Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling.

Disruptions in frontoparietal networks supporting emotion regulation have been long implicated in maladaptive childhood aggression. However, the association of connectivity between large-scale functional networks with aggressive behavior has not been tested. The present study examined whether the functional organization of the connectome predicts severity of aggression in children. This cross-sectional study included a transdiagnostic sample of 100 children with aggressive behavior (27 females) and 29 healthy controls without aggression or psychiatric disorders (13 females). Severity of aggression was indexed by the total score on the parent-rated Reactive-Proactive Aggression Questionnaire. During fMRI, participants completed a face emotion perception task of fearful and calm faces. Connectome-based predictive modeling with internal cross-validation was conducted to identify brain networks that predicted aggression severity. The replication and generalizability of the aggression predictive model was then tested in an independent sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Connectivity predictive of aggression was identified within and between networks implicated in cognitive control (medial-frontal, frontoparietal), social functioning (default mode, salience), and emotion processing (subcortical, sensorimotor) (r = 0.31, RMSE = 9.05, p = 0.005). Out-of-sample replication (p < 0.002) and generalization (p = 0.007) of findings predicting aggression from the functional connectome was demonstrated in an independent sample of children from the ABCD study (n = 1791; n = 1701). Individual differences in large-scale functional networks contribute to variability in maladaptive aggression in children with psychiatric disorders. Linking these individual differences in the connectome to variation in behavioral phenotypes will advance identification of neural biomarkers of maladaptive childhood aggression to inform targeted treatments.

Amygdala-prefrontal connectivity in children with maladaptive aggression is modulated by social impairment.

Aggressive behavior is common across childhood-onset psychiatric disorders and is associated with impairments in social cognition and communication. The present study examined whether amygdala connectivity and reactivity during face emotion processing in children with maladaptive aggression are moderated by social impairment. This cross-sectional study included a well-characterized transdiagnostic sample of 101 children of age 8-16 years old with clinically significant levels of aggressive behavior and 32 typically developing children without aggressive behavior. Children completed a face emotion perception task of fearful and calm faces during functional magnetic resonance imaging. Aggressive behavior and social functioning were measured by standardized parent ratings. Relative to controls, children with aggressive behavior showed reduced connectivity between the amygdala and the dorsolateral prefrontal cortex (PFC) during implicit emotion processing. In children with aggressive behavior, the association between reduced amygdala-ventrolateral PFC connectivity and greater severity of aggression was moderated by greater social impairment. Amygdala reactivity to fearful faces was also associated with severity of aggressive behavior for children without social deficits but not for children with social deficits. Social impairments entail difficulties in interpreting social cues and enacting socially appropriate responses to frustration or provocation, which increase the propensity for an aggressive response via diminished connectivity between the amygdala and the ventral PFC.

Perceptual and Semantic Phases of Face Identification Processing: A Multivariate Electroencephalography Study.

Rapid identification of a familiar face requires an image-invariant representation of person identity. A varying sample of familiar faces is necessary to disentangle image-level from person-level processing. We investigated the time course of face identity processing using a multivariate electroencephalography analysis. Participants saw ambient exemplars of celebrity faces that differed in pose, lighting, hairstyle, and so forth. A name prime preceded a face on half of the trials to preactivate person-specific information, whereas a neutral prime was used on the remaining half. This manipulation helped dissociate perceptual- and semantic-based identification. Two time intervals within the post-face onset electroencephalography epoch were sensitive to person identity. The early perceptual phase spanned 110-228 msec and was not modulated by the name prime. The late semantic phase spanned 252-1000 msec and was sensitive to person knowledge activated by the name prime. Within this late phase, the identity response occurred earlier in time (300-600 msec) for the name prime with a scalp topography similar to the FN400 ERP. This may reflect a matching of the person primed in memory with the face on the screen. Following a neutral prime, the identity response occurred later in time (500-800 msec) with a scalp topography similar to the P600f ERP. This may reflect activation of semantic knowledge associated with the identity. Our results suggest that processing of identity begins early (110 msec), with some tolerance to image-level variations, and then progresses in stages sensitive to perceptual and then to semantic features.

Sensitivity to Faces with Typical and Atypical Part Configurations within Regions of the Face-processing Network: An fMRI Study.

