Magnetoencephalography: Clinical and Research Practices

Magnetoencephalography (MEG) is a neurophysiological technique that detects the magnetic fields associated with brain activity. Synthetic aperture magnetometry (SAM), a MEG magnetic source imaging technique, can be used to construct both detailed maps of global brain activity as well as virtual electrode signals, which provide information that is similar to invasive electrode recordings. This innovative approach has demonstrated utility in both clinical and research settings. For individuals with epilepsy, MEG provides valuable, nonredundant information. MEG accurately localizes the irritative zone associated with interictal spikes, often detecting epileptiform activity other methods cannot, and may give localizing information when other methods fail. These capabilities potentially greatly increase the population eligible for epilepsy surgery and improve planning for those undergoing surgery. MEG methods can be readily adapted to research settings, allowing noninvasive assessment of whole brain neurophysiological activity, with a theoretical spatial range down to submillimeter voxels, and in both humans and nonhuman primates. The combination of clinical and research activities with MEG offers a unique opportunity to advance translational research from bench to bedside and back.

High-gamma activity in the human hippocampus during inter-trial rest periods of a virtual navigation task

In rodents, hippocampal cell assemblies formed during learning of a navigation task are observed to re-emerge during resting (offline) periods, accompanied by high-frequency oscillations (HFOs). This phenomenon is believed to reflect mechanisms for strengthening newly-formed memory traces. Using magnetoencephalography recordings and a beamforming source location algorithm (synthetic aperture magnetometry), we investigated high-gamma (80 – 140 Hz) oscillations in the hippocampal region in 18 human participants during inter-trial rest periods in a virtual navigation task. We found right hippocampal gamma oscillations mirrored the pattern of theta power in the same region during navigation, varying as a function of environmental novelty. Gamma power during inter-trial rest periods was positively correlated with theta power during navigation in the first training set when the environment was new and predicted faster learning in the subsequent training set two where the environment became familiar. These findings provide evidence for human hippocampal reactivation accompanied by high-gamma activities immediately after learning and establish a link between hippocampal high-gamma activities and memory consolidation.

Temporal accuracy of human cortico-cortical interactions

The precision in space and time of interactions among multiple cortical sites was evaluated by examining repeating precise spatiotemporal patterns of instances in which cortical currents showed brief amplitude undulations. The amplitudes of the cortical current dipoles were estimated by applying a variant of synthetic aperture magnetometry to magnetoencephalographic (MEG) recordings of subjects tapping to metric auditory rhythms of drum beats. Brief amplitude undulations were detected in the currents by template matching at a rate of 2–3 per second. Their timing was treated as point processes, and precise spatiotemporal patterns were searched for. By randomly teetering these point processes within a time window W, we estimated the accuracy of the timing of these brief amplitude undulations and compared the results with those obtained by applying the same analysis to traces composed of random numbers. The results demonstrated that the timing accuracy of patterns was better than 3 ms. Successful classification of two different cognitive processes based on these patterns suggests that at least some of the repeating patterns are specific to a cognitive process.

Language dominance and mapping based on neuromagnetic oscillatory changes: comparison with invasive procedures

Object Event-related cerebral oscillatory changes reflect regional brain activation. In a previous study, the authors proposed a new method to determine language dominance: examine frontal oscillatory changes during silent reading by using synthetic aperture magnetometry (SAM). The authors' aims in the present study were to establish a normal template for this method, to confirm the results of their previous study with a larger patient population, and to evaluate their method with respect to language localization. Methods A statistical group analysis of 14 healthy volunteers was conducted to establish a normal control. Language dominance and localization were then evaluated in a larger population of 123 consecutive patients. Study participants were instructed to silently read 100 visually presented words. Using SAM, the spatial distribution of the oscillatory changes was obtained as the Student t statistic by comparing the current density for each voxel between 1 second before and 1 second after each word presentation. Group analyses of the healthy volunteers were performed using statistical nonparametric mapping. Language dominance in the patients was determined according to the laterality index (LI) calculated using peak t values of the left and right frontal desynchronizations. Language dominance was prospectively assessed, and the results were compared with those of the Wada test (63 patients). Language localization results were quantitatively compared with those of stimulation mapping (17 patients). Results Group analysis of the healthy volunteers indicated β to low γ band desynchronization in the left frontal area and α to β desynchronization in the left parietotemporal areas. In patients, the frontal language areas were detected in 118 persons (95.9%). Lateralization of β or low γ desynchronization in the inferior or middle frontal gyri corresponded well with language dominance. The introduction of the LI resulted in a quantitative evaluation of language dominance, whose results were concordant with those of the Wada test in 51 (85.0%) of 60 cases. The distance between the estimated frontal language areas and stimulation-positive sites was 6.0 ± 7.1 mm (mean ± SD). Conclusions This study is the first in which magnetoencephalography (MEG) was used to determine language dominance in a large population, and the results were compared with those of the Wada test. Moreover, language localization results obtained using MEG were compared with those obtained by invasive mapping. The authors' method, which is based on neuromagnetic oscillatory changes, is a new approach for noninvasively evaluating the frontal language areas, a procedure that has been problematic using MEG dipole methods. Synthetic aperture magnetometry is a noninvasive alternative to Wada testing for language dominance and helps to determine stimulation sites for invasive mapping.

