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Challenges of recording human fetal auditory-evoked response using magnetoencephalography.

OBJECTIVE: Our goals were to successfully perform fetal auditory-evoked responses using the magnetoencephalography technique, understand its problems and limitations, and propose instrument design modifications to improve the signal quality and success rate. METHODS: Fetal auditory-evoked responses were recorded from four fetuses with gestational ages ranging from 33-40+ weeks. The signals were recorded using a gantry-based superconducting quantum interference device. Auditory stimulus was 1 kHz tone burst. The evoked signals were digitized and averaged over an 800 ms window. RESULTS: After several trials of positioning and repositioning the subjects, we were able to record auditory-evoked responses in three out of the four fetuses. Since the superconducting quantum interference device array design was not shaped to fit over the mother's abdomen, we experienced difficulty in positioning the sensors over the fetal head. CONCLUSIONS: Based on this pilot study, we propose instrument design that may improve signal quality and success rate of the fetal magnetic auditory-evoked response.

Equipment Design↗

Impaired visual word processing in dyslexia revealed with magnetoencephalography.

Dyslexia is most often attributed to phonological impairments, manifested in abnormal activation of the left temporal and temporoparietal cortex in response to auditorily presented language and possibly associated with anomalies in the cytoarchitecture and hemispheric symmetry of the plana temporale. The immediate cortical correlate of the severely impaired reading process has, however, remained obscure. Here we report on the distinct time courses of cortical activation in dyslexic and control subjects during passive viewing of single words, tracked with whole-head magnetoencephalography. A striking difference was found in the left inferior temporo-occipital region where intracranial recordings have recently identified word-specific responses within 200 msec after stimulus onset: controls showed a sharp activation at about 180 msec after word presentation, whereas dyslexics failed to activate this area entirely, or showed a slowly increasing late response. Perception of words as specific units thus seems to be impaired in dyslexics.

Adolescent↗

Functional and metabolic analysis of cerebral ischemia using magnetoencephalography and proton magnetic resonance spectroscopy.

The details of the relationship between brain function and metabolism in brain infarcts have not been studied. Using magnetoencephalography (MEG) and proton magnetic resonance spectroscopic imaging (1H MRSI), we localized sources of abnormal magnetic activities in ischemic brain regions and biochemical changes in suspected lesions showing pathological characteristics. Twelve patients with ischemic stroke were examined and the results of MEG and 1H MRSI were superimposed onto the corresponding MR images. The signal intensities of N-acetyl (NA) and lactate (Lac) were measured in the lesions with highly concentrated dipoles of slow wave activity. Eleven of 12 cases had increased slow wave activity in the cortical areas adjacent to the infarcts; 1 case was excluded because the infarct was too small (<1 cm in diameter). The signal intensity of NA in the regions with the highest slow wave activity was significantly reduced and was well correlated with the dipole density of slow waves. Though Lac was mildly accumulated in the lesions, the Lac level had no correlation with slow wave magnetic activity. The remaining and metabolically active cortical tissue showing NA signal produced the abnormal slow wave activity under lactic acidosis (mild accumulation of Lac).

Adult↗

Magnetoencephalography in partial epilepsy: clinical yield and localization accuracy.

The goals of this study were to determine (1) the yield of magnetoencephalography (MEG) according to epilepsy type, (2) if MEG spike sources colocalize with focal epileptogenic pathology, and (3) if MEG can identify the epileptogenic zone when scalp ictal electroencephalogram (EEG) or magnetic resonance imaging (MRI) fail to localize it. Twenty-two patients with mesial temporal (10 patients), neocortical temporal (3 patients), and extratemporal lobe epilepsy (9 patients) were studied. A 37-channel biomagnetometer was used for simultaneously recording MEG with EEG. During the typical 2-3-hour MEG recording session, interictal epileptiform activity was observed in 16 of 22 patients. MEG localization yield was greater in patients with neocortical epilepsy (92%) than in those with mesial temporal lobe epilepsy (50%). In 5 of 6 patients with focal epileptogenic pathology, MEG spike sources were colocalized with the lesions. In 11 of 12 patients with nonlocalizing (ambiguous abnormalities or normal) MRI, MEG spike sources were localized in the region of the epileptogenic zone as ultimately defined by all clinical and EEG information (including intracranial EEG). In conclusion, MEG can reliably localize sources of spike discharges in patients with temporal and extratemporal lobe epilepsy. MEG sometimes provides noninvasive localization data that are not otherwise available with MRI or conventional scalp ictal EEG.

