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Ritter, P.

Publications and source records attributed to Ritter, P..

At least 37 records · Page 2Linked to original sources

Lesion aware automated processing pipeline for multimodal neuroimaging stroke data and The Virtual Brain (TVB)

BackgroundProcessing stroke magnetic resonance imaging (MRI) brain data can be susceptible to lesion-based abnormalities. In this study we developed and validated the Lesion Aware automated Processing Pipeline (LeAPP) that incorporates mitigation measures, improving volumetric and connectomics outputs compared to current standards in automated MRI processing pipelines. MethodsBuilding upon the Human Connectome Project (HCP) minimal processing pipeline, we introduced correction measures, such as cost-function masking and virtual brain transplant, and extended functional and diffusion processing to match acquisition protocols often found in a clinical context. A total of 51 participants (36 stroke patients (65.7{+/-}12.96 years, 18 female) and 15 healthy controls (69.2{+/-}7.4 years, 7 female)) were processed across four time points for patients (3-5, 30-40, 85-95, 340-380 days after stroke onset) and one time point for controls. Artificially lesioned brains (N=82), derived from healthy brains and informed by real stroke lesions were created, thus generating ground-truth data for validation. The processing pipeline and validation framework are available as containerized open-source software. Reconstruction quality has been quantified on whole brain level and for lesion affected and unaffected regions-of-interest (ROIs) using metrics like dice score, volume difference and center-of-gravity distance. Global and local level connectome reconstruction was assessed using node strength, node centrality and clustering coefficient. ResultsThe new pipeline LeAPP provides close reconstructions of the ground truth. Deviations in reconstructed averaged whole brain node strength and all ROI based volume and connectome metrics were significantly reduced compared to the HCP pipeline without stroke specific mitigation measures. ConclusionsLeAPP improves reconstruction quality of multimodal MRI processing for brain parcellation and structural connectome estimation significantly over the non-adapted HCP in the presence of lesions and provides a robust framework for diffusion and functional image processing of clinical stroke data. This novel open-source automated processing pipeline contributes to a development towards reproducible research. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/555078v1_ufig1.gif" ALT="Figure 1"> View larger version (85K): org.highwire.dtl.DTLVardef@ca58aborg.highwire.dtl.DTLVardef@8342f4org.highwire.dtl.DTLVardef@1a0d4b9org.highwire.dtl.DTLVardef@1edf1cf_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Virtual brain simulations reveal network-specific parameters in neurodegenerative dementias

IntroductionNeural circuit alterations lay at the core of brain physiopathology, and yet are hard to unveil in living subjects. Virtual brain modelling (TVB), by exploiting structural and functional MRI, yields mesoscopic parameters of connectivity and synaptic transmission. MethodsWe used TVB to simulate brain networks, which are key for human brain function, in Alzheimers disease (AD) and Frontotemporal Dementia (FTD) patients, whose connectivity and synaptic parameters remain largely unknown; we then compared them to healthy controls, to reveal novel in vivo pathological hallmarks. ResultsThe pattern of simulated parameter differed between AD and FTD, shedding light on disease-specific alterations in brain networks. Individual subjects displayed subtle differences in network parameter patterns that significantly correlated with their individual neuropsychological, clinical, and pharmacological profiles. DiscussionThese TVB simulations, by informing about a new personalized set of networks parameters, open new perspectives for understanding dementias mechanisms and design personalized therapeutic approaches.

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Whole-brain modeling of the differential influences of Amyloid-Beta and Tau in Alzheimer's Disease

BackgroundAlzheimers Disease is a neurodegenerative condition associated with the accumulation of two misfolded proteins, amyloid-beta (A{beta}) and tau. We study their effect on neuronal activity, with the aim of assessing their individual and combined impact. MethodsWe use a whole-brain dynamic model to find the optimal parameters that best describe the effects of A{beta} and tau on the excitation-inhibition balance of the local nodes. ResultsWe found a clear dominance of A{beta} over tau in the early disease stages (MCI), while tau dominates over A{beta} in the latest stages (AD). We identify crucial roles for A{beta} and tau in complex neuronal dynamics and demonstrate the viability of using regional distributions to define models of large-scale brain function in AD. ConclusionsOur study provides further insight into the dynamics and complex interplay between these two proteins, opening the path for further investigations on biomarkers and candidate therapeutic targets in-silico.

