COVID-19 lockdown effects on adolescent brain structure suggest accelerated maturation that is more pronounced in females than in males.

Adolescence is a period of substantial social-emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain.

Human white matter myelinates faster in utero than ex utero.

The formation of myelin, the fatty sheath that insulates nerve fibers, is critical for healthy brain function. A fundamental open question is what impact being born has on myelin growth. To address this, we evaluated a large (n = 300) cross-sectional sample of newborns from the Developing Human Connectome Project (dHCP). First, we developed software for the automated identification of 20 white matter bundles in individual newborns that is well suited for large samples. Next, we fit linear models that quantify how T1w/T2w (a myelin-sensitive imaging contrast) changes over time at each point along the bundles. We found faster growth of T1w/T2w along the lengths of all bundles before birth than right after birth. Further, in a separate longitudinal sample of preterm infants (N = 34), we found lower T1w/T2w than in full-term peers measured at the same age. By applying the linear models fit on the cross-section sample to the longitudinal sample of preterm infants, we find that their delay in T1w/T2w growth is well explained by the amount of time they spent developing in utero and ex utero. These results suggest that white matter myelinates faster in utero than ex utero. The reduced rate of myelin growth after birth, in turn, explains lower myelin content in individuals born preterm and could account for long-term cognitive, neurological, and developmental consequences of preterm birth. We hypothesize that closely matching the environment of infants born preterm to what they would have experienced in the womb may reduce delays in myelin growth and hence improve developmental outcomes.

Development of the Alpha Rhythm Is Linked to Visual White Matter Pathways and Visual Detection Performance.

Alpha is the strongest electrophysiological rhythm in awake humans at rest. Despite its predominance in the EEG signal, large variations can be observed in alpha properties during development, with an increase in alpha frequency over childhood and adulthood. Here, we tested the hypothesis that these changes in alpha rhythm are related to the maturation of visual white matter pathways. We capitalized on a large diffusion MRI (dMRI)-EEG dataset (dMRI n = 2,747, EEG n = 2,561) of children and adolescents of either sex (age range, 5-21 years old) and showed that maturation of the optic radiation specifically accounts for developmental changes of alpha frequency. Behavioral analyses also confirmed that variations of alpha frequency are related to maturational changes in visual perception. The present findings demonstrate the close link between developmental variations in white matter tissue properties, electrophysiological responses, and behavior.

Ten simple rules for scientific code review.

As large, high-dimensional data have become more common, software development is playing an increasingly important role in research across many different fields. This creates a need to adopt software engineering practices in research settings. Code review is the engineering practice of giving and receiving detailed feedback on a computer program. Consistent and continuous examination of the evolution of computer programs by others has been shown to be beneficial, especially when reviewers are familiar with the technical aspects of the software and also when they possess relevant domain expertise. The rules described in the present article provide information about the why, when, and how of code review. They provide the motivation for continual code reviews as a natural part of a rigorous research program. They provide practical guidelines for conducting review of code both in person, as a "lab meeting for code," as well as asynchronously, using industry-standard online tools. A set of guidelines is provided for the nitty-gritty details of code review, as well as for the etiquette of such a review. Both the technical and the social aspects of code review are covered to provide the reader with a comprehensive approach that facilitates an effective, enjoyable, and educational approach to code review.

Diffusion MRI head motion correction methods are highly accurate but impacted by denoising and sampling scheme.

Head motion correction is particularly challenging in diffusion-weighted MRI (dMRI) scans due to the dramatic changes in image contrast at different gradient strengths and directions. Head motion correction is typically performed using a Gaussian Process model implemented in FSL's Eddy. Recently, the 3dSHORE-based SHORELine method was introduced that does not require shell-based acquisitions, but it has not been previously benchmarked. Here we perform a comprehensive evaluation of both methods on realistic simulations of a software fiber phantom that provides known ground-truth head motion. We demonstrate that both methods perform remarkably well, but that performance can be impacted by sampling scheme and the extent of head motion and the denoising strategy applied before head motion correction. Furthermore, we find Eddy benefits from denoising the data first with MP-PCA. In sum, we provide the most extensive known benchmarking of dMRI head motion correction, together with extensive simulation data and a reproducible workflow. PRACTITIONER POINTS: Both Eddy and SHORELine head motion correction methods performed quite well on a large variety of simulated data. Denoising with MP-PCA can improve head motion correction performance when Eddy is used. SHORELine effectively corrects motion in non-shelled diffusion spectrum imaging data.

QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data.

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images.

Optic radiations representing different eccentricities age differently.

The neural pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ on a large sample of diffusion MRI (dMRI) data from subjects with healthy vision in the U.K. Biobank dataset (UKBB; N = 5382; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.

Multidimensional analysis and detection of informative features in human brain white matter.

The white matter contains long-range connections between different brain regions and the organization of these connections holds important implications for brain function in health and disease. Tractometry uses diffusion-weighted magnetic resonance imaging (dMRI) to quantify tissue properties along the trajectories of these connections. Statistical inference from tractometry usually either averages these quantities along the length of each fiber bundle or computes regression models separately for each point along every one of the bundles. These approaches are limited in their sensitivity, in the former case, or in their statistical power, in the latter. We developed a method based on the sparse group lasso (SGL) that takes into account tissue properties along all of the bundles and selects informative features by enforcing both global and bundle-level sparsity. We demonstrate the performance of the method in two settings: i) in a classification setting, patients with amyotrophic lateral sclerosis (ALS) are accurately distinguished from matched controls. Furthermore, SGL identifies the corticospinal tract as important for this classification, correctly finding the parts of the white matter known to be affected by the disease. ii) In a regression setting, SGL accurately predicts "brain age." In this case, the weights are distributed throughout the white matter indicating that many different regions of the white matter change over the lifespan. Thus, SGL leverages the multivariate relationships between diffusion properties in multiple bundles to make accurate phenotypic predictions while simultaneously discovering the most relevant features of the white matter.

On the generalizability of diffusion MRI signal representations across acquisition parameters, sequences and tissue types: Chronicles of the MEMENTO challenge.

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. The received submissions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.

Development of the visual white matter pathways mediates development of electrophysiological responses in visual cortex.

The latency of neural responses in the visual cortex changes systematically across the lifespan. Here, we test the hypothesis that development of visual white matter pathways mediates maturational changes in the latency of visual signals. Thirty-eight children participated in a cross-sectional study including diffusion magnetic resonance imaging (MRI) and magnetoencephalography (MEG) sessions. During the MEG acquisition, participants performed a lexical decision and a fixation task on words presented at varying levels of contrast and noise. For all stimuli and tasks, early evoked fields were observed around 100 ms after stimulus onset (M100), with slower and lower amplitude responses for low as compared to high contrast stimuli. The optic radiations and optic tracts were identified in each individual's brain based on diffusion MRI tractography. The diffusion properties of the optic radiations predicted M100 responses, especially for high contrast stimuli. Higher optic radiation fractional anisotropy (FA) values were associated with faster and larger M100 responses. Over this developmental window, the M100 responses to high contrast stimuli became faster with age and the optic radiation FA mediated this effect. These findings suggest that the maturation of the optic radiations over childhood accounts for individual variations observed in the developmental trajectory of visual cortex responses.

Hack weeks as a model for data science education and collaboration.

Across many scientific disciplines, methods for recording, storing, and analyzing data are rapidly increasing in complexity. Skillfully using data science tools that manage this complexity requires training in new programming languages and frameworks as well as immersion in new modes of interaction that foster data sharing, collaborative software development, and exchange across disciplines. Learning these skills from traditional university curricula can be challenging because most courses are not designed to evolve on time scales that can keep pace with rapidly shifting data science methods. Here, we present the concept of a hack week as an effective model offering opportunities for networking and community building, education in state-of-the-art data science methods, and immersion in collaborative project work. We find that hack weeks are successful at cultivating collaboration and facilitating the exchange of knowledge. Participants self-report that these events help them in both their day-to-day research as well as their careers. Based on our results, we conclude that hack weeks present an effective, easy-to-implement, fairly low-cost tool to positively impact data analysis literacy in academic disciplines, foster collaboration, and cultivate best practices.