Adolescent↗

Pathogenesis of cortical myoclonus studied by magnetoencephalography.

Myoclonus-associated cortical activities were studied by simultaneous recording of a magnetoencephalogram and an electroencephalogram in 6 patients with cortical myoclonus due to various causes. Cortical activities were averaged, with respect to the precise onset of the myoclonic jerk, to evaluate the myoclonus-associated cortical magnetic fields. The estimated generator of their earliest peak was localized at the contralateral precentral gyrus in all patients. As judged from the direction of the electrical current, surface positive activity preceding the electromyographic discharge was detected in 3 patients with cortical reflex myoclonus and in 1 patient with possible corticobasal degeneration. In contrast, in the remaining 2 patients (Lennox-Gastaut syndrome and Alzheimer's disease), magnetic fields time-locked to the myoclonic jerk were associated with surface negative activity at the precentral cortex. The present study, applying for the first time an off-line jerk-locked back-averaging analysis to magnetoencephalography, demonstrated the important role of the precentral cortex in generating spontaneous myoclonus. It is most likely that the differing polarity of the electromagnetic activity reflects the differing activation patterns within the cortical laminar structure in the precentral area, underlying the generation of various types of myoclonus.

Adult↗

Mismatch responses to randomized gradient switching noise as reflected by fMRI and whole-head magnetoencephalography.

The central auditory system of the human brain uses a variety of mechanisms to analyze auditory scenes, among others, preattentive detection of sudden changes in the sound environment. Electroencephalography (EEG) and magnetoencephalography (MEG) provide a measure to monitor neuronal cortical currents. The mismatch negativity (MMN) or field (MMNm) reflect preattentive activation in response to deviants within a sequence of homogenous auditory stimuli. Functional magnetic resonance imaging (fMRI) allows for a higher spatial resolution as compared to the extracranial electrophysiological techniques. The image encoding gradients of echo planar imaging (EPI) sequences, however, elicit an interfering background noise. To circumvent this shortcoming, the present study applied multi-echo EPI mimicking an auditory oddball design. The gradient trains (SOA = 800 msec, 94.5 dB SPL, stimulus duration = 152 msec) comprised amplitude (-9 dB) and duration (76 msec) deviants in a randomized sequence. Moreover, the scanner noise was recorded and applied in a whole-head MEG device to validate the properties of this specific material. Robust fMRI activation patterns emerged in response to the deviant gradient switching. Changes in amplitude activated the entire auditory cortex, whereas the duration deviants elicited right-lateralized signal increase in secondary areas. The recorded scanner noise evoked reliably right-lateralized mismatch MEG responses. Source localization was in accordance with activation of secondary auditory cortex. The presented paradigm provides a robust and feasible tool to study the functional anatomy of early cognitive auditory processing in clinical populations such as schizophrenia.

Acoustic Stimulation↗

Human alpha rhythms during visual delayed choice reaction time tasks: a magnetoencephalography study.

Magnetoencephalography (MEG) includes fast and comfortable recording procedures very suitable for the neurophysiological study of cognitive functions in aged people. In this exploratory MEG study in normal young adults, we tested whether very simple short-term memory (STM) demands induce visible changes in amplitude and latency of surface alpha rhythms. Two delayed response tasks were used. In the STM condition, a simple cue stimulus (one bit) was memorized along a brief delay period (3.5-5.5 s). In the control (no short-term memory; NSTM) condition, the cue stimulus remained available along the delay period. To make extremely simple the tasks, the explicit demand was visuospatial but the retention could be also based on phonological and somatomotor coding. Compared to the control condition, the amplitude of the alpha 1 (6-8 Hz) ERD decreased in the left hemisphere, whereas the amplitude of the alpha 2 (8-10 Hz) and alpha 3 (10-12 Hz) event-related desynchronization (ERD) increased in right and left parietal areas, respectively. Furthermore, the latency of the alpha ERD peak was slightly but significantly (P < 0.05) later in STM compared to control condition. In conclusion, whole-head MEG technology and very simple STM demands revealed significant changes of human neuromagnetic alpha rhythms in normal young adults.

