Biology subjects

Laufs, H.

Publications and source records attributed to Laufs, H..

13 recordsLinked to original sources

bioRxiv2026

The effects of temporal smoothing and interpolation on EEG microstate parameters, syntax, and our view of resting-state brain dynamics

Microstate analysis studies dynamic brain activity through a discrete representation of electroencephalographic (EEG) signals and their topography. While the body of literature describing findings in diverse experimental and clinical settings is growing rapidly, the effects of several core components of the microstate algorithm are still insufficiently understood. This study systematically investigates how two common temporal smoothing algorithms, parametric smoothing and GFP peak interpolation, influence a wide range of microstate sequence parameters, and how they shape the integrated picture of brain dynamics inferred from these metrics. We study eyes-closed resting-state EEG recordings from N=201 healthy subjects from a public EEG database. For the elementary temporal metrics, we find that widening smoothing windows markedly increase microstate duration, reduce occurrence rates, but leave coverage mostly unaffected. In terms of simple syntax properties, smoothing windows above 30 ms yield an inconsistent picture with a memoryless, first-order Markov structure at short time scales, but a positive Hurst phenomenon suggestive of long-range correlations at long time scales. Evidence of asymmetry and non-equilibrium dynamics are suppressed by smoothing. At intermediate time scales, microstate periodicity was only observed up to a window size of 28 ms. Smoothing had a strong impact on the complexity metrics entropy rate and excess entropy, decreasing the former and increasing the latter. For most metrics, the effects of GFP peak interpolation were comparable to those of smoothing windows in the range between 28 ms and 44 ms. In conclusion, elementary and higher-order microstate parameters must be interpreted in the context of preprocessing, as many parameters change continuously with smoothing intensity. This limits the comparability of microstate parameters obtained with different preprocessing settings. Strong smoothing with a window size above 30 ms or GFP peak interpolation yields a fundamentally different picture of resting state brain dynamics, i.e. that of a memoryless, aperiodic, time-reversible first-order Markov chain. Since insights from other neurophysiological modalities suggest that time series memory and time-irreversibility are markers of normal brain activity, our recommendation is to avoid intense smoothing to minimize alterations of the initial sequences.

neuroscience↗

bioRxiv2025

A quantitative comparison of two methods for higher-order EEG microstate syntax analysis

Entropy rate (ER) and sample entropy (SE) are two metrics that have been used to quantify the syntactic complexity of electroencephalography (EEG) microstate sequences. We here present a theoretical and numerical comparison of these two metrics and apply them to a resting-state EEG dataset from individuals with Alzheimers disease (AD) and a control group. We first derive theoretical entropy rate and sample entropy estimates for first-order discrete Markov processes, providing a null hypothesis for statistical testing of higher-order syntax properties. Under the first-order syntax null hypothesis, we find a close mathematical relationship between both metrics that can be expressed by the microstate transition probability matrix. An inequality is derived that shows entropy rate to be an upper bound to sample entropy under the Markov approximation. We quantify accuracy and precision of the theoretical ER and SE estimates on EEG microstate sequences from the healthy control group. We then show that ER and SE identify significant higher-order syntax properties in microstate sequences from the control and AD groups. Group comparison demonstrates that continuous microstate sequences from the AD group have lower entropy values (ER, SE), whereas jump sequences from the AD group have higher entropy values compared to control. Finally, we introduce a new syntax metric that normalizes ER and SE values with respect to their first-order syntax levels, to assess differences that only depend on syntax order. This metric revealed no differences between control and AD groups for either continuous or jump microstate sequences. This study provides further insights into higher-order microstate syntax and how it can be quantified with respect to the underlying first-order syntax. Similarities and differences between ER and SE as syntax metrics are highlighted and exemplified on experimental data. Our results show that (i) EEG microstate sequences from control and AD subjects show higher-order syntax properties across the tested syntax levels, (ii) continuous and jump sequences from control and AD groups are syntactically different, and (iii) differences between the control and AD groups disappear when higher-order syntax properties are normalized to the group-specific Markov level.

