A Set of FMRI Quality Control Tools in AFNI: Systematic, in-depth and interactive QC with afni_proc.py and more.

Quality control (QC) assessment is a vital part of FMRI processing and analysis, and a typically under-discussed aspect of reproducibility. This includes checking datasets at their very earliest stages (acquisition and conversion) through their processing steps (e.g., alignment and motion correction) to regression modeling (correct stimuli, no collinearity, valid fits, enough degrees of freedom, etc.) for each subject. There are a wide variety of features to verify throughout any single subject processing pipeline, both quantitatively and qualitatively. We present several FMRI preprocessing QC features available in the AFNI toolbox, many of which are automatically generated by the pipeline-creation tool, afni_proc.py. These items include: a modular HTML document that covers full single subject processing from the raw data through statistical modeling; several review scripts in the results directory of processed data; and command line tools for identifying subjects with one or more quantitative properties across a group (such as triaging warnings, making exclusion criteria or creating informational tables). The HTML itself contains several buttons that efficiently facilitate interactive investigations into the data, when deeper checks are needed beyond the systematic images. The pages are linkable, so that users can evaluate individual items across a group, for increased sensitivity to differences (e.g., in alignment or regression modeling images). Finally, the QC document contains rating buttons for each "QC block", as well as comment fields for each, to facilitate both saving and sharing the evaluations. This increases the specificity of QC, as well as its shareability, as these files can be shared with others and potentially uploaded into repositories, promoting transparency and open science. We describe the features and applications of these QC tools for FMRI.

Improving 3D edge detection for visual inspection of MRI coregistration and alignment.

BACKGROUND: Visualizing edges is critical for neuroimaging. For example, edge maps enable quality assurance for the automatic alignment of an image from one modality (or individual) to another. NEW METHOD: We suggest that using the second derivative (difference of Gaussian, or DoG) provides robust edge detection. This method is tuned by size (which is typically known in neuroimaging) rather than intensity (which is relative). RESULTS: We demonstrate that this method performs well across a broad range of imaging modalities. The edge contours produced consistently form closed surfaces, whereas alternative methods may generate disconnected lines, introducing potential ambiguity in contiguity. COMPARISON WITH EXISTING METHODS: Current methods for computing edges are based on either the first derivative of the image (FSL), or a variation of the Canny Edge detection method (AFNI). These methods suffer from two primary limitations. First, the crucial tuning parameter for each of these methods relates to the image intensity. Unfortunately, image intensity is relative for most neuroimaging modalities making the performance of these methods unreliable. Second, these existing approaches do not necessarily generate a closed edge/surface, which can reduce the ability to determine the correspondence between a represented edge and another image. CONCLUSION: The second derivative is well suited for neuroimaging edge detection. We include this method as part of both the AFNI and FSL software packages, standalone code and online.

An open resource combining multi-contrast MRI and microscopy in the macaque brain.

Understanding brain structure and function often requires combining data across different modalities and scales to link microscale cellular structures to macroscale features of whole brain organisation. Here we introduce the BigMac dataset, a resource combining in vivo MRI, extensive postmortem MRI and multi-contrast microscopy for multimodal characterisation of a single whole macaque brain. The data spans modalities (MRI and microscopy), tissue states (in vivo and postmortem), and four orders of spatial magnitude, from microscopy images with micrometre or sub-micrometre resolution, to MRI signals on the order of millimetres. Crucially, the MRI and microscopy images are carefully co-registered together to facilitate quantitative multimodal analyses. Here we detail the acquisition, curation, and first release of the data, that together make BigMac a unique, openly-disseminated resource available to researchers worldwide. Further, we demonstrate example analyses and opportunities afforded by the data, including improvement of connectivity estimates from ultra-high angular resolution diffusion MRI, neuroanatomical insight provided by polarised light imaging and myelin-stained histology, and the joint analysis of MRI and microscopy data for reconstruction of the microscopy-inspired connectome. All data and code are made openly available.

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel.

BACKGROUND AND OBJECTIVE: Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. METHODS: Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. RESULTS: In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = -3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. CONCLUSIONS: Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects.

The Digital Brain Bank, an open access platform for post-mortem imaging datasets.

Post-mortem magnetic resonance imaging (MRI) provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes-Digital Neuroanatomist: datasets for detailed neuroanatomical investigations; Digital Brain Zoo: datasets for comparative neuroanatomy; and Digital Pathologist: datasets for neuropathology investigations. The first Digital Brain Bank data release includes 21 distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen nonhuman primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our lab's investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides cross-scale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies.

An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank.

UK Biobank is a major prospective epidemiological study, including multimodal brain imaging, genetics and ongoing health outcomes. Previously, we published genome-wide associations of 3,144 brain imaging-derived phenotypes, with a discovery sample of 8,428 individuals. Here we present a new open resource of genome-wide association study summary statistics, using the 2020 data release, almost tripling the discovery sample size. We now include the X chromosome and new classes of imaging-derived phenotypes (subcortical volumes and tissue contrast). Previously, we found 148 replicated clusters of associations between genetic variants and imaging phenotypes; in this study, we found 692, including 12 on the X chromosome. We describe some of the newly found associations, focusing on the X chromosome and autosomal associations involving the new classes of imaging-derived phenotypes. Our novel associations implicate, for example, pathways involved in the rare X-linked STAR (syndactyly, telecanthus and anogenital and renal malformations) syndrome, Alzheimer's disease and mitochondrial disorders.

