K. Lehnertz

Tonotopic organization of the human auditory cortex revealed by transient auditory evoked magnetic fields

The tonotopic organization of the human auditory cortex has been investigated by systematic measurements of magnetic fields evoked by tone-bursts with carrier frequencies of 250, 500, 1000, 2000 and 4000 Hz. The measured field distribution changes with both time elapsed since stimulus onset and frequency of the stimulus. Nevertheless, the field distribution has always the same overall features and can be approximated by that of an equivalent current dipole located in a semi-infinite volume. This model can be described in terms of 5 parameter values: 3 orthogonal coordinates specifying the dipole location, and amplitude and angle of the dipole moment. The amplitude of the dipole moment is maximal at about 100 msec (component 100m) and 160 msec (component 160m) after stimulus onset. The depth estimated for the generator site of the 100m component shows a logarithmic dependence on test frequency whereas no similar behaviour could be observed for the 160m component. Anatomical studies performed in cadaver heads suggest that the equivalent current dipoles of both the 100m and the 160m component are located in the transverse temporal gyri.

Neuromagnetic evidence of an amplitopic organization of the human auditory cortex

It is well known that the location of the source of cortical auditory evoked responses, which can be determined neuromagnetically in humans using the concept of an equivalent current dipole (ECD), shifts with changing stimulus frequency (tonotopic organization). Not investigated so far, however, is the question of whether there exists also an amplitopic organization of the human auditory cortex, i.e., a spatial distribution of neurons maximally responsive to respective best stimulus intensities. We measured, in the study presented here, in 3 normally hearing subjects the auditory evoked magnetic field (AEF) in response to tone-burst stimulation with a carrier frequency of 1000 Hz at 6 different intensities (30-80 dB HL in 10 dB steps). The influence of stimulus intensity was quantified in terms of changes in the ECD parameters (amplitude, direction and spatial coordinates) which were determined such that a maximum correspondence between observed and calculated field distributions was obtained. The results of the neuromagnetic measurements presented here prove that the ECD location also shifts with changing stimulus intensity. The depth of wave M100 (latency of about 100 msec) decreases monotonically with increasing stimulus intensity while the horizontal ECD position is slightly shifted in the anterior direction. The results imply that, while topical mechanisms of frequency coding are similar at cortex and at the cochlear level, topical mechanisms of intensity coding are different at these levels.

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.

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.

Auditory Cortical Basis of Tinnitus

The waveforms of the auditory evoked magnetic field (AEF) 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 significantly 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 both an increased excitability of the generators of a particular component of wave M100 and a sustained neural activity in the generators of one particular component 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. Our hypothesis has been supported by one exemplary case in which we were able to trace the process of tinnitus remission during a period of 256 days after acute onset of tinnitus (due to an acute noise trauma), showing a recovery of the amplitude ratio from an initial value of 0 to a normal value of approximately 1.

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.