Controlling false positive rates in mass-multivariate tests for electromagnetic responses.

We address the problem of controlling false positive rates in mass-multivariate tests for electromagnetic responses in compact regions of source space. We show that mass-univariate thresholds based on sensor level multivariate thresholds (approximated using Roy's union-intersection principle) are unduly conservative. We then consider a Bonferroni correction for source level tests based on the number of unique lead-field extrema. For a given source space, the sensor indices corresponding to the maxima and minima (for each dipolar lead field) are listed, and the number of unique extrema is given by the number of unique pairs in this list. Using a multivariate beamformer formulation, we validate this heuristic against empirical permutation thresholds for mass-univariate and mass-multivariate tests (of induced and evoked responses) for a variety of source spaces, using simulated and real data. We also show that the same approximations hold when dealing with a cortical manifold (rather than a volume) and for mass-multivariate minimum norm solutions. We demonstrate that the mass-multivariate framework is not restricted to tests on a single contrast of effects (cf, Roy's maximum root) but also accommodates multivariate effects (cf, Wilk's lambda).

Quantifying the Core Deficit in Classical Schizophrenia.

In the classical descriptions of schizophrenia, Kraepelin and Bleuler recognized disorganization and impoverishment of mental activity as fundamental symptoms. Their classical descriptions also included a tendency to persisting disability. The psychopathological processes underlying persisting disability in schizophrenia remain poorly understood. The delineation of a core deficit underlying persisting disability would be of value in predicting outcome and enhancing treatment. We tested the hypothesis that mental disorganization and impoverishment are associated with persisting impairments of cognition and role function, and together reflect a latent core deficit that is discernible in cases diagnosed by modern criteria. We used Confirmatory Factor Analysis to determine whether measures of disorganization, mental impoverishment, impaired cognition, and role functioning in 40 patients with schizophrenia represent a single latent variable. Disorganization scores were computed from the variance shared between disorganization measures from 3 commonly used symptom scales. Mental impoverishment scores were computed similarly. A single factor model exhibited a good fit, supporting the hypothesis that these measures reflect a core deficit. Persisting brain disorders are associated with a reduction in post-movement beta rebound (PMBR), the characteristic increase in electrophysiological beta amplitude that follows a motor response. Patients had significantly reduced PMBR compared with healthy controls. PMBR was negatively correlated with core deficit score. While the symptoms constituting impoverished and disorganized mental activity are dissociable in schizophrenia, nonetheless, the variance that these 2 symptom domains share with impaired cognition and role function, appears to reflect a pathophysiological process that might be described as the core deficit of classical schizophrenia.

Understanding gradient artefacts in simultaneous EEG/fMRI.

Implementation of concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recording results in the generation of large artefacts that can compromise the quality of EEG data. While much effort has been devoted towards studying the temporal variation of the artefact waveforms produced by time-varying magnetic field gradients, the spatial variation of the artefact voltage across EEG leads has not previously been investigated in any depth. The aim of this work is to develop an improved understanding of the spatial characteristics of the gradient artefacts and the mechanism which underlies their generation. This paper therefore presents physical models of the artefacts produced by the temporally-varying magnetic field gradients required for MRI. Novel analytic expressions for the artefact voltage that account for realistic shifts and rotations of the human head were calculated from electromagnetic theory, assuming a spherical, homogeneous head and longitudinal wirepaths for the EEG cap. These were then corroborated by comparison with numerical simulations using actual EEG wirepaths and with experimental measurements on an agar phantom and human head. The numerical simulations produced accurate reproductions of experimentally measured spatial patterns for both the spherical phantom and human head in a variety of orientations and gradient fields; correlation coefficients were as high as 0.98 for the phantom and 0.95 for the human head. Furthermore, it was determined that artefact voltages for both longitudinal and transverse gradients could be decreased by adjusting the subject's axial position with respect to the gradient coils. The accuracy of the modelled spatial maps along with the ability to model gradient artefacts for any given head orientation are a step towards developing improved artefact correction algorithms that incorporate motion tracking of the subject and selective filtering based on calculated spatial artefact templates, leading to greater fidelity in simultaneous EEG/fMRI data.