Selma Supek

EEG/MEG source imaging: methods, challenges, and open issues

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.

Neurodynamic Studies on Emotional and Inverted Faces in an Oddball Paradigm

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.

Single vs. paired visual stimulation: superposition of early neuromagnetic responses and retinotopy in extrastriate cortex in humans

Neuromagnetic techniques were used in conjunction with magnetic resonance imaging (MRI) techniques to: (1) localize and characterize cortical sources evoked by visual stimuli presented at different locations in the lower right visual field; (2) examine the superposition of cortical responses by comparing the summation of responses to the presentation of single stimuli with responses to paired stimuli; and (3) examine the spatial resolution of magnetoencephalographic (MEG) techniques by comparing the identified source locations evoked by the presentation of single vs. paired stimuli. Using multi-dipole, non-linear minimization analyses, three sources were localized for each stimulus condition during the initial 80-170 ms poststimulus interval for all subjects. In addition to an occipital source, two extrastriate sources were identified: occipital-parietal and occipital-temporal. Each source evidenced a systematic shift in location associated with changes in stimulus placement parallel to the vertical meridian. To our knowledge, this is the first demonstration of retinotopic organization of extrastriate areas, using non-invasive neuromagnetic techniques. The paired presentation of stimuli reflected superposition of the responses evoked by single stimuli but only for early activity up to 150 ms poststimulus. Undersummation was evident after 150 ms. All sources identified for single stimuli were also identified in the paired-stimulus responses; but at the expense of larger errors for some of the estimated parameters.

Spatio-Temporal Modeling of Neuromagnetic Data: I. Multi-Source Location Versus Time-Course Estimation Accuracy

Numerical simulations were conducted to examine multi‐source spatio‐temporal resolution for neuromagnetic field distributions “measured” by a large sensor array (i.e., 135). spatio‐temporal field distributions were generated by a series of two‐dipole and three‐dipole configurations in which source locations, orientations, and temporal dynamics of individual sources were systematically varied to represent classes of cases of interest for neuromagnetic studies. The specific goals of our numerical simulations were to examine multi‐source resolution and parameter estimation accuracy as a function of 1) specific multi‐source configurations; 2) different time courses, i.e., degree of temporal correlation; 3) measurement noise; 4) spatio‐temporal modeling strategy (i.e., sequential fitting of instantaneous field distributions, two‐step spatio‐temporal modeling); 5) source modeling assumptions associated with model order; and 6) effects of initial modeling assumptions (i.e., starting points for the nonlinear minimization procedure derived by MUltiple SIgnal Classification (MUSIC), sequential instantaneous fitting, and arbitrary selections). The ability to determine the number of active sources by different approaches is compared, and the consequences on the accuracy of estimated solutions for simulated data are discussed. In all cases, model adequacy was assessed using reduced chi‐square as a measure of goodness‐of‐fit. The present simulations demonstrate that location estimation was more robust and accurate compared to the estimation of temporal dynamics of individual sources. Implications for spatio‐temporal modeling of neuromagnetic empirical data are suggested. Hum. Brain Mapping 5:139–153, 1997.

Early cortical responses are sensitive to changes in face stimuli

Face-related processing has been demonstrated already in the early evoked response around 100 ms after stimulus. The aims of this study were to explore these early responses both at sensor and cortical source level and to explore to what extent they might be modulated by a change in face stimulus. Magnetoencephalographic (MEG) recordings, a visual oddball paradigm, and a semiautomated spatiotemporal source localization method were used to investigate cortical responses to changes in face stimuli. Upright and inverted faces were presented in an oddball paradigm with four conditions; standards and deviants differing in emotion or identity. The task in all conditions was silent counting of the target face with glasses. Deviant face stimuli elicited larger MEG responses at about 100 ms than standard ones did but only for upright faces. Spatiotemporal source localization up to 140 ms after stimulus revealed activation of parietal and temporal sources in addition to occipital ones, all of which demonstrated differences in locations and dynamics for standards, deviants, and targets. Peak latencies of the identified cortical sources were shorter for deviants than standards, again only for upright faces. Our results showed differences in cortical responses to standards and deviants that were more pronounced for upright than for inverted faces, suggesting early detection of face-related changes in visual stimulation. The observed effect provides new evidence for the face sensitivity of the early neuromagnetic response around 100 ms.

