Connectivity Matrices Research Articles

Dispersive currents explain patterns of population connectivity in an ecologically and economically important fish.

How to identify the drivers of population connectivity remains a fundamental question in ecology and evolution. Answering this question can be challenging in aquatic environments where dynamic lake and ocean currents coupled with high levels of dispersal and gene flow can decrease the utility of modern population genetic tools. To address this challenge, we used RAD-Seq to genotype 959 yellow perch (Perca flavescens), a species with an ~40-day pelagic larval duration (PLD), collected from 20 sites circumscribing Lake Michigan. We also developed a novel, integrative approach that couples detailed biophysical models with eco-genetic agent-based models to generate "predictive" values of genetic differentiation. By comparing predictive and empirical values of genetic differentiation, we estimated the relative contributions for known drivers of population connectivity (e.g., currents, behavior, PLD). For the main basin populations (i.e., the largest contiguous portion of the lake), we found that high gene flow led to low overall levels of genetic differentiation among populations (F ST = 0.003). By far the best predictors of genetic differentiation were connectivity matrices that were derived from periods of time when there were strong and highly dispersive currents. Thus, these highly dispersive currents are driving the patterns of population connectivity in the main basin. We also found that populations from the northern and southern main basin are slightly divergent from one another, while those from Green Bay and the main basin are highly divergent (F ST = 0.11). By integrating biophysical and eco-genetic models with genome-wide data, we illustrate that the drivers of population connectivity can be identified in high gene flow systems.

Symmetry-conserving maximally projected Wannier functions

Wannier functions are a powerful tool for the determination of topological properties of solids based on band structure calculations. Here, the authors present a simple and efficient scheme to obtain symmetry-conserving Wannier functions especially suitable for local orbital codes. They analyze which approximation of the basis contribution to the Berry connection and curvature matrices preserves symmetry and argue which Bloch function gauge is best suited for model systems, where the basis is not explicitly known.

Acupuncture Alters Brain's Dynamic Functional Network Connectivity in Stroke Patients with Motor Dysfunction: A Randomised Controlled Neuroimaging Trial.

Neuroimaging studies have confirmed that acupuncture can promote static functional reorganization in poststroke patients with motor dysfunction. But its effect on dynamic brain networks remains unclear. This study is aimed at investigating how acupuncture affected the brain's dynamic functional network connectivity (dFNC) after ischemic stroke. We conducted a single-center, randomised controlled neuroimaging study in ischemic stroke patients. A total of 53 patients were randomly divided into the true acupoint treatment group (TATG) and the sham acupoint treatment group (SATG) at a ratio of 2 : 1. Clinical assessments and magnetic resonance imaging (MRI) scans were performed on subjects before and after treatment. We used dFNC analysis to estimate distinct dynamic connectivity states. Then, the temporal properties and strength of functional connectivity (FC) matrix were compared within and between the two groups. The correlation analysis between dynamic characteristics and clinical scales was also calculated. All functional network connectivity (FNC) matrices were clustered into 3 connectivity states. After treatment, the TATG group showed a reduced mean dwell time and found attenuated FC between the sensorimotor network (SMN) and the frontoparietal network (FPN) in state 3, which was a sparsely connected state. The FC between the dorsal attention network (DAN) and the default mode network (DMN) was higher after treatment in the TATG group in state 1, which was a relative segregated state. The SATG group preferred to increase the mean dwell time and FC within FPN in state 2, which displayed a local tightly connected state. In addition, we found that the FC value increased between DAN and right frontoparietal network (RFPN) in state 1 in the TATG group after treatment compared to the SATG group. Correlation analyses before treatment showed that the Fugl-Meyer Assessment (FMA) lower score was negatively correlated with the mean dwell time in state 3. FMA score showed positive correlation with FC in RFPN-SMN in state 3. FMA-lower score was positively correlated with FC in DAN-DMN and DAN-RFPN in state 1. Acupuncture has the potential to modulate abnormal temporal properties and promote the balance of separation and integration of brain function. True acupoint stimulation may have a more positive effect on regulating the brain's dynamic function. Clinical Trial Registration. This trial is registered with Chinese Clinical Trials Registry (ChiCTR1800016263).

