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.
 
 

Audiology 1986;25(4-5):263-76
Causes of differences in the input-output characteristics of simultaneously recorded auditory evoked magnetic fields and potentials.
Pantev C, Hoke M, Lutkenhoner B, Lehnertz K, Spittka J

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.
 
 

Audiology 1986;25(1):54-61
Comparison between simultaneously recorded auditory-evoked magnetic fields and potentials elicited by ipsilateral, contralateral and binaural tone burst stimulation.
Pantev C, Lutkenhoner B, Hoke M, Lehnertz K

Both auditory-evoked magnetic fields (AEMF) and auditory-evoked potentials (AEP) mainly consist of three peaks with latencies of
about 50, 100 and 160 ms. Comparison of responses to ipsilateral, contralateral and binaural stimulation yields no significant
amplitude or latency differences of the AEP peaks whereas the simultaneously recorded AEMF peaks exhibit a 10 ms shorter latency and an approximately 38% greater amplitude for contralateral versus ipsilateral stimulation. This fact can be due to differences in the
strength, location (especially the depth) and the direction of the dipole source, and a decision cannot be made considering the data
recorded from just one position. Another finding is that binaural stimulation reduces the peak amplitudes by approximately 25%
compared with contralateral stimulation. This result indicates some kind of interference between the ipsilateral and contralateral
pathways ('binaural interaction').
 
Electroencephalogr Clin Neurophysiol 1988 Feb;69(2):160-70
Tonotopic organization of the human auditory cortex revealed by transient auditory evoked magnetic fields.
Pantev C, Hoke M, Lehnertz K, Lutkenhoner B, Anogianakis G, Wittkowski W

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.
 
 

Audiology 1989;28(3):152-70
Magnetic fields from the auditory cortex of a deaf human individual occurring spontaneously or evoked by stimulation through a cochlear prosthesis.
Hoke M, Pantev C, Lutkenhoner B, Lehnertz K, Surth W

In a postlingually deaf individual, the magnetic field evoked by stimulation through a cochlear prosthesis (extracochlear electrodes)
as well as of the spontaneous magnetoencephalogram was measured over the hemisphere contralateral to the prosthesis (CP), and
the results were compared with those obtained from normal-hearing subjects. The latency of the 2 best developed waves M100 and
M200 turned out to be prolonged in the CP patient by approximately 40 ms. The amplitude of wave M100 was significantly
diminished, while wave M200 was only poorly developed. Location and direction of the equivalent current dipole (ECD) calculated
for wave M100 was in good agreement with normal data, whereas the dipole moment was only about one third of the average dipole
moment found in normals. Furthermore, evidence was obtained for another magnetic field wave, preceding the delayed auditory
wave M100, which exhibits the same latency, ECD location and direction as reported in the literature for the somatosensory evoked
magnetic field. This wave probably results from stimulation, through the intratympanic electrodes, of somatosensory nerves
innervating the tympanic cavity. A potential clinical application of neuromagnetic measurements is discussed: The calculation of the
ECD moment from the auditory cortical magnetic field evoked by electrical stimulation at the promontory would allow to estimate,
prior to CP implantation, the number of persisting, excitable nerve fibres.
 
 

Hear Res 1989 Feb;37(3):281-6
Objective evidence of tinnitus in auditory evoked magnetic fields.
Hoke M, Feldmann H, Pantev C, Lutkenhoner B, Lehnertz K

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.
 
 

Electroencephalogr Clin Neurophysiol 1989 Mar;72(3):225-31
Neuromagnetic evidence of an amplitopic organization of the human auditory cortex.
Pantev C, Hoke M, Lehnertz K, Lutkenhoner B

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.
 

Hear Res 1989 Jul;40(3):261-4
Tinnitus remission objectified by neuromagnetic measurements.
Pantev C, Hoke M, Lutkenhoner B, Lehnertz K, Kumpf W

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.
 
 

Science 1989 Oct 27;246(4929):486-8
Tonotopic organization of the auditory cortex: pitch versus frequency representation.
Pantev C, Hoke M, Lutkenhoner B, Lehnertz K

According to the place principles of the classical hearing theory, the physical entity frequency is encoded in the auditory periphery as place information (tonotopic representation), which is decoded in more central parts of the auditory system to form the subjective
entity pitch. However, this relation is true only for pure-tone signals (spectral pitch); it can be quite different in the case of complex
auditory stimuli (virtual pitch), thus requiring a multistage process for pitch formation. Neuromagnetic measurements showed that the tonotopic organization of the primary auditory cortex reflects the pitch rather than the frequency of the stimulus; that is, the pitch
formation process must take place in subcortical regions.
 