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SEMPAI: a Self-Enhancing Multi-Photon Artificial Intelligence for prior-informed assessment of muscle function and pathology

Deep learning (DL) shows notable success in biomedical studies. However, most DL algorithms work as a black box, exclude biomedical experts, and need extensive data. We introduce the Self-Enhancing Multi-Photon Artificial Intelligence (SEMPAI), that integrates hypothesis-driven priors in a data-driven DL approach for research on multiphoton microscopy (MPM) of muscle fibers. SEMPAI utilizes meta-learning to optimize prior integration, data representation, and neural network architecture simultaneously. This allows hypothesis testing and provides interpretable feedback about the origin of biological information in MPM images. SEMPAI performs joint learning of several tasks to enable prediction for small datasets. The method is applied on an extensive multi-study dataset resulting in the largest joint analysis of pathologies and function for single muscle fibers. SEMPAI outperforms state-of-the-art biomarkers in six of seven predictive tasks, including those with scarce data. SEMPAIs DL models with integrated priors are superior to those without priors and to prior-only machine learning approaches.

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Overcoming the Reproducibility Crisis - Results of the first Community Survey of the German National Research Data Infrastructure for Neuroscience.

The lack of reproducibility of research results is a serious problem - known as "the reproducibility crisis". The German National Research Data Infrastructure (NFDI) initiative implemented by the German Research Foundation (DFG) aims to help overcoming this crisis by developing sustainable solutions for research data management (RDM). NFDI comprises domain specific consortia across all science disciplines. In the field of neuroscience, NFDI Neuroscience (NFDI-Neuro) contributes to the strengthening of systematic and standardized RDM in its research communities. NFDI-Neuro conducted a comprehensive survey amongst the neuroscience community to determine the current needs, challenges, and opinions with respect to RDM. The outcomes of this survey are presented here. The German neuroscience community perceives barriers with respect to RDM and data sharing mainly linked to (1) lack of data and metadata standards, (2) lack of community adopted provenance tracking methods, 3) lack of a privacy preserving research infrastructure for sensitive data (4) lack of RDM literacy and (5) lack of required time and resources for proper RDM. NFDI-Neuro aims to systematically address these barriers by leading and contributing to the development of standards, tools, and infrastructure and by providing training, education, and support, as well as additional resources for RDM to its research community. The RDM work of NFDI-Neuro is conducted in close collaboration with its partner EBRAINS AISBL, the coordinating entity of the EU Flagship Human Brain Project, and its Research Infrastructure (RI) EBRAINS with more than 5000 registered users and developers from more than 70 countries of all continents. While NFDI-Neuro aims to address the German national needs, it closely aligns with the international community and the topics of the Digital Europe Program and EU Data Spaces. Significance StatementA comprehensive survey amongst the neuroscience community in Germany determined the current needs, challenges, and opinions with respect to standardized research data management (RDM) to overcome the reproducibility crisis. Significant deficits were pointed out concerning the perceived lack of standards for data and metadata, lack of provenance tracking and versioning of data, lack of protected digital research infrastructure for sensitive data and the lack of education and resources for proper RDM. Yet, at the same time, an overwhelming majority of community members indicated that they would be willing to share their data with other researchers and are interested to increase their RDM skills. Thus, the survey results suggest that training, the provision of standards, tools, infrastructure and additional resources for RDM holds the potential to significantly facilitate reproducible research in neuroscience.

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White-matter degradation and dynamical compensation support age-related functional alterations in human brain

Structural connectivity of the brain at different ages is analyzed using diffusion-weighted Magnetic Resonance Imaging (MRI) data. The largest decrease of the number and average length of streamlines is found for the long inter-hemispheric links, with the strongest impact for frontal regions. From the BOLD functional MRI (fMRI) time series we identify age-related changes of dynamic functional connectivity (dFC) and spatial covariation features of the FC links captured by metaconnectivity (MC). They indicate more constant dFC, but wider range and variance of MC. Finally we applied computational whole-brain network model based on oscillators, which mechanistically expresses the impact of the spatio-temporal structure of the brain (weights and the delays) to the dynamics. With this we tested several hypothesis, which revealed that the spatio-temporal reorganization of the brain with ageing, supports the observed functional fingerprints only if the model accounts for: (i) compensation of the individual brains for the overall loss of structural connectivity, and (ii) decrease of propagation velocity due to the loss of myelination. We also show that having these two conditions, it is sufficient to decompose the time-delays as bimodal distribution that only distinguishes between intra- and inter-hemispheric delays, and that the same working point also captures the static FC the best.

