Improving data availability for brain image biobanking in healthy subjects: Practice-based suggestions from an international multidisciplinary working group.

Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining 'normality'); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function.

Teaching with Big Data: Report from the 2016 Society for Neuroscience Teaching Workshop.

As part of a series of workshops on teaching neuroscience at the Society for Neuroscience annual meetings, William Grisham and Richard Olivo organized the 2016 workshop on "Teaching Neuroscience with Big Data." This article presents a summary of that workshop. Speakers provided overviews of open datasets that could be used in teaching undergraduate courses. These included resources that already appear in educational settings, including the Allen Brain Atlas (presented by Joshua Brumberg and Terri Gilbert), and the Mouse Brain Library and GeneNetwork (presented by Robert Williams). Other resources, such as NeuroData (presented by William R. Gray Roncal), and OpenFMRI, NeuroVault, and Neurosynth (presented by Russell Poldrack) have not been broadly utilized by the neuroscience education community but offer obvious potential. Finally, William Grisham discussed the iNeuro Project, an NSF-sponsored effort to develop the necessary curriculum for preparing students to handle Big Data. Linda Lanyon further elaborated on the current state and challenges in educating students to deal with Big Data and described some training resources provided by the International Neuroinformatics Coordinating Facility. Neuroinformatics is a subfield of neuroscience that deals with data utilizing analytical tools and computational models. The feasibility of offering neuroinformatics programs at primarily undergraduate institutions was also discussed.

A Standards Organization for Open and FAIR Neuroscience: the International Neuroinformatics Coordinating Facility.

There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.

Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-Pick Type C patient.

New treatment options for Niemann-Pick Type C (NPC) have recently become available. To assess the efficiency and efficacy of these new treatment markers for disease status and progression are needed. Both the diagnosis and the monitoring of disease progression are challenging and mostly rely on clinical impression and functional testing of horizontal eye movements. Diffusion tensor imaging (DTI) provides information about the microintegrity especially of white matter. We show here in a case report how DTI and measures derived from this imaging method can serve as adjunct quantitative markers for disease management in Niemann-Pick Type C. Two approaches are taken--first, we compare the fractional anisotropy (FA) in the white matter globally between a 29-year-old NPC patient and 18 healthy age-matched controls and show the remarkable difference in FA relatively early in the course of the disease. Second, a voxelwise comparison of FA values reveals where white matter integrity is compromised locally and demonstrate an individualized analysis of FA changes before and after 1year of treatment with Miglustat. This method might be useful in future treatment trials for NPC to assess treatment effects.

Combined functional MRI and diffusion tensor imaging analysis of visual motion pathways.

BACKGROUND: Motion perception may be preserved after damage to striate cortex (primary visual cortex, area V1). Awareness and normal discrimination of fast-moving stimuli have been observed even in the complete absence of V1. These facts suggest that motion-sensitive cortex (the V5/MT complex or V5/MT+) may be activated by direct thalamic or collicular inputs that bypass V1. Such projections have been identified previously in monkeys but have not been shown in humans using neuroimaging techniques. METHODS: We used diffusion tensor imaging (DTI) tractography to visualize white matter fiber tracts connecting with V5/MT+ in 10 healthy volunteers. V5/MT+ was localized for each subject using functional MRI (fMRI). Functional activity maps were overlaid on high-resolution anatomical images and registered with the diffusion-weighted images to define V5/MT+ as the region of interest (ROI) for DTI tractography analysis. Fibers connecting to V1 were excluded from the analysis. RESULTS: Using conservative tractography parameters, we found connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus in 4 of 10 subjects. CONCLUSIONS: Connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus may explain visual motion awareness in the absence of a functioning V1.

Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study.

BACKGROUND: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. METHODS: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). FINDINGS: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]). INTERPRETATION: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes. FUNDING: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

Navigational skills correlate with hippocampal fractional anisotropy in humans.

Individuals vary widely in their ability to orient within the environment. We used diffusion tensor imaging to investigate whether this ability, as measured by navigational performance in a virtual environment, correlates with the anatomic structural properties of the hippocampus, i.e., fractional anisotropy. We found that individuals with high fractional anisotropy in the right hippocampus are (a) faster in forming a cognitive map of the environment, and (b) more efficient in using this map for the purpose of orientation, than individuals with low fractional anisotropy. These results are consistent with the role of the hippocampus in navigation, and suggest that its microstructural properties may contribute to the intersubject variability observed in spatial orientation.

Scan patterns during the processing of facial expression versus identity: an exploration of task-driven and stimulus-driven effects.

