Biology subjects

Keilholz, S.

Publications and source records attributed to Keilholz, S..

29 records · Page 2Linked to original sources

bioRxiv2021

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.

neuroscience↗

bioRxiv2021

Large-Scale Intrinsic Functional Brain Organization Emerges from Three Canonical Spatiotemporal Patterns

Resting-state functional MRI has yielded seemingly disparate insights into large-scale organization of the human brain. The brains large-scale organization can be divided into two broad categories - zero-lag representations of functional connectivity structure and time-lag representations of traveling wave or propagation structure. Here we sought to unify observed phenomena across these two categories in the form of three low-frequency spatiotemporal patterns composed of a mixture of standing and traveling wave dynamics. We showed that a range of empirical phenomena, including functional connectivity gradients, the task-positive/task-negative anti-correlation pattern, the global signal, time-lag propagation patterns, the quasiperiodic pattern, and the functional connectome network structure are manifestations of these three spatiotemporal patterns. These patterns account for much of the global spatial structure that underlies functional connectivity analyses, and unifies phenomena in resting-state functional MRI previously thought distinct.

neuroscience↗

bioRxiv2021

Spatiotemporal Trajectories in Resting-state FMRI Revealed by Convolutional Variational Autoencoder

Recent resting-state fMRI studies have shown that brain activity exhibits temporal variations in functional connectivity by using various approaches including sliding window correlation, co-activation patterns, independent component analysis, quasi-periodic patterns, and hidden Markov models. These methods often model the brain activity as a discretized hopping among several brain states that are defined by the spatial configurations of network activity. However, the discretized states are merely a simplification of what is likely to be a continuous process, where each network evolves over time following its unique path. To model these characteristic spatiotemporal trajectories, we trained a variational autoencoder using rs-fMRI data and evaluated the spatiotemporal features of the latent variables obtained from the trained networks. Our results suggest that there are a relatively small number of approximately orthogonal whole-brain spatiotemporal patterns that capture the most prominent features of rs-fMRI data, which can serve as the building blocks to construct all possible spatiotemporal dynamics in resting state fMRI. These spatiotemporal patterns provide insight into how activity flows across the brain in concordance with known network structures and functional connectivity gradients.

neuroscience↗

bioRxiv2020

Propagating patterns of intrinsic activity along macroscale gradients coordinate functional connections across the whole brain

The intrinsic activity of the human brain, observed with resting-state fMRI (rsfMRI) and functional connectivity, exhibits macroscale spatial organization such as resting-state networks (RSNs) and functional connectivity gradients (FCGs). Dynamic analysis techniques have shown that the time-averaged maps captured by functional connectivity are mere summaries of time-varying patterns with distinct spatial and temporal characteristics. A better understanding of these patterns might provide insight into aspects of the brains intrinsic activity that cannot be inferred by functional connectivity, RSNs or FCGs. Here, we describe three spatiotemporal patterns of coordinated activity across the whole brain obtained by averaging similar ~20-second-long segments of rsfMRI timeseries. In each of these patterns, activity propagates along a particular macroscale FCG, simultaneously across the cortical sheet and in most other brain regions. In some areas, like the thalamus, the propagation suggests previously-undescribed FCGs. The coordinated activity across areas is consistent with known tract-based connections, and nuanced differences in the timing of peak activity between brain regions point to plausible driving mechanisms. The magnitude of correlation within and particularly between RSNs is remarkably diminished when these patterns are regressed from the rsfMRI timeseries, a quantitative demonstration of their significant role in functional connectivity. Taken together, our results suggest that a few recurring patterns of propagating intrinsic activity along macroscale gradients give rise to and coordinate functional connections across the whole brain.

neuroscience↗

bioRxiv2020

Topological Segmentation of Time-Varying Functional Connectivity Highlights the Role of Preferred Cortical Circuits

Whereas brain imaging tools like functional Magnetic Resonance Imaging (fMRI) afford measurements of whole-brain activity, it remains unclear how best to interpret patterns found amid the datas apparent self-organization. To clarify how patterns of brain activity support brain function, one might identify metric spaces that optimally distinguish brain states across experimentally defined conditions. Therefore, the present study considers the relative capacities of several metric spaces to disambiguate experimentally defined brain states. One fundamental metric space interprets fMRI data topographically, i.e, as the vector of amplitudes of a multivariate signal, changing with time. Another perspective considers the condition-dependency of the brains Functional Connectivity (FC), i.e., the similarity matrix computed across the variables of a multivariate signal. More recently, metric spaces that think of the data topologically, e.g., as an abstract geometric object, have become available. In the abstract, uncertainty prevails regarding the distortions imposed by the mode of measurement upon the object under study. Features that are invariant under continuous deformations, such as rotation and inflation, constitute the features of topological data analysis. While there are strengths and weaknesses of each metric space, we find that metric spaces that track topological features are optimal descriptors of the brains experimentally defined states. AUTHOR SUMMARYTime-Varying Functional Connectivity (TVFC) leverages brain imaging data to interpret brain function as time-varying patterns of coordinating activity among brain regions. While many questions remain regarding the organizing principles through which brain function emerges from multi-regional interactions, advances in the mathematics of Topological Data Analysis (TDA) may provide new insights into the brains functional self-organization. One tool from TDA, "persistent homology", observes the occurrence and persistence of n-dimensional holes in a sequence of simplicial complexes extracted from a weighted graph. The occurrence of such holes within the TVFC graph may indicate preferred routes of information flow among brain regions. In the present study, we compare the use of persistence homology versus more traditional metrics at the task of segmenting brain states that differ across experimental conditions. We find that the structures identified by persistence homology more accurately segment the stimuli, more accurately segment high versus low performance levels under common stimuli, and generalize better across volunteers. These findings support the topological interpretation of brain dynamics.

