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Bodurka, J.

Publications and source records attributed to Bodurka, J..

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A library for fMRI real-time processing systems in python (RTPSpy) with comprehensive online noise reduction, fast and accurate anatomical image processing, and online processing simulation

Real-time fMRI (rtfMRI)has enormous potential for both mechanistic brain imaging studies or treatment-oriented neuromodulation. However, the adaption of rtfMRI has been limited due to technical difficulties implement an efficient computational framework. Here, we introduce a python library for real-time fMRI (rtfMRI) data processing systems, Real-Time Processing System in python (RTPSpy), to provide building blocks for a custom rtfMRI application with extensive and advanced functionalities. RTPSpy is a library package including 1) a fast, comprehensive, and flexible online fMRI image processing modules comparable to offline denoising, 2) utilities for fast and accurate anatomical image processing to define an anatomical target region, 3) a simulation system of online fMRI processing to optimize a pipeline and target signal calculation, 4) simple interface to an external application for feedback presentation, and 5) a boilerplate graphical user interface (GUI) integrating operations with RTPSpy library. The fast and accurate anatomical image processing utility wraps external tools, including FastSurfer, ANTs, and AFNI, to make tissue segmentation and region of interest masks. We confirmed that the quality of the output masks was comparable with FreeSurfer, and the anatomical image processing could complete in a few minutes. The modular nature of RTPSpy provides the ability to use it for a simulation analysis to optimize a processing pipeline and target signal calculation. We present a sample script for building a real-time processing pipeline and running a simulation using RTPSpy. The library also offers a simple signal exchange mechanism with an external application using a TCP/IP socket. While the main components of the RTPSpy are the library modules, we also provide a GUI class for easy access to the RTPSpy functions. The boilerplate GUI application provided with the package allows users to develop a customized rtfMRI application with minimum scripting labor. The limitations of the package as it relates to environment-specific implementations are discussed. These library components can be customized and can be used in parts. Taken together, RTPSpy is an efficient and adaptable option for developing rtfMRI applications. The package is available from GitHub (https://github.com/mamisaki/RTPSpy) with GPL3 license.

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fMRI Informed Montage Selection for Transcranial Electrical Stimulation: Frontoparietal Synchronization for Drug Cue Reactivity

BackgroundFrontoparietal network (FPN) with multiple cortical nodes is involved in executive functions. Transcranial electrical stimulation (tES) can potentially modulate interactions between these nodes using frontoparietal synchronization (FPS). Here we used fMRI and computational head models (CHMs) to inform electrode montage and dosage selection in FPS. MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Two sets of 4x1 HD electrodes with anode over F3 and F4 were simulated and spheres around maximum electric field in each hemisphere were defined as frontal seeds. Using frontal seeds, a task-based functional connectivity analysis was conducted based on a seed-to-whole brain generalized psychophysiological interaction (gPPI). Electrode placement for parietal sites was selected based on gPPI results. Task-based and resting-state connectivity were compared between fMRI-informed and classic F3-P3/F4-P4 montages. ResultsWhole-brain gPPI showed two significant clusters (left: 506 voxels P=0.006, right: 455 voxels P=0.016), located in the inferior parietal lobule under the CP5 and CP6 electrode location. Pair-wise ROI-based gPPI comparing informed (F3-CP5/F4-CP6) and classic (F3-P3/F4-P4) montages showed significant increased PPI and resting-state connectivity only in the informed montage. Cue-induced craving score was also correlated with left (F3-CP5) frontoparietal connectivity in the fMRI-informed montage. ConclusionThis study proposes an analytic pipeline to select electrode montage and dosage in dual site tES using CHMs and task-based connectivity. Stimulating F3-F4 can tap into both FPN and saliency network (SN) based on the montage selection. Using CHM and fMRI will be essential to navigating ample parameter space in the stimulation protocols for future tES studies. HighlightsO_LIWe demonstrated a methodology for montage selection in network-based tES C_LIO_LITask-based functional connectivity can inform dual-site tES montage selection C_LIO_LIHead models can help to induce balance tES dose in targeted brain regions C_LIO_LITargeting DLPFC with tES can tap into both saliency and frontoparietal networks C_LIO_LILower resting-state frontoparietal connectivity before cue exposure followed by a greater craving C_LI

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Online Closed-Loop Real-Time tES-fMRI for Brain Modulation: Feasibility, Noise/Safety and Pilot Study