Hierarchical Wilson-Cowan Models and Connection Matrices.

This work aims to study the interplay between the Wilson-Cowan model and connection matrices. These matrices describe cortical neural wiring, while Wilson-Cowan equations provide a dynamical description of neural interaction. We formulate Wilson-Cowan equations on locally compact Abelian groups. We show that the Cauchy problem is well posed. We then select a type of group that allows us to incorporate the experimental information provided by the connection matrices. We argue that the classical Wilson-Cowan model is incompatible with the small-world property. A necessary condition to have this property is that the Wilson-Cowan equations be formulated on a compact group. We propose a p-adic version of the Wilson-Cowan model, a hierarchical version in which the neurons are organized into an infinite rooted tree. We present several numerical simulations showing that the p-adic version matches the predictions of the classical version in relevant experiments. The p-adic version allows the incorporation of the connection matrices into the Wilson-Cowan model. We present several numerical simulations using a neural network model that incorporates a p-adic approximation of the connection matrix of the cat cortex.

Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes

BackgroundWe aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct...

Connective tissue matrices from placental disc for wound healing: mini-review.

Wound management is a complex procedure that includes multiple factors that play major roles in the healing process. Extracellular matrix-based approaches are emerging strategies for promoting wound healing. The extracellular matrix is an extensive three-dimensional molecular network comprising a variety of fibrous proteins, glycosaminoglycans, and proteoglycans. One of the rich sources of extracellular matrix components is placental tissues, which have a long history of use in tissue repair and regeneration. PURPOSE OF WORK: This mini-review focuses on essential characteristics of placental disc, comparison of four commercially available placental connective matrices (Axiofill, Dermavest, Plurivest, and Interfyl) obtained from the placental disc, and their supporting studies in the use of wound healing applications.

Developmental differences in functional organization of multispectral networks.

Assessing brain connectivity during rest has become a widely used approach to identify changes in functional brain organization during development. Generally, previous works have demonstrated that brain activity shifts from more local to more distributed processing from childhood into adolescence. However, the majority of those works have been based on functional magnetic resonance imaging measures, whereas multispectral functional connectivity, as measured using magnetoencephalography (MEG), has been far less characterized. In our study, we examined spontaneous cortical activity during eyes-closed rest using MEG in 101 typically developing youth (9-15years old; 51 females, 50 males). Multispectral MEG images were computed, and connectivity was estimated in the canonical delta, theta, alpha, beta, and gamma bands using the imaginary part of the phase coherence, which was computed between 200 brain regions defined by the Schaefer cortical atlas. Delta and alpha connectivity matrices formed more communities as a function of increasing age. Connectivity weights predominantly decreased with age in both frequency bands; delta-band differences largely implicated limbic cortical regions and alpha band differences in attention and cognitive networks. These results are consistent with previous work, indicating the functional organization of the brain becomes more segregated across development, and highlight spectral specificity across different canonical networks.

GLACIER: GLASS-BOX TRANSFORMER FOR INTERPRETABLE DYNAMIC NEUROIMAGING.

Deep learning models can perform as well or better than humans in many tasks, especially vision related. Almost exclusively, these models are used to perform classification or prediction. However, deep learning models are usually of black-box nature, and it is often difficult to interpret the model or the features. The lack of interpretability causes a restrain from applying deep learning to fields such as neuroimaging, where the results must be transparent, and interpretable. Therefore, we present a 'glass-box' deep learning model and apply it to the field of neuroimaging. Our model mixes spatial and temporal dimensions in succession to estimate dynamic connectivity between the brain's intrinsic networks. The interpretable connectivity matrices produced by our model result in beating state-of-the-art models on many tasks using multiple functional MRI datasets. More importantly, our model estimates task-based flexible connectivity matrices, unlike static methods such as Pearson's correlation coefficients.

