No abstract

Numerical simulation studies were performed using a multiple dipole source model and a spherical approximation of the head to examine how the resolution of simultaneously active neuromagnetic sources depends upon: 1) source modeling assumptions (i.e., number of assumed dipoles); 2) actual source parameters (e.g., location, orientation, and moment); and 3) measurement errors. Forward calculations were conducted for a series of source configurations in which the number of dipoles, specific dipole parameters, and noise levels were systematically varied. Simulated noisy field distributions were fit by multiple dipole models of increasing model order (1, 2, ..., 6 and alternative statistical approaches (i.e., percent of variance, reduced chi-square, and F-ratio) were compared for their effectiveness in determining adequate model order. Limits of spatial resolution were established for a variety of multi-source configurations and noise conditions. Implications for the analysis of empirical data are discussed.

Retinotopic mapping strategies similar to those used for invasive electrophysiological studies to identify multiple visual areas in monkeys have been adapted for noninvasive studies in humans, using magnetic recordings of brain activity in conjunction with anatomical magnetic resonance imaging. The retinotopic organization of the primary visual area (V1) in the left hemisphere of human subjects was examined by presenting a small patterned stimuli near the vertical and horizontal meridians in the lower right visual field. In contrast with the classical model of V1 retinotopy, our results suggest that the representation of the horizontal meridian does not necessarily correspond in a one-to-one manner with the base of the calcarine fissure and that some lower field stimuli can activate regions in the lower bank of the fissure. The results also indicate significant individual variability in the details of how V1 maps around the calcarine fissure.

We present the four key areas of research—preprocessing, the volume conductor, the forward problem, and the inverse problem—that affect the performance of EEG and MEG source imaging. In each key area we identify prominent approaches and methodologies that have open issues warranting further investigation within the community, challenges associated with certain techniques, and algorithms necessitating clarification of their implications. More than providing definitive answers we aim to identify important open issues in the quest of source localization.

The detection of a change in a face stimulus was studied in an oddball paradigm. Event-related potentials (ERPs) and MEG responses to face stimuli were recorded in four conditions: 1) happy standard, neutral deviant; 2) neutral standard, neutral deviant; 3) inverted happy standard, inverted neutral deviant; 4) inverted neutral standard, inverted neutral deviant. In all conditions, the target was a face with glasses. Neutral deviants elicited a negative deflection (with a maximum around 280 ms) in ERP and MEG responses, an effect similar to auditory mismatch negativity. Face inversion diminished deviance-related negativity, implying an important role of face recognition in the observed effect. Emotional content and larger physical differences between stimuli in conditions 1 and 3 compared to conditions 2 and 4 did not show statistically significant effect on the neutral-deviant-related negativity.

The amplitude variability of the M50 component of neuromagnetic responses is commonly used to explore the brain’s ability to modulate its response to incoming repetitive or novel auditory stimuli, a process conceptualized as a gating mechanism. The goal of this study was to identify the spatial and temporal characteristics of the cortical sources underlying the M50 network evoked by tones in a passive oddball paradigm. Twenty elderly subjects [10 patients diagnosed with mild cognitive impairment (MCI) or probable Alzheimer disease (AD) and 10 age-matched controls] were examined using magnetoencephalographic (MEG) recordings and the multi-dipole Calibrated Start Spatio-Temporal (CSST) source localization method. We identified three cortical regions underlying the M50 network: prefrontal cortex (PF) in addition to bilateral activation of the superior temporal gyrus (STG). The cortical dynamics of the PF source within the 30–100 ms post-stimulus interval was characterized and was found to be comprised of two subcomponents, Mb1c and Mb2c. The PF source was localized for 10/10 healthy subjects, whereas 9/10 MCI/AD patients were lacking the PF source for both tone conditions. The selective activation of the PF source in healthy controls along with inactivation of the PF region for MCI/AD patients, enabled us to examine the dynamics of this network of activity when it was functional and dysfunctional, respectively. We found significantly enhanced activity of the STG sources in response to both tone conditions for all subjects who lacked a PF source. The reported results provide novel insights into the topology and neurodynamics of the M50 auditory network, which suggest an inhibitory role of the PF source that normally suppresses activity of the STG sources.

Results are reviewed from several neuromagnetic studies which characterize the temporal dynamics of neural sources contributing to the visual evoked response and effects of attention on these sources. Different types of pattern-onset stimuli (< or = 2 degrees) were presented sequentially to a number of field locations in the right visual field. Multiple dipole models were applied to a sequence of instantaneous field distributions constructed at 10 ms intervals. Best-fitting source parameters were superimposed on Magnetic Resonance images (MRI) of each subject to identify the anatomical structure(s) giving rise to the surface patterns. At least three sources, presumably corresponding to different visual areas, were routinely identified from 80-150 ms following the onset of visual stimulation. This observation was consistent across subjects and studies. The temporal sequence and strength of activation of these sources, however, were dependent upon the specific stimulus parameters used to evoke the response (e.g., eccentricity) and on the relevance of the stimulus to the subject. In addition, our results provide evidence for the recurrence of activity in striate and extrastriate regions, following the initial cycle of responses.

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer’s disease (AD). In this study we used MEG source estimates of auditory gating generators, non-linear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in re-categorizing the participant categories in: 1) controls with mPFC generator localized in response to both the standard and deviant tones; 2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and 3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a non-invasive biomarker of AD pathology during putative preclinical and clinical stages.