The neural sources of N170: Understanding timing of activation in face-selective areas.

The N170 ERP component has been widely identified as a face-sensitive neural marker. Despite extensive investigations conducted to examine the neural sources of N170, there are two issues in prior literature: (a) few studies used individualized anatomy as head model for the cortical source analysis of the N170, and (b) the relationship between the N170 and face-selective regions from fMRI studies is unclear. Here, we addressed these questions by presenting pictures of faces and houses to the same group of healthy adults and recording structural MRI, fMRI, and high-density ERPs in separate sessions. Source analysis based on the participant's anatomy showed that the middle and posterior fusiform gyri were the primary neural sources for the face-sensitive aspects of the N170. Source analysis based on regions of interest from the fMRI revealed that the fMRI-defined fusiform face area was the major contributor to the N170. The current study suggests that the fusiform gyrus is a major neural contributor to the N170 ERP component and provides further insights about the spatiotemporal characteristics of face processing.

Visual Simultaneity Judgments Activate a Bilateral Frontoparietal Timing System.

In everyday life, we often make judgments regarding the sequence of events, for example, deciding whether a baseball runner's foot hit the plate before or after the ball hit the glove. Numerous studies have examined the functional correlates of temporal processing using variations of the temporal order judgment and simultaneity judgment (SJ) tasks. To perform temporal order judgment tasks, observers must bind temporal information with identity and/or spatial information relevant to the task itself. SJs, on the other hand, require observers to detect stimulus asynchrony but not the order of stimulus presentation and represent a purer measure of temporal processing. Some previous studies suggest that these temporal decisions rely primarily on right-hemisphere parietal structures, whereas others provide evidence that temporal perception depends on bilateral TPJ or inferior frontal regions (inferior frontal gyrus). Here, we report brain activity elicited by a visual SJ task. Our methods are unique given our use of two orthogonal control conditions, discrimination of spatial orientation and color, which were used to control for brain activation associated with the classic dorsal ("where/how") and ventral ("what") visual pathways. Our neuroimaging experiment shows that performing the SJ task selectively activated a bilateral network in the parietal (TPJ) and frontal (inferior frontal gyrus) cortices. We argue that SJ tasks are a purer measure of temporal perception because they do not require observers to process either identity or spatial information, both of which may activate separate cognitive networks.

Regional Brain Dysfunction Associated with Semantic Errors in Comprehension.

Here we illustrate how investigation of individuals acutely after stroke, before structure/function reorganization through recovery or rehabilitation, can be helpful in answering questions about the role of specific brain regions in language functions. Although there is converging evidence from a variety of sources that the left posterior-superior temporal gyrus plays some role in spoken word comprehension, its precise role in this function has not been established. We hypothesized that this region is essential for distinguishing between semantically related words, because it is critical for linking the spoken word to the complete semantic representation. We tested this hypothesis in 127 individuals with 48 hours of acute ischemic stroke, before the opportunity for reorganization or recovery. We identified tissue dysfunction (acute infarct and/or hypoperfusion) in gray and white matter parcels of the left hemisphere, and we evaluated the association between rate of semantic errors in a word-picture verification tasks and extent of tissue dysfunction in each region. We found that after correcting for lesion volume and multiple comparisons, the rate of semantic errors correlated with the extent of tissue dysfunction in left posterior-superior temporal gyrus and retrolenticular white matter.

Important considerations in lesion-symptom mapping: Illustrations from studies of word comprehension.

Lesion-symptom mapping is an important method of identifying networks of brain regions critical for functions. However, results might be influenced substantially by the imaging modality and timing of assessment. We tested the hypothesis that brain regions found to be associated with acute language deficits depend on (1) timing of behavioral measurement, (2) imaging sequences utilized to define the "lesion" (structural abnormality only or structural plus perfusion abnormality), and (3) power of the study. We studied 191 individuals with acute left hemisphere stroke with MRI and language testing to identify areas critical for spoken word comprehension. We use the data from this study to examine the potential impact of these three variables on lesion-symptom mapping. We found that only the combination of structural and perfusion imaging within 48 h of onset identified areas where more abnormal voxels was associated with more severe acute deficits, after controlling for lesion volume and multiple comparisons. The critical area identified with this methodology was the left posterior superior temporal gyrus, consistent with other methods that have identified an important role of this area in spoken word comprehension. Results have implications for interpretation of other lesion-symptom mapping studies, as well as for understanding areas critical for auditory word comprehension in the healthy brain. We propose that lesion-symptom mapping at the acute stage of stroke addresses a different sort of question about brain-behavior relationships than lesion-symptom mapping at the chronic stage, but that timing of behavioral measurement and imaging modalities should be considered in either case. Hum Brain Mapp 38:2990-3000, 2017. © 2017 Wiley Periodicals, Inc.