LOCUS: A REGULARIZED BLIND SOURCE SEPARATION METHOD WITH LOW-RANK STRUCTURE FOR INVESTIGATING BRAIN CONNECTIVITY.

Network-oriented research has been increasingly popular in many scientific areas. In neuroscience research, imaging-based network connectivity measures have become the key for understanding brain organizations, potentially serving as individual neural fingerprints. There are major challenges in analyzing connectivity matrices, including the high dimensionality of brain networks, unknown latent sources underlying the observed connectivity, and the large number of brain connections leading to spurious findings. In this paper we propose a novel blind source separation method with low-rank structure and uniform sparsity (LOCUS) as a fully data-driven decomposition method for network measures. Compared with the existing method that vectorizes connectivity matrices ignoring brain network topology, LOCUS achieves more efficient and accurate source separation for connectivity matrices using low-rank structure. We propose a novel angle-based uniform sparsity regularization that demonstrates better performance than the existing sparsity controls for low-rank tensor methods. We propose a highly efficient iterative node-rotation algorithm that exploits the block multiconvexity of the objective function to solve the nonconvex optimization problem for learning LOCUS. We illustrate the advantage of LOCUS through extensive simulation studies. Application of LOCUS to Philadelphia Neurodevelopmental Cohort neuroimaging study reveals biologically insightful connectivity traits which are not found using the existing method.

A Convolutional Neural Network-Based Connectivity Enhancement Approach for Autism Spectrum Disorder Detection.

Autism spectrum disorder (ASD) represents an ongoing obstacle facing many researchers to achieving early diagnosis with high accuracy. To advance developments in ASD detection, the corroboration of findings presented in the existing body of autism-based literature is of high importance. Previous works put forward theories of under- and over-connectivity deficits in the autistic brain. An elimination approach based on methods that are theoretically comparable to the aforementioned theories proved the existence of these deficits. Therefore, in this paper, we propose a framework that takes into account the properties of under- and over-connectivity in the autistic brain using an enhancement approach coupled with deep learning through convolutional neural networks (CNN). In this approach, image-alike connectivity matrices are created, and then connections related to connectivity alterations are enhanced. The overall objective is the facilitation of early diagnosis of this disorder. After conducting tests using information from the large multi-site Autism Brain Imaging Data Exchange (ABIDE I) dataset, the results show that this approach provides an accurate prediction value reaching up to 96%.

Resting-state MRI functional connectivity as a neural correlate of multidomain lifestyle adherence in older adults at risk for Alzheimer’s disease

Prior research has demonstrated the importance of a healthy lifestyle to protect brain health and diminish dementia risk in later life. While a multidomain lifestyle provides an ecological perspective to voluntary engagement, its association with brain health is still under-investigated. Therefore, understanding the neural mechanisms underlying multidomain lifestyle engagement, particularly in older adults at risk for Alzheimer’s disease (AD), gives valuable insights into providing lifestyle advice and intervention for those in need. The current study included 139 healthy older adults with familial risk for AD from the Prevent-AD longitudinal aging cohort. Self-reported exercise engagement, cognitive activity engagement, healthy diet adherence, and social activity engagement were included to examine potential phenotypes of an individual’s lifestyle adherence. Two adherence profiles were discovered using data-driven clustering methodology [i.e., Adherence to healthy lifestyle (AL) group and Non-adherence to healthy lifestyle group]. Resting-state functional connectivity matrices and grey matter brain features obtained from magnetic resonance imaging were used to classify the two groups using a support vector machine (SVM). The SVM classifier was 75% accurate in separating groups. The features that show consistently high importance to the classification model were functional connectivity mainly between nodes located in different prior-defined functional networks. Most nodes were located in the default mode network, dorsal attention network, and visual network. Our results provide preliminary evidence of neurobiological characteristics underlying multidomain healthy lifestyle choices.