Size matters: MEG empirical and simulation study on source localization of the earliest visual activity in the occipital cortex

While the relationship between sensory stimulation and tasks and the size of the cortical activations is generally unknown, the visual modality offers a unique possibility of an experimental manipulation of stimulus size-related increases of the spatial extent of cortical activation even during the earliest activity in the retinotopically organized primary visual cortex. We used magnetoecephalography (MEG), visual stimuli of increasing size, and numerical simulations on realistic cortical surfaces to explore the effects of increasing spatial extent of the activated cortical sources on the neuromagnetic fields, location estimation biases, and source resolution. Source localization was performed assuming multiple dipoles in a sphere model using an efficient, automatically restarted multi-start simplex minimizer within the Calibrated Start Spatio-Temporal (CSST) algorithm. We found size-related effects on amplitude and latencies and differences in relative locations of the earliest occipital sources evoked by stimuli of increasing size presented at the same eccentricity. This finding was confirmed by single patch simulations. Additionally, simulations of multiple extended sources demonstrated size-related increase in limits in source resolution for bilaterally simulated sources, biases in location estimates for a given separation of sources, and limits in source resolution due to source multiplicity within a hemisphere.

Early dissociation of face and object processing: A magnetoencephalographic study

The early dissociation in cortical responses to faces and objects was explored with magnetoencephalographic (MEG) recordings and source localization. To control for differences in the low‐level stimulus features, which are known to modulate early brain responses, we created a novel set of stimuli so that their combinations did not have any differences in the visual‐field location, spatial frequency, or luminance contrast. Differing responses to face and object (flower) stimuli were found at about 100 ms after stimulus onset in the occipital cortex. Our data also confirm that the brain response to a complex visual stimulus is not merely a sum of the responses to its constituent parts; the nonlinearity in the response was largest for meaningful stimuli. Hum Brain Mapp, 2009.

High-resolution EEG analysis of power spectral density maps and coherence networks in a proportional reasoning task.

Proportional reasoning is very important logical skill required in mathematics and science problem solving as well as in everyday life decisions. However, there is a lack of studies on neurophysiological correlates of proportional reasoning. To explore the brain activity of healthy adults while performing a balance scale task, we used high-resolution EEG techniques and graph-theory based connectivity analysis. After unskilled subjects learned how to properly solve the task, their cortical power spectral density (PSD) maps revealed an increased parietal activity in the beta band. This indicated that subjects started to perform calculations. In addition, the number of inter-hemispheric connections decreased after learning, implying a rearrangement of the brain activity. Repeated performance of the task led to the PSD decrease in the beta and gamma bands among parietal and frontal regions along with a synchronization of lower frequencies. These findings suggest that repetition led to a more automatic task performance. Subjects were also divided in two groups according to their scores on the test of logical thinking (TOLT). Although no group differences in the accuracy and reaction times were found, EEG data showed higher activity in the beta and gamma bands for the group that scored better on TOLT. Learning and repetition induced changes in the pattern of functional connectivity were evident for all frequency bands. Overall, the results indicated that higher frequency oscillations in frontal and parietal regions are particularly important for proportional reasoning.

Face activated neurodynamic cortical networks

Previous neuroimaging studies have shown that complex visual stimuli, such as faces, activate multiple brain regions, yet little is known on the dynamics and complexity of the activated cortical networks during the entire measurable evoked response. In this study, we used simulated and face-evoked empirical MEG data from an oddball study to investigate the feasibility of accurate, efficient, and reliable spatio-temporal tracking of cortical pathways over prolonged time intervals. We applied a data-driven, semiautomated approach to spatio-temporal source localization with no prior assumptions on active cortical regions to explore non-invasively face-processing dynamics and their modulation by task. Simulations demonstrated that the use of multi-start downhill simplex and data-driven selections of time intervals submitted to the Calibrated Start Spatio-Temporal (CSST) algorithm resulted in improved accuracy of the source localization and the estimation of the onset of their activity. Locations and dynamics of the identified sources indicated a distributed cortical network involved in face processing whose complexity was task dependent. This MEG study provided the first non-invasive demonstration, agreeing with intracranial recordings, of an early onset of the activity in the fusiform face gyrus (FFG), and that frontal activation preceded parietal for responses elicited by target faces.

Modulatory role of the prefrontal generator within the auditory M50 network

The amplitude variability of the M50 component of neuromagnetic responses is commonly used to explore the brains 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 the 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.