 

Electroencephalogr Clin Neurophysiol 1990 Mar;75(3):173-84
Identification of sources of brain neuronal activity with high spatiotemporal resolution through combination of neuromagnetic source localization (NMSL) and magnetic resonance imaging (MRI).
Pantev C, Hoke M, Lehnertz K, Lutkenhoner B, Fahrendorf G, Stober U

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.
 
 

Acta Otolaryngol Suppl (Stockh) 1991;491:106-114; discussion 115
Neuromagnetic evidence of functional organization of the auditory cortex in humans.
Pantev C, Hoke M, Lutkenhoner B, Lehnertz K

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.
 
 

Acta Otolaryngol Suppl (Stockh) 1991;491:176-81; discussion 182
Auditory cortical basis of tinnitus.
Hoke M, Pantev C, Lutkenhoner B, Lehnertz K

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.
 
 

Acta Otolaryngol Suppl (Stockh) 1991;491:94-104; discussion 105
On the biomagnetic inverse problem in the case of multiple dipoles.
Lutkenhoner B, Lehnertz K, Hoke M, Pantev C

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.
 
 

Electroencephalogr Clin Neurophysiol 1995 Jul;95(1):53-62
Alterations of intrahippocampal cognitive potentials in temporal lobe epilepsy.
Grunwald T, Elger CE, Lehnertz K, Van Roost D, Heinze HJ

During presurgical evaluation event-related potentials were recorded with depth electrodes located longitudinally within the
hippocampus in 25 patients suffering from unilateral temporal lobe epilepsy. Rare stimuli in a visual oddball paradigm elicited a
pronounced negativity ("NO") in the hippocampal body. Amplitudes were significantly reduced on the side of the primary
epileptogenic area. Visual presentations of words in a recognition paradigm evoked an earlier negativity ("ENW") in anterior and a
later negativity ("LNW") in posterior hippocampal structures. Both were sensitive for recognition effects and showed reduced
amplitudes on the side of the primary epileptogenic area. Relating the differences of left and right hippocampal "NO" and "ENW"
amplitudes proved to be a sensitive method for topological diagnosis and allowed a correct lateralization of the primary epileptogenic area in all patients. Amplitudes of the hippocampal ENW, evoked in the dominant hemisphere by first presentations, strongly
correlated with the recognition rate, when the primary epileptogenic area was situated in the contralateral temporal lobe. This
correlation was reduced by the presence of ipsilateral epileptogenic foci. Published errata appear in Electroencephalogr Clin
Neurophysiol 1995 Dec;95(6):481
 
 

Electroencephalogr Clin Neurophysiol 1995 Aug;95(2):108-17
Spatio-temporal dynamics of the primary epileptogenic area in temporal lobe epilepsy characterized by neuronal complexity loss.
Lehnertz K, Elger CE

Neurons involved in the epileptic processes exhibit high frequency discharges scarcely modulated by physiological brain activity.
This behaviour should be accompanied by a loss of complexity in the corresponding electrographic signal. From the theory of
non-linear dynamics it is known that the correlation dimension allows a quantitative description of complexity in terms of the number
of degrees of freedom. To test whether a relationship exists between spatio-temporal alterations of neuronal complexity and spatial
extent and temporal dynamics of the epileptogenic area, a moving-window correlation dimension analysis was applied to
intracranially recorded electrocorticograms of 20 patients with unilateral temporal lobe epilepsy. Dimension as a function of time was
calculated for interictal activity (n = 98) and seizure activity including the pre- and postictal phase (n = 28) from recording locations
within the epileptogenic area, in adjacent areas and in homologous contralateral sites. Pronounced changes of the dimension in time
were found, gradually decreasing with increasing distance from the focal area. Extraction of a single value quantifying the dimension
variance of interictal activity allowed the primary epileptogenic area to be laterized in exact agreement with the results of the
presurgical work-up and the confirmation of the postoperative outcome, without the necessity of observing actual seizure activity.
 