Microstructural Brain Pathology in Paranoid Schizophrenia (According to Magnetic Resonance Tractography)

Background: inconsistency of the obtained results of research on the pathology of microstructural connectivity in schizophrenia on the basis of tractography, absence of clinical application of special MRI techniques justify the need to continue scientific search in this direction. Objective: to identify the features of microstructural pathology of the brain in paranoid schizophrenia. Patients and methods: 25 patients diagnosed with paranoid schizophrenia (F20.0) were included in the main group, 30 healthy subjects without neurological and somatic diseases made up the control group. Instrumental studies were carried out on a Philips Ingenia magnetic resonance tomograph (magnetic field strength 1.5 T) using a DTI pulse sequence. Subsequent processing was carried out using “DSI Studio” (software for the analysis of tractor data). Results and discussion: the resulting microstructural brain changes demonstrated differences in the microstructural connectivity of the brain in patients with paranoid schizophrenia compared to the control group. Significant connections were revealed (at the given parameters for constructing connectivity matrices) between the hippocampus and the cingulate gyrus, the hippocampus and thalamus, thalamus and structures of the striopallidar system, and the absence of significant connections between the amygdala in the main group compared to the control group. The results of graph theoretical analysis of neural network indicators of the brain demonstrated higher values of indicators of “clustering” and the “small world” coefficient, characteristic path length, transitivity, density, and lower values of the global efficiency indicator of the main group compared to the control group. Conclusion: the obtained results demonstrate microstructural semiotics of neural network changes of brain in paranoid schizophrenia. Changes in the connectivity of the hippocampus, thalamus, and amygdala appear to be important tractographic semiotic features of the microstructural pathology of the brain in paranoid schizophrenia. The study is one of the stages of the search for a method of objectification and detection of disruption of brain neuroplasticity processes in the endogenous pathology of the schizophrenic spectrum.

Altered longitudinal structural connectome in paediatric mild traumatic brain injury: an Advancing Concussion Assessment in Paediatrics study.

Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48 h of sustaining a concussion (n = 360; 56% male) or mild orthopaedic injury (n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3 T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients.

Normalization effect of dopamine replacement therapy on brain functional connectome in Parkinson's disease.

Dopamine replacement therapy (DRT) represents the standard treatment for Parkinson's disease (PD), however, instant and long-term medication influence on patients' brain function have not been delineated. Here, a total of 97 drug-naïve patients, 43 patients under long-term DRT, and 94 normal control (NC) were, retrospectively, enrolled. Resting-state functional magnetic resonance imaging data and motor symptom assessments were conducted before and after levodopa challenge test. Whole-brain functional connectivity (FC) matrices were constructed. Network-based statistics were performed to assess FC difference between drug-naïve patients and NC, and these significant FCs were defined as disease-related connectomes, which were used for further statistical analyses. Patients showed better motor performances after both long-term DRT and levodopa challenge test. Two disease-related connectomes were observed with distinct patterns. The FC of the increased connectome, which mainly consisted of the motor, visual, subcortical, and cerebellum networks, was higher in drug-naïve patients than that in NC and was normalized after long-term DRT (p-value <.050). The decreased connectome was mainly composed of the motor, medial frontal, and salience networks and showed significantly lower FC in all patients than NC (p-value <.050). The global FC of both increased and decreased connectome was significantly enhanced after levodopa challenge test (q-value <0.050, false discovery rate-corrected). The global FC of increased connectome in ON-state was negatively associated with levodopa equivalency dose (r = -.496, q-value = 0.007). Higher global FC of the decreased connectome was related to better motor performances (r = -.310, q-value = 0.022). Our findings provided insights into brain functional alterations under dopaminergic medication and its benefit on motor symptoms.

Structural connectivity-based predictors of cognitive impairment in stroke patients attributable to aging.

