Towards linking diffusion MRI based macro- and microstructure measures with cortico-cortical transmission in brain tumor patients.

We aimed to link macro- and microstructure measures of brain white matter obtained from diffusion MRI with effective connectivity measures based on a propagation of cortico-cortical evoked potentials induced with intrasurgical direct electrical stimulation. For this, we compared streamline lengths and log-transformed ratios of streamlines computed from presurgical diffusion-weighted images, and the delays and amplitudes of N1 peaks recorded intrasurgically with electrocorticography electrodes in a pilot study of 9 brain tumor patients. Our results showed positive correlation between these two modalities in the vicinity of the stimulation sites (Pearson coefficient 0.54±0.13 for N1 delays, and 0.47±0.23 for N1 amplitudes), which could correspond to the neural propagation via U-fibers. In addition, we reached high sensitivities (0.78±0.07) and very high specificities (0.93±0.03) in a binary variant of our comparison. Finally, we used the structural connectivity measures to predict the effective connectivity using a multiple linear regression model, and showed a significant role of brain microstructure-related indices in this relation.

A comprehensive study on electroencephalography and magnetoencephalography sensitivity to cortical and subcortical sources.

Signal-to-noise ratio (SNR) maps are a good way to visualize electroencephalography (EEG) and magnetoencephalography (MEG) sensitivity. SNR maps extend the knowledge about the modulation of EEG and MEG signals by source locations and orientations and can therefore help to better understand and interpret measured signals as well as source reconstruction results thereof. Our work has two main objectives. First, we investigated the accuracy and reliability of EEG and MEG finite element method (FEM)-based sensitivity maps for three different head models, namely an isotropic three and four-compartment and an anisotropic six-compartment head model. As a result, we found that ignoring the cerebrospinal fluid leads to an overestimation of EEG SNR values. Second, we examined and compared EEG and MEG SNR mappings for both cortical and subcortical sources and their modulation by source location and orientation. Our results for cortical sources show that EEG sensitivity is higher for radial and deep sources and MEG for tangential ones, which are the majority of sources. As to the subcortical sources, we found that deep sources with sufficient tangential source orientation are recordable by the MEG. Our work, which represents the first comprehensive study where cortical and subcortical sources are considered in highly detailed FEM-based EEG and MEG SNR mappings, sheds a new light on the sensitivity of EEG and MEG and might influence the decision of brain researchers or clinicians in their choice of the best modality for their experiment or diagnostics, respectively.

The effect of familiarity on neural tracking of music stimuli is modulated by mind wandering.

One way to investigate the cortical tracking of continuous auditory stimuli is to use the stimulus reconstruction approach. However, the cognitive and behavioral factors impacting this cortical representation remain largely overlooked. Two possible candidates are familiarity with the stimulus and the ability to resist internal distractions. To explore the possible impacts of these two factors on the cortical representation of natural music stimuli, forty-one participants listened to monodic natural music stimuli while we recorded their neural activity. Using the stimulus reconstruction approach and linear mixed models, we found that familiarity positively impacted the reconstruction accuracy of music stimuli and that this effect of familiarity was modulated by mind wandering.

Identifying subcortical connectivity during brain tumor surgery: a multimodal study.

Bipolar direct electrical stimulation (DES) of an awake patient is the reference technique for identifying brain structures to achieve maximal safe tumor resection. Unfortunately, DES cannot be performed in all cases. Alternative surgical tools are, therefore, needed to aid identification of subcortical connectivity during brain tumor removal. In this pilot study, we sought to (i) evaluate the combined use of evoked potential (EP) and tractography for identification of white matter (WM) tracts under the functional control of DES, and (ii) provide clues to the electrophysiological effects of bipolar stimulation on neural pathways. We included 12 patients (mean age of 38.4 years) who had had a dMRI-based tractography and a functional brain mapping under awake craniotomy for brain tumor removal. Electrophysiological recordings of subcortical evoked potentials (SCEPs) were acquired during bipolar low frequency (2 Hz) stimulation of the WM functional sites identified during brain mapping. SCEPs were successfully triggered in 11 out of 12 patients. The median length of the stimulated fibers was 43.24 ± 19.55 mm, belonging to tracts of median lengths of 89.84 ± 24.65 mm. The electrophysiological (delay, amplitude, and speed of propagation) and structural (number and lengths of streamlines, and mean fractional anisotropy) measures were correlated. In our experimental conditions, SCEPs were essentially limited to a subpart of the bundles, suggesting a selectivity of action of the DES on the brain networks. Correlations between functional, structural, and electrophysiological measures portend the combined use of EPs and tractography as a potential intraoperative tool to achieve maximum safe resection in brain tumor surgery.

