C. Pantev

Identification of sources of brain neuronal activity with high spatiotemporal resolution through combination of neuromagnetic source localization (NMSL) and magnetic resonance imaging (MRI)

The locations of the origin of wave M100 of the auditory evoked magnetic field in response to tone bursts of different carrier frequencies, obtained through dipole localization methods (DLM), were related to cerebral structures, displayed by coronal MRI (magnetic resonance imaging) tomograms of the respective subjects. This was done by displaying the landmarks which served as reference for the neuromagnetic measurements in MRI tomogram (reference plane). All calculated source locations project exactly onto the transverse temporal gyri (Heschl) in which the primary auditory cortex, the supposed origin of wave M100, is located. The results highlight the exceptional capabilities of a combination of these 2 non-invasive, high-resolution techniques for functional diagnosis.

Objective evidence of tinnitus in auditory evoked magnetic fields

The waveforms of the auditory evoked magnetic field in normal-hearing individuals and patients suffering from tinnitus are distinctly different. In tinnitus patients, the magnetic wave M200 (corresponding to the electric wave P200, or P2) is delayed and only poorly developed or even completely missing, while the amplitude of the magnetic wave M100 (corresponding to the electric wave N100, or N1) is significally augmented. A very characteristic feature turned out to be the amplitude ratio of the two waves M200 and M100. Below the age of 50, the amplitude ratio M200/M100 represents a clear-cut criterion to distinguish between tinnitus patients and individuals without tinnitus. In tinnitus patients, the ratio is less than 0.5, independent of age, whereas, in young and middle-aged normal-hearing individuals, it is greater than 0.5. Since in normal-hearing individuals the average amplitude ratio decreases linearly with age, the clusters of amplitude ratios of the two groups begin to overlap beyond the age of 50. The hypothesis is put forward that the decrease of the average amplitude ratio in normal-hearing individuals reflects a degenerative process, probably initiated by multiple exogenous and endogenous factors, which leads to sustained neural activity in the generators of wave M200 and eventually gives rise to the sensation of tinnitus. The absence or poor development of wave M200 is a concomitant phenomenon, resulting from the involved generators being less responsive to external stimuli.

Tinnitus remission objectified by neuromagnetic measurements

In a previous paper of ours (Hoke et al., 1989a) the hypothesis was put forward that the amplitude ratio of the two major waves of the auditory evoked magnetic field (AEF), M200/M100, is an objective measure which allows to discriminate between individuals suffering from tinnitus (ratio less than 0.5) and individuals without tinnitus (ratio greater than 0.5). We have now been able to trace the process of tinnitus remission in one exemplary case during a period of 256 days after acute onset of tinnitus (due to a noise trauma), in which the amplitude ratio recovered from 0 to a normal value of approximately 1. This very first objectification of tinnitus remission strongly supports our hypothesis and indicates that AEF may become an indispensable, invaluable tool in both tinnitus research and management.

Biomagnetic Measurements Using Squids

Systematic studies of the magnetoencephalogram (MEG) in normal and pathological subjects (mainly with focal epilepsies) showed that the MEG may evidence significant brain activities even if they are not present in the electroencephalogram (EEG). They also showed that the MEG has a considerably higher spatial resolution than the EEG. A novel mapping technique was introduced to get such a representation of the data that would enable the investigator to draw his conclusions mainly from inspecting the plots. This technique is characterized by an isospectral amplitude (iso-SA) mapping of the scalp distribution of specified spectral components or frequency bands of the MEG power spectrum. With the above method we were able to localize an epileptiform focus using a noninvasive technique without applying an eliciting stimulus. Furthermore using SQUID measurements we were able to describe the behavior of the MEG when the brains of different subjects were subjected to low frequency sinusoidal binaural stimuli. Under these conditions it has been shown that the MEG tends to organize around discrete frequencies that depend on the interference pattern (beat) between the two inputs.

Neuromagnetic Evidence of Functional Organization of the Auditory Cortex in Humans

The influence of two physical stimulus parameters (frequency and intensity) and of one sensation parameter (pitch) on the auditory evoked magnetic field (AEF) was quantified by approximating the measured magnetic field distribution by that of an equivalent current dipole (ECD) embedded in a homogeneous semi-infinite volume conductor. The main results are as follows: The depth of the ECD increases with increasing frequency, but decreases with increasing intensity. In the case of a complex tone with missing fundamental it is the virtual pitch that determines the ECD location and not the spectral contents of the stimulus.