Perception of faces has been shown to engage a domain-specific set of brain regions, including the occipital face area (OFA) and the fusiform face area (FFA). It is commonly held that the OFA is responsible for the detection of faces in the environment, whereas the FFA is responsible for processing the identity of the face. However, an alternative model posits that the FFA is responsible for face detection and subsequently recruits the OFA to analyze the face parts in the service of identification. An essential prediction of the former model is that the OFA is not sensitive to the arrangement of internal face parts. In the current fMRI study, we test the sensitivity of the OFA and FFA to the configuration of face parts. Participants were shown faces in which the internal parts were presented in a typical configuration (two eyes above a nose above a mouth) or in an atypical configuration (the locations of individual parts were shuffled within the face outline). Perception of the atypical faces evoked a significantly larger response than typical faces in the OFA and in a wide swath of the surrounding posterior occipitotemporal cortices. Surprisingly, typical faces did not evoke a significantly larger response than atypical faces anywhere in the brain, including the FFA (although some subthreshold differences were observed). We propose that face processing in the FFA results in inhibitory sculpting of activation in the OFA, which accounts for this region's weaker response to typical than to atypical configurations.

Category representations in the brain are both discretely localized and widely distributed.

Whether category information is discretely localized or represented widely in the brain remains a contentious issue. Initial functional MRI studies supported the localizationist perspective that category information is represented in discrete brain regions. More recent fMRI studies using machine learning pattern classification techniques provide evidence for widespread distributed representations. However, these latter studies have not typically accounted for shared information. Here, we find strong support for distributed representations when brain regions are considered separately. However, localized representations are revealed by using analytical methods that separate unique from shared information among brain regions. The distributed nature of shared information and the localized nature of unique information suggest that brain connectivity may encourage spreading of information but category-specific computations are carried out in distinct domain-specific regions. NEW & NOTEWORTHY Whether visual category information is localized in unique domain-specific brain regions or distributed in many domain-general brain regions is hotly contested. We resolve this debate by using multivariate analyses to parse functional MRI signals from different brain regions into unique and shared variance. Our findings support elements of both models and show information is initially localized and then shared among other regions leading to distributed representations being observed.

The Effects of Face Inversion and Face Race on the P100 ERP.

Research about the neural basis of face recognition has investigated the timing and anatomical substrates of different stages of face processing. Scalp-recorded ERP studies of face processing have focused on the N170, an ERP with a peak latency of ∼170 msec that has long been associated with the initial structural encoding of faces. However, several studies have reported earlier ERP differences related to faces, suggesting that face-specific processes might occur before N170. Here, we examined the influence of face inversion and face race on the timing of face-sensitive scalp-recorded ERPs by examining neural responses to upright and inverted line-drawn and luminance-matched white and black faces in a sample of white participants. We found that the P100 ERP evoked by inverted faces was significantly larger than that evoked by upright faces. Although this inversion effect was statistically significant at 100 msec, the inverted-upright ERP difference peaked at 138 msec, suggesting that it might represent an activity in neural sources that overlap with P100. Inverse modeling of the inversion effect difference waveform suggested possible neural sources in pericalcarine extrastriate visual cortex and lateral occipito-temporal cortex. We also found that the inversion effect difference wave was larger for white faces. These results are consistent with behavioral evidence that individuals process the faces of their own races more configurally than faces of other races. Taken together, the inversion and race effects observed in the current study suggest that configuration influences face processing by at least 100 msec.

Functional Heterogeneity and Convergence in the Right Temporoparietal Junction.

The right temporoparietal junction (rTPJ) is engaged by tasks that manipulate biological motion processing, Theory of Mind attributions, and attention reorienting. The proximity of activations elicited by these tasks raises the question of whether these tasks share common cognitive component processes that are subserved by common neural substrates. Here, we used high-resolution whole-brain functional magnetic resonance imaging in a within-subjects design to determine whether these tasks activate common regions of the rTPJ. Each participant was presented with the 3 tasks in the same imaging session. In a whole-brain analysis, we found that only the right and left TPJs were activated by all 3 tasks. Multivoxel pattern analysis revealed that the regions of overlap could still discriminate the 3 tasks. Notably, we found significant cross-task classification in the right TPJ, which suggests a shared neural process between the 3 tasks. Taken together, these results support prior studies that have indicated functional heterogeneity within the rTPJ but also suggest a convergence of function within a region of overlap. These results also call for further investigation into the nature of the function subserved in this overlap region.

The Function Biomedical Informatics Research Network Data Repository.

