producing symbols in real time on the surface where they are producing them-allowing for more ecologically valid fMRI studies of production. We conducted a study to determine whether the participation of posterior parietal cortex during symbol production was affected by the pairing of motor production and visual feedback associated with the two types of tablets. We performed ROI analyses in intraparietal sulcus while adult participants produced letters to dictation using either a touchscreen-only tablet (no visual guidance of the hand) (n = 14) or using a touchscreen-and-video-display tablet (visual guidance of the hand) (n = 14). We found that left posterior intraparietal sulcus was more active during production with the touchscreen-only tablet than during production with the touchscreen-and-video-display tablet. These results suggest that posterior parietal involvement during production tasks is associated with the somewhat artificial visual-motor pairing that is introduced by the techniques used in some studies of symbol production.

Constraining Stroke Order During Manual Symbol Learning Hinders Subsequent Recognition in Children Under 4 1/2 Years.

In the age of technology, writing by hand has become less common than texting and keyboarding. Learning letters by hand, however, has been shown to have profound developmental importance. One aspect of writing by hand that has been understudied is the effect of learning symbols stroke-by-stroke, a dynamic action that does not occur with keyboarding. We trained children to draw novel symbols in either an instructed stroke order or in a self-directed stroke order and tested: (1) whether learning novel symbols in a self-directed stroke order benefits subsequent recognition more than learning in a specified stroke order, (2) whether seeing novel symbols unfold in the stroke order that was taught would aid in recognition, and (3) whether any effects are age-dependent. Our results demonstrate that producing a symbol with a self-directed stroke order provides more benefit to symbol recognition than instructed stroke orders in 4.0-4.5-year-old children but not in 4.5-5.0-year-old children. We found, further, that the observed recognition benefits were not affected by seeing the symbol unfold in the same stroke order it was learned during testing, suggesting that the learning was not reliant upon the exact stroke order experienced during learning. These results stress the importance of allowing children to produce symbols in a self-directed manner and, by extension, that constraining how a child learns to write can adversely affect subsequent recognition.

Visual experiences during letter production contribute to the development of the neural systems supporting letter perception.

Letter production through handwriting creates visual experiences that may be important for the development of visual letter perception. We sought to better understand the neural responses to different visual percepts created during handwriting at different levels of experience. Three groups of participants, younger children, older children, and adults, ranging in age from 4.5 to 22 years old, were presented with dynamic and static presentations of their own handwritten letters, static presentations of an age-matched control's handwritten letters, and typeface letters during fMRI. First, data from each group were analyzed through a series of contrasts designed to highlight neural systems that were most sensitive to each visual experience in each age group. We found that younger children recruited ventral-temporal cortex during perception and this response was associated with the variability present in handwritten forms. Older children and adults also recruited ventral-temporal cortex; this response, however, was significant for typed letter forms but not variability. The adult response to typed letters was more distributed than in the children, including ventral-temporal, parietal, and frontal motor cortices. The adult response was also significant for one's own handwritten letters in left parietal cortex. Second, we compared responses among age groups. Compared to older children, younger children demonstrated a greater fusiform response associated with handwritten form variability. When compared to adults, younger children demonstrated a greater response to this variability in left parietal cortex. Our results suggest that the visual perception of the variability present in handwritten forms that occurs during handwriting may contribute to developmental changes in the neural systems that support letter perception.

An Analysis of the Brain Systems Involved with Producing Letters by Hand.