Despite the rising global burden of stroke and its socio-economic implications, the neuroimaging predictors of subsequent cognitive impairment are still poorly understood. We address this issue by studying the relationship of white matter integrity assessed within ten days after stroke and patients' cognitive status one year after the attack. Using diffusion-weighted imaging, we apply the Tract-Based Spatial Statistics analysis and construct individual structural connectivity matrices by employing deterministic tractography. We further quantify the graph-theoretical properties of individual networks. The Tract-Based Spatial Statistic did identify lower fractional anisotropy as a predictor of cognitive status, although this effect was mostly attributable to the age-related white matter integrity decline. We further observed the effect of age propagating into other levels of analysis. Specifically, in the structural connectivity approach we identified pairs of regions significantly correlated with clinical scales, namely memory, attention, and visuospatial functions. However, none of them persisted after the age correction. Finally, the graph-theoretical measures appeared to be more robust towards the effect of age, but still were not sensitive enough to capture a relationship with clinical scales. In conclusion, the effect of age is a dominant confounder especially in older cohorts, and unless appropriately addressed, may falsely drive the results of the predictive modelling.

Towards reliable reconstruction of the mouse brain corticothalamic connectivity using diffusion MRI

Diffusion magnetic resonance imaging (dMRI) tractography has yielded intriguing insights into brain circuits and their relationship to behavior in response to gene mutations or neurological diseases across a number of species. Still, existing tractography approaches suffer from limited sensitivity and specificity, leading to uncertain interpretation of the reconstructed connections. Hence, in this study, we aimed to optimize the imaging and computational pipeline to achieve the best possible spatial overlaps between the tractography and tracer-based axonal projection maps within the mouse brain corticothalamic network. We developed a dMRI-based atlas of the mouse forebrain with structural labels imported from the Allen Mouse Brain Atlas (AMBA). Using the atlas and dMRI tractography, we first reconstructed detailed node-to-node mouse brain corticothalamic structural connectivity matrices using different imaging and tractography parameters. We then investigated the effects of each condition for accurate reconstruction of the corticothalamic projections by quantifying the similarities between the tractography and the tracer data from the Allen Mouse Brain Connectivity Atlas (AMBCA). Our results suggest that these parameters significantly affect tractography outcomes and our atlas can be used to investigate macroscopic structural connectivity in the mouse brain. Furthermore, tractography in mouse brain gray matter still face challenges and need improved imaging and tractography methods.

Recursive inverse dynamics sensitivity analysis of open-tree-type multibody systems

We present a first-order recursive approach to sensitivity analysis based on the application of the direct differentiation method to the inverse Lagrangian dynamics of rigid multibody systems. Our method is simple and efficient and is characterized by the following features. Firstly, it describes the kinematics of multibody systems using branch connectivity graphs and joint-branch connectivity matrices. For most mechanical systems with an open-tree kinematic structure, this method turns out to be more efficient compared to other kinematic descriptions employing joint or link connectivity graphs. Secondly, a recursive sensitivity analysis is presented for a dynamic system with an open-tree kinematic structure and inverse dynamic equations described in terms of the Lagrangian formalism. Thirdly, known approaches to recursive inverse dynamic and sensitivity analyses are modified to include dynamic systems with external forces and torques acting simultaneously at all joints. Finally, the proposed method for sensitivity analysis is easy to implement and computationally efficient. It can be utilized to evaluate the derivatives of the dynamic equations of multibody systems in gradient-based optimization algorithms. It also allows less experienced users to perform sensitivity analyses using the power of high-level programming languages such as MATLAB. To illustrate the method, simulation results for a human body model are discussed. The shortcomings of the method and possible directions for future work are outlined.

Identifying the engagement of a brain network during a targeted tDCS-fMRI experiment using a machine learning approach.