neuroscience↗

bioRxiv2019

Brain Network Constraints and Recurrent Neural Networks reproduce unique Trajectories and State Transitions seen over the span of minutes in resting state fMRI

Large scale patterns of spontaneous whole brain activity seen in resting state functional Magnetic Resonance Imaging (rsfMRI), are in part believed to arise from neural populations interacting through the structural fiber network [18]. Generative models that simulate this network activity, called Brain Network Models (BNM), are able to reproduce global averaged properties of empirical rsfMRI activity such as functional connectivity (FC) [7, 27]. However, they perform poorly in reproducing unique trajectories and state transitions that are observed over the span of minutes in whole brain data [20]. At very short timescales between measurements, it is not known how much of the variance these BNM can explain because they are not currently synchronized with the measured rsfMRI. We demonstrate that by solving for the initial conditions of BNM from an observed data point using Recurrent Neural Networks (RNN) and integrating it to predict the next time step, the trained network can explain large amounts of variance for the 5 subsequent time points of unseen future trajectory. The RNN and BNM combined system essentially models the network component of rsfMRI, and where future activity is solely based on previous neural activity propagated through the structural network. Longer instantiations of this generative model simulated over the span of minutes can reproduce average FC and the 1/f power spectrum from 0.01 to 0.3 Hz seen in fMRI. Simulated data also contain interesting resting state dynamics, such as unique repeating trajectories, called QPPs [22] that are highly correlated to the empirical trajectory which spans over 20 seconds. Moreover, it exhibits complex states and transitions as seen using k-Means analysis on windowed FC matrices [1]. This suggests that by combining BNMs with RNN to accurately predict future resting state activity at short timescales, it is learning the manifold of the network dynamics, allowing it to simulate complex resting state trajectories at longer time scales. We believe that our technique will be useful in understanding the large-scale functional organization of the brain and how different BNMs recapitulate different aspects of the system dynamics.

bioengineering↗

bioRxiv2019

The Relationship between BOLD and Neural Activity Arises from Temporally Sparse Events

Resting state functional magnetic resonance (rs-fMRI) imaging offers insights into how different brain regions are connected into functional networks. It was recently shown that networks that are almost identical to the ones created from conventional correlation analysis can be obtained from a subset of high-amplitude data, suggesting that the functional networks may be driven by instantaneous co-activations of multiple brain regions rather than ongoing oscillatory processes. The rs-fMRI studies, however, rely on the blood oxygen level dependent (BOLD) signal, which is only indirectly sensitive to neural activity through neurovascular coupling. To provide more direct evidence that the neuronal co-activation events produce the time-varying network patterns seen in rs-fMRI studies, we examined the simultaneous rs-fMRI and local field potential (LFP) recordings in rats performed in our lab over the past several years. We developed complementary analysis methods that focus on either the temporal or spatial domain, and found evidence that the interaction between LFP and BOLD may be driven by instantaneous co-activation events as well. BOLD maps triggered on high-amplitude LFP events resemble co-activation patterns created from rs-fMRI data alone, though the co-activation time points are defined differently in the two cases. Moreover, only LFP events that fall into the highest or lowest thirds of the amplitude distribution result in a BOLD signal that can be distinguished from noise. These findings provide evidence of an electrophysiological basis for the time-varying co-activation patterns observed in previous studies.

neuroscience↗

bioRxiv2018

Quasi-periodic patterns of brain activity in individuals with Attention-Deficit/Hyperactivity Disorder