neuroscience↗

bioRxiv2025

Higher-order EEG microstate syntax and surrogate testing

Higher-order syntax properties of EEG microstate sequences offer insight into the transition dynamics of functional brain networks. We here define higher-order syntax as microstate sequence properties that are not explained by the first-order transition matrix, and we postulate three requirements that surrogate data should fulfill to provide a null hypothesis for higher-order syntax tests. We then compare two general approaches to surrogate data generation that have been used in microstate research, (a) surrogates from a first-order Markov chain model, and, (b) surrogates obtained from sequence shuffling. There are two different ways of representing microstate sequences, and syntax analyses can be applied to both, continuous microstate sequences, where each time sample is assigned the nearest microstate cluster, or to jump sequences which record only non-identical transitions by removing adjacent duplicates. We show that jump sequences have at least first-order syntax properties, whereas continuous sequences allow for zero-order and first-order surrogates. Markov chain generated surrogates fulfill the three requirements, i.e. they preserve the microstate distribution and transition matrix, and have no higher-order properties. Jump sequence shuffling, on the other hand, yields first-order surrogates whose first-order parameters are markedly different from the original sequence. Using a large open-access resting-state EEG dataset we show that jump sequence shuffling almost certainly produces microstate word probabilities that are significantly different from first-order expected word frequencies, erroneously indicating higher-order syntax properties. Markov chain surrogates reproduce the expected word probabilities of first-order sequences and correctly reject higher-order syntax properties in these cases. We conclude that jump sequence shuffling does not produce adequate surrogates for higher-order syntax investigations. The proposed Markov chain generative method for surrogate data synthesis is computationally efficient and allows the generation of surrogate sequences of arbitrary length, whereas shuffling can lead to sequences that are shorter than the original sequence and have variable length. Sample code in Python and MATLAB is provided.

neuroscience↗

bioRxiv2022

Low-dimensional organization of global brain states of reduced consciousness

Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unknown. We combined whole-brain modelling, data augmentation and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to brain injured patients is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, both increasing alongside loss of consciousness. Finally, we investigated the effects of model perturbations, providing geometrical interpretation for the stability and reversibility of states. We conclude that conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.

neuroscience↗

bioRxiv2022

Data-driven discovery of canonical large-scale brain dynamics

Human behavior and cognitive function correlate with complex patterns of spatio-temporal brain dynamics, which can be simulated using computational models with different degrees of biophysical realism. We used a data-driven optimization algorithm to determine and classify the types of local dynamics that enable the reproduction of different observables derived from functional magnetic resonance recordings. The phase space analysis of the resulting equations revealed a predominance of stable spiral attractors, which optimized the similarity with the empirical data in terms of the synchronization, metastability, and functional connectivity dynamics. For stable limit cycles, departures from harmonic oscillations improved the fit in terms of functional connectivity dynamics. Eigenvalue analyses showed that the proximity to Hopf bifurcations improved the accuracy of the simulation for wakefulness, while deep sleep was associated with increased stability. Our results provide testable predictions that constrain the landscape of suitable biophysical models, while supporting noise-driven dynamics close to a bifurcation as a canonical mechanism underlying the complex fluctuations that characterize endogenous brain activity.

neuroscience↗

bioRxiv2021

Unifying turbulent dynamics framework distinguishes different brain states

Recently, significant advances have been made by identifying the levels of synchronicity of the underlying dynamics of a given brain state. This research has demonstrated that unconscious dynamics tend to be more synchronous than those found in conscious states, which are more asynchronous. Here we go beyond this dichotomy to demonstrate that the different brain states are always underpinned by spatiotemporal chaos but with dissociable turbulent dynamics. We investigated human neuroimaging data from different brain states (resting state, meditation, deep sleep, and disorders of consciousness after coma) and were able to distinguish between them using complementary model-free and model-based measures of turbulent information transmission. Our model-free approach used recent advances describing a measure of information cascade across spatial scales using tools from turbulence theory. Complementarily, our model-based approach used exhaustive in silico perturbations of whole-brain models fitted to the empirical neuroimaging data, which allowed us to study the information encoding capabilities of the brain states. Overall, the current framework demonstrates that different levels of turbulent dynamics are fundamental for describing and differentiating between brain states.

neuroscience↗

bioRxiv2021

Decoding brain states on the intrinsic manifold of human brain dynamics across wakefulness and sleep

