Robert Oostenveld

Neuronal Oscillations with Non-sinusoidal Morphology Produce Spurious Phase-to-Amplitude Coupling and Directionality

Neuronal oscillations support cognitive processing. Modern views suggest that neuronal oscillations do not only reflect coordinated activity in spatially distributed networks, but also that there is interaction between the oscillations at different frequencies. For example, invasive recordings in animals and humans have found that the amplitude of fast oscillations (>40 Hz) occur non-uniformly within the phase of slower oscillations, forming the so-called cross-frequency coupling (CFC). However, the CFC patterns might be influenced by features in the signal that do not relate to underlying physiological interactions. For example, CFC estimates may be sensitive to spectral correlations due to non-sinusoidal properties of the alpha band wave morphology. To investigate this issue, we performed CFC analysis using experimental and synthetic data. The former consisted in a double-blind magnetoencephalography pharmacological study in which participants received either placebo, 0.5 or 1.5 mg of lorazepam (LZP; GABAergic enhancer) in different experimental sessions. By recording oscillatory brain activity with during rest and working memory (WM), we were able to demonstrate that posterior alpha (8–12 Hz) phase was coupled to beta-low gamma band (20–45 Hz) amplitude envelope during all sessions. Importantly, bicoherence values around the harmonics of the alpha frequency were similar both in magnitude and topographic distribution to the cross-frequency coherence (CFCoh) values observed in the alpha-phase to beta-low gamma coupling. In addition, despite the large CFCoh we found no significant cross-frequency directionality (CFD). Critically, simulations demonstrated that a sizable part of our empirical CFCoh between alpha and beta-low gamma coupling and the lack of CFD could be explained by two-three harmonics aligned in zero phase-lag produced by the physiologically characteristic alpha asymmetry in the amplitude of the peaks relative to the troughs. Furthermore, we showed that periodic signals whose waveform deviate from pure sine waves produce non-zero CFCoh with predictable CFD. Our results reveal the important role of the non-sinusoidal wave morphology on state of the art CFC metrics and we recommend caution with strong physiological interpretations of CFC and suggest basic data quality checks to enhance the mechanistic understanding of CFC.

The FieldTrip-SimBio pipeline for EEG forward solutions

BackgroundAccurately solving the electroencephalography (EEG) forward problem is crucial for precise EEG source analysis. Previous studies have shown that the use of multicompartment head models in combination with the finite element method (FEM) can yield high accuracies both numerically and with regard to the geometrical approximation of the human head. However, the workload for the generation of multicompartment head models has often been too high and the use of publicly available FEM implementations too complicated for a wider application of FEM in research studies. In this paper, we present a MATLAB-based pipeline that aims to resolve this lack of easy-to-use integrated software solutions. The presented pipeline allows for the easy application of five-compartment head models with the FEM within the FieldTrip toolbox for EEG source analysis.MethodsThe FEM from the SimBio toolbox, more specifically the St. Venant approach, was integrated into the FieldTrip toolbox. We give a short sketch of the implementation and its application, and we perform a source localization of somatosensory evoked potentials (SEPs) using this pipeline. We then evaluate the accuracy that can be achieved using the automatically generated five-compartment hexahedral head model [skin, skull, cerebrospinal fluid (CSF), gray matter, white matter] in comparison to a highly accurate tetrahedral head model that was generated on the basis of a semiautomatic segmentation with very careful and time-consuming manual corrections.ResultsThe source analysis of the SEP data correctly localizes the P20 component and achieves a high goodness of fit. The subsequent comparison to the highly detailed tetrahedral head model shows that the automatically generated five-compartment head model performs about as well as a highly detailed four-compartment head model (skin, skull, CSF, brain). This is a significant improvement in comparison to a three-compartment head model, which is frequently used in praxis, since the importance of modeling the CSF compartment has been shown in a variety of studies.ConclusionThe presented pipeline facilitates the use of five-compartment head models with the FEM for EEG source analysis. The accuracy with which the EEG forward problem can thereby be solved is increased compared to the commonly used three-compartment head models, and more reliable EEG source reconstruction results can be obtained.

Similarities and differences between on-scalp and conventional in-helmet magnetoencephalography recordings

The development of new magnetic sensor technologies that promise sensitivities approaching that of conventional MEG technology while operating at far lower operating temperatures has catalysed the growing field of on-scalp MEG. The feasibility of on-scalp MEG has been demonstrated via benchmarking of new sensor technologies performing neuromagnetic recordings in close proximity to the head surface against state-of-the-art in-helmet MEG sensor technology. However, earlier work has provided little information about how these two approaches compare, or about the reliability of observed differences. Herein, we present such a comparison, based on recordings of the N20m component of the somatosensory evoked field as elicited by electric median nerve stimulation. As expected from the proximity differences between the on-scalp and in-helmet sensors, the magnitude of the N20m activation as recorded with the on-scalp sensor was higher than that of the in-helmet sensors. The dipole pattern of the on-scalp recordings was also more spatially confined than that of the conventional recordings. Our results furthermore revealed unexpected temporal differences in the peak of the N20m component. An analysis protocol was therefore developed for assessing the reliability of this observed difference. We used this protocol to examine our findings in terms of differences in sensor sensitivity between the two types of MEG recordings. The measurements and subsequent analysis raised attention to the fact that great care has to be taken in measuring the field close to the zero-line crossing of the dipolar field, since it is heavily dependent on the orientation of sensors. Taken together, our findings provide reliable evidence that on-scalp and in-helmet sensors measure neural sources in mostly similar ways.

Metacognition of attention during tactile discrimination.

ABSTRACT The ability to monitor the success of cognitive processing is referred to as metacognition. Studies of metacognition typically probe post‐decision judgments of confidence, showing that we can report on the success of wide range of cognitive processes. Much less is known about our ability to monitor and report on the degree of top‐down attention, an ability of paramount importance in tasks requiring sustained attention. However, it has been repeatedly shown that the degree and locus of top‐down attention modulates alpha (8–14 Hz) power in sensory cortices. In this study we investigated whether self‐reported ratings of attention are reflected by sensory alpha power, independent from confidence and task difficulty. Subjects performed a stair‐cased tactile discrimination task requiring sustained somatosensory attention. Each discrimination response was followed by a rating of their attention at the moment of stimulation, or their confidence in the discrimination response. MEG was used to estimate trial‐by‐trial alpha power preceding stimulation. Staircasing of task‐difficulty successfully equalized performance between conditions. Both attention and confidence ratings reflected subsequent discrimination performance. Task difficulty specifically influenced confidence ratings. As expected, specifically attention ratings, but not confidence ratings, correlated negatively with contralateral somatosensory alpha power preceding tactile stimuli. Taken together, these results demonstrate that the degree of attention can be subjectively experienced and reported accurately, independent from task difficulty and knowledge about task performance. HIGHLIGHTSAttention and confidence are reported after a stair‐cased tactile discrimination task.Metacognitive accuracy based on attention ratings were on par with confidence ratings.Attention but not confidence correlated negatively with somatosensory alpha power.Confidence but not attention corresponded to task difficulty.

Integrated analysis of anatomical and electrophysiological human intracranial data

Human intracranial electroencephalography (iEEG) recordings provide data with much greater spatiotemporal precision than is possible from data obtained using scalp EEG, magnetoencephalography (MEG), or functional MRI. Until recently, the fusion of anatomical data (MRI and computed tomography (CT) images) with electrophysiological data and their subsequent analysis have required the use of technologically and conceptually challenging combinations of software. Here, we describe a comprehensive protocol that enables complex raw human iEEG data to be converted into more readily comprehensible illustrative representations. The protocol uses an open-source toolbox for electrophysiological data analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible analysis methods that, over the past decade, have been developed and used by a large research community. In this protocol, we describe how to analyze complex iEEG datasets by providing an intuitive and rapid approach that can handle both neuroanatomical information and large electrophysiological datasets. We provide a worked example using an example dataset. We also explain how to automate the protocol and adjust the settings to enable analysis of iEEG datasets with other characteristics. The protocol can be implemented by a graduate student or postdoctoral fellow with minimal MATLAB experience and takes approximately an hour to execute, excluding the automated cortical surface extraction.This protocol describes how to computationally process, integrate, visualize, and analyze anatomical and functional data obtained during intracranial electroencephalography (iEEG) of the human brain.