Perceptual studies suggest that processing facial identity emphasizes upper-face information, whereas processing expressions of anger or happiness emphasizes the lower-face. The two goals of the present study were to determine (a) if the distributions of eye fixations reflect these upper/lower-face biases, and (b) whether this bias is task- or stimulus-driven. We presented a target face followed by a probe pair of morphed faces, neither of which was identical to the target. Subjects judged which of the pair was more similar to the target face while eye movements were recorded. In Experiment 1 the probe pair always differed from each other in both identity and expression on each trial. In one block subjects judged which probe face was more similar to the target face in identity, and in a second block subjects judged which probe face was more similar to the target face in expression. In Experiment 2 the two probe faces differed in either expression or identity, but not both. Subjects were not informed which dimension differed, but simply asked to judge which probe face was more similar to the target face. We found that subjects scanned the upper-face more than the lower-face during the identity task but the lower-face more than the upper-face during the expression task in Experiment 1 (task-driven effects), with significantly less variation in bias in Experiment 2 (stimulus-driven effects). We conclude that fixations correlate with regional variations of diagnostic information in different processing tasks, but that these reflect top-down task-driven guidance of information acquisition more than stimulus-driven effects.

Proposed Training to Meet Challenges of Large-Scale Data in Neuroscience.

The scale of data being produced in neuroscience at present and in the future creates new and unheralded challenges, outstripping conventional ways of handling, considering, and analyzing data. As neuroinformatics enters into this big data era, a need for a highly trained and perhaps unique workforce is emerging. To determine the staffing needs created by the impending era of big data, a workshop (iNeuro Project) was convened November 13-14, 2014. Participants included data resource providers, bioinformatics/analytics trainers, computer scientists, library scientists, and neuroscience educators. These individuals provided perspectives on the challenges of big data, the preparation of a workforce to meet these challenges, and the present state of training programs. Participants discussed whether suitable training programs will need to be constructed from scratch or if existing programs can serve as models. Currently, most programs at the undergraduate and graduate levels are located in Europe-participants knew of none in the United States. The skill sets that training programs would need to provide as well as the curriculum necessary to teach them were also discussed. Consistent with Vision and Change in Undergraduate Biology Education: A Call to Action, proposed curricula included authentic, hands-on research experiences. Further discussions revolved around the logistics and barriers to creating such programs. The full white paper, iNeuro Project Workshop Report, is available from iNeuro Project.

A model of active visual search with object-based attention guiding scan paths.

When a monkey searches for a colour and orientation feature conjunction target, the scan path is guided to target coloured locations in preference to locations containing the target orientation [Vision Res. 38 (1998b) 1805]. An active vision model, using biased competition, is able to replicate this behaviour. As object-based attention develops in extrastriate cortex, featural information is passed to posterior parietal cortex (LIP), enabling it to represent behaviourally relevant locations [J. Neurophysiol. 76 (1996) 2841] and guide the scan path. Attention evolves from an early spatial effect to being object-based later in the response of the model neurons, as has been observed in monkey single cell recordings. This is the first model to reproduce these effects with temporal precision and is reported here at the systems level allowing the replication of psychophysical scan paths.

Visual search and line bisection in hemianopia: computational modelling of cortical compensatory mechanisms and comparison with hemineglect.

Hemianopia patients have lost vision from the contralateral hemifield, but make behavioural adjustments to compensate for this field loss. As a result, their visual performance and behaviour contrast with those of hemineglect patients who fail to attend to objects contralateral to their lesion. These conditions differ in their ocular fixations and perceptual judgments. During visual search, hemianopic patients make more fixations in contralesional space while hemineglect patients make fewer. During line bisection, hemianopic patients fixate the contralesional line segment more and make a small contralesional bisection error, while hemineglect patients make few contralesional fixations and a larger ipsilesional bisection error. Hence, there is an attentional failure for contralesional space in hemineglect but a compensatory adaptation to attend more to the blind side in hemianopia. A challenge for models of visual attentional processes is to show how compensation is achieved in hemianopia, and why such processes are hindered or inaccessible in hemineglect. We used a neurophysiology-derived computational model to examine possible cortical compensatory processes in simulated hemianopia from a V1 lesion and compared results with those obtained with the same processes under conditions of simulated hemineglect from a parietal lesion. A spatial compensatory bias to increase attention contralesionally replicated hemianopic scanning patterns during visual search but not during line bisection. To reproduce the latter required a second process, an extrastriate lateral connectivity facilitating form completion into the blind field: this allowed accurate placement of fixations on contralesional stimuli and reproduced fixation patterns and the contralesional bisection error of hemianopia. Neither of these two cortical compensatory processes was effective in ameliorating the ipsilesional bias in the hemineglect model. Our results replicate normal and pathological patterns of visual scanning, line bisection, and differences between hemianopia and hemineglect, and may explain why compensatory processes that counter the effects of hemianopia are ineffective in hemineglect.

Functional organisation of visual pathways in a patient with no optic chiasm.