Recent studies suggest that transcranial electrical stimulation (tES) can be performed during functional magnetic resonance imaging (fMRI). The novel approach of using concurrent tES-fMRI to modulate and measure targeted brain activity/connectivity may provide unique insights into the causal interactions between the brain neural responses and psychiatric/neurologic signs and symptoms, and importantly, guide the development of new treatments. However, tES stimulation parameters to optimally influence the underlying brain activity in health and disorder may vary with respect to phase, frequency, intensity and electrodes montage. Here, we delineate how a closed-loop tES-fMRI study of frontoparietal network modulation can be designed and performed. We also discuss the challenges of running a concurrent tES-fMRI, describing how we can distinguish clinically meaningful physiological changes caused by tES from tES-related artifacts. There is a large methodological parameter space including electrode types, electrolytes, electrode montages, concurrent tES-fMRI hardware, online fMRI processing pipelines and closed-loop optimization algorithms that should be carefully selected for closed-loop tES-fMRI brain modulation. We also provide technical details on how safety and quality of tES-fMRI settings can be tested, and how these settings can be monitored during the study to ensure they do not exceed safety standards. The initial results of feasibility and applicability of closed-loop tES-fMRI are reported and potential hypotheses for the outcomes are discussed. Highlight pointsO_LIMethodological details of a closed-loop tES-fMRI study protocol are provided. C_LIO_LIThe protocol is performed successfully on a frontoparietal network without side-effects. C_LIO_LIThe temperature of electrodes in concurrent tES-fMRI remains in the safe range. C_LIO_LIProperly setup concurrent tES does not introduce MRI artifacts and noise. C_LIO_LISimplex optimizer could be used to find an optimal tES stimulation parameter. C_LI

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The impact of real-time fMRI denoising on online evaluation of brain activity and functional connectivity

ObjectiveComprehensive denoising is imperative in fMRI analysis to reliably evaluate neural activity from the blood oxygenation level dependent signal. In real-time fMRI, however, only a minimal denoising process has been applied and the impact of insufficient denoising on online brain activity estimation has not been assessed comprehensively. This study evaluated the noise reduction performance of online fMRI processes in a real-time estimation of regional brain activity and functional connectivity. ApproachWe performed a series of real-time processing simulations of online fMRI processing, including slice-timing correction, motion correction, spatial smoothing, signal scaling, and noise regression with high-pass filtering, motion parameters, motion derivatives, global signal, white matter/ventricle average signals, and physiological noise models with image-based retrospective correction of physiological motion effects (RETROICOR) and respiration volume per time (RVT). Main resultsAll the processing was completed in less than 400 ms for whole-brain voxels. Most processing had a benefit for noise reduction except for RVT that did not work due to the limitation of the online peak detection. The global signal regression, white matter/ventricle signal regression, and RETORICOR had a distinctive noise reduction effect, depending on the target signal, and could not substitute for each other. Global signal regression could eliminate the noise-associated bias in the mean dynamic functional connectivity across time. SignificanceThe results indicate that extensive real-time denoising is possible and highly recommended for real-time fMRI applications.

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Neural indicators of human gut feelings

Understanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the bodys interior. Here, we investigated neural responses to gastrointestinal sensation using a minimally invasive mechanosensory probe by quantifying brain, stomach, and perceptual responses following the ingestion of a vibrating capsule. Participants successfully perceived capsule stimulation under two vibration conditions (normal and enhanced), as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with a more rapid detection of the stimulation and reduced reaction time variability. Stomach stimulation induced early and late neural responses in parieto-occipital leads near the midline. Moreover, these gastric evoked potentials showed intensity-dependent increases in amplitude and were significantly correlated with perceptual accuracy. These findings highlight a unique form of enterically-focused sensory monitoring within the human brain, with implications for understanding gut-brain interactions in healthy and clinical populations.

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Determinants of Real-Time fMRI Neurofeedback Performance and Improvement: a Machine Learning Mega-Analysis

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in Open Science and data sharing.

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Predicting Sex from Resting-State fMRI Across Multiple Independent Acquired Datasets

Sex is an important biological variable often used in analyzing and describing the functional organization of the brain during cognitive and behavioral tasks. Several prior studies have shown that blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) functional connectivity (FC) can be used to differentiate sex among individuals. Herein, we demonstrate that sex can be further classified with high accuracy using the intrinsic BOLD signal fluctuations from resting-state fMRI (rs-fMRI). We adopted the amplitude of low-frequency fluctuation (ALFF), and the fraction of ALFF (fALFF) features from the automated anatomical atlas (AAL) and Powers functional atlas as an input to different machine learning (ML) methods. Using datasets from five independently acquired subject cohorts and with eight fMRI scanning sessions, we comprehensively assessed unbiased performance using nested-cross validation for within-sample and across sample accuracies. The results demonstrated high prediction accuracies for the Human Connectome Project (HCP) dataset (area under cure (AUC) > 0.89). The yielded accuracies suggest that sex difference is embodied and well-pronounced in the low-frequency BOLD signal fluctuation. The performance degrades with the heterogeneity of the cohort and suggests that other factors.e.g. psychiatric disorders and demographics influences the BOLD signal and may interact with the classification of sex. In addition, the results revealed high learning generalizability with the HCP scan, but not across different datasets. The intraclass correlation coefficient (ICC) across HCP scans showed moderate-to-good reliability based on atlas selection (ICC = 0.65 [0.63-0.67] and ICC= 0.78 [0.76-0.80].). We also assessed the effect of scan duration on the predictability of sex and showed that sex differences could be detected even with a short rs-fMRI scan (e.g., 2 minutes). Moreover, we provided statistical maps of the brain regions differentially recruited by or predicting sex using Shapely values and determined an overlap with previous reports of brain response due to sex differences. Altogether, our analysis suggests that sex differences are well-pronounced in rs-fMRI and should be considered seriously in any study design, analysis, or interpretation.