Modeling of the neurovascular coupling in epileptic discharges.

Despite the interest in simultaneous EEG-fMRI studies of epileptic spikes, the link between epileptic discharges and their corresponding hemodynamic responses is poorly understood. In this context, biophysical models are promising tools for investigating the mechanisms underlying observed signals. Here, we apply a metabolic-hemodynamic model to simulated epileptic discharges, in part generated by a neural mass model. We analyze the effect of features specific to epileptic neuronal activity on the blood oxygen level dependent (BOLD) response, focusing on the issues of linearity in neurovascular coupling and on the origin of negative BOLD signals. We found both sub- and supra-linearity in simulated BOLD signals, depending on whether one observes the early or the late part of the BOLD response. The size of these non-linear effects is determined by the spike frequency, as well as by the amplitude of the excitatory activity. Our results additionally indicate a minor deviation from linearity at the neuronal level. According to a phase space analysis, the possibility to obtain a negative BOLD response to an epileptic spike depends on the existence of a long and strong excitatory undershoot. Moreover, we strongly suggest that a combined EEG-fMRI modeling approach should include spatial assumptions. The present study is a step towards an increased understanding of the link between epileptic spikes and their BOLD responses, aiming to improve the interpretation of simultaneous EEG-fMRI recordings in epilepsy.

Current distribution of distributed all-polar cochlear implant stimulation mode measured in-situ.

Oticon Medical cochlear implants use a stimulation mode called Distributed All-Polar (DAP) that connects all non-stimulating available intracochlear electrodes and an extracochlear reference electrode. It results in a complex distribution of current that is yet undescribed. The present study aims at providing a first characterization of this current distribution. A Neuro Zti was modified to allow the measurement of current returning to each electrode during a DAP stimulation and was implanted in an ex-vivo human head. Maps of distributed current were then created for different stimulation conditions with different charge levels. Results show that, on average, about 20% of current returns to the extracochlear reference electrode, while the remaining 80% is distributed between intracochlear electrodes. The position of the stimulating electrode changed this ratio, and about 10% more current to the extracochlear return in case of the first 3 basal electrodes than for apical and mid position electrodes was observed. Increasing the charge level led to small but significant change in the ratio, and about 4% more current to the extracochlear return was measured when increasing the charge level from 11.7 to 70 nC. Further research is needed to show if DAP yields better speech understanding than other stimulation modes.

Tracking cortical activity from M/EEG using graph cuts with spatiotemporal constraints.

This work proposes to use magnetoencephalography (MEG) and electroencephalography (EEG) source imaging to provide cinematic representations of the temporal dynamics of cortical activations. Cortical activation maps, seen as images of the active brain, are scalar maps defined at the vertices of a triangulated cortical surface. They can be computed from M/EEG data using a linear inverse solver every millisecond. Taking as input these activation maps and exploiting both the graph structure of the cortical mesh and the high sampling rate of M/EEG recordings, neural activations are tracked over time using an efficient graph cut based algorithm. The method estimates the spatiotemporal support of the active brain regions. It consists in computing a minimum cut on a particularly designed weighted graph imposing spatiotemporal regularity constraints on the activation patterns. Each node of the graph is assigned a label (active or non active). The method works globally on the full time-period of interest, can cope with spatially extended active regions and allows the active domain to exhibit topology changes over time. The algorithm is illustrated and validated on synthetic data. Results of the method are provided on two MEG cognitive experiments in the visual and somatosensory cortices, demonstrating the ability of the algorithm to handle various types of data.

