Magnetographic assessment of fetal hiccups and their effect on fetal heart rhythm.

Fetal hiccups emerge as early as nine weeks post-conception, being the predominant diaphragmatic movement before 26 weeks of gestation. They are considered as a programmed isometric inspiratory muscle exercise of the fetus in preparation for the post-natal respiratory function, or a manifestation of a reflex circuitry underlying the development of suckling and gasping patterns. The present paper provides the first evidence of non-invasive biomagnetic measurements of the diaphragm spasmodic contractions associated with fetal hiccups. The magnetic field patterns generated by fetal hiccups exhibit well-defined morphological features, consisting of an initial high frequency transient waveform followed by a more prolonged low frequency component. This pattern is consistent across recordings obtained from two fetal subjects, and it is confirmed by signals recorded in a neonatal subject. These results demonstrate that fetal biomagnetometry can provide insights into the electrophysiological mechanisms of diaphragm motor function in the fetus. Additionally, we study the correlation between hiccup events and fetal cardiac rhythm and provide evidence that hiccups may modulate the fetal heart rate during the last trimester of pregnancy.

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 significa

Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma.

BACKGROUND AND PURPOSE: Patients with mild traumatic brain injury (TBI) often show significant neuropsychological dysfunction despite the absence of abnormalities on traditional neuroradiologic examinations or EEG. Our objective was to determine if magnetic source imaging (MSI), using a combination of MR imaging and magnetoencephalography (MEG), is more sensitive than EEG and MR imaging in providing objective evidence of minor brain injury. METHODS: Four subject groups were evaluated with MR, MSI, and EEG. Group A consisted of 20 neurologically normal control subjects without histories of head trauma. Group B consisted of 10 subjects with histories of mild head trauma but complete recovery. Group C consisted of 20 subjects with histories of mild head injury and persistent postconcussive symptoms. The 15 subjects included in group D underwent repeat examinations at an interval of 2 to 4 months. RESULTS: No MR abnormalities were seen in the normal control group or the asymptomatic group, but five (20%) of the patients with persistent postconcussive symptoms had abnormal MR findings. EEG was abnormal for one subject (5%) from the normal control group, one (10%) from the asymptomatic group, and five (20%) from the group with persistent postconcussive symptoms. MSI was abnormal for one subject (5%) from the normal control group, one (10%) from the asymptomatic group, and 13 (65%) from the group with persistent postconcussive symptoms. There was a direct correlation between symptom resolution and MSI findings for the symptomatic head trauma group. CONCLUSION: MSI indicated brain dysfunction in significantly more patients with postconcussive symptoms than either EEG or MR imaging (P < .01). The presence of excessive abnormal low-frequency magnetic activity provides objective evidence of brain injury in patients with postconcussive syndromes and correlates well with the degree of symptomatic recovery.

Integration of preoperative and intraoperative functional brain mapping in a frameless stereotactic environment for lesions near eloquent cortex. Technical note.

The authors present a method of incorporating preoperative noninvasive functional brain mapping data into the frameless stereotactic magnetic resonance (MR) imaging dataset used for image-guided resection of brain lesions located near eloquent cortex. They report the use of functional (f)MR imaging and magnetic source (MS) imaging for preoperative mapping of eloquent cortex in difficult cases of brain tumor resection such as those in which there are large expansive masses or in which reoperations are required and the anatomy is distorted from prior treatments. To correlate methods of preoperative and intraoperative mapping localization directly, the authors have developed techniques of importing preoperative MS and fMR imaging data into an image-guided frameless stereotactic computer workstation. The data appear as a seamless overlay on the same preoperative volumetric MR imaging dataset used for stereotactic guidance during the operation. Intraoperatively identified functional locations mapped by cortical stimulation are recorded as digitally registered points. This approach should prove useful in assessing the accuracy and reliability of various preoperative functional brain mapping techniques.

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.

A study of dipole localization accuracy for MEG and EEG using a human skull phantom.

OBJECTIVE: To investigate the accuracy of forward and inverse techniques for EEG and MEG dipole localization. DESIGN AND METHODS: A human skull phantom was constructed with brain, skull and scalp layers and realistic relative conductivities. Thirty two independent current dipoles were distributed within the 'brain' region and EEG and MEG data collected separately for each dipole. The true dipole locations and orientations and the morphology of the brain, skull and scalp layers were extracted from X-ray CT data. The location of each dipole was estimated from the EEG and MEG data using the R-MUSIC inverse method and forward models based on spherical and realistic head geometries. Additional computer simulations were performed to investigate the factors affecting localization accuracy. RESULTS: Localization errors using the relatively simpler locally fitted sphere approach are only slightly greater than those using a BEM approach. The average localization error over the 32 dipoles was 7-8 mm for EEG and 3 mm for MEG. CONCLUSION: The superior performance of MEG over EEG appears to be because the latter is more sensitive to errors in the forward model arising from simplifying assumptions concerning the conductivity of the skull, scalp and brain.

Spontaneous brain magnetic activity in schizophrenia patients treated with aripiprazole.