Adult↗

A new approach to neuroimaging with magnetoencephalography.

We discuss the application of beamforming techniques to the field of magnetoencephalography (MEG). We argue that beamformers have given us an insight into the dynamics of oscillatory changes across the cortex not explored previously with traditional analysis techniques that rely on averaged evoked responses. We review several experiments that have used beamformers, with special emphasis on those in which the results have been compared to those observed in functional magnetic resonance imaging (fMRI) and on those studying induced phenomena. We suggest that the success of the beamformer technique, despite the assumption that there are no linear interactions between the mesoscopic local field potentials across distinct cortical areas, may tell us something of the balance between functional integration and segregation in the human brain. What is more, MEG beamformer analysis facilitates the study of these complex interactions within cortical networks that are involved in both sensory-motor and cognitive processes.

Algorithms↗

Oscillations of the human sensorimotor system as revealed by magnetoencephalography.

Neurons in the human brain, especially in thalamic nuclei and the cerebral cortex, exhibit intrinsic membrane oscillations, which may be synchronized into network oscillations and form the macroscopic rhythms detectable with electroencephalography (EEG) and magnetoencephalography (MEG). Recent data also suggest that certain neurologic disorders may be associated with the occurrence of pathologically synchronized oscillatory brain activity. Human tremors may be the behavioral correlate of such abnormal brain rhythms. This article summarizes the current literature about sensorimotor oscillatory activity in people recorded by MEG and discusses the possible functional significance of the findings for motor control in health and disease.

Biological Clocks↗

Simultaneous magnetoencephalography and SQUID detected nuclear MR in microtesla magnetic fields.

A system that simultaneously measures magnetoencephalography (MEG) and nuclear magnetic resonance (NMR) signals from the human brain was designed and fabricated. A superconducting quantum interference device (SQUID) sensor coupled to a gradiometer pickup coil was used to measure the NMR and MEG signals. 1H NMR spectra with typical Larmor frequencies from 100-1000 Hz acquired simultaneously with the evoked MEG response from a stimulus to the median nerve are reported. The single SQUID gradiometer was placed approximately over the somatosensory cortex of a human subject to noninvasively record the signals. These measurements demonstrate, for the first time, the feasibility of simultaneous MRI and MEG. NMR in the microtesla regime provides narrow linewidths and the potential for high spatial resolution imaging, while SQUID sensors enable direct measurement of neuronal activity with high temporal resolution via MEG.

Humans↗

Signal processing in magnetoencephalography.

The subject of this article is detection of brain magnetic fields, or magnetoencephalography (MEG). The brain fields are many orders of magnitude smaller than the environmental magnetic noise and their measurement represent a significant metrological challenge. The only detectors capable of resolving such small fields and at the same time handling the large dynamic range of the environmental noise are superconducting quantum interference devices (or SQUIDs). The SQUIDs are coupled to the brain magnetic fields using combinations of superconducting coils called flux transformers (primary sensors). The environmental noise is attenuated by a combination of shielding, primary sensor geometry, and synthetic methods. One of the most successful synthetic methods for noise elimination is synthetic higher-order gradiometers. How the gradiometers can be synthesized is shown and examples of their noise cancellation effectiveness are given. The MEG signals measured on the scalp surface must be interpreted and converted into information about the distribution of currents within the brain. This task is complicated by the fact that such inversion is nonunique. Additional mathematical simplifications, constraints, or assumptions must be employed to obtain useful source images. Methods for the interpretation of the MEG signals include the popular point current dipole, minimum norm methods, spatial filtering, beamformers, MUSIC, and Bayesian techniques. The use of synthetic aperture magnetometry (a class of beamformers) is illustrated in examples of interictal epileptic spiking and voluntary hand-motor activity.

Brain↗

Accuracy and limitation of functional magnetic resonance imaging for identification of the central sulcus: comparison with magnetoencephalography in patients with brain tumors.