The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical data sets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 data set consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 T scanners. The FBIRN Phase 2 and Phase 3 data sets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN's multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data.

Reactivation during encoding supports the later discrimination of similar episodic memories.

Episodic memory is characterized by remembering events as unique combinations of features. Even when some features of events overlap, we are later often able to discriminate among them. Here we ask whether hippocampally mediated reactivation of an earlier event when a similar one occurs supports subsequent memory that two similar but not identical events occurred (mnemonic discrimination). In two experiments, participants viewed objects (Experiment 1) or scenes (Experiment 2) during functional MRI (fMRI). After scanning, participants had to remember whether repeated items had been identical or similar. In Experiment 2, representational similarity between the 1st and 2nd presentation predicted participants' ability to remember that the presentations were different, suggesting that the first item was reactivated while viewing the second. A similar but weaker result was found in Experiment 1 that did not survive correction for multiple comparisons. Furthermore, both experiments yielded evidence that the hippocampus was involved in reactivation; hippocampal pattern similarity (and, in Experiment 2, hippocampal activity during the 2nd presentation) correlated with pattern similarity in several regions of visual cortex. These results provide the first fMRI evidence that hippocampally mediated reactivation contributes to the later memory that two similar, but different events occurred. © 2016 Wiley Periodicals, Inc.

Electrophysiological Correlates of Refreshing: Event-related Potentials Associated with Directing Reflective Attention to Face, Scene, or Word Representations.

Refreshing is the component cognitive process of directing reflective attention to one of several active mental representations. Previous studies using fMRI suggested that refresh tasks involve a component process of initiating refreshing as well as the top-down modulation of representational regions central to refreshing. However, those studies were limited by fMRI's low temporal resolution. In this study, we used EEG to examine the time course of refreshing on the scale of milliseconds rather than seconds. ERP analyses showed that a typical refresh task does have a distinct electrophysiological response as compared to a control condition and includes at least two main temporal components: an earlier (∼400 msec) positive peak reminiscent of a P3 response and a later (∼800-1400 msec) sustained positivity over several sites reminiscent of the late directing attention positivity. Overall, the evoked potentials for refreshing representations from three different visual categories (faces, scenes, words) were similar, but multivariate pattern analysis showed that some category information was nonetheless present in the EEG signal. When related to previous fMRI studies, these results are consistent with a two-phase model, with the first phase dominated by frontal control signals involved in initiating refreshing and the second by the top-down modulation of posterior perceptual cortical areas that constitutes refreshing a representation. This study also lays the foundation for future studies of the neural correlates of reflective attention at a finer temporal resolution than is possible using fMRI.

Repetition suppression of face-selective evoked and induced EEG recorded from human cortex.

In functional MRI studies, repetition suppression refers to the reduction of hemodynamic activation to repeated stimulus presentation. For example, the repeated presentation of a face reduces the hemodynamic response evoked by faces in the fusiform gyrus. The neural events that underlie repetition suppression are not well understood. Indeed, in contrast to the hemodynamic response, the face-specific N200 recorded from subdural electrodes on the ventral occipitotemporal cortex, primarily along the fusiform gyrus, has been reported to be insensitive to face-identity repetition. We have previously described a face-specific broadband gamma (30-100 Hz) response at ventral face-specific N200 sites that is functionally dissociable from the N200. In this study, we investigate whether gamma and other components of the electroencephalogram spectrum are affected by face-identity repetition independently of the N200. Participants viewed sequentially presented identical faces. At sites on and around the fusiform gyrus, we found that face repetition modulated alpha (8-12 Hz), low-gamma (30-60 Hz), and high-gamma (60-100 Hz) synchrony, but not the N200. These findings provide evidence of a spatially co-localized progression of face processing. Whereas the N200 reflects an initial obligatory response that is less sensitive to face-identity repetition, the subsequent spectral fluctuations reflect more elaborative face processing and are thus sensitive to face novelty. It is notable that the observed modulations were different for different frequency bands. We observed repetition suppression of broadband gamma, but repetition enhancement of alpha synchrony. This difference is discussed with regard to an existing model of repetition suppression and behavioral repetition priming.

Neural circuit disruptions of eye gaze processing in autism spectrum disorder and schizophrenia: An activation likelihood estimation meta-analysis.

