Applying stochastic spike train theory for high-accuracy MEG/EEG

Abstract The accuracy of electroencephalography (EEG) and magnetoencephalography (MEG) is challenged by overlapping sources from within the brain. This lack of accuracy is a severe limitation to the possibilities and reliability of modern stimulation protocols in basic research and clinical diagnostics. As a solution, we here introduce a theory of stochastic neuronal spike timing probability densities for describing the large-scale spiking activity in neural networks, and a novel spike density component analysis (SCA) method for isolating specific neural sources. Three studies are conducted based on 564 cases of evoked responses to auditory stimuli from 94 human subjects each measured with 60 EEG electrodes and 306 MEG sensors. In the first study we show that the large-scale spike timing (but not non-encephalographic artifacts) in MEG/EEG waveforms can be modeled with Gaussian probability density functions with high accuracy (median 99.7%-99.9% variance explained), while gamma and sine functions fail describing the MEG and EEG waveforms. In the second study we confirm that SCA can isolate a specific evoked response of interest. Our findings indicate that the mismatch negativity (MMN) response is accurately isolated with SCA, while principal component analysis (PCA) fails supressing interference from overlapping brain activity, e.g. from P3a and alpha waves, and independent component analysis (ICA) distorts the evoked response. Finally, we confirm that SCA accurately reveals inter-individual variation in evoked brain responses, by replicating findings relating individual traits with MMN variations. The findings of this paper suggest that the commonly overlapping neural sources in single-subject or patient data can be more accurately separated by applying the introduced theory of large-scale spike timing and method of SCA in comparison to PCA and ICA. Significance statement Electroencephalography (EEG) and magnetoencelopraphy (MEG) are among the most applied non-invasive brain recording methods in humans. They are the only methods to measure brain function directly and in time resolutions smaller than seconds. However, in modern research and clinical diagnostics the brain responses of interest cannot be isolated, because of interfering signals of other ongoing brain activity. For the first time, we introduce a theory and method for mathematically describing and isolating overlapping brain signals, which are based on prior intracranial in vivo research on brain cells in monkey and human neural networks. Three studies mutually support our theory and suggest that a new level of accuracy in MEG/EEG can achieved by applying the procedures presented in this paper.