 

Neuropsychologia 1997 May;35(5):657-67
Human temporal lobe potentials in verbal learning and memory processes.
Elger CE, Grunwald T, Lehnertz K, Kutas M, Helmstaedter C, Brockhaus A, Van Roost D, Heinze HJ

Animal experiments and lesion studies have shown the importance of temporal lobe structures for language and memory. We
recorded intracranial cognitive potentials from the human lateral and medial temporal lobe in 26 patients with temporal lobe epilepsy
undergoing presurgical evaluation, using a word- and a picture-recognition paradigm. Neuropsychological testing included word
fluency, verbal reasoning, sustained attention and a verbal learning memory test (VLMT), which was an adapted version of the Rey
auditory verbal learning test. Word-specific N400-potentials elicited in the middle temporal gyrus of the dominant left hemisphere
(LTL-N400) predicted immediate recall performance after learning, whereas N400s, elicited by words but not pictures in the left
anterior medial temporal lobe (AMTL-N400), predicted delayed recall. The number of words that were learned but forgotten after a
30-min delay correlated only with N400s elicited by words in the left anterior medial temporal lobe. Thus, intracranial recordings
indicated that different electrophysiological responses in different temporal lobe structures were linked to memory scores from
specific neuropsychological tests.
 
 

Electroencephalogr Clin Neurophysiol 1997 May;102(5):423-36
Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.
Brockhaus A, Lehnertz K, Wienbruch C, Kowalik A, Burr W, Elbert T, Hoke M, Elger CE

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study.
Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG)
recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing
power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model
were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at
least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the
presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of
shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.
 
 

Electroencephalogr Clin Neurophysiol 1997 Sep;103(3):376-80
Neuronal complexity loss in temporal lobe epilepsy: effects of carbamazepine on the dynamics of the epileptogenic focus.
Lehnertz K, Elger CE

Analysis methods derived from the theory of non-linear dynamics have been shown to provide new information about the complex
spatio-temporal behaviour of neuronal networks involved in temporal lobe epilepsy. To test whether day to day alterations in
neuronal complexity are influenced by changes in serum level of carbamazepine (CBZ), a moving-window correlation dimension
analysis was applied to electrocorticographic and stereoelectroencephalographic recordings of 10 patients with unilateral temporal
lobe epilepsy. Data sets (n = 78) were obtained from interictal states at subsequent days during the presurgical evaluation with
strongly variant CBZ serum levels. The so-called neuronal complexity loss L* was used to quantify the change of dimensionality in
brain electrical activity recorded under different levels of medication. We found a significant inverse relationship between L* and
CBZ serum level spatially restricted to the primary epileptogenic area. This finding can be assumed to reflect the mechanism of
action of CBZ attributed to an inhibition of sustained high-frequency firing of bursting neurons.
 
 

Brain Cogn 1997 Oct;35(1):110-31
Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy.
Helmstaedter C, Grunwald T, Lehnertz K, Gleissner U, Elger CE

A wealth of animal and human research has pointed to a significant involvement of the temporal lobes in memory processing, and yet the different functional roles of temporal cortical vs. mesial structures remain unclear. We studied verbal declarative memory, by
using a word list paradigm that differentiates among learning (immediate recall), memory (delayed recall), and recognition, in epilepsy patients being considered for surgical resection of the left temporal lobe. Verbal memory was evaluated preoperatively and during the recording of intracranial event related potentials and postoperatively after selective hippocampectomy, temporal cortical lesionectomy, or anterior two-thirds en bloc temporal lobe resection procedures. Preoperative differences in verbal memory
performance as a function of differences in underlying neuropathology, concurrent event-related potentials, and specific patterns of
postoperative memory impairments lead to converging evidence that verbal declarative memory relies on a synergistic interaction of
at least two functionally distinct brain systems. Material-specific data acquisition, or working memory, is mediated by neocortical
temporal structures, whereas long-term consolidation/retrieval is particularly mediated by temporomesial structures. In contrast to the left temporal neocortex, the function of the temporomesial system appears to be material nonspecific. Apparently, its preferential
involvement in verbal memory is due to its close interaction with overlying neocortical structures that are specialized for language
processing.
 