Phase delays within visual cortex shape the response to steady-state visual stimulation.

Although the spatial organization of visual areas can be revealed by functional Magnetic Resonance Imaging (fMRI), the synoptic, non-invasive access to the temporal characteristics of the information flow amongst distributed visual processes remains a technical and methodological challenge. Using frequency-encoded steady-state visual stimulation together with a combination of time-resolved functional magnetic source imaging from magnetoencephalography (MEG) and anatomical magnetic resonance imaging (MRI), this study evidences maps of visuotopic sustained oscillatory neural responses distributed across the visual cortex. Our results further reveal relative phase delays across responding striate and extra-striate visual areas, which thereby shape the chronometry of neural processes amongst these regions. The methodology developed in this study points at further developments in time-resolved analyses of distributed visual processes in the millisecond range, and to new ways of exploring the dynamics of functional processes within the human visual cortex non-invasively.

Relationship between flow and metabolism in BOLD signals: insights from biophysical models.

In many physiological or pathological situations, the interpretation of BOLD signals remains elusive as the intimate link between neuronal activity and subsequent flow/metabolic changes is not fully understood. During the past decades, a number of biophysical models of the neurovascular coupling have been proposed. It is now well-admitted that these models may bridge between observations (fMRI data) and underlying biophysical and (patho-)physiological mechanisms (related to flow and metabolism) by providing mechanistic explanations. In this study, three well-established models (Buxton's, Friston's and Sotero's) are investigated. An exhaustive parameter sensitivity analysis (PSA) was conducted to study the marginal and joint influences of model parameters on the three main features of the BOLD response (namely the principal peak, the post-stimulus undershoot and the initial dip). In each model, parameters that have the greatest (and least) influence on the BOLD features as well as on the direction of variation of these features were identified. Among the three studied models, parameters were shown to affect the output features in different manners. Indeed, the main parameters revealed by the PSA were found to strongly depend on the way the flow(CBF)-metabolism(CMRO(2)) relationship is implemented (serial vs. parallel). This study confirmed that the model structure which accounts for the representation of the CBF-CMRO(2) relationship (oxygen supply by the flow vs. oxygen demand from neurons) plays a key role. More generally, this work provides substantial information about the tuning of parameters in the three considered models and about the subsequent interpretation of BOLD signals based on these models.

Long Multi-Stage Training for a Motor-Impaired User in a BCI Competition.

In a Mental Imagery Brain-Computer Interface the user has to perform a specific mental task that generates electroencephalography (EEG) components, which can be translated in commands to control a BCI system. The development of a high-performance MI-BCI requires a long training, lasting several weeks or months, in order to improve the ability of the user to manage his/her mental tasks. This works aims to present the design of a MI-BCI combining mental imaginary and cognitive tasks for a severely motor impaired user, involved in the BCI race of the Cybathlon event, a competition of people with severe motor disability. In the BCI-race, the user becomes a pilot in a virtual race game against up to three other pilots, in which each pilot has to control his/her virtual car by his/her mental tasks. We present all the procedures followed to realize an effective MI-BCI, from the user's first contact with a BCI technology to actually controlling a video-game through her EEG. We defined a multi-stage user-centered training protocol in order to successfully control a BCI, even in a stressful situation, such as that of a competition. We put a specific focus on the human aspects that influenced the long training phase of the system and the participation to the competition.

OpenMEEG: opensource software for quasistatic bioelectromagnetics.