Activity associated with speech articulation measured through direct cortical recordings.

The insula has been credited with a role in a number of functions, including speech production. Here, we recorded electrocorticography (ECoG) signals from the left insula during pseudoword articulation in two patients undergoing pre-surgical monitoring for the management of medically-intractable epilepsy. Event-related band power (ERBP) activity from electrodes implanted in the superior precentral gyrus of the insula (SPGI) was compared to that of other left hemisphere regions implicated in speech production. Results showed that SPGI contacts demonstrated significantly greater ERBP within the high-gamma frequency range (75-150Hz) during articulation compared to a listening condition. However, frontal and post-central regions demonstrated significantly greater responses to the articulation task compared to the SPGI. Results suggest the SPGI is active during articulation, but frontal and post-central regions demonstrate significantly more robust responses. Given the small sample size, and number of electrodes implanted in the SPGI, further study is warranted to confirm these findings.

Is the preference of natural versus man-made scenes driven by bottom-up processing of the visual features of nature?

Previous research has shown that viewing images of nature scenes can have a beneficial effect on memory, attention, and mood. In this study, we aimed to determine whether the preference of natural versus man-made scenes is driven by bottom-up processing of the low-level visual features of nature. We used participants' ratings of perceived naturalness as well as esthetic preference for 307 images with varied natural and urban content. We then quantified 10 low-level image features for each image (a combination of spatial and color properties). These features were used to predict esthetic preference in the images, as well as to decompose perceived naturalness to its predictable (modeled by the low-level visual features) and non-modeled aspects. Interactions of these separate aspects of naturalness with the time it took to make a preference judgment showed that naturalness based on low-level features related more to preference when the judgment was faster (bottom-up). On the other hand, perceived naturalness that was not modeled by low-level features was related more to preference when the judgment was slower. A quadratic discriminant classification analysis showed how relevant each aspect of naturalness (modeled and non-modeled) was to predicting preference ratings, as well as the image features on their own. Finally, we compared the effect of color-related and structure-related modeled naturalness, and the remaining unmodeled naturalness in predicting esthetic preference. In summary, bottom-up (color and spatial) properties of natural images captured by our features and the non-modeled naturalness are important to esthetic judgments of natural and man-made scenes, with each predicting unique variance.

The perception of naturalness correlates with low-level visual features of environmental scenes.

Previous research has shown that interacting with natural environments vs. more urban or built environments can have salubrious psychological effects, such as improvements in attention and memory. Even viewing pictures of nature vs. pictures of built environments can produce similar effects. A major question is: What is it about natural environments that produces these benefits? Problematically, there are many differing qualities between natural and urban environments, making it difficult to narrow down the dimensions of nature that may lead to these benefits. In this study, we set out to uncover visual features that related to individuals' perceptions of naturalness in images. We quantified naturalness in two ways: first, implicitly using a multidimensional scaling analysis and second, explicitly with direct naturalness ratings. Features that seemed most related to perceptions of naturalness were related to the density of contrast changes in the scene, the density of straight lines in the scene, the average color saturation in the scene and the average hue diversity in the scene. We then trained a machine-learning algorithm to predict whether a scene was perceived as being natural or not based on these low-level visual features and we could do so with 81% accuracy. As such we were able to reliably predict subjective perceptions of naturalness with objective low-level visual features. Our results can be used in future studies to determine if these features, which are related to naturalness, may also lead to the benefits attained from interacting with nature.

StimSync: open-source hardware for behavioral and MRI experiments.

BACKGROUND: Many neuroscience experiments rely on presenting stimuli and measuring participants' responses to these events. Often computer screens, speakers and keyboards are sufficient. However, these devices are not appropriate for some situations. For example, some studies present tactile or olfactory stimuli or brain stimulation. Likewise, keyboard buttons are not appropriate for use with vocal responses, small animals or individuals with motor impairments. NEW METHOD: We describe StimSync, which simulates USB keyboard inputs, allowing use with most experimental software. StimSync can measure button presses, optical signals from magnetic resonance imaging systems, changes in ambient light (e.g. synchronizing intracranial electrography), and auditory events (a voice key). In addition to the USB keyboard mode (necessarily millisecond precision), StimSync can also be set to provide higher precision timing. This feature can be used to validate timing, ensuring event synchronization (e.g. auditory events, visual events, brain stimulation). In addition to recording inputs, StimSync provides seven digital outputs for controlling external devices. Finally, StimSync can record analog inputs; we illustrate how this can be used to evaluate the rise time for computer displays. RESULTS: We observed outputs with a mean latency of 2.1ms (sd=0.17ms) and USB inputs with a mean latency of 2ms (sd=0.54ms). COMPARISON WITH EXISTING METHOD(S): StimSync statistically outperforms two professional solutions and numerically outperforms other devices described in the literature. CONCLUSIONS: StimSync (http://www.mccauslandcenter.sc.edu/CRNL/tools/stimsync) provides an open-source solution for controlling and validating neuroscience experiments. In addition to sharing the design, we have produced a batch of devices to demonstrate the market for professional implementations.