BACKGROUND: Impairment in social cognition, particularly eye gaze processing, is a shared feature common to autism spectrum disorder (ASD) and schizophrenia. However, it is unclear if a convergent neural mechanism also underlies gaze dysfunction in these conditions. The present study examined whether this shared eye gaze phenotype is reflected in a profile of convergent neurobiological dysfunction in ASD and schizophrenia. METHODS: Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates across the whole brain to identify spatial convergence. Functional coactivation with regions emerging as significant was assessed using meta-analytic connectivity modeling. Functional decoding was also conducted. RESULTS: Fifty-six experiments (n = 30 with schizophrenia and n = 26 with ASD) from 36 articles met inclusion criteria, which comprised 354 participants with ASD, 275 with schizophrenia and 613 healthy controls (1242 participants in total). In ASD, aberrant activation was found in the left amygdala relative to unaffected controls during gaze processing. In schizophrenia, aberrant activation was found in the right inferior frontal gyrus and supplementary motor area. Across ASD and schizophrenia, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the left amygdala to domains related to emotion processing and cognition, the right inferior frontal gyrus to cognition and perception, and the right fusiform gyrus to visual perception, spatial cognition, and emotion perception. These regions also showed meta-analytic connectivity to frontoparietal and frontotemporal circuitry. CONCLUSION: Alterations in frontoparietal and frontotemporal circuitry emerged as neural markers of gaze impairments in ASD and schizophrenia. These findings have implications for advancing transdiagnostic biomarkers to inform targeted treatments for ASD and schizophrenia.

Dissociating the detection of intentionality from animacy in the right posterior superior temporal sulcus.

Certain motion patterns can cause even simple geometric shapes to be perceived as animate. Viewing such displays evokes strong activation in temporoparietal cortex, including areas in and near the (predominantly right) posterior superior temporal sulcus (pSTS). These brain regions are sensitive to socially relevant information, but the nature of the social information represented in pSTS is unclear. For example, previous studies have been unable to explore the perception of shifting intentions beyond animacy. This is due in part to the ubiquitous use of complex displays that combine several types of social information, with little ability to control lower-level visual cues. Here we address this challenge by manipulating intentionality with parametric precision while holding cues to animacy constant. Human subjects were exposed to a "wavering wolf" display, in which one item (the wolf) chased continuously, but its goal (i.e., the sheep) frequently switched among other shapes. By contrasting this with three other control displays, we find that the wolf's changing intentions gave rise to strong selective activation in the right pSTS, compared with (1) a wolf that chases with a single unchanging intention, (2) very similar patterns of motion (and motion change) that are not perceived as goal-directed, and (3) abrupt onsets and offsets of moving objects. These results demonstrate in an especially well controlled manner that right pSTS is involved in social perception beyond physical properties such as motion energy and salience. More importantly, these results demonstrate for the first time that this region represents perceived intentions beyond animacy.

Probabilistic atlases for face and biological motion perception: an analysis of their reliability and overlap.

Neuroimaging research has identified several category-selective regions in visual cortex that respond most strongly when viewing an exemplar image from a preferred category, such as faces. Recent studies, however, have suggested a more complex pattern of activation that has been heretofore unrecognized, e.g., the presence of additional patches of activation to faces beyond the well-studied fusiform face area, and the activation of ostensible face selective regions by animate motion of non-biological forms. Here, we characterize the spatial pattern of brain activity evoked by viewing faces or biological motion in large fMRI samples (N>120). We create probabilistic atlases for both face and biological motion activation, and directly compare their spatial patterns of activation. Our findings support the suggestion that the fusiform face area is composed of at least two separable foci of activation. The face-evoked response in the fusiform and nearby ventral temporal cortex has good reliability across runs; however, we found surprisingly high variability in lateral brain regions by faces, and for all brain regions by biological motion, which had an overall much lower effect size. We found that faces and biological motion evoke substantially overlapping activation distributions in both ventral and lateral occipitotemporal cortices. The peaks of activation for these different categories within these overlapping regions were close but distinct.

Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans.

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n = 30) with comorbid PTSD and depression and non-TBI participants from primary (n = 42) and confirmatory (n = 28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter-specific registration followed by whole-brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (P < 0.05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, and splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with "feeling dazed or confused," but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast- and impact-related mild TBI that involves a cascade of inflammatory and neurochemical events.

Goal-directed actions activate the face-sensitive posterior superior temporal sulcus and fusiform gyrus in the absence of human-like perceptual cues.