BACKGROUND: Interpreting and controlling bioelectromagnetic phenomena require realistic physiological models and accurate numerical solvers. A semi-realistic model often used in practise is the piecewise constant conductivity model, for which only the interfaces have to be meshed. This simplified model makes it possible to use Boundary Element Methods. Unfortunately, most Boundary Element solutions are confronted with accuracy issues when the conductivity ratio between neighboring tissues is high, as for instance the scalp/skull conductivity ratio in electro-encephalography. To overcome this difficulty, we proposed a new method called the symmetric BEM, which is implemented in the OpenMEEG software. The aim of this paper is to present OpenMEEG, both from the theoretical and the practical point of view, and to compare its performances with other competing software packages. METHODS: We have run a benchmark study in the field of electro- and magneto-encephalography, in order to compare the accuracy of OpenMEEG with other freely distributed forward solvers. We considered spherical models, for which analytical solutions exist, and we designed randomized meshes to assess the variability of the accuracy. Two measures were used to characterize the accuracy. the Relative Difference Measure and the Magnitude ratio. The comparisons were run, either with a constant number of mesh nodes, or a constant number of unknowns across methods. Computing times were also compared. RESULTS: We observed more pronounced differences in accuracy in electroencephalography than in magnetoencephalography. The methods could be classified in three categories: the linear collocation methods, that run very fast but with low accuracy, the linear collocation methods with isolated skull approach for which the accuracy is improved, and OpenMEEG that clearly outperforms the others. As far as speed is concerned, OpenMEEG is on par with the other methods for a constant number of unknowns, and is hence faster for a prescribed accuracy level. CONCLUSIONS: This study clearly shows that OpenMEEG represents the state of the art for forward computations. Moreover, our software development strategies have made it handy to use and to integrate with other packages. The bioelectromagnetic research community should therefore be able to benefit from OpenMEEG with a limited development effort.

Fast Approximation of EEG Forward Problem and Application to Tissue Conductivity Estimation.

Bioelectric source analysis in the human brain from scalp electroencephalography (EEG) signals is sensitive to the conductivities of different head tissues. The conductivity of tissues is subject dependent, so non-invasive methods for conductivity estimation are necessary to fine tune EEG models. To do so, the EEG forward problem solution (so-called lead field matrix) must be computed for a large number of conductivity configurations. Computing a lead field requires a matrix inversion which is computationally intensive for realistic head models. Thus, the required time for computing a large number of lead fields can become impractical. In this work, we propose to approximate the lead field matrix for a set of conductivity configurations, using the exact solution only for a small set of support points in the conductivity space. Our approach accelerates the computation time, while controlling the approximation error. Our method is tested on simulated and measured EEG data for brain and skull conductivity estimation. This test demonstrates that the approximation does not introduce any bias and runs significantly faster than if exact lead field were to be computed.

The adjoint method for general EEG and MEG sensor-based lead field equations.

Most of the methods for the inverse source problem in electroencephalography (EEG) and magnetoencephalography (MEG) use a lead field as an input. The lead field is the function which relates any source in the brain to its measurements at the sensors. For complex geometries, there is no analytical formula of the lead field. The common approach is to numerically compute the value of the lead field for a finite number of point sources (dipoles). There are several drawbacks: the model of the source space is fixed (a set of dipoles), and the computation can be expensive for as much as 10,000 dipoles. The common idea to bypass these problems is to compute the lead field from a sensor point of view. In this paper, we use the adjoint method to derive general EEG and MEG sensor-based lead field equations. Within a simple framework, we provide a complete review of the explicit lead field equations, and we are able to extend these equations to non-pointlike sensors.

Brain computer interface with the P300 speller: Usability for disabled people with amyotrophic lateral sclerosis.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, restricts patients' communication capacity a few years after onset. A proof-of-concept of brain-computer interface (BCI) has shown promise in ALS and "locked-in" patients, mostly in pre-clinical studies or with only a few patients, but performance was estimated not high enough to support adoption by people with physical limitation of speech. Here, we evaluated a visual BCI device in a clinical study to determine whether disabled people with multiple deficiencies related to ALS would be able to use BCI to communicate in a daily environment. METHODS: After clinical evaluation of physical, cognitive and language capacities, 20 patients with ALS were included. The P300 speller BCI system consisted of electroencephalography acquisition connected to real-time processing software and separate keyboard-display control software. It was equipped with original features such as optimal stopping of flashes and word prediction. The study consisted of two 3-block sessions (copy spelling, free spelling and free use) with the system in several modes of operation to evaluate its usability in terms of effectiveness, efficiency and satisfaction. RESULTS: The system was effective in that all participants successfully achieved all spelling tasks and was efficient in that 65% of participants selected more than 95% of the correct symbols. The mean number of correct symbols selected per minute ranged from 3.6 (without word prediction) to 5.04 (with word prediction). Participants expressed satisfaction: the mean score was 8.7 on a 10-point visual analog scale assessing comfort, ease of use and utility. Patients quickly learned how to operate the system, which did not require much learning effort. CONCLUSION: With its word prediction and optimal stopping of flashes, which improves information transfer rate, the BCI system may be competitive with alternative communication systems such as eye-trackers. Remaining requirements to improve the device for suitable ergonomic use are in progress.

Can a Subjective Questionnaire Be Used as Brain-Computer Interface Performance Predictor?

Predicting a subject's ability to use a Brain Computer Interface (BCI) is one of the major issues in the BCI domain. Relevant applications of forecasting BCI performance include the ability to adapt the BCI to the needs and expectations of the user, assessing the efficiency of BCI use in stroke rehabilitation, and finally, homogenizing a research population. A limited number of recent studies have proposed the use of subjective questionnaires, such as the Motor Imagery Questionnaire Revised-Second Edition (MIQ-RS). However, further research is necessary to confirm the effectiveness of this type of subjective questionnaire as a BCI performance estimation tool. In this study we aim to answer the following questions: can the MIQ-RS be used to estimate the performance of an MI-based BCI? If not, can we identify different markers that could be used as performance estimators? To answer these questions, we recorded EEG signals from 35 healthy volunteers during BCI use. The subjects had previously completed the MIQ-RS questionnaire. We conducted an offline analysis to assess the correlation between the questionnaire scores related to Kinesthetic and Motor imagery tasks and the performances of four classification methods. Our results showed no significant correlation between BCI performance and the MIQ-RS scores. However, we reveal that BCI performance is correlated to habits and frequency of practicing manual activities.

Model based optimal multipolar stimulation without a priori knowledge of nerve structure: application to vagus nerve stimulation.

OBJECTIVE: Multipolar cuff electrode can selectively stimulate areas of peripheral nerves and therefore enable to control independent functions. However, the branching and fascicularization are known for a limited set of nerves and the specific organization remains subject-dependent. This paper presents general modeling and optimization methods in the context of multipolar stimulation using a cuff electrode without a priori knowledge of the nerve structure. Vagus nerve stimulation experiments based on the optimization results were then investigated. APPROACH: The model consisted of two independent components: a lead field matrix representing the transfer function from the applied current to the extracellular voltage present on the nodes of Ranvier along each axon, and a linear activation model. The optimization process consisted in finding the best current repartition (ratios) to reach activation of a targeted area depending on three criteria: selectivity, efficiency and robustness. MAIN RESULTS: The results showed that state-of-the-art configurations (tripolar transverse, tripolar longitudinal) were part of the optimized solutions but new ones could emerge depending on the trade-off between the three criteria and the targeted area. Besides, the choice of appropriate current ratios was more important than the choice of the stimulation amplitude for a stimulation without a priori knowledge of the nerve structure. We successfully assessed the solutions in vivo to selectively induce a decrease in cardiac rhythm through vagus nerve stimulation while limiting side effects. Compared to the standard whole ring configuration, a selective solution found by simulation provided on average 2.6 less adverse effects. SIGNIFICANCE: The preliminary results showed the rightness of the simulation, using a generic nerve geometry. It suggested that this approach will have broader applications that would benefit from multicontact cuff electrodes to elicit selective responses. In the context of the vagus nerve stimulation for heart failure therapy, we show that the simulation results were confirmed and improved the therapy while decreasing the side effects.

Unimodal Versus Bimodal EEG-fMRI Neurofeedback of a Motor Imagery Task.

Neurofeedback is a promising tool for brain rehabilitation and peak performance training. Neurofeedback approaches usually rely on a single brain imaging modality such as EEG or fMRI. Combining these modalities for neurofeedback training could allow to provide richer information to the subject and could thus enable him/her to achieve faster and more specific self-regulation. Yet unimodal and multimodal neurofeedback have never been compared before. In the present work, we introduce a simultaneous EEG-fMRI experimental protocol in which participants performed a motor-imagery task in unimodal and bimodal NF conditions. With this protocol we were able to compare for the first time the effects of unimodal EEG-neurofeedback and fMRI-neurofeedback versus bimodal EEG-fMRI-neurofeedback by looking both at EEG and fMRI activations. We also propose a new feedback metaphor for bimodal EEG-fMRI-neurofeedback that integrates both EEG and fMRI signal in a single bi-dimensional feedback (a ball moving in 2D). Such a feedback is intended to relieve the cognitive load of the subject by presenting the bimodal neurofeedback task as a single regulation task instead of two. Additionally, this integrated feedback metaphor gives flexibility on defining a bimodal neurofeedback target. Participants were able to regulate activity in their motor regions in all NF conditions. Moreover, motor activations as revealed by offline fMRI analysis were stronger during EEG-fMRI-neurofeedback than during EEG-neurofeedback. This result suggests that EEG-fMRI-neurofeedback could be more specific or more engaging than EEG-neurofeedback. Our results also suggest that during EEG-fMRI-neurofeedback, participants tended to regulate more the modality that was harder to control. Taken together our results shed first light on the specific mechanisms of bimodal EEG-fMRI-neurofeedback and on its added-value as compared to unimodal EEG-neurofeedback and fMRI-neurofeedback.

Generalized head models for MEG/EEG: boundary element method beyond nested volumes.

Accurate geometrical models of the head are necessary for solving the forward and inverse problems of magneto- and electro-encephalography (MEG/EEG). Boundary element methods (BEMs) require a geometrical model describing the interfaces between different tissue types. Classically, head models with a nested volume topology have been used. In this paper, we demonstrate how this constraint can be relaxed, allowing us to model more realistic head topologies. We describe the symmetric BEM for this new model. The symmetric BEM formulation uses both potentials and currents at the interfaces as unknowns and is in general more accurate than the alternative double-layer formulation.

A Study on the Effect of Electrical Stimulation as a User Stimuli for Motor Imagery Classification in Brain-Machine Interface.

Functional Electrical Stimulation (FES) provides a neuroprosthetic interface to non-recovered muscle groups by stimulating the affected region of the human body. FES in combination with Brain-machine interfacing (BMI) has a wide scope in rehabilitation because this system directly links the cerebral motor intention of the users with its corresponding peripheral muscle activations. In this paper, we examine the effect of FES on the electroencephalography (EEG) during motor imagery (left- and right-hand movement) training of the users. Results suggest a significant improvement in the classification accuracy when the subject was induced with FES stimuli as compared to the standard visual one.

A common formalism for the integral formulations of the forward EEG problem.

The forward electroencephalography (EEG) problem involves finding a potential V from the Poisson equation inverted Delta x (sigma inverted Delta V) f, in which f represents electrical sources in the brain, and sigma the conductivity of the head tissues. In the piecewise constant conductivity head model, this can be accomplished by the boundary element method (BEM) using a suitable integral formulation. Most previous work uses the same integral formulation, corresponding to a double-layer potential. In this paper we present a conceptual framework based on a well-known theorem (Theorem 1) that characterizes harmonic functions defined on the complement of a bounded smooth surface. This theorem says that such harmonic functions are completely defined by their values and those of their normal derivatives on this surface. It allows us to cast the previous BEM approaches in a unified setting and to develop two new approaches corresponding to different ways of exploiting the same theorem. Specifically, we first present a dual approach which involves a single-layer potential. Then, we propose a symmetric formulation, which combines single- and double-layer potentials, and which is new to the field of EEG, although it has been applied to other problems in electromagnetism. The three methods have been evaluated numerically using a spherical geometry with known analytical solution, and the symmetric formulation achieves a significantly higher accuracy than the alternative methods. Additionally, we present results with realistically shaped meshes. Beside providing a better understanding of the foundations of BEM methods, our approach appears to lead also to more efficient algorithms.