Complex visual-motor behaviors dominate human-environment interactions. Letter production, writing individual letters by hand, is an example of a complex visual-motor behavior composed of numerous behavioral components, including the required motor movements and the percepts that those motor movements create. By manipulating and isolating components of letter production, we provide experimental evidence that this complex visual-motor behavior is supported by a widespread neural system that is composed of smaller subsystems related to different sensorimotor components. Adult participants hand-printed letters with and without "ink" on an MR-safe digital writing tablet, perceived static and dynamic representations of their own handwritten letters, and perceived typeface letters during fMRI scanning. Our results can be summarized by three main findings: (1) Frontoparietal systems were associated with the motor component of letter production, whereas temporo-parietal systems were more associated with the visual component. (2) The more anterior regions of the left intraparietal sulcus were more associated with the motor component, whereas the more posterior regions were more associated with the visual component, with an area of visual-motor overlap in the posterior intraparietal sulcus. (3) The left posterior intraparietal sulcus and right fusiform gyrus responded similarly to both visual and motor components, and both regions also responded more during the perception of one's own handwritten letters compared with perceiving typed letters. These findings suggest that the neural systems recruited during complex visual-motor behaviors are composed of a set of interrelated sensorimotor subsystems that support the full behavior in different ways and, furthermore, that some of these subsystems can be rerecruited during passive perception in the absence of the full visual-motor behavior.

The MRItab: A MR-compatible touchscreen with video-display.

BACKGROUND: A touchscreen interface permits rich user interactions for research in many fields, but is rarely found within a Magnetic Resonance Imaging (MRI) environment due to difficulties adapting conventional technologies to the strong electromagnetic fields. Conventional MR-compatible video display technology uses either large-screen displays that are placed outside of the bore of the MRI itself, or projectors located beyond the participant's reach, making touch interfaces impossible. NEW METHOD: Here, we describe the MR-compatibility of the 'MRItab' in terms of MR safety and image quality. The MRItab adapts inexpensive off-the-shelf components with special signal-driver circuitry and shielding to bring the touchscreen interface into the MR environment, without adversely affecting MRI image quality, thereby making touch interfaces possible. RESULTS: Our testing demonstrated that the functioning of the MRItab was not affected by the functioning of the MRI scanner and that the MRItab did not adversely affect the image data acquired. Participants were able to interact naturally with the MRItab during MRI scanning. COMPARISON WITH OTHER METHOD (S): The MRItab is the first MR-compatible touchscreen device with video-display screen capabilities designed for use in the MRI environment. This interactive digital device is the first to allow participants to see their hands directly as they interact with a touch-sensitive display screen, resulting in high ecological validity. CONCLUSIONS: The MRItab provides a methodological advantage for research in many fields, given the realistic human-computer interaction it supports.

Neural substrates of sensorimotor processes: letter writing and letter perception.

Writing and perceiving letters are thought to share similar neural substrates; however, what constitutes a neural representation for letters is currently debated. One hypothesis is that letter representation develops from sensorimotor experience resulting in an integrated set of modality-specific regions, whereas an alternative account suggests that letter representations may be abstract, independent of modality. Studies reviewed suggest that letter representation consists of a network of modality-responsive brain regions that may include an abstract component.

Relation over time between facial measurements and cognitive outcomes in fetal alcohol-exposed children.

BACKGROUND: The identification of individuals exposed prenatally to alcohol can be challenging, with only those having the characteristic pattern of facial features, central nervous system abnormality, and growth retardation receiving a clinical diagnosis of fetal alcohol syndrome (FAS). METHODS: Seventeen anthropometric measurements were obtained at 5 and 9 years from 125 Cape Town, South African children, studied since birth. The children were divided into 3 groups: FAS or partial FAS (PFAS), heavily exposed nonsyndromal (HE), and non-alcohol-exposed controls (C). Anthropometric measurements were evaluated for mean group differences. Logistic regression models were used to identify the subset of anthropometric measures that best predicted group membership. Anthropometric measurements were examined at the 2 ages in relation to prenatal alcohol exposure obtained prospectively from the mothers during pregnancy. Correlation of these facial measurements with key neurobehavioral outcomes including Wechsler Intelligence Scales for Children-IV IQ and eyeblink conditioning was used to assess their utility as indicators of alcohol-related central nervous system impairment. RESULTS: Significant group differences were found for the majority of the anthropometric measures, with means of these measures smaller in the FAS/PFAS compared with HE or C. Upper facial widths, ear length, lower facial depth, and eye widths were consistent predictors distinguishing those exposed to alcohol from those who were not. Using longitudinal data, unique measures were identified that predicted facial anomalies at one age but not the other, suggesting the face changes as the individual matures. And 41% of the FAS/PFAS group met criteria for microtia at both ages. Three of the predictive anthropometric measures were negatively related to measures of prenatal alcohol consumption, and all were positively related to at least 1 neurobehavioral outcome. CONCLUSIONS: The analysis of longitudinal data identified a common set of predictors, as well as some that are unique at each age. Prenatal alcohol exposure appears to have its primary effect on brain growth, reflected by smaller forehead widths, and may suppress neural crest migration to the branchial arches, reflected by deficits in ear length and mandibular dimensions. These results may improve diagnostic resolution and enhance our understanding of the relation between the face and the neuropsychological deficits that occur.