Congenital achiasma offers a rare opportunity to study reorganization and inter-hemispheric communication in the face of anomalous inputs to striate cortex. We report neuroimaging studies of a patient with seesaw nystagmus, achiasma, and full visual fields. The subject underwent structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) studies, and functional MRI (fMRI) using monocular stimulation with checkerboards, motion, objects and faces, as well as retinotopic quadrantic mapping. Structural MRI confirmed the absence of an optic chiasm, which was corroborated by DTI tractography. Lack of a functioning decussation was confirmed by fMRI that showed activation of only ipsilateral medial occipital cortex by monocular stimulation. The corpus callosum was normal in size and anterior and posterior commissures were identifiable. In terms of the hierarchy of visual areas, V5 was the lowest level region to be activated binocularly, as were regions in the fusiform gyri responding to faces and objects. The retinotopic organization of striate cortex was studied with quadrantic stimulation. This showed that, in support of recent findings, rather than projecting to an ectopic location contiguous with the normal retinotopic map of the ipsilateral temporal hemi-retina, the nasal hemi-retina's representation overlapped that of the temporal hemi-retina. These findings show that congenital achiasma can be an isolated midline crossing defect, that information transfer does not occur in early occipital cortex but at intermediate and higher levels of the visual hierarchy, and that the functional reorganisation of striate cortex in this condition is consistent with normal axon guidance by a chemoaffinity gradient.

Sensitivity and bias in decision-making under risk: evaluating the perception of reward, its probability and value.

BACKGROUND: There are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour. OBJECTIVE: We designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk. DESIGN/METHODS: Twenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%. RESULTS: Subjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a 'risk premium' of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability. CONCLUSIONS: This simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia.

Line bisection under an attentional gradient induced by simulated neglect in healthy subjects.

Whether an attentional gradient favouring the ipsilesional side is responsible for the line bisection errors in visual neglect is uncertain. We explored this by using a conjunction-search task on the right side of a computer screen to bias attention while healthy subjects performed line bisection. The first experiment used a probe detection task to confirm that the conjunction-search task created a rightward attentional gradient, as manifest in response times, detection rates, and fixation patterns. In the second experiment subjects performed line bisection with or without a simultaneous conjunction-search task. Fixation patterns in the latter condition were biased rightwards as in visual neglect, and bisection also showed a rightward bias, though modest. A third experiment using the probe detection task again showed that the attentional gradient induced by the conjunction-search task was reduced when subjects also performed line bisection, perhaps explaining the modest effects on bisection bias. Finally, an experiment with briefly viewed pre-bisected lines produced similar results, showing that the small size of the bisection bias was not due to an unlimited view allowing deployment of attentional resources to counteract the conjunction-search task's attentional gradient. These results show that an attentional gradient induced in healthy subjects can produce visual neglect-like visual scanning and a rightward shift of perceived line midpoint, but the modest size of this shift points to limitations of this physiological model in simulating the pathologic effects of visual neglect.

Modelling visual neglect: computational insights into conscious perception.

BACKGROUND: Visual neglect is an attentional deficit typically resulting from parietal cortex lesion and sometimes frontal lesion. Patients fail to attend to objects and events in the visual hemifield contralateral to their lesion during visual search. METHODOLOGY/PRINCIPAL FINDING: The aim of this work was to examine the effects of parietal and frontal lesion in an existing computational model of visual attention and search and simulate visual search behaviour under lesion conditions. We find that unilateral parietal lesion in this model leads to symptoms of visual neglect in simulated search scan paths, including an inhibition of return (IOR) deficit, while frontal lesion leads to milder neglect and to more severe deficits in IOR and perseveration in the scan path. During simulations of search under unilateral parietal lesion, the model's extrastriate ventral stream area exhibits lower activity for stimuli in the neglected hemifield compared to that for stimuli in the normally perceived hemifield. This could represent a computational correlate of differences observed in neuroimaging for unconscious versus conscious perception following parietal lesion. CONCLUSIONS/SIGNIFICANCE: Our results lead to the prediction, supported by effective connectivity evidence, that connections between the dorsal and ventral visual streams may be an important factor in the explanation of perceptual deficits in parietal lesion patients and of conscious perception in general.

Modelling attention in individual cells leads to a system with realistic saccade behaviours.

Single cell recordings in monkey inferior temporal cortex (IT) and area V4 during visual search tasks indicate that modulation of responses by the search target object occurs in the late portion of the cell's sensory response (Chelazzi et al. in J Neurophysiol 80:2918-2940, 1998; Cereb Cortex 11:761-772, 2001) whereas attention to a spatial location influences earlier responses (Luck et al. in J Neurophysiol 77:24-42, 1997). Previous computational models have not captured differences in the latency of these attentional effects and yet the more protracted development of the object-based effect could have implications for behaviour. We present a neurodynamic biased competition model of visual attention in which we aimed to model the timecourse of spatial and object-based attention in order to simulate cellular responses and saccade onset times observed in monkey recordings. In common with other models, a top-down prefrontal signal, related to the search target, biases activity in the ventral visual stream. However, we conclude that this bias signal is more complex than modelled elsewhere: the latency of object-based effects in V4 and IT, and saccade onset, can be accurately simulated when the target object feedback bias consists of a sensory response component in addition to a mnemonic response. These attentional effects in V4 and IT cellular responses lead to a system that is able to produce search scan paths similar to those observed in monkeys and humans, with attention being guided to locations containing behaviourally relevant stimuli. This work demonstrates that accurate modelling of the timecourse of single cell responses can lead to biologically realistic behaviours being demonstrated by the system as a whole.