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A DEEP LEARNING APPROACH TO ESTIMATING INITIAL CONDITIONS OF BRAIN NETWORK MODELS IN REFERENCE TO MEASURED FMRI DATA

1.Brain Network Models (BNMs) are a family of dynamical systems that simulate whole brain activity using neural mass models to represent local activity in different brain regions that influence each other via a global structural network. Research has been interested in using these network models to explain measured whole brain activity measured via resting state functional magnetic resonance imaging (rs-fMRI). Properties computed over longer periods of simulated and measured data such as average functional connectivity (FC), have shown to be comparable with similar properties estimated from measured rs-fMRI data. While this shows that these network models have similar properties over the dynamical landscape, it is unclear how well simulated trajectories compare with empirical trajectories on a timepoint-by-timepoint basis. Previous studies have shown that BNMs are able to produce relevant features at shorter timescales, but analysis of short-term trajectories or transient dynamics as defined by synchronized predictions from BNM made at the same timescale as the collected data has not yet been conducted. Relevant neural processes exist in the time frame of measurements and are often used in task fMRI studies to understand neural responses to behavioral cues. Therefore, it is important to investigate how much of these dynamics are captured by our current brain simulations. To test the nature of BNMs short term trajectories against observed data, we utilize a deep learning technique known as Neural ODE that based on an observed sequence of fMRI measurements, estimates the initial conditions such that the BNMs simulation is synchronized to produce the closest trajectory relative to the observed data. We test to see if the parameterization of a specific well studied BNM, the Firing Rate Model, calculated by maximizing its accuracy in reproducing observed short term trajectories matches with the parameterized model that produces the best average long-term metrics. Our results show that such an agreement between parameterization using long and short simulation analysis exists if also considering other factors such as the sensitivity in accuracy with relative to changes in structural connectivity. Therefore, we conclude that there is evidence that by solving for initial conditions, BNMs can be simulated in a meaningful way when comparing against measured data trajectories, although future studies are necessary to establish how BNM activity relate to behavioral variables or to faster neural processes during this time period.

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Virtual deep brain stimulation: Multiscale co-simulation of a spiking basal ganglia model and a whole-brain mean-field model with The Virtual Brain

Deep brain stimulation (DBS) has been successfully applied in various neurodegenerative diseases as an effective symptomatic treatment. However, its mechanisms of action within the brain network are still poorly understood. Many virtual DBS models analyze a subnetwork around the basal ganglia and its dynamics as a spiking network with their details validated by experimental data. However, connectomic evidence shows widespread effects of DBS affecting many different cortical and subcortical areas. From a clinical perspective, various effects of DBS besides the motoric impact have been demonstrated. The neuroinformatics platform The Virtual Brain (TVB) offers a modeling framework allowing us to virtually perform stimulation, including DBS, and forecast the outcome from a dynamic systems perspective prior to invasive surgery with DBS lead placement. For an accurate prediction of the effects of DBS, we implement a detailed spiking model of the basal ganglia, which we combine with TVB via our previously developed co-simulation environment. This multiscale co-simulation approach builds on the extensive previous literature of spiking models of the basal ganglia while simultaneously offering a whole-brain perspective on widespread effects of the stimulation going beyond the motor circuit. In the first demonstration of our model, we show that virtual DBS can move the firing rates of a Parkinsons disease patients thalamus - basal ganglia network towards the healthy regime while, at the same time, altering the activity in distributed cortical regions with a pronounced effect in frontal regions. Thus, we provide proof of concept for virtual DBS in a co-simulation environment with TVB. The developed modeling approach has the potential to optimize DBS lead placement and configuration and forecast the success of DBS treatment for individual patients. Highlights- We implement and validate a co-simulation approach of a spiking network model for subcortical regions in and around the basal ganglia and interface it with mean-field network models for each cortical region. - Our simulations are based on a normative connectome including detailed tracts between the cortex and the basal ganglia regions combined with subject-specific optimized weights for a healthy control and a patient with Parkinsons disease. - We provide proof of concept by demonstrating that the implemented model shows biologically plausible dynamics during resting state including decreased thalamic activity in the virtual patient and during virtual deep brain stimulation including normalized thalamic activity and distributed altered cortical activity predominantly in frontal regions. - The presented co-simulation model can be used to tailor deep brain stimulation for individual patients.

