New approach to localize speech relevant brain areas and hemispheric dominance using spatially filtered magnetoencephalography.

We used a current localization by spatial filtering-technique to determine primary language areas with magnetoencephalography (MEG) using a silent reading and a silent naming task. In all cases we could localize the sensory speech area (Wernicke) in the posterior part of the left superior temporal gyrus (Brodmann area 22) and the motor speech area (Broca) in the left inferior frontal gyrus (Brodmann area 44). Left hemispheric speech dominance was determined in all cases by a laterality index comparing the current source strength of the activated left side speech areas to their right side homologous. In 12 cases we found early Wernicke and later Broca activation corresponding to the Wernicke-Geschwind model. In three cases, however, we also found early Broca activation indicating that speech-related brain areas need not necessarily be activated sequentially but can also be activated simultaneously. Magnetoencephalography can be a potent tool for functional mapping of speech-related brain areas in individuals, investigating the time-course of brain activation, and identifying the speech dominant hemisphere. This may have implications for presurgical planning in epilepsy and brain tumor patients.

A combined study of tumor-related brain lesions using MEG and proton MR spectroscopic imaging.

The purpose of this study is to localize, in cases of brain tumors, pathological magnetic brain activities and to analyze metabolic alterations in functionally abnormal lesions using magnetoencephalography (MEG) and proton magnetic resonance spectroscopic imaging (1H MRSI). The study focused on 10 healthy volunteers and seven patients with common brain tumors, namely astrocytic tumor and meningioma. In spontaneous MEG, the pathological brain activities (slow, fast waves and spikes) were localized using a single equivalent dipole model. After the results of MEG and 1H MRSI were superimposed onto the corresponding MR images, the signal intensities of spectroscopically visible metabolites were analyzed in the regions where the dipoles of the pathological activities were concentrated. Increased slow wave activity was observed in four cases and fast wave or spike activity was significantly increased in one case. These pathological activities were localized in surrounding regions of the bulk of tumors, where mild reduction of N-acetyl aspartate (NAA) and slight accumulation of lactate (Lac) consistently existed. Preserved cortical areas, which are indicated by residual NAA, might be able to generate pathological magnetic activities under lactic acidosis. Such areas could be understood as a border zone between normal and seriously damaged brain tissue by tumors or associated brain edema. This combined technique with the different modalities gives insight into functional as well as metabolic aspects of pathological brain conditions.

Time course of focal slow wave activity in transient ischemic attacks and transient global amnesia as measured by magnetoencephalography.

In this longitudinal study multichannel MEG was used to localize and to quantify focal pathological spontaneous neuromagnetic activity in six patients with transient ischemic attacks (TIA) and two patients with transient global amnesia (TGA). Slow (2-6 Hz) and beta (14-30 Hz) activity were monitored up to 10 weeks. Results were compared with normative data, and changes over time were statistically analyzed. MEG detected pathological activity that persisted clinical symptoms. Focal slow activity originating from sensorimotor (TIA) and mesiotemporal (TGA) cortices exceeded normal values up to 14 times during the first hours after the attack and recovered to normal within 11 days. Focal beta activity was not useful to monitor the time course of TIA or TGA.

The electrical and magnetical cerebral responses evoked by electrical stimulation of the esophagus and the location of their cerebral sources.

OBJECTIVES: After electrical stimulation of the esophagus cerebral responses are recordable, their cortical source is under discussion. Brain mapping using electroencephalography recordings demonstrated partially controversial results. Sources of evoked responses can be localized more easily using magnetoencephalography than electroencephalography. METHODS: We examined 22 volunteers by recording electrical somatosensory potentials after electrical stimulation of the esophagus. In 9 of these 22 subjects additional recording of magnetic fields was performed and the sources of the evoked magnetic fields were computed. RESULTS: The evoked potentials after electrical stimulation of the esophagus had a similar latency as the previously published data. The source localization done by magnetoencephalography suggest that first a region of the postcentral gyrus is activated which is temporo-lateral to the primary somatosensory cortex of the pharynx. This region is suggested to be the primary somatosensory region of the esophagus. This source was followed by a source in the parietal operculum thought being part of the secondary somatosensory cortex. Simultaneously the insular cortex was activated pointing to a parallel neuronal pathway to the central autonomic nervous system. CONCLUSION: After electrical stimulation of the esophagus somatosensory cortical areas of the temporal postcentral gyrus and the operculum are activated. In parallel activation of the insular cortex as part of the central autonomic network was found.

Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex.