Current state-of-the-art functional magnetic resonance imaging (fMRI) offers remarkable imaging quality and resolution, yet, the intrinsic dimensionality of brain dynamics in different states (wakefulness, light and deep sleep) remains unknown. Here we present a novel method to reveal the low dimensional intrinsic manifold underlying human brain dynamics, which is invariant of the high dimensional spatio-temporal representation of the neuroimaging technology. By applying this novel intrinsic manifold framework to fMRI data acquired in wakefulness and sleep, we reveal the nonlinear differences between wakefulness and three different sleep stages, and successfully decode these different brain states with an average accuracy of 96%. Remarkably, a further group analysis shows that the intrinsic manifolds of all participants share a common topology. Overall, our results reveal the intrinsic manifold underlying the spatiotemporal dynamics of brain activity and demonstrate how this manifold enables the decoding of different brain states such as wakefulness and various sleep stages.

neuroscience↗

bioRxiv2020

Noise-driven multistability versus deterministic chaos in phenomenological semi-empirical models of whole brain activity

An outstanding open problem in neuroscience is to understand how neural systems are capable of producing and sustaining complex spatiotemporal dynamics. Computational models that combine local dynamics with in vivo measurements of anatomical and functional connectivity can be used to test potential mechanisms underlying this complexity. We compared two conceptually different mechanisms: noise-driven switching between equilibrium solutions (modeled by coupled Stuart-Landau oscillators) and deterministic chaos (modeled by coupled Rossler oscillators). We found that both models struggled to simultaneously reproduce multiple observables computed from the empirical data. This issue was especially manifest in the case of noise-driven dynamics close to a bifurcation, which imposed overly strong constraints on the optimal model parameters. In contrast, the chaotic model could produce complex behavior over an ampler range of parameters, thus being capable of capturing multiple observables at the same time with good performance. Our observations support the view of the brain as a non-equilibrium system able to produce endogenous variability. We presented a simple model capable of jointly reproducing functional connectivity computed at different temporal scales. Besides adding to our conceptual understanding of brain complexity, our results inform and constraint the future development of biophysically realistic large-scale models. The quote "What I cannot create, I do not understand" was found written in the blackboard of celebrated physicist Richard Feynman at the time of his death. This sentence suggests a way forward for neuroscientists interested in unravelling the principles behind the richness and complexity of spontaneous brain dynamics. Over the last decades, tremendous advances in neuroimaging enabled the construction of whole-brain activity models with real predictive power in the statistical sense. It is now possible to create realistic complex dynamics, instead of passively screening for their presence in neuroimaging data. We contrasted two different types of building blocks (i.e. two choices of local dynamics) and tested their capacity to reproduce the empirical data, with the purpose of increasing our conceptual understanding of the mechanisms behind large-scale spontaneous activity in the human brain.

neuroscience↗

bioRxiv2020

Perturbations in dynamical models of whole-brain activity dissociate between the level and stability of consciousness

Consciousness transiently fades away during deep sleep, more stably under anesthesia, and sometimes permanently due to brain injury. The development of an index to quantify the level of consciousness across these different states is regarded as a key problem both in basic and clinical neuroscience. We argue that this problem is ill-defined since such an index would not exhaust all the relevant information about a given state of consciousness. While the level of consciousness can be taken to describe the actual brain state, a complete characterization should also include its potential behavior against external perturbations. We developed and analyzed whole-brain computational models to show that the stability of conscious states provides information complementary to their similarity to conscious wakefulness. Our work leads to a novel methodological framework to sort out different brain states by their stability and reversibility, and illustrates its usefulness to dissociate between physiological (sleep), pathological (brain-injured patients), and pharmacologically-induced (anesthesia) loss of consciousness.

neuroscience↗

bioRxiv2020

Data augmentation based on dynamical systems for the classification of brain states