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Multi-scale brain simulation with integrated positron emission tomography yields hidden local field potential activity that augments machine-learning classification of Alzheimer's disease

INTRODUCTIONComputational brain network modeling using The Virtual Brain (TVB) simulation platform acts synergistically with machine learning and multi-modal neuroimaging to reveal mechanisms and improve diagnostics in Alzheimers disease. METHODSWe enhance large-scale whole-brain simulation in TVB with a cause-and-effect model linking local Amyloid {beta} PET with altered excitability. We use PET and MRI data from 33 participants of Alzheimers Disease Neuroimaging Initiative (ADNI3) combined with frequency compositions of TVB-simulated local field potentials (LFP) for machine-learning classification. RESULTSThe combination of empirical neuroimaging features and simulated LFPs significantly outperformed the classification accuracy of empirical data alone by about 10% (weighted F1-score empirical 64.34% vs. combined 74.28%). Informative features showed high biological plausibility regarding the Alzheimers-typical spatial distribution. DISCUSSIONThe cause-and-effect implementation of local hyperexcitation caused by Amyloid {beta} can improve the machine-learning-driven classification of Alzheimers and demonstrates TVBs ability to decode information in empirical data employing connectivity-based brain simulation. RESEARCH IN CONTEXTO_LISYSTEMATIC REVIEW. Machine-learning has been proven to augment diagnostics of dementia in several ways. Imaging-based approaches enable early diagnostic predictions. However, individual projections of long-term outcome as well as differential diagnosis remain difficult, as the mechanisms behind the used classifying features often remain unclear. Mechanistic whole-brain models in synergy with powerful machine learning aim to close this gap. C_LIO_LIINTERPRETATION. Our work demonstrates that multi-scale brain simulations considering Amyloid {beta} distributions and cause-and-effect regulatory cascades reveal hidden electrophysiological processes that are not readily accessible through measurements in humans. We demonstrate that these simulation-inferred features hold the potential to improve diagnostic classification of Alzheimers disease. C_LIO_LIFUTURE DIRECTIONS. The simulation-based classification model needs to be tested for clinical usability in a larger cohort with an independent test set, either with another imaging database or a prospective study to assess its capability for long-term disease trajectories. C_LI

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Effect of aging-related network changes on unimanual sensorimotor learning - a simultaneous EEG-fMRI study

Sensorimotor coordination requires orchestrated network activity mediated by inter- and intra-hemispheric, excitatory and inhibitory neuronal interactions. Aging-related structural changes may alter these interactions. Disbalancing strength and timing of excitation and inhibition may limit motor performance. This is particularly true during motor coordination tasks that have to be learned through practice. To investigate this, we simultaneously acquired electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in two groups of healthy adults (young N=13: 20-25y and elderly N=14: 59-70y), while they were practicing a unimanual motor task. Both groups learned the task during brain scanning, which was confirmed by a 24h follow-up retention test. On average, quality of performance of older participants stayed significantly below that of the younger ones. Accompanying decreases in motor-event-related EEG-source beta band power ({beta}, 15-30 Hz) were lateralized in both groups towards the contralateral side, albeit more so in younger participants. In the latter, the mean {beta}-power during motor learning in bilateral pre-motor cortex (PM1) was significantly higher than in the older group. Combined EEG/fMRI analysis revealed positive correlations between fMRI signals and source-reconstructed {beta}-amplitude time courses in contralateral and ipsilateral M1, and negative correlations in bilateral PM1 for both groups. The {beta}-positive fMRI response in bilateral M1 might be explained by an increased cross-talk between hemispheres during periods of pronounced {beta}-activity. During learning, the Rolandic {beta}-power relative to rest was higher in bilateral PM1 in younger participants, suggesting less task-related beta band desynchronization in this (better performing) group. We also found positive correlations between Rolandic {beta}-amplitude and fMRI-BOLD in bilateral M1 and negative correlations bilateral in PM1. This indicates that increased {beta}-amplitudes are associated with increased M1 "activity" (positive BOLD response) and decreased PM1 "activity" (negative BOLD response). Our results point at decreased pre-motor inhibitory inputs to M1 as possible source for increased interhemispheric crosstalk and an aging-related decline in motor performance. HighlightsO_LISensorimotor coordination performance decreases with increasing age. C_LIO_LIDuring motor learning the {beta}-power in pre-motor areas is reduced with age. C_LIO_LIEEG/fMRI points at less effective inhibitory inputs from PM1 to ipsilateral M1 in older adults. C_LI

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Identifying optimal working points of individual Virtual Brains: A large-scale brain network modelling study

Brain network modeling studies are often limited with respect to the number of data features fitted, although capturing multiple empirical features is important to validate the models overall biological plausibility. Here we construct personalized models from multimodal data of 50 healthy individuals (18-80 years) with The Virtual Brain and demonstrate that an individuals brain has its own converging optimal working point in the parameter space that predicts multiple empirical features in functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). We further show that bimodality in the alpha band power - as an explored novel feature - arises as a function of global coupling and exhibits inter-regional differences depending on the degree. Reliable inter-individual differences with respect to these optimal working points were found that seem to be driven by the individual structural rather than by the functional connectivity. Our results provide the groundwork for future multimodal brain modeling studies.

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Modeling brain dynamics after tumor resection using The Virtual Brain

Brain tumor patients scheduled for tumor resection often face significant uncertainty, as the outcome of neurosurgery is difficult to predict at the individual patient level. Recently, computational modeling of brain activity using so-called brain network models has been introduced as a promising tool for this purpose. However, brain network models first have to be validated, before they can be used to predict brain dynamics. In prior work, we optimized individual brain network model parameters to maximize the fit with empirical brain activity. In this study, we extend this line of research by examining the stability of fitted parameters before and after tumor resection, and compare it with baseline parameter variability using data from healthy control subjects. Based on these findings, we perform the first \"virtual neurosurgery\" analyses to evaluate the potential of brain network modeling in predicting brain dynamics after tumor resection.\n\nWe find that brain network model parameters are relatively stable over time in brain tumor patients who underwent tumor resection, compared with baseline variability in healthy control subjects. In addition, we identify several robust associations between individually optimized model parameters, structural network topology and cognitive performance from pre-to post-operative assessment. Concerning the virtual neurosurgery analyses, we obtain promising results in some patients, whereas the predictive accuracy of the currently applied model is poor in others. These findings reveal interesting avenues for future research, as well as important limitations that warrant further investigation.

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Complexity matching: brain signals mirror environment information patterns during music listening and reward

Understanding how the human brain integrates information from the environment with ongoing, internal brain signals in order to produce individual perspective is an essential element of understanding the human mind. Brain signal complexity, measured with multiscale entropy, has been employed as a measure of information processing in the brain (Carpentier et al., 2016), and we propose that it can also be used to measure the information available from a stimulus. We can directly assess the correspondence, or functional isomorphism, between brain signal complexity and stimulus complexity as an indication of how well the brain reflects the content of the environment in an analysis that we termed complexity matching. Music makes an ideal stimulus input because it is a multidimensional, complex signal, and because of its emotion and reward-inducing potential. We found that electroencephalography (EEG) complexity was lower and more closely resembled the musical complexity when participants performed a perceptual task that required them to closely track the acoustics, compared to an emotional task that asked them to think about how the music made them feel. Music-derived reward scores on the Barcelona Music Reward Questionnaire (Mas-Herrero et al., 2013) correlated with worse complexity matching and higher EEG complexity. Compared to perceptual-level processing, emotional and reward responses are associated with additional internal information processes above and beyond those in the external stimulus.\n\nSignificance StatementExperience of our world is combination of the input from the environment, our expectations, and individual responses. For example, the same piece of music can elict happiness in one person and sadness in another. We researched this by measuring the information in pieces of music and whether listeners brain more closely followed that, or whether additional information was added by the brain. We noted when listeners were reacting to how music made them feel, their brains added more information and the degree to which this occurred related to how much they find music rewarding. Thus, we were able to provide clues as to how the brain integrates incoming information, adding to it to provide a richer perceptual and emotional experience.

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Linking molecular pathways and large-scale computational modeling to assess candidate disease mechanisms and pharmacodynamics in Alzheimer's disease

IntroductionWhile the prevalence of neurodegenerative diseases associated with dementia such as Alzheimers disease (AD) increases, our knowledge on the underlying mechanisms, outcome predictors, or therapeutic targets is limited. In this work, we demonstrate how computational multi-scale brain modelling links phenomena of different scales and therefore identifies potential disease mechanisms leading the way to improved diagnostics and treatment. MethodsThe Virtual Brain (TVB; thevirtualbrain.org) neuroinformatics platform allows standardized large-scale structural connectivity-based simulations of whole brain dynamics. We provide proof of concept for a novel approach that quantitatively links the effects of altered molecular pathways onto neuronal population dynamics. As a novelty, we connect chemical compounds measured with positron emission tomography (PET) with neural function in TVB addressing the phenomenon of hyperexcitability in AD related to the protein amyloid beta (Abeta). We construct personalized virtual brains based on individual PET derived distributions of Abeta in patients with mild cognitive impairment (MCI, N=8) and Alzheimers Disease (AD, N=10) and in age-matched healthy controls (HC, N=15) using data from ADNI-3 data base (http://adni.lni.usc.edu). In the personalized virtual brains, individual Abeta burden modulates regional inhibition, leading to disinhibition and hyperexcitation with high Abeta loads. We analyze simulated regional neural activity and electroencephalograms (EEG). ResultsKnown empirical alterations of EEG in patients with AD compared to HCs were reproduced by simulations. The virtual AD group showed slower frequencies in simulated local field potentials and EEG compared to MCI and HC groups. The heterogeneity of the Abeta load is crucial for the virtual EEG slowing which is absent for control models with homogeneous Abeta distributions. Slowing phenomena primarily affect the network hubs, independent of the spatial distribution of Abeta. Modeling the N-methyl-D-aspartate (NMDA) receptor antagonism of memantine in local population models, reveals potential functional reversibility of the observed large-scale alterations (reflected by EEG slowing) in virtual AD brains. DiscussionWe demonstrate how TVB enables the simulation of systems effects caused by pathogenetic molecular candidate mechanisms in human virtual brains.

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Differentiation of Alzheimer’s disease based on local and global parameters in personalized Virtual Brain models

Alzheimers disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, \"The Virtual Brain (TVB)\", based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioral spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

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Subject-specificity of the correlation between large-scale structural and functional connectivity

Structural connectivity (SC), the physical pathways connecting regions in the brain, and functional connectivity (FC), the temporal co-activations, are known to be tightly linked. However, the nature of this relationship is still not understood. In the present study, we examined this relation more closely in six separate human neuroimaging datasets with different acquisition and preprocessing methods. We show that using simple linear associations, the relation between an individuals SC and FC is not subject-specific for five of the datasets. Subject-specificity of SC-FC fit is achieved only for one of the six datasets, the multi-modal Glasser HCP parcellated dataset. We show that subject-specificity of SC-FC correspondence is limited across datasets due to relatively small variability between subjects in SC compared to the larger variability in FC.

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Modeling brain dynamics in brain tumor patients using The Virtual Brain

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, non-invasive neuroimaging techniques such as functional MRI and diffusion weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex non-linear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics.\n\nAs a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed.\n\nResults showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance.

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Inferring multi-scale neural mechanisms with brain network modelling

The neurophysiological processes underlying non-invasive brain activity measurements are not well understood. Here, we developed a novel connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) slow resting-state fMRI oscillations, (2) spatial topologies of functional connectivity networks, (3) excitation-inhibition balance, (4, 5) pulsed inhibition on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies.

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