OBJECT: The authors conducted a study to evaluate the clinical outcome in 50 patients with lesions around the motor cortex who underwent surgery in which functional neuronavigation was performed. METHODS: The sensorimotor cortex was identified in all patients with the use of magnetoencephalography (MEG). The MEG-source localizations were superimposed onto a three-dimensional magnetic resonance image and the image data set was implemented into a neuronavigation system. Based on this setup, the surgeon chose the best surgical strategy. During surgery, the pre- and postcentral gyri were identified by neuronavigation and, in addition, the central sulcus was localized using intraoperative recording of somatosensory evoked potentials. In all cases MEG localizations of the sensory or motor cortex were correct. In 30% of the patients preoperative paresis improved, in 66% no additional deficits occurred, and in only 4% (two patients) deterioration of neurological function occurred. In one of these patients the deterioration was not related to the procedure. CONCLUSIONS: The method of incorporating functional data into neuronavigation systems is a promising tool that can be used in more radical surgery to lessen morbidity around eloquent brain areas.

Spontaneous slow and fast MEG activity in male schizophrenics treated with clozapine.

RATIONALE: The atypical neuroleptic clozapine induces specific electroencephalogram changes, which have not been investigated using the technique of magnetoencephalography (MEG). OBJECTIVE: The present study investigated whether spontaneous magnetoencephalographic (MEG) activity in patients treated with clozapine differs from that in patients treated with haloperidol and untreated control subjects. METHODS: A 2 x 37 channel biomagnetic system was used to record spontaneous magnetic activity for the frequency ranges (2-6 Hz), (7.5-12 Hz), (12.5-30 Hz) in schizophrenic patients and controls in two trials within 3 weeks. After data acquisition, the processed data were digitally filtered and the spatial distribution of dipoles was determined by a 3-D convolution with a Gaussian envelope. The dipole localisation was calculated by the dipole density plot and the principal component analysis. The target parameters were absolute dipole values and the dipole localisations. The relationship between absolute dipole values, dipole localisations and psychopathological findings (documented by the use of the PANSS, BPRS-scale) during a 3 week period with constant doses of clozapine and haloperidol was investigated using correlation analysis. RESULTS: Our results lend strong support to the assumption of a significant elevation of absolute dipole values [dipole density maximum (Dmax), dipole number (Dtotal), absolute and relative dipole density] in the fast frequency range (12.5-30 Hz) over the left hemisphere, especially in the temporoparietal region by clozapine. In this area, we found a dipole concentration effect only in patients treated with the atypical neuroleptic, whereas the dipole distribution in patients treated with haloperidol and healthy controls was concentrated in the central region. With regard to the absolute dipole values in the frequency ranges 2-6 Hz (delta, theta) and 7.5-12 Hz (alpha), we found no statistically significant differences between the groups investigated. In the slow frequency range (2-6 Hz) no difference was found between the clozapine and haloperidol group for the dipole localisation, which predominated in the temporoparietal region, in contrast to the central dipole distribution in control subjects. CONCLUSIONS: The results of an increase in beta activity under clozapine demonstrate a smaller reduction in activity in terms of unspecific sensory and motor paradigms in comparison with typical neuroleptics. The temporoparietal concentration of dipoles, in particular over the left half of the brain, might illustrate either their special role in the disease process, or the effects of the medication. The latter possibility was supported by the differing dipole distribution in the clozapine group with a left temporoparietal centre in both frequency ranges, and a deviating central dipole localisation in the fast activity range in the haloperidol group.

Focal slow and beta brain activity in patients with multiple sclerosis revealed by magnetoencephalography.

In multiple sclerosis (MS) inflammatory infiltrations cause white matter lesions. Magnetoencephalography (MEG) offers the opportunity to localize abnormal electric activity of neurons with a high spatio-temporal resolution. In this study, we investigated patients with MS in order to find if abnormal cortical activity is associated with (subcortical) MS lesions using simultaneous bilateral recording of biomagnetic activity. Eight patients suffering from definite laboratory-supported MS with mainly somatosensory deficits and multiple bihemispheric plaques revealed by MRI were included in the study. To obtain normative data, 8 healthy volunteers were investigated following the same measuring protocol. Spontaneous magnetic brain activity was recorded using a 2x37-channel biomagnetic system (BTI, USA). Offline analysis included digital filtering (to separately investigate slow and beta wave activity), a Principle Component Analysis and the Dipole Density Plot. Localization results were inserted into MR images using our contour fit procedure. The dipole distribution in the brain was quantified and compared between the groups by statistical analysis. In all MS patients, the maximum of focal abnormal activity was localized in cortical areas adjacent to the fiber lesions. In the healthy subjects, no focal abnormal brain activity could be found. However, the standardized maximum concentrations of dipoles were significantly higher in the MS patients than in the healthy control group both in the slow and in the beta wave analysis. These results let assume that subcortical lesions can occur together with abnormal cortical neuronal activity. The results are discussed in respect to their impact on the interpretation of the analysis of spontaneous magnetic brain activity.