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Canonical EEG Microstate Dynamic Properties and Their Associations with fMRI Signals at Resting Brain

Electroencephalography microstates (EEG-ms) capture and reflect the spatio-temporal neural dynamics of the brain. A growing literature is employing EEG-ms-based analyses to study various mental illnesses and to evaluate brain mechanisms implicated in cognitive and emotional processing. The spatial and functional interpretation of the EEG-ms is still being investigated. Previous works studied the association of EEG-ms time courses with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal and suggested an association between EEG-ms and resting-state networks (RSNs). However, the distinctive association between EEG-ms temporal dynamics and brain neuronal activities is still not clear, despite the assumption that EEG-ms are an electrophysiological representation of RSNs activity. Recent works suggest a role for brain spontaneous EEG rhythms in contributing to and modulating canonical EEG-ms topographies and determining their classes (coined A through D) and metrics. This work simultaneously utilized EEG and fMRI to understand the EEG-ms and their properties further. We adopted the canonical EEG-ms analysis to extract three types of regressors for EEG-informed fMRI analyses: EEG-ms direct time courses, temporal activity per microstate, and pairwise temporal transitions among microstates (the latter two coined activity regressors). After convolving EEG-ms regressors with a hemodynamic response function, a generalized linear model whole-brain voxel-wise analysis was conducted to associate EEG-ms regressors with fMRI signals. The direct time course regressors replicated prior findings of the association between the fMRI signal and EEG-ms time courses but to a smaller extent. Notably, EEG-ms activity regressors were mostly anticorrelated with fMRI, including brain regions in the somatomotor, visual, dorsal attention, and ventral attention fMRI networks with no significant overlap for default mode, limbic or frontoparietal networks. A similar pattern emerged in using the transition regressors among microstates but not in self-transitions. The relatively short duration of each EEG-ms and the significant association of EEG-ms activity regressors with fMRI signals suggest that EEG-ms manifests successive transition from one brain functional state to another rather than being associated with specific brain functional state or RSN networks.

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Connectome-wide search for functional connectivity locus associated with pathological rumination as a target for real-time fMRI neurofeedback intervention

Real-time fMRI neurofeedback (rtfMRI-nf) enables noninvasive targeted intervention in brain activation with high spatial specificity. To achieve this promise of rtfMRI-nf, we introduced and demonstrated a data-driven framework to design a rtfMRI-nf intervention through the discovery of precise target location associated with clinical symptoms and neurofeedback signal optimization. Specifically, we identified the functional connectivity locus associated with rumination symptoms, utilizing a connectome-wide search in resting-state fMRI data from a large cohort of mood and anxiety disorder individuals (N=223) and healthy controls (N=45). Then, we performed a rtfMRI simulation analysis to optimize the online functional connectivity neurofeedback signal for the identified functional connectivity. The connectome-wide search was performed in the medial prefrontal cortex and the posterior cingulate cortex/precuneus brain regions to identify the precise location of the functional connectivity associated with rumination severity as measured by the ruminative response style (RRS) scale. The analysis found that the functional connectivity between the loci in the precuneus (-6, -54, 48 mm in MNI) and the right temporo-parietal junction (RTPJ; 49, -49, 23 mm) was positively correlated with RRS scores (depressive, p < 0.001; brooding, p < 0.001; reflective, p = 0.002) in the mood and anxiety disorder group. We then performed a rtfMRI processing simulation to optimize the online computation of the precuneus-RTPJ connectivity. We determined that the two-point method without a control region was appropriate as a functional connectivity neurofeedback signal with less dependence on signal history and its accommodation of head motion. The present study offers a discovery framework for the precise location of functional connectivity targets for rtfMRI-nf intervention, which could help directly translate neuroimaging findings into clinical rtfMRI-nf interventions.

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Can we predict real-time fMRI neurofeedback learning success from pre-training brain activity?

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large interindividual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pre-training functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pre-training activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.

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Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.\n\nHighlightsO_LIAn overview of the MRI processing pipeline for the ABCD Study\nC_LIO_LIA discussion on the challenges of large, multisite population studies\nC_LIO_LIA methodological reference for users of publicly shared data from the ABCD Study\nC_LI

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