Postscript

As is evident from the scientific chapters of this book, the technology of magnetoencephalography offers a combination of spatial, temporal, and spectral resolution, unique among neuroimaging technologies. While functional magnetic resonance imaging (fMRI) accommodates spatial resolution, it lacks the millisecond resolution (because of the reliance on a slow hemodynamic response) to identify subtle latency shifts, or the specificity to distinguish theta- versus alpha- versus gamma-band oscillatory activity. While electroencephalography (EEG) offers the needed temporal resolution, it fails to adequately localize brain sources, owing to the physics of inverse modeling and the dependence of scalp electric potentials on tissue electrical conductivity. Thus, although fMRI may see “activity,” it cannot characterize important attributes of its nature. Conversely, EEG may detect “anomalies” but not be able to attribute them to a particular spatial source....

Magnetoencephalography in Alzheimer Disease

There are two basic ways Magnetoencephalography (MEG) has been applied. The most typical way is recording brain signals related to specific stimuli and tasks or signals indicative of focal pathology as in presurgical brain mapping and epilepsy localization. The second way is recording patterns of spontaneous activity characteristic of particular states or traits. An example of the latter application is described in this chapter that details efforts of deriving brain activity patterns characteristic of Alzheimer’s dementia. The derivation of such patterns will be of great value in diagnosis, prognosis, as well as monitoring progress (or the process of amelioration) of diseases.

Functional Wounds of an Invisible Injury

In this chapter we review magnetoencephalography (MEG) studies of post-traumatic stress disorder (PTSD). The work reviewed spans multiple analytical approaches, including task-evoked and induced studies, primarily examining cognitive and behavioral dysfunction in the disorder, as well as resting-state studies of regional oscillatory power and synchrony. Disordered memory, elevated threat perception, and dysfunctional emotional control are primary symptoms of PTSD, but there are also secondary “knock-on” effects to cognition and executive functioning that can be debilitating. MEG approaches have proved to be a powerful way to examine maladaptive neural circuits underlying these deficits in PTSD, particularly the brain networks involving the hippocampi, amygdalae, and ventral medial prefrontal cortex. Finally, the authors briefly discuss these findings in relation to mild traumatic brain injury, a physical as opposed to psychological injury that can nevertheless leave mental wounds that exhibit a similar presentation to PTSD, and how MEG can be used to tease apart these different types of trauma.

Language Mapping with Magnetoencephalography

This chapter explores the applications of magnetoencephalography (MEG) to the study of the brain mechanisms for language functions. Language mapping with MEG has proved helpful in presurgical estimates of the location and extent of language-related cortex as well as in the intraoperative identification of these cortical patches. In fact, in several neurosurgical centers around the world, such assessments are part of the protocol of surgical interventions, especially in the case of epilepsy. Moreover, MEG alone or in combination with other imaging methods, such as functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS), is extensively used for the testing of alternative models of cortical organization for language in normal populations. However, applications of MEG to language mapping face most of the limitations that characterize brain imaging techniques relying on hemodynamic measures. Perhaps the most fundamental of these limitations concerns the degree of specificity of results: Activation profiles feature brain regions that may not be indispensable for a particular target function. This problem is particularly serious in the case of language mapping and to a lesser degree in motor cortex mapping.

Clinical Motor Mapping with Magnetoencephalography

This chapter examines clinical motor mapping with magnetoencephalography (MEG). Motor cortex functional mapping procedures were first conducted by neurosurgeons who famously stimulated their patient’s exposed brain during surgery and then systematically documented the responses observed from the activated muscles of the body. Numerous neuroimaging-based functional mapping techniques followed, such as functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), high-density electroencephalography (HD-EEG), and MEG, which are currently used to map the motor areas in relation to isolated volitional movements. The use of MEG for presurgical functional mapping has become a standard component of clinical MEG practice. Indeed, knowledge regarding the location of eloquent MEG motor representations is valuable for presurgical planning and can improve outcomes by limiting the production of postsurgical deficits of motor function. Meanwhile, source localization challenges using equivalent current dipole (ECD) models have given way to newer methods, such as beamformer spatial filters, which have been validated clinically using electrical stimulation. It should also be noted that it is becoming increasingly evident that motor cortical oscillations are changing consistently over the life span, and thus consideration of the patient’s age will likely aid the interpretation of results.

