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Source localization by electroencephalography (EEG) requires an accurate model of head geometry and tissue conductivity. The estimation of source time courses from EEG or from EEG in conjunction with magnetoencephalography (MEG) requires a forward model consistent with true activity for the best outcome. Although MRI provides an excellent description of soft tissue anatomy, a high resolution model of the skull (the dominant resistive component of the head) requires CT, which is not justified for routine physiological studies. Although a number of techniques have been employed to estimate tissue conductivity, no present techniques provide the noninvasive 3D tomographic mapping of conductivity that would be desirable. We introduce a formalism for probabilistic forward modeling that allows the propagation of uncertainties in model parameters into possible errors in source localization. We consider uncertainties in the conductivity profile of the skull, but the approach is general and can be extended to other kinds of uncertainties in the forward model. We and others have previously suggested the possibility of extracting conductivity of the skull from measured electroencephalography data by simultaneously optimizing over dipole parameters and the conductivity values required by the forward model. Using Cramer-Rao bounds, we demonstrate that this approach does not improve localization results nor does it produce reliable conductivity estimates. We conclude that the conductivity of the skull has to be either accurately measured by an independent technique, or that the uncertainties in the conductivity values should be reflected in uncertainty in the source location estimates.

Most existing spatiotemporal multi-dipole approaches for MEG/EEG source localization assume that the dipoles are active for the full time range being analysed. If the actual time range of activity of sources is significantly shorter than the time range being analysed, the detectability, localization and time-course determination of such sources may be adversely affected, especially for weak sources. In order to improve detectability and reconstruction of such sources, it is natural to add active time range information (starting time point and ending time point of source activation) for each candidate source as unknown parameters in the analysis. However, this adds additional nonlinear free parameters that could burden the analysis and could be unfeasible for some methods. Recently, we described a spatiotemporal Bayesian inference multi-dipole analysis for the MEG/EEG inverse problem. This approach treated the number of dipoles as a free parameter, produced realistic uncertainty estimates using a Markov chain Monte Carlo numerical sampling of the posterior distribution and included a method to reduce the unwanted effects of local minima. In this paper, our spatiotemporal Bayesian inference multi-dipole analysis is extended to incorporate active time range parameters of starting and stopping time points. The properties of this analysis in comparison to the previous one without active time range parameters are demonstrated through extensive studies using both simulated and empirical MEG data.

Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuro-imaging methods.