The conditions under which we identify entities as animate agents and the neural mechanisms supporting this ability are central questions in social neuroscience. Prior studies have focused upon 2 perceptual cues for signaling animacy: 1) surface features representing body forms such as faces, torsos, and limbs and 2) motion cues associated with biological forms. Here, we consider a third cue--the goal-directedness of an action. Regions in the social brain network, such as the right posterior superior temporal sulcus (pSTS) and fusiform face area (FFA), are activated by human-like motion and body form perceptual cues signaling animacy. Here, we investigate whether these same brain regions are activated by goal-directed motion even when performed by entities that lack human-like perceptual cues. We observed an interaction effect whereby the presence of either human-like perceptual cues or goal-directed actions was sufficient to activate the right pSTS and FFA. Only stimuli that lacked human-like perceptual cues and goal-directed actions failed to activate the pSTS and FFA at the same level.

Category-selective background connectivity in ventral visual cortex.

Ventral visual cortex contains specialized regions for particular object categories, but little is known about how these regions interact during object recognition. Here we examine how the face-selective fusiform gyrus (FG) and the scene-selective parahippocampal cortex (PHC) interact with each other and with the rest of the brain during different visual tasks. To assess these interactions, we developed a novel approach for identifying patterns of connectivity associated with specific task sets, independent of stimulus-evoked responses. We tested whether this "background connectivity" between the FG and PHC was modulated when subjects engaged in face and scene processing tasks. In contrast to what would be predicted from biased competition or intrinsic activity accounts, we found that the strength of FG-PHC background connectivity depended on which category was task relevant: connectivity increased when subjects attended to scenes (irrespective of whether a competing face was present) and decreased when subjects attended to faces (irrespective of competing scenes). We further discovered that posterior occipital cortex was correlated selectively with the FG during face tasks and the PHC during scene tasks. These results suggest that category specificity exists not only in which regions respond most strongly but also in how these and other regions interact.

The fMRI BOLD signal tracks electrophysiological spectral perturbations, not event-related potentials.

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are primary tools of the psychological neurosciences. It is therefore important to understand the relationship between hemodynamic and electrophysiological responses. An early study by Huettel and colleagues found that the coupling of fMRI blood-oxygen-level-dependent signal (BOLD) and subdurally-recorded signal-averaged event-related potentials (ERPs) was not consistent across brain regions. Instead, a growing body of evidence now indicates that hemodynamic changes measured by fMRI reflect non-phase-locked changes in high frequency power rather than the phase-locked ERP. Here, we revisit the data from Huettel and colleagues and measure event-related spectral perturbations (ERSPs) to examine the time course of frequency changes. We found that, unlike the ERP, γ-ERSP power was consistently coupled with the hemodynamic response across three visual cortical regions. Stimulus duration modulated the BOLD signal and the γ-ERSP in the peri-calcarine and fusiform cortices, whereas there was no such modulation of either physiological signal in the lateral temporal-occipital cortex. This finding reconciles the original report with the more recent literature and demonstrates that the ERP and ERSP reflect dissociable aspects of neural activity.

Neural systems for guilt from actions affecting self versus others.

Guilt is a core emotion governing social behavior by promoting compliance with social norms or self-imposed standards. The goal of this study was to contrast guilty responses to actions that affect self versus others, since actions with social consequences are hypothesized to yield greater guilty feelings due to adopting the perspective and subjective emotional experience of others. Sixteen participants were presented with brief hypothetical scenarios in which the participant's actions resulted in harmful consequences to self (guilt-self) or to others (guilt-other) during functional MRI. Participants felt more intense guilt for guilt-other than guilt-self and guilt-neutral scenarios. Guilt scenarios revealed distinct regions of activity correlated with intensity of guilt, social consequences of actions, and the interaction of guilt by social consequence. Guilt intensity was associated with activation of the dorsomedial PFC, superior frontal gyrus, supramarginal gyrus, and anterior inferior frontal gyrus. Guilt accompanied by social consequences was associated with greater activation than without social consequences in the ventromedial and dorsomedial PFC, precuneus, posterior cingulate, and posterior superior temporal sulcus. Finally, the interaction analysis highlighted select regions that were more strongly correlated with guilt intensity as a function of social consequence, including the left anterior inferior frontal gyrus, left ventromedial PFC, and left anterior inferior parietal cortex. Our results suggest these regions intensify guilt where harm to others may incur a greater social cost.

Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies.

This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery.