Dimitrios Pantazis

Brainstorm: a user-friendly application for MEG/EEG analysis

Brainstorm is a collaborative open-source application dedicated to magnetoencephalography (MEG) and electroencephalography (EEG) data visualization and processing, with an emphasis on cortical source estimation techniques and their integration with anatomical magnetic resonance imaging (MRI) data. The primary objective of the software is to connect MEG/EEG neuroscience investigators with both the best-established and cutting-edge methods through a simple and intuitive graphical user interface (GUI).

Mapping human brain function with MEG and EEG: methods and validation.

We survey the field of magnetoencephalography (MEG) and electroencephalography (EEG) source estimation. These modalities offer the potential for functional brain mapping with temporal resolution in the millisecond range. However, the limited number of spatial measurements and the ill-posedness of the inverse problem present significant limits to our ability to produce accurate spatial maps from these data without imposing major restrictions on the form of the inverse solution. Here we describe approaches to solving the forward problem of computing the mapping from putative inverse solutions into the data space. We then describe the inverse problem in terms of low dimensional solutions, based on the equivalent current dipole (ECD), and high dimensional solutions, in which images of neural activation are constrained to the cerebral cortex. We also address the issue of objective assessment of the relative performance of inverse procedures by the free-response receiver operating characteristic (FROC) curve. We conclude with a discussion of methods for assessing statistical significance of experimental results through use of the bootstrap for determining confidence regions in dipole-fitting methods, and random field (RF) and permutation methods for detecting significant activation in cortically constrained imaging studies.

Coherent neural representation of hand speed in humans revealed by MEG imaging

The spiking activity of single neurons in the primate motor cortex is correlated with various limb movement parameters, including velocity. Recent findings obtained using local field potentials suggest that hand speed may also be encoded in the summed activity of neuronal populations. At this macroscopic level, the motor cortex has also been shown to display synchronized rhythmic activity modulated by motor behavior. Yet whether and how neural oscillations might be related to limb speed control is still poorly understood. Here, we applied magnetoencephalography (MEG) source imaging to the ongoing brain activity in subjects performing a continuous visuomotor (VM) task. We used coherence and phase synchronization to investigate the coupling between the estimated activity throughout the brain and the simultaneously recorded instantaneous hand speed. We found significant phase locking between slow (2- to 5-Hz) oscillatory activity in the contralateral primary motor cortex and time-varying hand speed. In addition, we report long-range task-related coupling between primary motor cortex and multiple brain regions in the same frequency band. The detected large-scale VM network spans several cortical and subcortical areas, including structures of the frontoparietal circuit and the cerebello–thalamo–cortical pathway. These findings suggest a role for slow coherent oscillations in mediating neural representations of hand kinematics in humans and provide further support for the putative role of long-range neural synchronization in large-scale VM integration. Our findings are discussed in the context of corticomotor communication, distributed motor encoding, and possible implications for brain–machine interfaces.

Resolving human object recognition in space and time

A comprehensive picture of object processing in the human brain requires combining both spatial and temporal information about brain activity. Here we acquired human magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) responses to 92 object images. Multivariate pattern classification applied to MEG revealed the time course of object processing: whereas individual images were discriminated by visual representations early, ordinate and superordinate category levels emerged relatively late. Using representational similarity analysis, we combined human fMRI and MEG to show content-specific correspondence between early MEG responses and primary visual cortex (V1), and later MEG responses and inferior temporal (IT) cortex. We identified transient and persistent neural activities during object processing with sources in V1 and IT. Finally, we correlated human MEG signals to single-unit responses in monkey IT. Together, our findings provide an integrated space- and time-resolved view of human object categorization during the first few hundred milliseconds of vision.

Autism as a disorder of prediction

Significance Autism is characterized by diverse behavioral traits. Guided by theoretical considerations and empirical data, this paper develops the hypothesis that many of autisms salient traits may be manifestations of an underlying impairment in predictive abilities. This impairment renders an otherwise orderly world to be experienced as a capriciously “magical” one. The hypothesis elucidates the information-processing roots of autism and, thereby, can aid the identification of neural structures likely to be differentially affected. Behavioral and neural measures of prediction might serve as early assays of predictive abilities in infants, and serve as useful tools in intervention design and in monitoring their effectiveness. The hypothesis also points to avenues for further research to determine molecular and circuit-level causal underpinnings of predictive impairments. A rich collection of empirical findings accumulated over the past three decades attests to the diversity of traits that constitute the autism phenotypes. It is unclear whether subsets of these traits share any underlying causality. This lack of a cohesive conceptualization of the disorder has complicated the search for broadly effective therapies, diagnostic markers, and neural/genetic correlates. In this paper, we describe how theoretical considerations and a review of empirical data lead to the hypothesis that some salient aspects of the autism phenotype may be manifestations of an underlying impairment in predictive abilities. With compromised prediction skills, an individual with autism inhabits a seemingly “magical” world wherein events occur unexpectedly and without cause. Immersion in such a capricious environment can prove overwhelming and compromise one’s ability to effectively interact with it. If validated, this hypothesis has the potential of providing unifying insights into multiple aspects of autism, with attendant benefits for improving diagnosis and therapy.

A comparison of random field theory and permutation methods for the statistical analysis of MEG data

We describe the use of random field and permutation methods to detect activation in cortically constrained maps of current density computed from MEG data. The methods are applicable to any inverse imaging method that maps event-related MEG to a coregistered cortical surface. These approaches also extend directly to images computed from event-related EEG data. We determine statistical thresholds that control the familywise error rate (FWER) across space or across both space and time. Both random field and permutation methods use the distribution of the maximum statistic under the null hypothesis to find FWER thresholds. The former methods make assumptions on the distribution and smoothness of the data and use approximate analytical solutions, the latter resample the data and rely on empirical distributions. Both methods account for spatial and temporal correlation in the cortical maps. Unlike previous nonparametric work in neuroimaging, we address the problem of nonuniform specificity that can arise without a Gaussianity assumption. We compare and evaluate the methods on simulated data and experimental data from a somatosensory-evoked response study. We find that the random field methods are conservative with or without smoothing, though with a 5 vertex FWHM smoothness, they are close to exact. Our permutation methods demonstrated exact specificity in simulation studies. In real data, the permutation method was not as sensitive as the RF method, although this could be due to violations of the random field theory assumptions.

Comparison of landmark-based and automatic methods for cortical surface registration

Group analysis of structure or function in cerebral cortex typically involves, as a first step, the alignment of cortices. A surface-based approach to this problem treats the cortex as a convoluted surface and coregisters across subjects so that cortical landmarks or features are aligned. This registration can be performed using curves representing sulcal fundi and gyral crowns to constrain the mapping. Alternatively, registration can be based on the alignment of curvature metrics computed over the entire cortical surface. The former approach typically involves some degree of user interaction in defining the sulcal and gyral landmarks while the latter methods can be completely automated. Here we introduce a cortical delineation protocol consisting of 26 consistent landmarks spanning the entire cortical surface. We then compare the performance of a landmark-based registration method that uses this protocol with that of two automatic methods implemented in the software packages FreeSurfer and BrainVoyager. We compare performance in terms of discrepancy maps between the different methods, the accuracy with which regions of interest are aligned, and the ability of the automated methods to correctly align standard cortical landmarks. Our results show similar performance for ROIs in the perisylvian region for the landmark-based method and FreeSurfer. However, the discrepancy maps showed larger variability between methods in occipital and frontal cortex and automated methods often produce misalignment of standard cortical landmarks. Consequently, selection of the registration approach should consider the importance of accurate sulcal alignment for the specific task for which coregistration is being performed. When automatic methods are used, the users should ensure that sulci in regions of interest in their studies are adequately aligned before proceeding with subsequent analysis.

Comparison of deep neural networks to spatio-temporal cortical dynamics of human visual object recognition reveals hierarchical correspondence

The complex multi-stage architecture of cortical visual pathways provides the neural basis for efficient visual object recognition in humans. However, the stage-wise computations therein remain poorly understood. Here, we compared temporal (magnetoencephalography) and spatial (functional MRI) visual brain representations with representations in an artificial deep neural network (DNN) tuned to the statistics of real-world visual recognition. We showed that the DNN captured the stages of human visual processing in both time and space from early visual areas towards the dorsal and ventral streams. Further investigation of crucial DNN parameters revealed that while model architecture was important, training on real-world categorization was necessary to enforce spatio-temporal hierarchical relationships with the brain. Together our results provide an algorithmically informed view on the spatio-temporal dynamics of visual object recognition in the human visual brain.

Identifying true cortical interactions in MEG using the nulling beamformer

Modeling functional brain interaction networks using non-invasive EEG and MEG data is more challenging than using intracranial recording data. This is because most interaction measures are not robust to the cross-talk (interference) between cortical regions, which may arise due to the limited spatial resolution of EEG/MEG inverse procedures. In this article, we describe a modified beamforming approach to accurately measure cortical interactions from EEG/MEG data, designed to suppress cross-talk between cortical regions. We estimate interaction measures from the output of the modified beamformer and test for statistical significance using permutation tests. Since the underlying neuronal sources and their interactions are unknown in real MEG data, we demonstrate the performance of the proposed beamforming method in a novel simulation scheme, where intracranial recordings from a macaque monkey are used as neural sources to simulate realistic MEG signals. The advantage of this approach is that local field potentials are more realistic representations of true neuronal sources than simulation models and therefore are more suitable to indicate the performance of our nulling beamforming method.

A Note on the Phase Locking Value and its Properties

We investigate the properties of the Phase Locking Value (PLV) and the Phase Lag Index (PLI) as metrics for quantifying interactions in bivariate local field potential (LFP), electroencephalography (EEG) and magnetoencephalography (MEG) data. In particular we describe the relationship between nonparametric estimates of PLV and PLI and the parameters of two distributions that can both be used to model phase interactions. The first of these is the von Mises distribution, for which the sample PLV is a maximum likelihood estimator. The second is the relative phase distribution associated with bivariate circularly symmetric complex Gaussian data. We derive an explicit expression for the PLV for this distribution and show that it is a function of the cross-correlation between the two signals. We compare the bias and variance of the sample PLV and the PLV computed from the cross-correlation. We also show that both the von Mises and Gaussian models are suitable for representing relative phase in application to LFP data from a visually-cued motor study in macaque. We then compare results using the two different PLV estimators and conclude that, for this data, the sample PLV provides equivalent information to the cross-correlation of the two complex time series.