The Discontinuous Galerkin Finite Element Method for Solving the MEG and the Combined MEG/EEG Forward Problem

In Electro- (EEG) and Magnetoencephalography (MEG), one important requirement of source reconstruction is the forward model. The continuous Galerkin finite element method (CG-FEM) has become one of the dominant approaches for solving the forward problem over the last decades. Recently, a discontinuous Galerkin FEM (DG-FEM) EEG forward approach has been proposed as an alternative to CG-FEM (Engwer et al., 2017). It was shown that DG-FEM preserves the property of conservation of charge and that it can, in certain situations such as the so-called skull leakages, be superior to the standard CG-FEM approach. In this paper, we developed, implemented, and evaluated two DG-FEM approaches for the MEG forward problem, namely a conservative and a non-conservative one. The subtraction approach was used as source model. The validation and evaluation work was done in statistical investigations in multi-layer homogeneous sphere models, where an analytic solution exists, and in a six-compartment realistically shaped head volume conductor model. In agreement with the theory, the conservative DG-FEM approach was found to be superior to the non-conservative DG-FEM implementation. This approach also showed convergence with increasing resolution of the hexahedral meshes. While in the EEG case, in presence of skull leakages, DG-FEM outperformed CG-FEM, in MEG, DG-FEM achieved similar numerical errors as the CG-FEM approach, i.e., skull leakages do not play a role for the MEG modality. In particular, for the finest mesh resolution of 1 mm sources with a distance of 1.59 mm from the brain-CSF surface, DG-FEM yielded mean topographical errors (relative difference measure, RDM%) of 1.5% and mean magnitude errors (MAG%) of 0.1% for the magnetic field. However, if the goal is a combined source analysis of EEG and MEG data, then it is highly desirable to employ the same forward model for both EEG and MEG data. Based on these results, we conclude that the newly presented conservative DG-FEM can at least complement and in some scenarios even outperform the established CG-FEM approaches in EEG or combined MEG/EEG source analysis scenarios, which motivates a further evaluation of DG-FEM for applications in bioelectromagnetism.

Lead-DBS v2: Towards a comprehensive pipeline for deep brain stimulation imaging

&NA; Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead‐DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural/functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead‐DBS using a single patient example with state‐of‐the‐art high‐field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co‐registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole‐brain tractography algorithms are applied to the patients preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the preprocessing method of choice. This work represents a multi‐institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field. HighlightsComprehensive and advanced processing pipeline for Deep Brain Stimulation imaging.Seamless Deep Brain Stimulation and Structural / Functional Connectomics Pipelines.DBS stimulation volume explains clinical improvement in Parkinsons Disease cohort.Overview of current methods & default processing pipeline in Lead‐DBS software.

Entrainment for attentional selection in Parkinson's disease

Neural entrainment plays a crucial role in perception and action, especially when stimuli possess a certain temporal regularity, and is also suggested to serve as a neural process to select and attend the relevant stream in situations where there are competing stimulus streams. Beneficial effects of entrainment have led to the suggestion that rhythmic stimuli can improve motor function in patients with Parkinsons disease (PD). Behavioural studies support this suggestion, but neurophysiological studies have shown reduced entrainment of motor areas in PD. However, oscillatory entrainment in PD has only been tested in paradigms with a single isochronous stimulus stream, whereas entrainment has an enhanced benefit in situations where one rhythmic stimulus stream has to be segregated from distractor stimuli. Therefore, we here used an intermodal selective attention task with concurrent auditory and visual stimulus streams while recording oscillatory brain activity with Magnetoencephalography (MEG). We aimed to (i) replicate earlier findings of deficient motor entrainment in PD patients in conditions where there is a single stimulus stream, and (ii) to evaluate whether increasing the benefit of entrainment by introducing a distractor stream would lead to entrainment in PD patients not seen otherwise. Contrary to this hypothesis, PD patients showed reduced motor entrainment compared to controls during both conditions, as indexed by beta oscillatory activity. These results suggest that entrainment in PD patients is deficient, even under conditions that encourage entrainment.