SPoC: a novel framework for relating the amplitude of neuronal oscillations to behaviorally relevant parameters.

Previously, modulations in power of neuronal oscillations have been functionally linked to sensory, motor and cognitive operations. Such links are commonly established by relating the power modulations to specific target variables such as reaction times or task ratings. Consequently, the resulting spatio-spectral representation is subjected to neurophysiological interpretation. As an alternative, independent component analysis (ICA) or alternative decomposition methods can be applied and the power of the components may be related to the target variable. In this paper we show that these standard approaches are suboptimal as the first does not take into account the superposition of many sources due to volume conduction, while the second is unable to exploit available information about the target variable. To improve upon these approaches we introduce a novel (supervised) source separation framework called Source Power Comodulation (SPoC). SPoC makes use of the target variable in the decomposition process in order to give preference to components whose power comodulates with the target variable. We present two algorithms that implement the SPoC approach. Using simulations with a realistic head model, we show that the SPoC algorithms are able extract neuronal components exhibiting high correlation of power with the target variable. In this task, the SPoC algorithms outperform other commonly used techniques that are based on the sensor data or ICA approaches. Furthermore, using real electroencephalography (EEG) recordings during an auditory steady state paradigm, we demonstrate the utility of the SPoC algorithms by extracting neuronal components exhibiting high correlation of power with the intensity of the auditory input. Taking into account the results of the simulations and real EEG recordings, we conclude that SPoC represents an adequate approach for the optimal extraction of neuronal components showing coupling of power with continuously changing behaviorally relevant parameters.

On the interpretation of weight vectors of linear models in multivariate neuroimaging.

The increase in spatiotemporal resolution of neuroimaging devices is accompanied by a trend towards more powerful multivariate analysis methods. Often it is desired to interpret the outcome of these methods with respect to the cognitive processes under study. Here we discuss which methods allow for such interpretations, and provide guidelines for choosing an appropriate analysis for a given experimental goal: For a surgeon who needs to decide where to remove brain tissue it is most important to determine the origin of cognitive functions and associated neural processes. In contrast, when communicating with paralyzed or comatose patients via brain-computer interfaces, it is most important to accurately extract the neural processes specific to a certain mental state. These equally important but complementary objectives require different analysis methods. Determining the origin of neural processes in time or space from the parameters of a data-driven model requires what we call a forward model of the data; such a model explains how the measured data was generated from the neural sources. Examples are general linear models (GLMs). Methods for the extraction of neural information from data can be considered as backward models, as they attempt to reverse the data generating process. Examples are multivariate classifiers. Here we demonstrate that the parameters of forward models are neurophysiologically interpretable in the sense that significant nonzero weights are only observed at channels the activity of which is related to the brain process under study. In contrast, the interpretation of backward model parameters can lead to wrong conclusions regarding the spatial or temporal origin of the neural signals of interest, since significant nonzero weights may also be observed at channels the activity of which is statistically independent of the brain process under study. As a remedy for the linear case, we propose a procedure for transforming backward models into forward models. This procedure enables the neurophysiological interpretation of the parameters of linear backward models. We hope that this work raises awareness for an often encountered problem and provides a theoretical basis for conducting better interpretable multivariate neuroimaging analyses.

Binary classification with pFDR-pFNR losses.

Connecting multiple testing with binary classification, we derive a false discovery rate-based classification approach for two-class mixture models, where the available data (represented as feature vectors) for each individual comparison take values in Rd for some d≥1 and may exhibit certain forms of autocorrelation. This generalizes previous findings for the independent case in dimension d=1. Two resulting classification procedures are described which allow for incorporating prior knowledge about class probabilities and for user-supplied weighting of the severity of misclassifying a member of the "0"-class as "1" and vice versa. The key mathematical tools to be employed are multivariate estimation methods for probability density functions or density ratios. We compare the two algorithms with respect to their theoretical properties and with respect to their performance in practice. Computer simulations indicate that they can both successfully be applied to autocorrelated time series data with moving average structure. Our approach was inspired and its practicability will be demonstrated by applications from the field of brain-computer interfacing and the processing of electroencephalography data.