Slow Endogenous Fluctuations in Cortical fMRI Signals Correlate with Reduced Performance in a Visual Detection Task and Are Suppressed by Spatial Attention.

Spatial attention improves performance on visual tasks, increases neural responses to attended stimuli, and reduces correlated noise in visual cortical neurons. In addition to being visually responsive, many retinotopic visual cortical areas exhibit very slow (<0.1 Hz) endogenous fluctuations in functional magnetic resonance imaging signals. To test whether these fluctuations degrade stimulus representations, thereby impairing visual detection, we recorded functional magnetic resonance imaging responses while human participants performed a target detection task that required them to allocate spatial attention to either a rotating wedge stimulus or a central fixation point. We then measured the effects of spatial attention on response amplitude at the frequency of wedge rotation and on the amplitude of endogenous fluctuations at nonstimulus frequencies. We found that, in addition to enhancing stimulus-evoked responses, attending to the wedge also suppressed slow endogenous fluctuations that were unrelated to the visual stimulus in topographically defined areas in early visual cortex, posterior parietal cortex, and lateral occipital cortex, but not in a nonvisual cortical control region. Moreover, attentional enhancement of response amplitude and suppression of endogenous fluctuations were dissociable across cortical areas and across time. Finally, we found that the amplitude of the stimulus-evoked response was not correlated with a perceptual measure of visual target detection. Instead, perceptual performance was accounted for by the amount of suppression of slow endogenous fluctuations. Our results indicate that the amplitude of slow fluctuations of cortical activity is influenced by spatial attention and suggest that these endogenous fluctuations may impair perceptual processing in topographically organized visual cortical areas.

Generalized diffusion spectrum magnetic resonance imaging (GDSI) for model-free reconstruction of the ensemble average propagator.

Diffusion spectrum MRI (DSI) provides model-free estimation of the diffusion ensemble average propagator (EAP) and orientation distribution function (ODF) but requires the diffusion data to be acquired on a Cartesian q-space grid. Multi-shell diffusion acquisitions are more flexible and more commonly acquired but have, thus far, only been compatible with model-based analysis methods. Here, we propose a generalized DSI (GDSI) framework to recover the EAP from multi-shell diffusion MRI data. The proposed GDSI approach corrects for q-space sampling density non-uniformity using a fast geometrical approach. The EAP is directly calculated in a preferable coordinate system by multiplying the sampling density corrected q-space signals by a discrete Fourier transform matrix, without any need for gridding. The EAP is demonstrated as a way to map diffusion patterns in brain regions such as the thalamus, cortex and brainstem where the tissue microstructure is not as well characterized as in white matter. Scalar metrics such as the zero displacement probability and displacement distances at different fractions of the zero displacement probability were computed from the recovered EAP to characterize the diffusion pattern within each voxel. The probability averaged across directions at a specific displacement distance provides a diffusion property based image contrast that clearly differentiates tissue types. The displacement distance at the first zero crossing of the EAP averaged across directions orthogonal to the primary fiber orientation in the corpus callosum is found to be larger in the body (5.65 ±â€¯0.09 µm) than in the genu (5.55 ±â€¯0.15 µm) and splenium (5.4 ±â€¯0.15 µm) of the corpus callosum, which corresponds well to prior histological studies. The EAP also provides model-free representations of angular structure such as the diffusion ODF, which allows estimation and comparison of fiber orientations from both the model-free and model-based methods on the same multi-shell data. For the model-free methods, detection of crossing fibers is found to be strongly dependent on the maximum b-value and less sensitive compared to the model-based methods. In conclusion, our study provides a generalized DSI approach that allows flexible reconstruction of the diffusion EAP and ODF from multi-shell diffusion data and data acquired with other sampling patterns.