On the Biomagnetic Inverse Problem in the Case of Multiple Dipoles

Series of Monte Carlo simulations have been carried out which were based on the assumption that two dipoles with a distance of 0.5-2 cm are located in a homogeneous semi-infinite volume conductor (depth 3 cm), and that the magnetic field component perpendicular to the surface of the volume conductor is recorded by means of a magnetometer with infinitesimal coil diameter. Moving-dipole models (all parameters time-dependent), rotating-dipole models (dipole locations fixed, dipole orientation and amplitudes time-dependent) as well as fixed-dipole models (dipole locations and orientations fixed, amplitudes time-dependent) were considered. The algorithm used to retrieve the model parameters from the simulated field distributions (biomagnetic inverse procedure) was based on a transformation of the standard least-squares fit procedure into a minimization procedure with respect to the nonlinear parameters (dipole locations and orientations), which was solved iteratively by means of the Fletcher-Powell algorithm. It was found that the resolving power of the biomagnetic inverse procedure is highly dependent on the relative orientation of the two dipoles, the temporal overlap of the dipole moments, and the correlation of successive samples of the superimposed noise. The results obtained in this study suggest that the resolving power of the biomagnetic inverse procedure for conditions typically found in the case of auditory evoked magnetic fields is not better than 2 cm for the moving-dipole approach, and not better than 1 cm for the fixed-dipole approach, provided that no additional a priori information is available. In practice, the situation is probably even worse since the depth of the generators is usually larger than assumed in this study.

A Timesaving BERA Technique for Frequency-specific Assessment of the Auditory Threshold through tone-pulse Series Stimulation (TOPSTIM) with Simultaneous Gliding High-pass Noise Masking (GHINOMA)

A new stimulation paradigm is described for eliciting frequency-specific auditory brainstem responses (ABR) by stimulation with a series of seven Gaussian-shaped tone pulses with carrier frequencies descending, in half-octave steps, from 4,000 to 500 Hz, and an interstimulus interval between consecutive pulses of 18 ms. The pause between two consecutive series is 54 ms so that the interval between two tone pulses of the same frequency is 162 ms (stimulus repetition rate approximately 6/s). Simultaneously a high-pass noise masker is presented whose lower cut-off frequency is continuously diminished in such a way that, when a tone pulse is presented, the cut-off frequency of the masker is exactly one octave above the carrier frequency of the pulse. Forward masking effects of preceding tone pulses as well as forward and simultaneous masking effects of the high-pass noise suppress activity originating from those regions of the cochlea which are located basalwards to the region to be stimulated by the respective pulse, thus enhancing the frequency specificity, especially for low-frequency stimuli of higher intensity. The new stimulation paradigm was tested in 12 normal hearing subjects and turned out to be suitable to elicit frequency-specific ABR with frequencies as low as 500 Hz and intensities as low as 10 dB nHL. The main advantage of the described technique is that the time required for a complete assessment of the auditory threshold at seven test frequencies (covering the relevant speech frequency range) is substantially shorter as compared to conventional techniques so that it can routinely be employed in pedaudiology, where infants usually have to be investigated in sedation.

Mapping of MEG Amplitude Spectra: Its Significance for the Diagnosis of Focal Epilepsy

An epileptic seizure is a paroxysmal disturbance of brain function resulting from highly synchronized pathological activities of groups of neurons. The epileptic event is characterized by typical clinical phenomena, normally accompanied by characteristic, steeply rising field potentials of high amplitude which can be picked up by surface electroencephalogram (EEG) recordings. However, several experimental and clinical studies have clearly demonstrated that epileptiform potentials in the surface EEG do not necessarily reflect epileptic events in deeper cortical layers or brain structures (Elger and Speckmann 1983; Wieser 1983). This holds true especially for epileptic foci in the limbic system, which most often give rise to a pharmacoresistant temporal lobe epilepsy (Wieser 1983).

Randomized Data Acquisition Paradigm for the Measurement of Auditory Evoked Magnetic Fields

The high variability of both amplitude and latency measures of the components of the auditory evoked magnetic field (AEMF), which we have attributed primarily to changes in the state of vigilance, makes it often impossible to compute significant isofield contour maps. Using a randomized data acquisition paradigm we have been able to considerably reduce the time-dependent fluctuations of the state of vigilance resulting in more stable latencies and in more stable and higher amplitudes of the AEMF components.

Causes of Differences in the Input-Output Characteristics of Simultaneously Recorded Auditory Evoked Magnetic Fields and Potentials: Causes de différences dans les caractéristiques d' entrée-sortie des champs magnétiques évoqués et des potentiels évoqués auditifs enregistrés simultanément

The input-output characteristics of amplitude and latency of simultaneously recorded auditory-evoked magnetic fields (AEMF) and auditory-evoked potentials (AEP) are significantly different, although they are closely related to the same excitation process of the auditory system. As the source of both AEMF and AEP an equivalent-current dipole lying in the auditory cortex can be assumed. Differences in the input-output characteristics of AEMF and AEP can be explained by changes of one or more parameters of this dipole (depth, location in the tangential x-y plane and direction). Maps of the field distribution obtained at 60 and 80 dB HL indeed reveal a change of the location of the dipole in the x-y plane and the direction of the dipole momentum, whereas the depth of the dipole was found to be more or less constant.