Revisional Analysis of Electroencephalography and Magnetoencephalography Based on Comprehensive Epilepsy Conference

This chapter highlights the importance of the revised analysis of electroencephalography (EEG) and magnetoencephalography (MEG) spike source estimation based on comprehensive case conference discussion. It discusses two typical cases of localization-related epilepsy: case 1 as a simple situation and case 2 as a complicated situation. No “gold standard” for epileptic spike analysis in EEG or MEG has been established, so several methods must be adopted to achieve the most reasonable interpretation. However, such intense and revisional analyses may be too time-consuming in clinical settings and result in arbitrary conclusions. Therefore, the authors currently use a simple method first, that is, a single dipole model for the peak or preceding upward slope of unaveraged single spikes. In the following case conference, EEG and MEG data are reviewed with seizure semiology, anatomical magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). If all the findings almost agree, the clinical decision can be easily made. If not, revisional analysis of EEG/MEG is recommended using averaged spikes and principal component analysis models as well as distributed source models. In addition to EEG/MEG, the authors often order revisional analysis and additional MRI and FDG-PET studies after the conference. Even further history taking will be recommended if necessary.

Beyond the Irritative Zone

In this chapter, the authors reflect on the uses of MEG to better characterize different cortical zones within the epileptic network. First, they review the role of MEG in the presurgical workout under the classical model of epileptic zones. Under this model, MEG had been incorporated as a noninvasive tool to define the irritative zones based on recordings of interictal events. Then, they review evidence that support, in certain situations, the use of MEG to make valid predictions about other zones: the functional deficit zone and the ictal onset zone. Finally, a workflow that integrates MEG findings with findings from other noninvasive procedures is proposed.

Biomarkers in Pediatric Magnetoencephalography

The use of magnetoencephalography (MEG) to understand alterations in brain development in children has increased rapidly over the past two decades. Investigators have argued that MEG is an ideal neuroimaging tool for children because the technology is quiet and it provides high-density sensor systems. This participant-friendly technology has led to exploration of the use of MEG to identify biomarkers for atypical brain development to facilitate early diagnosis and intervention. Prior studies provide evidence that MEG is sensitive to a number of pediatric clinical disorders demonstrated through significant differences (e.g., latency, amplitude, spectral power) in children with autism spectrum disorder, children born prematurely, and children with fetal alcohol spectrum disorder, to name a few. At the same time, differences in age range, stimulus parameters, and study population characteristics contribute to variability in results across independent laboratories. While the current studies provide strong evidence for the sensitivity of MEG to identify brain abnormalities in children, replication studies are needed to validate biomarkers of atypical brain development to identify children at risk for atypical brain development. Additional studies are also needed to understand the dynamic changes in these brain markers across the age spectrum. Finally, future directions include gaining a broader understanding of typical and atypical brain development to identify neural targets for intervention.

Applications of Magnetoencephalography to Autism Spectrum Disorder

Magnetoencephalography (MEG) has a unique combination of attributes allowing the probing of brain function, with resolution of space, time, and spectral content. These attributes lend themselves to the study of disorders characterized by no conspicuous structural brain anomalies, but rather anomalies of neural signals and communication. This chapter reviews the use of diverse MEG techniques and paradigms to study one such disorder, autism spectrum disorder (ASD). The authors focus on MEG as a probe of auditory and face processing anomalies in ASD. Impairments in auditory processing in ASD have been identified as objective markers of language and communication ability, general cognitive ability, and abnormal sensory sensitivity. Most MEG studies have observed that atypical auditory responses such as components of the early auditory evoked field (i.e., M50, M100), mismatch fields, or gamma-band oscillatory activity occur in individuals with ASD compared with typically developing children. Maturational trajectories of such measures also deviate from neurotypical patterns. Similarly, impairments in face perception are characteristic of ASD and have been a large focus of MEG studies, as a model probe for the social impairment phenotype. MEG research has demonstrated atypical source localization of activity during face processing in children through adults as well as in executive functions, including working memory and inhibition. Interregional differences in synchrony of neural oscillations have been elaborated by MEG in emotional face processing tasks, with visual perceptual processing underscoring gamma-band atypicalities in ASD. We highlight MEG as a promising approach for establishing clinical biomarkers of ASD and informing mechanistic neuroscience.

Epileptic Slow Wave Activity

In recent years, novel markers for the epileptic network beyond interictal spikes and ictal seizure correlates have been described. Slow activity in theta, delta, and lower frequency ranges have been detected using invasive electroencephalography (EEG) and noninvasive magnetoencephalography (MEG)/EEG. While such activity also occurs that is associated, for example, with large lesions and after intracranial surgery, certain subtypes may be used to localize the epileptic network. This chapter provides an overview of MEG slow frequency markers in patients with focal epilepsy. It covers the application of slow activity–based focus localization in patients undergoing workup for epilepsy surgery and discusses the relation to conventional spike-based analysis as well as the potential value of slow activity analysis in patients with previous surgery and persisting or recurring seizures.