This magnetoencaphalographic (MEG) study was conducted as part of a multicenter clinical trial to study the efficacy of aripiprazole. Participants included 5 DSM-IV schizophrenia subjects and 10 age-matched normal controls. The schizophrenia subjects underwent a second MEG recording after 8 weeks of open-label treatment with aripiprazole. Overall, control subjects showed no abnormal spontaneous magnetic brain activity. At washout, 3 patients showed increased delta and theta activity along with paraxosymal bitemporal slow waves. In 2 of these patients, the slow waves were generated in the superior temporal plane, as determined by dipole modeling. In the third patient, the slow waves appeared to have been generated at multiple regions throughout the temporal and inferior parietal lobes. As a group, schizophrenia patients, when compared with normal controls, demonstrated significant decreases in alpha peak frequency and power. Following treatment, aripiprazole had a significant normalizing effect on delta and theta activity. Patients on aripiprazole continued to demonstrate significant abnormalities in alpha frequency and power.

Retinotopic organization of human visual cortex: departures from the classical model.

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.

Magnetoencephalographic assessment of spontaneous brain activity in schizophrenia.

Magnetoencephalography (MEG) offers an attractive alternative to electroencephalography (EEG) in the assessment of psychiatric patients. In this study, a whole-head biomagnetometer equipped with 122 super-cooled sensors was used to assess spontaneous neuromagnetic activity in 11 unmedicated schizophrenic patients and 8 schizophrenic patients medicated for more than 8 weeks with novel antipsychotics (5 of whom were initially studied as part of the unmedicated group). Ten normal (nonpsychiatric) controls were also examined. For each subject, 5 minutes of data were collected in an eyes-closed state. Data were visually inspected for gross MEG abnormalities, and average power spectra were calculated for the data at each sensor. No gross abnormalities were identified for control subjects. One unmedicated schizophrenic patient showed epileptiform sharp waves, and 4 showed abnormal slow waves. No gross MEG abnormalities were found for the medicated schizophrenic group (which included 3 patients who had previously shown slow waves in the unmedicated state). Spectral analyses showed that the schizophrenia patients demonstrated lower alpha power and peak frequency than controls. The data are interpreted within the context of previously reported magnetic resonance abnormalities of the thalamus.

Comparison of primary motor cortex localization using functional magnetic resonance imaging and magnetoencephalography.

The primary goal of the study was to compare estimates of motor cortex localization from functional magnetic resonance imaging (FMRI) and magnetoencephalography (MEG). Thirteen normal volunteers were studied using both methods. FMRI was performed on a clinical 1.5 T system using gradient-echo acquisitions and basic t-test processing. MEG primary motor field was characterized by a single dipole model. Comparisons between the location of the best-fitting MEG dipole and the FMRI activation results were made using both fixed regions-of-interest weighted averaging and clustering analysis to reduce the observed FMRI activations to a single representative location. Both FMRI and MEG identified expected anatomic regions of primary motor activity and there was overall agreement to within 10 mm between these two functional imaging modalities. Given the observed agreement between these two techniques, it does not appear that the proposed artifactual mechanisms of local bulk motions or large-vessel sensitivity will seriously preclude the clinical utility of FMRI for preoperative localization of sensorimotor cortex.

Spike and slow wave localization by magnetoencephalography.

At institutions where MEG is available, it is now considered a standard part of the diagnostic workup of most patients with epilepsy. Available data indicate that interictal MEG can be an effective tool for localization of the epileptic irritative zone, and in some cases it can even indicate the seizure onset site. Both spike and ALFMA examinations are clinically viable because of the availability of large-array systems. The current cost of acquiring MEG technology is high (greater than 2 million dollars), but recent technical developments should soon yield more cost-effective systems. It is anticipated that the increasing applicability of this technology to conditions beyond epilepsy (e.g., head trauma, ischemic disease, dementia, and psychiatric dysfunction) will soon render MEG a critical element in the general armamentarium of diagnostic procedures available to epileptologists, radiologists, neurologists, neurosurgeons, and psychiatrists.

Mapping function in the human brain with magnetoencephalography, anatomical magnetic resonance imaging, and functional magnetic resonance imaging.

Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuro-imaging methods.

Pediatric magnetic source imaging.

Magnetic source imaging has changed the perspective of managing pediatric patients with epilepsy since its introduction into clinical imaging in the pediatric population. Magnetic source imaging can be important in understanding pediatric functional neuroanatomy and for epileptic surgery in children with intractable seizures. The use and efficacy of magnetic source imaging for surgical planning and patient management is demonstrated by case reports presented in this article.

Multichannel magnetoencephalography in ablative seizure surgery outside the anteromesial temporal lobe.

Magnetoencephalography (MEG) was used to evaluate 40 candidates for seizure surgery thought to have foci outside the anteromesial temporal lobe. Of 29 cases with electrographic data suggesting a convexity focus, MEG spikes were recorded from 28. In 21, MEG and electrographic data were localized to the same area. Invasive studies were, or could have been, avoided in 13 cases based on MEG and other noninvasive data. MEG was not localizing value in 4 orbitofrontal or 7-depth-nonlocalized cases. Seventeen patients with MEG epileptiform data have had postoperative follow-up. Eight of 13 with electrographic and MEG data localized to the same area are seizure free. None of 4 with spatial discordance of MEG electrographic data are seizure free.