Jeffrey D. Lewine

Dynamic Statistical Parametric Mapping: Combining fMRI and MEG for High-Resolution Imaging of Cortical Activity

Functional magnetic resonance imaging (fMRI) can provide maps of brain activation with millimeter spatial resolution but is limited in its temporal resolution to the order of seconds. Here, we describe a technique that combines structural and functional MRI with magnetoencephalography (MEG) to obtain spatiotemporal maps of human brain activity with millisecond temporal resolution. This new technique was used to obtain dynamic statistical parametric maps of cortical activity during semantic processing of visually presented words. An initial wave of activity was found to spread rapidly from occipital visual cortex to temporal, parietal, and frontal areas within 185 ms, with a high degree of temporal overlap between different areas. Repetition effects were observed in many of the same areas following this initial wave of activation, providing evidence for the involvement of feedback mechanisms in repetition priming.

Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders

Background. One-third of children diagnosed with autism spectrum disorders (ASDs) are reported to have had normal early development followed by an autistic regression between the ages of 2 and 3 years. This clinical profile partly parallels that seen in Landau-Kleffner syndrome (LKS), an acquired language disorder (aphasia) believed to be caused by epileptiform activity. Given the additional observation that one-third of autistic children experience one or more seizures by adolescence, epileptiform activity may play a causal role in some cases of autism. Objective. To compare and contrast patterns of epileptiform activity in children with autistic regressions versus classic LKS to determine if there is neurobiological overlap between these conditions. It was hypothesized that many children with regressive ASDs would show epileptiform activity in a multifocal pattern that includes the same brain regions implicated in LKS. Design. Magnetoencephalography (MEG), a noninvasive method for identifying zones of abnormal brain electrophysiology, was used to evaluate patterns of epileptiform activity during stage III sleep in 6 children with classic LKS and 50 children with regressive ASDs with onset between 20 and 36 months of age (16 with autism and 34 with pervasive developmental disorder–not otherwise specified). Whereas 5 of the 6 children with LKS had been previously diagnosed with complex-partial seizures, a clinical seizure disorder had been diagnosed for only 15 of the 50 ASD children. However, all the children in this study had been reported to occasionally demonstrate unusual behaviors (eg, rapid blinking, holding of the hands to the ears, unprovoked crying episodes, and/or brief staring spells) which, if exhibited by a normal child, might be interpreted as indicative of a subclinical epileptiform condition. MEG data were compared with simultaneously recorded electroencephalography (EEG) data, and with data from previous 1-hour and/or 24-hour clinical EEG, when available. Multiple-dipole, spatiotemporal modeling was used to identify sites of origin and propagation for epileptiform transients. Results. The MEG of all children with LKS showed primary or secondary epileptiform involvement of the left intra/perisylvian region, with all but 1 child showing additional involvement of the right sylvian region. In all cases of LKS, independent epileptiform activity beyond the sylvian region was absent, although propagation of activity to frontal or parietal regions was seen occasionally. MEG identified epileptiform activity in 41 of the 50 (82%) children with ASDs. In contrast, simultaneous EEG revealed epileptiform activity in only 68%. When epileptiform activity was present in the ASDs, the same intra/perisylvian regions seen to be epileptiform in LKS were active in 85% of the cases. Whereas primary activity outside of the sylvian regions was not seen for any of the children with LKS, 75% of the ASD children with epileptiform activity demonstrated additional nonsylvian zones of independent epileptiform activity. Despite the multifocal nature of the epileptiform activity in the ASDs, neurosurgical intervention aimed at control has lead to a reduction of autistic features and improvement in language skills in 12 of 18 cases. Conclusions. This study demonstrates that there is a subset of children with ASDs who demonstrate clinically relevant epileptiform activity during slow-wave sleep, and that this activity may be present even in the absence of a clinical seizure disorder. MEG showed significantly greater sensitivity to this epileptiform activity than simultaneous EEG, 1-hour clinical EEG, and 24-hour clinical EEG. The multifocal epileptiform pattern identified by MEG in the ASDs typically includes the same perisylvian brain regions identified as abnormal in LKS. When epileptiform activity is present in the ASDs, therapeutic strategies (antiepileptic drugs, steroids, and even neurosurgery) aimed at its control can lead to a significant improvement in language and autistic features. autism, pervasive developmental disorder–not otherwise specified, epilepsy, magnetoencephalography, Landau-Kleffner syndrome.

Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI.

ObjectiveTo determine to what extent magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and magnetoencephalography (MEG) can provide objective evidence of brain injury in adult patients with persistent (>1 year) postconcussive symptoms following mild blunt head trauma. DesignA retrospective and blind review of imaging data with respect to the presence of specific somatic, psychiatric, and cognitive complaints. Setting/ParticipantsThirty complete data sets (with MRI, SPECT, MEG, and neuropsychological testing results) were collected between 1994 and 2000 from the MEG programs at the Albuquerque VAMC and the University of Utah. Main Outcome MeasuresMRI data were evaluated for focal and diffuse structural abnormalities, SPECT data for regions of hypoperfusion, and resting MEG data for abnormal dipolar slow wave activity (DSWA) and epileptiform transients. ResultsStructural MRI was abnormal for 4 patients. SPECT showed regions of hypoperfusion in 12 patients, while MEG showed abnormal activity in 19 patients. None of the imaging methods produced findings statistically associated with postconcussive psychiatric symptoms. A significant association was found between basal ganglia hypoperfusion and postconcussive headaches. For patients with cognitive complaints, abnormalities were more likely to be detected by MEG (86%) than either SPECT (40%) or MRI (18%) (P < .01). MEG also revealed significant (P < .01) associations between temporal lobe DSWA and memory problems, parietal DSWA and attention problems, and frontal DSWA and problems in executive function. ConclusionsFunctional brain imaging data collected in a resting state can provide objective evidence of brain injury in mild blunt head trauma patients with persistent postconcussive somatic and/or cognitive symptoms. MEG proved to be particularly informative for patients with cognitive symptoms.

CHAPTER 9 – Magnetoencephalography and Magnetic Source Imaging

Publisher Summary nThis chapter discusses megnetocephalography and magnetic source imaging. Neuromagnetic recordings offer several advantages over alternative noninvasive imaging modalities. Magnetoencephalography (MEG), as with electroencephalography (EEG), provides for real-time, direct assessment of brain electrophysiology. MEG, therefore, provides an important complement to structural imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) and to hemodynamic and metabolic techniques such as functional MRI (fMRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). MEG affords certain advantages over EEG. The most salient of these is that neuromagnetic signals penetrate the skull and scalp without significant distortion. The spatial resolution of MEG is higher than that for EEG, and mathematical analyses of the spatial pattern of the neuromagnetic field can offer accurate spatial localization of the neurons responsible for generating neuromagnetic signals. Of the available noninvasive neuroimaging techniques, MEG provides the best balance of temporal and spatial sensitivity to brain physiology.

Clinical Electroencephalography and Event-Related Potentials

Publisher Summary This chapter focuses on clinical applications of electroencephalography (EEG) and event-related potentials (ERPs). There are two basic types of neuroelectric examinations: (1) EEG studies that involve inspection of spontaneous brain activity and (2) ERP studies that use signal-averaging techniques to extract neuroelectric activity that is time-locked to specific sensory, motor, or cognitive events. There are two types of brain cells, namely, neurons and glia, and both contribute to the EEG. Nerve cells display two distinct classes of neuroelectric events: (1) graded synaptic potentials and (2) action potentials. Glia are known to show slow changes in their resting membrane potentials. The extracellular current sinks and sources cause an electrical potential distribution in the conductive media, with the magnitude of the potential decreasing with increasing distance from the neuron. The exact manner in which the potential changes within the media partly depends on the configuration of the relevant currents. Currents associated with individual action potentials are generally much stronger than synaptic currents, but postsynaptic potentials generally make the more significant contribution to the EEG.

The Relationship of Magnetic Source Imaging to Ictal Electrocorticography in a Neuronavigational Workspace

Magnetic source imaging (MSI) registers magnetoencephalographic (MEG) activity to a three-dimensional MRI volume. State-of-the-art MSI allows concurrent whole head coverage, but is practically restricted to interictal recording. However, the purpose of the presurgical evaluation of epileptic patients, in which MSI is playing an increasing role, is the elucidation of the ictal epileptogenic focus. The manner in which interictal MSI activity relates to the ictal focus has not yet been adequately examined. To facilitate this analysis, we are developing techniques to precisely coregister MSI to the ictal onset zone as defined by extraoperative intracranial grid/strip monitoring. The neuronavigational workspace is a convenient area in which to precisely coregister these (and other) imaging and physiological data sets.