A combined study of tumor-related brain lesions by using magnetoencephalography and 1H magnetic resonance spectroscopic imaging. Technical note.

The purpose of this study was to localize pathological magnetic brain activities and to analyze metabolic alterations in functionally abnormal lesions by using magnetoencephalography (MEG) and (1)H magnetic resonance (MR) spectroscopy in patients with brain tumors. The authors studied 10 healthy volunteers and seven patients who harbored common brain tumors, namely astrocytic tumors and meningioma. In spontaneous MEG the pathological brain activities (slow waves, fast waves, and spikes) were localized using a single equivalent dipole model. After the results of MEG and (1)H MR spectroscopy were superimposed onto the corresponding MR images, the signal intensities of spectroscopically visible metabolites were analyzed in the regions in which the dipoles of the pathological activities were concentrated. Increased slow-wave activity was observed in four cases, and fast-wave or spike activity was significantly increased in one case each, respectively. These pathological activities were localized at almost the same cortical areas adjacent to the bulk of tumors, where mild reduction of N-acetyl aspartate (NAA) and slight accumulation of lactate consistently existed. Preserved and metabolically active cortical areas, which are indicated by residual NAA, might be able to generate pathological magnetic activities under lactic acidosis. Such an area could be understood as a border zone between normal brain tissue and brain tissue that has been seriously damaged by tumors or associated edema, which should be intensively treated. This combination of imaging techniques gives insight into functional as well as metabolic aspects of pathological brain conditions.

Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex.

The authors conducted a study to evaluate the clinical outcome in 50 patients with lesions around the motor cortex who underwent surgery in which functional neuronavigation was performed. The sensorimotor cortex was identified in all patients with the use of magnetoencephalography (MEG). The MEG-source localizations were superimposed onto a three-dimensional magnetic resonance image, and the image data set was then implemented into a neuronavigation system. Based on this setup, the surgeon chose the best surgical strategy. During surgery, the pre- and postcentral gyrus were identified by neuronavigation, and in addition, the central sulcus was localized using intraoperative recording of somatosensory evoked potentials. In all cases MEG localizations of the sensory or motor cortex were correct. In 30% of the patients preoperative paresis improved, in 66% no additional deficits occurred, and in only 4% (two patients) deterioration of neurological function occurred. In one of these patients the deterioration was not related to the method. The method of incorporating functional data into neuronavigation systems is a promising tool that can be used in more radical surgery to cause less morbidity around eloquent brain areas.

Responses to silent Kanji reading of the native Japanese and German in task subtraction magnetoencephalography.

The neuromagnetic activities evoked by semantic processing were localized by magnetoencephalography (MEG). We observed distinct time courses of the activities in native speaking Japanese subjects (Japanese speaker) and German subjects (German speaker) during silent reading of Japanese letters; Kanji and meaningless figures made by deforming the Arabian letters. There were significant differences in amplitude of the activities between Kanji and meaningless figure stimuli. The responses with meaningless figure stimuli were subtracted from those with Kanji stimuli to demonstrate the semantic responses. Earlier responses peaked at about 273.3+/-50. 8 and 245.0+/-23.8 ms (mean+/-S.D.) and were mainly located in the right fusiform gyrus (FuG) in the Japanese and German speakers, respectively. All the Japanese speakers constantly showed additional later responses in the left superior temporal gyrus (STG) and the supramarginal gyrus (SmG) at approximately 616.1+/-105.5 ms, whereas no further activity was observed in the German speakers who did not know the meaning of each Kanji. Because the later responses in the STG and SmG in the Japanese speakers were only observed in their dominant hemisphere, we believe the source of these responses to be part of the neural basis of Kanji semantic processing. The task subtraction MEG analysis could be a powerful method to discriminate distinct responses and visualize the neural networks involved in semantic processing.

Motor, somatosensory and auditory cortex localization by fMRI and MEG.

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were performed in six subjects during self-paced finger movement performance, tactile somatosensory stimulation and binaural auditory stimulation using identical stimulation paradigms. Both functional imaging modalities localized brain activity in adjacent areas of anatomically correct cortex. The mean distances measured between fMRI activity and the corresponding MEG dipoles were 10.1 mm (motor), 10.7 mm (somatosensory), 13.5 mm (auditory right hemisphere) and 14.3 mm (auditory left hemisphere). The distances found may reflect the correlation between electrophysiological and hemodynamic responses due to the different underlying substrates of neurophysiology measured by fMRI and MEG: BOLD contrast vs neuronal biomagnetic activity.

Localization analysis of neuronal activities in benign rolandic epilepsy using magnetoencephalography.