Estimating true brain connectivity from EEG/MEG data invariant to linear and static transformations in sensor space.

The imaginary part of coherency is a measure to investigate the synchronization of brain sources on the EEG/MEG sensor level, robust to artifacts of volume conduction meaning that independent sources cannot generate a significant result. It does not mean, however, that volume conduction is irrelevant when true interactions are present. Here, we analyze in detail the possibilities to construct measures of true brain interactions which are strictly invariant to linear spatial transformations of the sensor data. Specifically, such measures can be constructed from maximization of imaginary coherency in virtual channels, bivariate measures as a corrected variate of imaginary coherence, and global measures indicating the total interaction contained within a space or between two spaces. A complete theoretic framework on this question is provided for second order statistical moments. Relations to existing linear and nonlinear approaches are presented. We applied the methods to resting state EEG data, showing clear interactions at all bands, and to a combined measurement of EEG and MEG during rest condition and a finger tapping task. We found that MEG was capable of observing brain interactions which were not observable in the EEG data.

Improved decoding of neural activity from fMRI signals using non-separable spatiotemporal deconvolutions.

The goal of most functional Magnetic Resonance Imaging (fMRI) analyses is to investigate neural activity. Many fMRI analysis methods assume that the temporal dynamics of the hemodynamic response function (HRF) to neural activation is separable from its spatial dynamics. Although there is empirical evidence that the HRF is more complex than suggested by space-time separable canonical HRF models, it is difficult to assess how much information about neural activity is lost when assuming space-time separability. In this study we directly test whether spatiotemporal variability in the HRF that is not captured by separable models contains information about neural signals. We predict intracranially measured neural activity from simultaneously recorded fMRI data using separable and non-separable spatiotemporal deconvolutions of voxel time series around the recording electrode. Our results show that abandoning the spatiotemporal separability assumption consistently improves the decoding accuracy of neural signals from fMRI data. We compare our findings with results from optical imaging and fMRI studies and discuss potential implications for classical fMRI analyses without invasive electrophysiological recordings.

Finding stationary subspaces in multivariate time series.

Identifying temporally invariant components in complex multivariate time series is key to understanding the underlying dynamical system and predict its future behavior. In this Letter, we propose a novel technique, stationary subspace analysis (SSA), that decomposes a multivariate time series into its stationary and nonstationary part. The method is based on two assumptions: (a) the observed signals are linear superpositions of stationary and nonstationary sources; and (b) the nonstationarity is measurable in the first two moments. We characterize theoretical and practical properties of SSA and study it in simulations and cortical signals measured by electroencephalography. Here, SSA succeeds in finding stationary components that lead to a significantly improved prediction accuracy and meaningful topographic maps which contribute to a better understanding of the underlying nonstationary brain processes.

A mathematical model for the two-learners problem.

OBJECTIVE: We present the first generic theoretical formulation of the co-adaptive learning problem and give a simple example of two interacting linear learning systems, a human and a machine. APPROACH: After the description of the training protocol of the two learning systems, we define a simple linear model where the two learning agents are coupled by a joint loss function. The simplicity of the model allows us to find learning rules for both human and machine that permit computing theoretical simulations. MAIN RESULTS: As seen in simulations, an astonishingly rich structure is found for this eco-system of learners. While the co-adaptive learners are shown to easily stall or get out of sync for some parameter settings, we can find a broad sweet spot of parameters where the learning system can converge quickly. It is defined by mid-range learning rates on the side of the learning machine, quite independent of the human in the loop. Despite its simplistic assumptions the theoretical study could be confirmed by a real-world experimental study where human and machine co-adapt to perform cursor control under distortion. Also in this practical setting the mid-range learning rates yield the best performance and behavioral ratings. SIGNIFICANCE: The results presented in this mathematical study allow the computation of simple theoretical simulations and performance of real experimental paradigms. Additionally, they are nicely in line with previous results in the BCI literature.

Identifying interactions in mixed and noisy complex systems.