The aim of the present study was to clarify the accuracy and limitation of functional magnetic resonance imaging (fMRI) for the identification of the central sulcus affected by brain tumors. Twelve normal volunteers and 11 patients with intracranial tumors adjacent to the central sulcus underwent fMRI and magnetoencephalography (MEG). Three patients were evaluated again after surgery. fMRI was performed with a 1.5 Tesla scanner during repetitive opening and closing of each hand. Cross-correlation function was used to identify activation areas, and the central sulcus was defined as the nearest sulcus to the highest activation spots that were determined by elevating correlation coefficient threshold. Somatosensory-evoked fields were measured using a whole head MEG system. The central sulcus was defined as the nearest sulcus to the N20m for the median nerve stimulus. fMRI and MEG coincided in defining the central sulcus in all 24 hemispheres of volunteers and all 10 examined nonaffected hemispheres of patients. The fMRI-defined central sulcus coincided with the MEG-defined central sulcus in nine (82%) but did not in two (18%) affected hemispheres of patients. The preoperative mismatch disappeared after surgery in one of the two patients. The present study indicates that fMRI successfully defined the central sulcus in most of the patients with brain tumors. However, in a few cases, fMRI was not reliable probably due to venous flow changes by tumor compression and/or compensational activity by brain tissues surrounding the primary sensorimotor cortex. For precise functional assessment of the brain affected by intracranial tumors, combination of fMRI and MEG will be recommended.

Adult↗

Supplementary motor area activation preceding voluntary movement is detectable with a whole-scalp magnetoencephalography system.

Despite the fact that the knowledge about the structure and the function of the supplementary motor area (SMA) is steadily increasing, the role of the SMA in the human brain, e.g., the contribution of the SMA to the Bereitschaftspotential, still remains unclear and controversial. The goal of this study was to contribute further to this discussion by taking advantage of the increased spatial information of a whole-scalp magnetoencephalography (MEG) system enabling us to record the magnetic equivalent of the Bereitschaftspotential 1, the Bereitschaftsfeld 1 (BF 1) or readiness field 1. Five subjects performed a complex, and one subject a simple, finger-tapping task. It was possible to record the BF 1 for all subjects. The first appearance of the BF 1 was in the range of -1.9 to -1.7 s prior to movement onset, except for the subject performing the simple task (-1 s). Analysis of the development of the magnetic field distribution and the channel waveforms showed the beginning of the Bereitschaftsfeld 2 (BF 2) or readiness field 2 at about -0.5 s prior to movement onset. In the time range of BF 1, dipole source analysis localized the source in the SMA only, whereas dipole source analysis containing also the time range of BF 2 resulted in dipole models, including dipoles in the primary motor area. In summary, with a whole-head MEG system, it was possible for the first time to detect SMA activity in healthy subjects with MEG.

Adult↗

Movement-related desynchronization of the cerebral cortex studied with spatially filtered magnetoencephalography.

Event-related desynchronization (ERD) within the alpha and beta bands on unilateral index finger extension and hand grasping was investigated on six normal volunteers with magnetoencephalography (MEG). A novel spatial filtering technique for imaging cortical source power, synthetic aperture magnetometry (SAM), was employed for the tomographic demonstration of ERD. SAM source image results were transformed into statistical parametric images. On the same hand grasping task, a functional MRI (fMRI) study was conducted on two subjects and compared with the ERD result. When the MEG data were analyzed with the fast Fourier transformation, power attenuation within the alpha and beta bands was evident on the contralateral sensorimotor area just prior to movement onset. The tomographic distribution of ERD was clearly obtained with SAM statistical imaging analysis. The equivalent current dipole (ECD) for the signal-averaged motor field was localized to the hemisphere contralateral to the hand movement, roughly at the center of the region displaying beta-band ERD. The signal increase on fMRI roughly colocalized with the ERD on the contralateral sensorimotor area. In conclusion, with the novel spatial filtering technique for the brain magnetic field, SAM, cortical regions contributing to ERD on finger movement were successfully demonstrated in a tomographic manner. The relative colocalization of the contralateral SAM ERD with ECD as well as the fMRI activation suggests that SAM is a practically useful technique to extract event-related signals from brain noise.