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical syndrome characterized by partial sensorimotor seizures with centrotemporal spikes. We report a detailed localization analysis of spontaneous magnetic brain activities in seven BECRS patients using magnetoencephalography (MEG). All patients had BECRS diagnosis with typical seizures and electroencephalographic findings and five patients had minor psychomotor deficits. MEG was recorded over both parieto-temporal regions using a 2x37-channel biomagnetic system. The collected data were digitally bandpass-filtered (2-6, 14-30, or 1-70 Hz) to analyze slow- and fast-wave magnetic activities and rolandic spikes. Slow-wave activity was increased in four hemispheres of three patients. Increased fast-wave activity was found in all five patients with minor neuropsychological deficits. The presence of increased fast-wave magnetic brain activity appeared to cause functional anomalies in the higher brain function processes. In the spike analysis, the dipoles of rolandic spikes which constantly manifested anterior positivity in direction were concentrated in the superior rolandic region in four cases and the inferior rolandic region in three cases. The localizations of increased slow- and fast-wave activities were identical with those of the spikes. The seizure profiles were frequently characterized by the spike locations. Source localizations of the focal brain activities and rolandic spikes by MEG will contribute to the different diagnosis and pathophysiological elucidation of BECRS.

Magnetic source imaging combined with image-guided frameless stereotaxy: a new method in surgery around the motor strip.

OBJECTIVE: In this study, information about the localization of the central sulcus obtained by magnetic source imaging (MSI) was intraoperatively translated to the brain, using frameless image-guided stereotaxy. In the past, the MSI results could be translated to the surgical space only by indirect methods (e.g., the comparison of the MSI results, displayed in surface renderings, with bony landmarks or blood vessels on the exposed brain surface). METHODS: Somatosensory evoked fields were recorded with a MAGNES II biomagnetometer (Biomagnetic Technologies Inc., San Diego, CA). Using the single equivalent current dipole model, the localization of the somatosensory cortex was superimposed on magnetic resonance imaging with a self-developed contour fit program. The magnetic resonance image set containing the magnetoencephalographic dipole was then transferred to a frameless image-guided stereotactic system. Intraoperatively, the gyrus containing the dipole was identified as the postcentral gyrus, using neuronavigation, and the next anterior sulcus was regarded as the central sulcus. With intraoperative cortical recording of somatosensory evoked potentials, this assumption was verified in each case. RESULTS: In all cases, the preoperatively assumed localization of the central sulcus and motor cortex with MSI agreed with the intraoperative identification of the central sulcus using the phase reversal technique. CONCLUSION: The combined use of MSI and a frameless stereotactic system allows a fast orientation of eloquent brain areas during surgery. This may contribute to a safer and more radical surgery in lesions adjacent to the motor cortex.

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).

A multivariate analysis of evoked responses in EEG and MEG data.

This paper presents a multivariate analysis of evoked responses and their spatiotemporal dynamics as measured with electro- or magnetoencephalography. This analysis uses standard techniques (ManCova) to make possible statistical inference about differential responses, after the data have been transformed using singular value decomposition. The generality of this approach is limited only by the assumptions implicit in the general linear model and can range from simple analyses like Hotelling's T2 test (in comparing evoked responses among different conditions) to complex analyses of a multivariate regression type (e.g., characterizing the response components associated with a behavioral or psychophysical parameter). To illustrate the technique we have characterized time-dependent changes (both within and between trials) in magnetic fields, evoked by self-paced movements. Our illustrative analysis showed that movement-evoked components were less prone to adaptation than premovement components, suggesting that functionally distinct (preparatory and early executive) biomagnetic signals show differential adaptation.

Sources of spontaneous slow waves associated with brain lesions, localized by using the MEG.

Electric or magnetic slow wave brain activity can be associated with brain lesions. For an accurate source localization we transformed the magnetoencephalographic (MEG) coordinate system to the magnetic resonance imaging (MRI) system by using a surface fit of the digitally measured head surface and the reconstructed surface of the MRI scan. Furthermore we solved the problem to separate sources of focal activity from other multiple sources by introducing a spatial average, the Dipole Density Plot (DDP). The DDP shows in a quantified manner concentrations of dipoles across time. The DDP uses the single dipole model adequately, because only those signal sections will be analyzed, where one component contributes to the signal predominantly. In all cases, where multiple sources concurrently active are to be localized, a current distribution analysis will be used, the Current Localization by Spatial Filtering (CLSF). All source localization procedures were tested using structural brain lesions, which were verified by imaging techniques (MRI or CT), showing the results in close topographical relation to the lesions. The results so far let us assume, that the DDP and the CLSF are valuable tools to localize sources of focal spontaneous slow wave electrical brain activity.