We present a technique that identifies truly interacting subsystems of a complex system from multichannel data if the recordings are an unknown linear and instantaneous mixture of the true sources. The method is valid for arbitrary noise structure. For this, a blind source separation technique is proposed that diagonalizes antisymmetrized cross-correlation or cross-spectral matrices. The resulting decomposition finds truly interacting subsystems blindly and suppresses any spurious interaction stemming from the mixture. The usefulness of this interacting source analysis is demonstrated in simulations and for real electroencephalography data.

EEG-based usability assessment of 3D shutter glasses.

OBJECTIVE: Neurotechnology can contribute to the usability assessment of products by providing objective measures of neural workload and can uncover usability impediments that are not consciously perceived by test persons. In this study, the neural processing effort imposed on the viewer of 3D television by shutter glasses was quantified as a function of shutter frequency. In particular, we sought to determine the critical shutter frequency at which the 'neural flicker' vanishes, such that visual fatigue due to this additional neural effort can be prevented by increasing the frequency of the system. APPROACH: Twenty-three participants viewed an image through 3D shutter glasses, while multichannel electroencephalogram (EEG) was recorded. In total ten shutter frequencies were employed, selected individually for each participant to cover the range below, at and above the threshold of flicker perception. The source of the neural flicker correlate was extracted using independent component analysis and the flicker impact on the visual cortex was quantified by decoding the state of the shutter from the EEG. MAIN RESULT: Effects of the shutter glasses were traced in the EEG up to around 67 Hz-about 20 Hz over the flicker perception threshold-and vanished at the subsequent frequency level of 77 Hz. SIGNIFICANCE: The impact of the shutter glasses on the visual cortex can be detected by neurotechnology even when a flicker is not reported by the participants. Potential impact. Increasing the shutter frequency from the usual 50 Hz or 60 Hz to 77 Hz reduces the risk of visual fatigue and thus improves shutter-glass-based 3D usability.

A resampling approach to estimate the stability of one-dimensional or multidimensional independent components.

When applying unsupervised learning techniques in biomedical data analysis, a key question is whether the estimated parameters of the studied system are reliable. In other words, can we assess the quality of the result produced by our learning technique? We propose resampling methods to tackle this question and illustrate their usefulness for blind-source separation (BSS). We demonstrate that our proposed reliability estimation can be used to discover stable one-dimensional or multidimensional independent components, to choose the appropriate BSS-model, to enhance significantly the separation performance, and, most importantly, to flag components that carry physical meaning. Application to different biomedical testbed data sets (magnetoencephalography (MEG)/electrocardiography (ECG)-recordings) underline the usefulness of our approach.

Transferring subspaces between subjects in brain--computer interfacing.

Compensating changes between a subjects' training and testing session in brain-computer interfacing (BCI) is challenging but of great importance for a robust BCI operation. We show that such changes are very similar between subjects, and thus can be reliably estimated using data from other users and utilized to construct an invariant feature space. This novel approach to learning from other subjects aims to reduce the adverse effects of common nonstationarities, but does not transfer discriminative information. This is an important conceptual difference to standard multisubject methods that, e.g., improve the covariance matrix estimation by shrinking it toward the average of other users or construct a global feature space. These methods do not reduces the shift between training and test data and may produce poor results when subjects have very different signal characteristics. In this paper, we compare our approach to two state-of-the-art multisubject methods on toy data and two datasets of EEG recordings from subjects performing motor imagery. We show that it can not only achieve a significant increase in performance, but also that the extracted change patterns allow for a neurophysiologically meaningful interpretation.

Explorative data analysis for changes in neural activity.

Neural recordings are non-stationary time series, i.e. their properties typically change over time. Identifying specific changes, e.g., those induced by a learning task, can shed light on the underlying neural processes. However, such changes of interest are often masked by strong unrelated changes, which can be of physiological origin or due to measurement artifacts. We propose a novel algorithm for disentangling such different causes of non-stationarity and in this manner enable better neurophysiological interpretation for a wider set of experimental paradigms. A key ingredient is the repeated application of Stationary Subspace Analysis (SSA) using different temporal scales. The usefulness of our explorative approach is demonstrated in simulations, theory and EEG experiments with 80 brain-computer interfacing subjects.