Prefrontal Cortex Modulation during Anticipation of Working Memory Demands as Revealed by Magnetoencephalography

During the anticipation of task demands frontal control is involved in the assembly of stimulus-response mappings based on current goals. It is not clear whether prefrontal modulations occur in higher-order cortical regions, likely reflecting cognitive anticipation processes. The goal of this paper was to investigate prefrontal modulation during anticipation of upcoming working memory demands as revealed by magnetoencephalography (MEG). Twenty healthy volunteers underwent MEG while they performed a variation of the Sternberg Working Memory (WM) task. Beta band (14–30 Hz) SAM (Synthetic Aperture Magnetometry) analysis was performed. During the preparatory periods there was an increase in beta power (event-related synchronization) in dorsolateral prefrontal cortex (DLPFC) bilaterally, left inferior prefrontal gyrus, left parietal, and temporal areas. Our results provide support for the hypothesis that, during preparatory states, the prefrontal cortex is important for biasing higher order brain regions that are going to be engaged in the upcoming task.

Localization of epileptic foci in children with intractable epilepsy secondary to multiple cortical tubers by using synthetic aperture magnetometry kurtosis

Object Magnetoencephalography (MEG) has been typically used to localize epileptic activity by modeling interictal activity as equivalent current dipoles (ECDs). Synthetic aperture magnetometry (SAM) is a recently developed adaptive spatial filtering algorithm for MEG that provides some advantages over the ECD approach. The SAM-kurtosis algorithm (also known as SAM[g2]) additionally provides automated temporal detection of spike sources by using excess kurtosis value (steepness of epileptic spike on virtual sensors). To evaluate the efficacy of the SAM(g2) method, the authors applied it to readings obtained in children with intractable epilepsy secondary to tuberous sclerosis complex (TSC), and compared them to localizations obtained with ECDs. Methods The authors studied 13 children with TSC (7 girls) whose ages ranged from 13 months to 16.3 years (mean 7.3 years). Video electroencephalography, MR imaging, and MEG studies were analyzed. A single ECD model was applied to localize ECD clusters. The SAM(g2) value was calculated at each SAM(g2) virtual voxel in the patient's MR imaging–defined brain volume. The authors defined the epileptic voxels of SAM(g2) (evSAM[g2]) as those with local peak kurtosis values higher than half of the maximum. A clustering of ECDs had to contain ≥ 6 ECDs within 1 cm of each other, and a grouping of evSAM(g2)s had to contain ≥ 3 evSAM(g2)s within 1 cm of each other. The authors then compared both ECD clusters and evSAM(g2) groups with the resection area and correlated these data with seizure outcome. Results Seizures started when patients were between 6 weeks and 8 years of age (median 6 months), and became intractable secondary to multiple tubers in all cases. Ictal onset on scalp video electroencephalography was lateralized in 8 patients (62%). The MEG studies showed multiple ECD clusters in 7 patients (54%). The SAM(g2) method showed multiple groups of epileptic voxels in 8 patients (62%). Colocalization of grouped evSAM(g2) with ECD clusters ranged from 20 to 100%, with a mean of 82%. Eight patients underwent resection of single (1 patient) and multiple (7 patients) lobes, with 6 patients achieving freedom from seizures. Of 8 patients who underwent surgery, in 7 the resection area covered ECD clusters and grouped evSAM(g2)s. In the remaining patient the resection area partially included the ECD cluster and grouped evSAM(g2)s. Six of the 7 patients became seizure free. Conclusions The combination of SAM(g2) and ECD analyses succeeded in localizing the complex epileptic zones in children with TSC who had intractable epilepsy secondary to multiple cortical tubers. For the subset of children with TSC who present with early-onset and nonlateralized seizures, MEG studies in which SAM(g2) and ECD are used might identify suitable candidates for resection to control seizures.