Transcranial direct current stimulation (tDCS) can noninvasively modulate behavior, cognition, and physiologic brain functions depending on polarity and dose of stimulation as well as montage of electrodes. Concurrent tDCS-fMRI presents a novel way to explore the parameter space of non-invasive brain stimulation and to inform the experimenter as well as the participant if a targeted brain region or a network of spatially separate brain regions has been engaged and modulated. We compared a multi-electrode (ME) with a single electrode (SE) montage and both active conditions with a no-stimulation (NS) control condition to assess the engagement of a brain network and the ability of different electrode montages to modulate network activity. The multi-electrode montage targeted nodal regions of the right Arcuate Fasciculus Network (AFN) with anodal electrodes placed over the skull position of the posterior superior temporal/middle temporal gyrus (STG/MTG), supramarginal gyrus (SMG), posterior inferior frontal gyrus (IFG) and a return cathodal electrode over the left supraorbital region. In comparison, the single electrode montage used only one anodal electrode over a nodal brain region of the AFN, but varied the location between STG/MTG, SMG, and posterior IFG for different participants. Whole-brain rs-fMRI was obtained approximately every three seconds. The tDCS-stimulator was turned on at 3 minutes after the scanning started. A 4D rs-fMRI data set was converted to dynamic functional connectivity (DFC) matrices using a set of ROI pairs belonging to the AFN as well as other unrelated brain networks. In this study, we evaluated the performance of five algorithms to classify the DFC matrices from the three conditions (ME, SE, NS) into three different categories. The highest accuracy of 0.92 was obtained for the classification of the ME condition using the K Nearest Neighbor (KNN) algorithm. In other words, applying the classification algorithm allowed us to identify the engagement of the AFN and the ME condition was the best montage to achieve such an engagement. The top 5 ROI pairs that made a major contribution to the classification of participant's rs-fMRI data were identified using model performance parameters; ROI pairs were mainly located within the right AFN. This proof-of-concept study using a classification algorithm approach can be expanded to create a near real-time feedback system at a participant level to detect the engagement and modulation of a brain network that spans multiple brain lobes.

Structural and functional connectivity reconstruction with CATO - A Connectivity Analysis TOolbox

We describe a Connectivity Analysis TOolbox (CATO) for the reconstruction of structural and functional brain connectivity based on diffusion weighted imaging and resting-state functional MRI data. CATO is a multimodal software package that enables researchers to run end-to-end reconstructions from MRI data to structural and functional connectome maps, customize their analyses and utilize various software packages to preprocess data. Structural and functional connectome maps can be reconstructed with respect to user-defined (sub)cortical atlases providing aligned connectivity matrices for integrative multimodal analyses. We outline the implementation and usage of the structural and functional processing pipelines in CATO. Performance was calibrated with respect to simulated diffusion weighted imaging data from the ITC2015 challenge and test-retest diffusion weighted imaging data and resting-state functional MRI data from the Human Connectome Project. CATO is open-source software distributed under the MIT License and available as a MATLAB toolbox and as a stand-alone application at www.dutchconnectomelab.nl/CATO.

354 Unitary neural correlates of executive control in pediatric transdiagnostic psychopathology

OBJECTIVES/GOALS: Childhood psychiatric symptoms are highly comorbid. Their co-occurrence and association with negative life outcomes is partially explained by deficits in executive control, or processes enabling self-regulation. Here, we test a novel executive neural target in three fMRI tasks and its relevance to shared psychopathology. METHODS/STUDY POPULATION: We studied 60 children [15 F/45 M; mean age (SD)=11.6 years (1.62)] with diverse diagnoses including attention deficit disorder (n=26) and autism spectrum disorder (n=22). We extracted a latent general factor of psychopathology using principal component analyses applied to parent-report Child Behavior Checklist syndrome scores. Subjects completed 3 executive control fMRI probes, tapping adaptive control, working memory, and inhibition. Correlational psychophysiological interaction (cPPI) analysis measured correlations between executive control-related modulations of activity in 414 network-affiliated parcels. We selected parcels exhibiting control-related cross-network correlations as well as control-related activity across all tasks and tested them for association with psychopathology. RESULTS/ANTICIPATED RESULTS: cPPI connectivity matrices were thresholded and graphs were identified using the Network-Based Statistic toolbox (p90th percentile PC) as well as control-related activation (&gt;10% activated voxels; p DISCUSSION/SIGNIFICANCE: Our results examine cross-network interactions between brain regions during 3 fMRI tasks and their role in explaining individual variation in psychopathology. As executive control links to both comorbidity and life outcomes, identifying the clinically-relevant neural correlates of controlled behavior may lead to transdiagnostic treatments.