Evaluating arcuate fasciculus laterality measurements across dataset and tractography pipelines.

The arcuate fasciculi are white-matter pathways that connect frontal and temporal lobes in each hemisphere. The arcuate plays a key role in the language network and is believed to be left-lateralized, in line with left hemisphere dominance for language. Measuring the arcuate in vivo requires diffusion magnetic resonance imaging-based tractography, but asymmetry of the in vivo arcuate is not always reliably detected in previous studies. It is unknown how the choice of tractography algorithm, with each method's freedoms, constraints, and vulnerabilities to false-positive and -negative errors, impacts findings of arcuate asymmetry. Here, we identify the arcuate in two independent datasets using a number of tractography strategies and methodological constraints, and assess their impact on estimates of arcuate laterality. We test three tractography methods: a deterministic, a probabilistic, and a tractography-evaluation (LiFE) algorithm. We extract the arcuate from the whole-brain tractogram, and compare it to an arcuate bundle constrained even further by selecting only those streamlines that connect to anatomically relevant cortical regions. We test arcuate macrostructure laterality, and also evaluate microstructure profiles for properties such as fractional anisotropy and quantitative R1. We find that both tractography choice and implementing the cortical constraints substantially impact estimates of all indices of arcuate laterality. Together, these results emphasize the effect of the tractography pipeline on estimates of arcuate laterality in both macrostructure and microstructure.

Evaluation and statistical inference for human connectomes.

Diffusion-weighted imaging coupled with tractography is currently the only method for in vivo mapping of human white-matter fascicles. Tractography takes diffusion measurements as input and produces the connectome, a large collection of white-matter fascicles, as output. We introduce a method to evaluate the evidence supporting connectomes. Linear fascicle evaluation (LiFE) takes any connectome as input and predicts diffusion measurements as output, using the difference between the measured and predicted diffusion signals to quantify the prediction error. We use the prediction error to evaluate the evidence that supports the properties of the connectome, to compare tractography algorithms and to test hypotheses about tracts and connections.

Diffusion MRI microstructure models with in vivo human brain Connectome data: results from a multi-group comparison.

A large number of mathematical models have been proposed to describe the measured signal in diffusion-weighted (DW) magnetic resonance imaging (MRI). However, model comparison to date focuses only on specific subclasses, e.g. compartment models or signal models, and little or no information is available in the literature on how performance varies among the different types of models. To address this deficiency, we organized the 'White Matter Modeling Challenge' during the International Symposium on Biomedical Imaging (ISBI) 2015 conference. This competition aimed to compare a range of different kinds of models in their ability to explain a large range of measurable in vivo DW human brain data. Specifically, we assessed the ability of models to predict the DW signal accurately for new diffusion gradients and b values. We did not evaluate the accuracy of estimated model parameters, as a ground truth is hard to obtain. We used the Connectome scanner at the Massachusetts General Hospital, using gradient strengths of up to 300 mT/m and a broad set of diffusion times. We focused on assessing the DW signal prediction in two regions: the genu in the corpus callosum, where the fibres are relatively straight and parallel, and the fornix, where the configuration of fibres is more complex. The challenge participants had access to three-quarters of the dataset and their models were ranked on their ability to predict the remaining unseen quarter of the data. The challenge provided a unique opportunity for a quantitative comparison of diverse methods from multiple groups worldwide. The comparison of the challenge entries reveals interesting trends that could potentially influence the next generation of diffusion-based quantitative MRI techniques. The first is that signal models do not necessarily outperform tissue models; in fact, of those tested, tissue models rank highest on average. The second is that assuming a non-Gaussian (rather than purely Gaussian) noise model provides little improvement in prediction of unseen data, although it is possible that this may still have a beneficial effect on estimated parameter values. The third is that preprocessing the training data, here by omitting signal outliers, and using signal-predicting strategies, such as bootstrapping or cross-validation, could benefit the model fitting. The analysis in this study provides a benchmark for other models and the data remain available to build up a more complete comparison in the future.