Alcohol-induced facial dysmorphology in C57BL/6 mouse models of fetal alcohol spectrum disorder.

Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder (FASD), which includes a range of developmental deficits. Fetal alcohol syndrome is the most severe form of FASD and can be diagnosed with pathognomonic facial features such as a smooth philtrum, short palpebral fissure, and thin upper vermilion. However, many children with developmental damage because of prenatal alcohol exposure exhibit none, or only a subset, of the above features, making diagnosis difficult. This study explored novel analyses to quantify the effect of a known dose of alcohol on specific facial measurements in substrains C57BL/B6J (B6J) and C57BL/6NHsd (B6N) mice. Mouse dams were provided alcohol (Alc) consisting of 4.8% (vol/vol) alcohol in a liquid diet for 16 days prepregnancy and chow and water diet during mating, and then the alcohol liquid diet was reinstated on gestational days 7 (E7) to gestational day 17 (E17). Treatment controls included a pair-fed (PF) group given matched volumes of an alcohol-free liquid diet made isocalorically and a group given ad lib access to lab chow and water (Chow). Maternal diet intake (Alc and PF), blood alcohol concentrations (BACs), embryo weights, and 15 morphometric facial measurements for E17 embryos were analyzed. B6N dams drank more alcohol during pregnancy and generated higher BAC than B6J dams. Both the Alc and PF treatments induced significant reductions in embryo weights relative to Chow in both substrains. Alcohol treatments produced significant changes, relative to controls, in 4 of the 15 facial measures for the B6N substrain but only in two measures for the B6J substrain. Discriminant analysis demonstrated successful classification of the alcohol-exposed versus nonalcohol-exposed B6N embryos, with a high sensitivity of 86%, specificity 80%, and overall classification (total correct 83%), whereas B6J mice yielded sensitivity of 80%, specificity 78%, and overall correct classification in 79%. In addition, B6N mice showed significantly more effects of pair feeding on these facial measures than did B6J mice, suggesting that the B6N substrain may be more vulnerable to nutritional stress during pregnancy. Overall, these data indicate that both B6N and B6J mice were vulnerable to alcohol but show differences in the severity and location of alcohol-induced dysmorphic facial features and may parallel findings from human studies comparing different ethnic groups. Furthermore, these findings suggest that discriminant analysis may be useful in predicting alcohol exposure in either mouse substrains.

Facial Image Classification of Mouse Embryos for the Animal Model Study of Fetal Alcohol Syndrome.

Fetal Alcohol Syndrome (FAS) is a developmental disorder caused by maternal drinking during pregnancy. Computerize imaging techniques have been applied to study human facial dysmorphology associated with FAS. This paper describes a new facial image analysis method based on a multi-angle image classification technique using micro-video images of mouse embryo. Images taken from several different angles are analyzed separately, and the results are combined for classifications that separate embryos with and without alcohol exposures. Analysis results from animal models provide critical references for the understanding of FAS and potential therapy solutions for human patients.