Feature extraction for change-point detection using stationary subspace analysis.

Detecting changes in high-dimensional time series is difficult because it involves the comparison of probability densities that need to be estimated from finite samples. In this paper, we present the first feature extraction method tailored to change-point detection, which is based on an extended version of stationary subspace analysis. We reduce the dimensionality of the data to the most nonstationary directions, which are most informative for detecting state changes in the time series. In extensive simulations on synthetic data, we show that the accuracy of three change-point detection algorithms is significantly increased by a prior feature extraction step. These findings are confirmed in an application to industrial fault monitoring.

Analysis of multimodal neuroimaging data.

Each method for imaging brain activity has technical or physiological limits. Thus, combinations of neuroimaging modalities that can alleviate these limitations such as simultaneous recordings of neurophysiological and hemodynamic activity have become increasingly popular. Multimodal imaging setups can take advantage of complementary views on neural activity and enhance our understanding about how neural information processing is reflected in each modality. However, dedicated analysis methods are needed to exploit the potential of multimodal methods. Many solutions to this data integration problem have been proposed, which often renders both comparisons of results and the choice of the right method for the data at hand difficult. In this review we will discuss different multimodal neuroimaging setups, the advances achieved in basic research and clinical application and the methods used. We will provide a comprehensive overview of mathematical tools reoccurring in multimodal neuroimaging studies for artifact removal, data-driven and model-driven analyses, enabling the practitioner to try established or new combinations from these algorithmic building blocks.

Finding stationary brain sources in EEG data.

Neurophysiological measurements obtained from e.g. EEG or fMRI are inherently non-stationary because the properties of the underlying brain processes vary over time. For example, in Brain-Computer-Interfacing (BCI), deteriorating performance (bitrate) is a common phenomenon since the parameters determined during the calibration phase can be suboptimal under the application regime, where the brain state is different, e.g. due to increased tiredness or changes in the experimental paradigm. We show that Stationary Subspace Analysis (SSA), a time series analysis method, can be used to identify the underlying stationary and non-stationary brain sources from high-dimensional EEG measurements. Restricting the BCI to the stationary sources found by SSA can significantly increase the performance. Moreover, SSA yields topographic maps corresponding to stationary- and non-stationary brain sources which reveal their spatial characteristics.

Relationship between neural and hemodynamic signals during spontaneous activity studied with temporal kernel CCA.

Functional magnetic resonance imaging (fMRI) based on the so-called blood oxygen level-dependent (BOLD) contrast is a powerful tool for studying brain function not only locally but also on the large scale. Most studies assume a simple relationship between neural and BOLD activity, in spite of the fact that it is important to elucidate how the "when" and "what" components of neural activity are correlated to the "where" of fMRI data. Here we conducted simultaneous recordings of neural and BOLD signal fluctuations in primary visual (V1) cortex of anesthetized monkeys. We explored the neurovascular relationship during periods of spontaneous activity by using temporal kernel canonical correlation analysis (tkCCA). tkCCA is a multivariate method that can take into account any features in the signals that univariate analysis cannot. The method detects filters in voxel space (for fMRI data) and in frequency-time space (for neural data) that maximize the neurovascular correlation without any assumption of a hemodynamic response function (HRF). Our results showed a positive neurovascular coupling with a lag of 4-5 s and a larger contribution from local field potentials (LFPs) in the γ range than from low-frequency LFPs or spiking activity. The method also detected a higher correlation around the recording site in the concurrent spatial map, even though the pattern covered most of the occipital part of V1. These results are consistent with those of previous studies and represent the first multivariate analysis of intracranial electrophysiology and high-resolution fMRI.

Measuring phase synchronization of superimposed signals.

Phase synchronization is an important phenomenon that occurs in a wide variety of complex oscillatory processes. Measuring phase synchronization can therefore help to gain fundamental insight into nature. In this Letter we point out that synchronization analysis techniques can detect spurious synchronization, if they are fed with a superposition of signals such as in electroencephalography or magnetoencephalography data. We show how techniques from blind source separation can help to nevertheless measure the true synchronization and avoid such pitfalls.