A Major Human White Matter Pathway Between Dorsal and Ventral Visual Cortex.

Human visual cortex comprises many visual field maps organized into clusters. A standard organization separates visual maps into 2 distinct clusters within ventral and dorsal cortex. We combined fMRI, diffusion MRI, and fiber tractography to identify a major white matter pathway, the vertical occipital fasciculus (VOF), connecting maps within the dorsal and ventral visual cortex. We use a model-based method to assess the statistical evidence supporting several aspects of the VOF wiring pattern. There is strong evidence supporting the hypothesis that dorsal and ventral visual maps communicate through the VOF. The cortical projection zones of the VOF suggest that human ventral (hV4/VO-1) and dorsal (V3A/B) maps exchange substantial information. The VOF appears to be crucial for transmitting signals between regions that encode object properties including form, identity, and color and regions that map spatial information.

The vertical occipital fasciculus: a century of controversy resolved by in vivo measurements.

The vertical occipital fasciculus (VOF) is the only major fiber bundle connecting dorsolateral and ventrolateral visual cortex. Only a handful of studies have examined the anatomy of the VOF or its role in cognition in the living human brain. Here, we trace the contentious history of the VOF, beginning with its original discovery in monkey by Wernicke (1881) and in human by Obersteiner (1888), to its disappearance from the literature, and recent reemergence a century later. We introduce an algorithm to identify the VOF in vivo using diffusion-weighted imaging and tractography, and show that the VOF can be found in every hemisphere (n = 74). Quantitative T1 measurements demonstrate that tissue properties, such as myelination, in the VOF differ from neighboring white-matter tracts. The terminations of the VOF are in consistent positions relative to cortical folding patterns in the dorsal and ventral visual streams. Recent findings demonstrate that these same anatomical locations also mark cytoarchitectonic and functional transitions in dorsal and ventral visual cortex. We conclude that the VOF is likely to serve a unique role in the communication of signals between regions on the ventral surface that are important for the perception of visual categories (e.g., words, faces, bodies, etc.) and regions on the dorsal surface involved in the control of eye movements, attention, and motion perception.

The visual white matter: The application of diffusion MRI and fiber tractography to vision science.

Visual neuroscience has traditionally focused much of its attention on understanding the response properties of single neurons or neuronal ensembles. The visual white matter and the long-range neuronal connections it supports are fundamental in establishing such neuronal response properties and visual function. This review article provides an introduction to measurements and methods to study the human visual white matter using diffusion MRI. These methods allow us to measure the microstructural and macrostructural properties of the white matter in living human individuals; they allow us to trace long-range connections between neurons in different parts of the visual system and to measure the biophysical properties of these connections. We also review a range of findings from recent studies on connections between different visual field maps, the effects of visual impairment on the white matter, and the properties underlying networks that process visual information supporting visual face recognition. Finally, we discuss a few promising directions for future studies. These include new methods for analysis of MRI data, open datasets that are becoming available to study brain connectivity and white matter properties, and open source software for the analysis of these data.

Evaluating quantitative proton-density-mapping methods.

Quantitative magnetic resonance imaging (qMRI) aims to quantify tissue parameters by eliminating instrumental bias. We describe qMRI theory, simulations, and software designed to estimate proton density (PD), the apparent local concentration of water protons in the living human brain. First, we show that, in the absence of noise, multichannel coil data contain enough information to separate PD and coil sensitivity, a limiting instrumental bias. Second, we show that, in the presence of noise, regularization by a constraint on the relationship between T1 and PD produces accurate coil sensitivity and PD maps. The ability to measure PD quantitatively has applications in the analysis of in-vivo human brain tissue and enables multisite comparisons between individuals and across instruments. Hum Brain Mapp 37:3623-3635, 2016. © 2016 Wiley Periodicals, Inc.