The application of machine learning algorithms to neuroimaging data shows great promise for the classification of physiological and pathological brain states. However, classifiers trained on high dimensional data are prone to overfitting, especially for a low number of training samples. We describe the use of whole-brain computational models for data augmentation in brain state classification. Our low dimensional model is based on nonlinear oscillators coupled by the empirical SC of the brain. We use this model to enhance a dataset consisting of functional magnetic resonance imaging recordings acquired during all stages of the human wake-sleep cycle. After fitting the model to the average FC of each state, we show that the synthetic data generated by the model yields classification accuracies comparable to those obtained from the empirical data. We also show that models fitted to individual subjects generate surrogates with enough information to train classifiers that present significant transfer learning accuracy to the whole sample. Whole-brain computational modeling represents a useful tool to produce large synthetic datasets for data augmentation in the classification of certain brain states, with potential applications to computer-assisted diagnosis and prognosis of neuropsychiatric disorders.

biophysics↗

bioRxiv2019

Dynamical informational structures characterize the different human brain states of wakefulness and deep sleep

The dynamical activity of the human brain describes an extremely complex energy landscape changing over time and its characterisation is central unsolved problem in neuroscience. We propose a novel mathematical formalism for characterizing how the landscape of attractors sustained by a dynamical system evolves in time. This mathematical formalism is used to distinguish quantitatively and rigorously between the different human brain states of wakefulness and deep sleep. In particular, by using a whole-brain dynamical ansatz integrating the underlying anatomical structure with the local node dynamics based on a Lotka-Volterra description, we compute analytically the global attractors of this cooperative system and their associated directed graphs, here called the informational structures. The informational structure of the global attractor of a dynamical system describes precisely the past and future behaviour in terms of a directed graph composed of invariant sets (nodes) and their corresponding connections (links). We characterize a brain state by the time variability of these informational structures. This theoretical framework is potentially highly relevant for developing reliable biomarkers of patients with e.g. neuropsychiatric disorders or different levels of coma.

neuroscience↗

bioRxiv2019

BOLD signatures of sleep

Sleep can be distinguished from wake by changes in brain electrical activity, typically assessed using electroencephalography (EEG). The hallmark of non-rapid-eye-movement sleep are two major EEG events: slow waves and spindles. Here we sought to identify possible signatures of sleep in brain hemodynamic activity, using simultaneous fMRI-EEG. We found that, during the transition from wake to sleep, blood-oxygen-level-dependent (BOLD) activity evolved from a mixed-frequency pattern to one dominated by two distinct oscillations: a low-frequency (~0.05Hz) oscillation prominent in light sleep and a high-frequency (~0.17Hz) oscillation in deep sleep. The two BOLD oscillations correlated with the occurrences of spindles and slow waves, respectively. They were detectable across the whole brain, cortically and subcortically, but had different regional distributions and opposite onset patterns. These spontaneous BOLD oscillations provide fMRI signatures of basic sleep processes, which may be employed to study human sleep at spatial resolution and brain coverage not achievable using EEG. HIGHLIGHTSspontaneous BOLD oscillations differentiate sleep from wake low-frequency BOLD oscillation tracks sleep spindles high-frequency BOLD oscillation tracks sleep slow waves BOLD oscillations provide fMRI signatures of key sleep processes

neuroscience↗

bioRxiv2018

Connectivity dynamics from wakefulness to sleep

Interest in time-resolved connectivity in fMRI has grown rapidly in recent years. The most widely used technique for studying connectivity changes over time utilizes a sliding windows approach. There has been some debate about the utility of shorter versus longer windows, the use of fixed versus adaptive windows, as well as whether observed resting state dynamics during wakefulness may be predominantly due to changes in sleep state and subject head motion. In this work we use an independent component analysis (ICA)-based pipeline applied to concurrent EEG/fMRI data collected during wakefulness and various sleep stages and show: 1) connectivity states obtained from clustering sliding windowed correlations of resting state functional network time courses well classify the sleep states obtained from EEG data, 2) using shorter sliding windows instead of longer non-overlapping windows improves the ability to capture transition dynamics even at windows as short as 30 seconds, 3) motion appears to be mostly associated with one of the states rather than spread across all of them 4) a fixed tapered sliding window approach outperforms an adaptive dynamic conditional correlation approach, and 5) consistent with prior EEG/fMRI work, we identify evidence of multiple states within the wakeful condition which are able to be classified with high accuracy. Classification of wakeful only states suggest the presence of time-varying changes in connectivity in fMRI data beyond sleep state or motion. Results also inform about advantageous technical choices, and the identification of different clusters within wakefulness that are separable suggest further studies in this direction.

neuroscience↗