Adult↗

Functional magnetic resonance imaging evidence for a representation of the ear in human primary somatosensory cortex: comparison with magnetoencephalography study.

Our previous study (T. Nihashi et al., 2001, Neuro- Image 13: 295-304), using magnetoencephalography (MEG), revealed somatotopy of the ear in the human primary somatosensory cortex (SI); that is, the signals following stimulation of the ear reach both the neck and face areas of the SI. However, since this was the first report on somatotopy of the ear in humans, we performed an fMRI activation study to confirm the somatotopic representation, and compared the electrical activity by MEG and the cerebral blood flow change by fMRI. We studied eight healthy subjects using 3-T MRI. We stimulated three parts of the left ear: the helix, the lobulus, and the tragus. First, we identified the location of the ear area in the SI based on our previous MEG study, in which equivalent current dipoles (ECDs) were located in the neck and/or face areas of the SI. Then, we determined the search volume as a sphere with a 15-mm radius, which was placed in the neck and/or face area. We analyzed whether or not fMRI activation occurred inside such spheres. Stimulation of the helix activated the neck area of the SI in four of eight subjects, and both the neck and face areas in two. No activation was observed in two subjects. Stimulation of the lobulus activated the neck area in one subject, the face area in two, both in four, and neither in one. Stimulation of the tragus activated the face in four, both in three, and neither in one. These fMRI findings confirm the result of MEG that the representation of the ear in the SI is separated into neck and face areas.

Adult↗

N400-like magnetoencephalography responses modulated by semantic context, word frequency, and lexical class in sentences.

Words have been found to elicit a negative potential at the scalp peaking at approximately 400 ms that is strongly modulated by semantic context. The current study used whole-head magnetoencephalography (MEG) as male subjects read sentences ending with semantically congruous or incongruous words. Compared with congruous words, sentence-terminal incongruous words consistently evoked a large magnetic field over the left hemisphere, peaking at approximately 450 ms. Source modeling at this latency with conventional equivalent current dipoles (ECDs) placed the N400 m generator in or near the left superior temporal sulcus. A distributed solution constrained to the cortical surface suggested a sequence of differential activation, beginning in Wernicke's area at approximately 250 ms, spreading to anterior temporal sites at approximately 270 ms, to Broca's area by approximately 300 ms, to dorsolateral prefrontal cortices by approximately 320 ms, and to anterior orbital and frontopolar cortices by approximately 370 ms. Differential activity was exclusively left-sided until >370 ms, and then involved right anterior temporal and orbital cortices. At the peak of the N400 m, activation in the left hemisphere was estimated to be widespread in the anterior temporal, perisylvian, orbital, frontopolar, and dorsolateral prefrontal cortices. In the right hemisphere, the orbital, as well as, weakly, the right anterior temporal cortices were activated. Similar but weaker field patterns were evoked by intermediate words in the sentences, especially to low-frequency words occurring in early sentence positions where there is little preceding context. The locations of the N400 m sources identified with the distributed solution correspond well with those previously demonstrated with direct intracranial recordings, and suggested by functional magnetic resonance imaging (fMRI). These results help identify a distributed cortical network that supports online semantic processing.

Adult↗

What is magnetoencephalography and why it is relevant to neurosurgery?

Magnetoencephalography (MEG) is a relatively novel technique that allows the study of the dynamic properties of cortical activity. The functional localization of brain sources of MEG signals depends on the models used and it always has a certain degree of uncertainty. Nevertheless, MEG can be very useful in assisting the neurosurgeon in planning and carrying out brain surgery in, or around, eloquent brain areas, and in epilepsy surgery in pharmaco-resistant patients. The following three areas of application of MEG in neurosurgery are reviewed: (i) Presurgical functional localization of somatomotor eloquent cortex; (ii) Presurgical evaluation of epileptic patients. (iii) Functional localization of speech relevant brain areas. The performance of MEG in comparison with EEG and fMRI is discussed.

Brain Mapping↗

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials.

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during hand-squeezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions.

Adult↗