Individuals with attention-deficit/hyperactivity disorder have been shown to have disrupted functional connectivity in the default mode and task positive networks. Traditional fMRI analysis techniques that focus on static changes in functional connectivity have been successful in identifying differences between healthy controls and individuals with ADHD. However, such analyses are unable to explain the mechanisms behind the functional connectivity differences observed. Here, we study dynamic changes in functional connectivity in individuals with ADHD through investigation of quasi-periodic patterns (QPPs). QPPs are reliably recurring low-frequency spatiotemporal patterns in the brain linked to infra-slow electrical activity. They have been shown to contribute to functional connectivity observed through static analysis techniques. We find that QPPs contribute to functional connectivity specifically in regions that are disrupted during ADHD. Individuals with ADHD also show differences in the spatiotemporal pattern observed within the QPPs. This difference results in a weaker contribution of QPPs to functional connectivity in the default mode and task positive networks. We conclude that quasi-periodic patterns provide insight into the mechanisms behind functional connectivity differences seen in individuals with ADHD. This allows for a better understanding of the etiology of the disorder and development of effective treatments.\n\nHighlights O_LIDefault mode and task positive network connectivity is disrupted in ADHD\nC_LIO_LIQuasi-periodic patterns contribute to typical functional connectivity in the DMN and TPN\nC_LIO_LIThe contribution of QPPs to functional connectivity is diminished in individuals with ADHD\nC_LIO_LIQPPs could explain BOLD dynamics underlying static functional connectivity differences in ADHD\nC_LI

neuroscience↗

bioRxiv2018

Dynamic Properties of Simulated Brain Network Models and Empirical Resting State Data

Brain Network Models have become a promising theoretical framework in simulating signals that are representative of whole brain activity such as resting state fMRI. However, it has been difficult to compare the complex brain activity between simulated and empirical data. Previous studies have used simple metrics that surmise coordination between regions such as functional connectivity, and we extend on this by using various different dynamical analysis tools that are currently used to understand resting state fMRI. We show that certain properties correspond to the structural connectivity input that is shared between the models, and certain dynamic properties relate more to the mathematical description of the Brain Network Model. We conclude that the dynamic properties that gauge more temporal structure rather than spatial coordination in the rs-fMRI signal seem to provide the largest contrasts between different BNMs and the unknown empirical dynamical system. Our results will be useful in constraining and developing more realistic simulations of whole brain activity.

neuroscience↗

bioRxiv2018

Quasi-periodic patterns contribute to functional connectivity in the brain

Functional connectivity is widely used to study the coordination of activity between brain regions over time. Functional connectivity in the default mode and task positive networks is particularly important for normal brain function. However, the processes that give rise to functional connectivity in the brain are not fully understood. It has been postulated that low-frequency neural activity plays a key role in establishing the functional architecture of the brain. Quasi-periodic patterns (QPPs) are a reliably observable form of low-frequency neural activity that involve the default mode and task positive networks. Here, QPPs from resting-state and working memory task-performing individuals were acquired. The spatiotemporal pattern, strength, and frequency of the QPPs between the two groups were compared and the contribution of QPPs to functional connectivity in the brain was measured. In task-performing individuals, the spatiotemporal pattern of the QPP changes, particularly in task-relevant regions, and the QPP tends to occur with greater strength and frequency. Differences in the QPPs between the two groups could partially account for the variance in functional connectivity between resting-state and task-performing individuals. The QPPs contribute strongly to connectivity in the default mode and task positive networks and to the strength of anti-correlation seen between the two networks. Many of the connections affected by QPPs are also disrupted during several neurological disorders. These findings contribute to understanding the dynamic neural processes that give rise to functional connectivity in the brain and how they may be disrupted during disease.\n\nHighlightsO_LIQuasi-periodic patterns (QPPs) of low-frequency activity contribute to functional connectivity\nC_LIO_LIThe spatiotemporal pattern of QPPs differs between resting-state and task-performing individuals\nC_LIO_LIQPPs account for significant functional connectivity in the DMN and TPN during rest and task performance\nC_LIO_LIChanges in functional connectivity in these networks may reflect differences in QPPs\nC_LI

neuroscience↗

bioRxiv2017

Instantaneous Brain Dynamics Mapped to a Continuous State Space

Measures of whole-brain activity, from techniques such as functional Magnetic Resonance Imaging, provide a means to observe the brains dynamical operations. However, interpretation of whole-brain dynamics has been stymied by the inherently high-dimensional structure of brain activity. The present research addresses this challenge through a series of scale transformations in the spectral, spatial, and relational domains. Instantaneous multispectral dynamics are first developed from input data via a wavelet filter bank. Voxel-level signals are then projected onto a representative set of spatially independent components. The correlation distance over the instantaneous wavelet-ICA state vectors is a graph that may be embedded onto a lower-dimensional space to assist the interpretation of state-space dynamics. Applying this procedure to a large sample of resting and task data (acquired through the Human Connectome Project), we segment the empirical state space into a continuum of stimulus-dependent brain states. We also demonstrate that resting brain activity includes brain states that are very similar to those adopted during some tasks, as well as brain states that are distinct from experimentally-defined tasks. Back-projection of segmented brain states onto the brains surface reveals the patterns of brain activity that support each experimental state.

neuroscience↗