 

Brain Topogr 1997 Fall;10(1):41-7
Methohexital-induced changes in spectral power of neuromagnetic signals: beta augmentation is smaller over the hemisphere containing the epileptogenic focus.
Wienbruch C, Eulitz C, Lehnertz K, Brockhaus A, Elger CE, Elbert T, Hoke M

Previous research has suggested that methohexital, a short-term barbiturate, alters activity in the primary epileptogenic area. It can be
assumed that drug-induced activation of the epileptogenic focus provides a rapid and safe method to obtain a sufficient amount of
information relevant for the lateralization and localisation of the primary epileptogenic area. This study shows that methohexital
changes spectral power in the beta band derived from magnetoencephalographic (MEG) signals over the hemisphere ipsilateral to the primary epileptogenic area. This effect was demonstrated for 10/13 of the investigated patients suffering from unilateral temporal
lobe epilepsy (TLE). The side and location of the primary epileptogenic area of these patients (5 left TLE, 8 right TEL) was
determined invasively during presurgical evaluation. During a 1-2 minute interval after intravenous bolus injection of 100 mg
methohexital a clear lateralization effect in the beta band was observed, which differed marginally between fronto-central,
fronto-temporal and temporo-parietal brain regions. In addition, bilateral spectral power changes were obtained in the theta, alpha
and gamma bands that differed between brain regions. Analyses of simultaneously recorded scalp electroencephalographic (EEG)
data revealed effects consistent with those of the MEG analysis. The reduced enhancement of beta band spectral power of MEG
recordings provides a potential application for the non-invasive lateralization of the primary epileptogenic area.
 
 

Proc Natl Acad Sci U S A 1998 Mar 17;95(6):3193-7
Verbal novelty detection within the human hippocampus proper.
Grunwald T, Lehnertz K, Heinze HJ, Helmstaedter C, Elger CE

Animal studies and neuropsychological tests of patients with temporal lobe epilepsy have demonstrated the importance of human
medial temporal lobes for memory formation. In addition, more recent studies have shown that the human hippocampal region is
also involved in novelty detection. However, the exact contribution of the hippocampus proper to these processes is still unknown.
To examine further its role we compared event-related potentials recorded within the medial temporal lobes in 29 temporal lobe
epilepsy patients with and 21 without hippocampal sclerosis. While in patients with extrahippocampal lesions but without
hippocampal sclerosis event-related potentials to first presentations and repetitions of words were reduced on the side of the
epileptogenic focus, in patients with hippocampal sclerosis only those to first presentations but not to repetitions were affected.
Because sclerosis of the hippocampus proper selectively reduced event-related potentials to new but not old verbal stimuli, it can be
concluded that the human hippocampus proper contributes to verbal novelty detection.
 
 

Brain Topogr 1998 Summer;10(4):283-90
Properties of advanced headmodelling and source reconstruction for the localization of epileptiform activity.
Waberski TD, Buchner H, Lehnertz K, Hufnagel A, Fuchs M, Beckmann R, Rienacker A

During the last decade multiple work has been done to determine the sources of epileptiform activity by means of dipole source
localization based on recordings of the magnetoencephalogram (MEG) or the electroencephalogram (EEG). The actual available
advanced volume conductor models and the multiple source reconstruction by regularization may give new impulse to EEG based
source analyses in epilepsy patients. This study demonstrates the principal properties of these techniques. We applied two different
EEG source reconstruction techniques within different volume conductor models to localize induced spike activity in a selected
patient suffering from medically intractable temporal lobe epilepsy: 1) single moving dipole solution in a 3-shell spherical model
versus individual head models (boundary-element-model, BEM, and finite-element-model, FEM); 2) a regularization technique for
current density reconstructions using both BEM and FEM. When compared to findings of invasive recordings no adequate source
locations were derived from the moving dipole solution in both the 3-shell head model and BEM. In contrast, a high congruence of
source reconstruction and invasive determination of the focus was obtained using the regularization techniques in both BEM and
FEM, indicating the high spatial accuracy of this technique in individual head models.
 
 

Epilepsia 1998 Sep;39(9):922-7
Neuronal complexity loss in interictal EEG recorded with foramen ovale electrodes predicts side of primary epileptogenic area in temporal lobe epilepsy: a replication study.
Weber B, Lehnertz K, Elger CE, Wieser HG

PURPOSE: To investigate whether a correct lateralization of the primary epileptogenic area by means of neuronal complexity loss
analysis can be obtained from interictal EEG recordings using semi-invasive foramen ovale electrodes. In a previous study with
recordings from intrahippocampal depth and subdural strip electrodes it was shown that the dynamics of the primary epileptogenic
area can be characterized by an increased loss of neuronal complexity in patients with unilateral temporal lobe epilepsy (TLE).
METHODS: Neuronal complexity loss analysis was applied. This analysis method is derived from the theory of nonlinear dynamics
and provides a topological diagnosis even in cases where no actual seizure activity can be recorded. We examined interictal EEG
recorded intracranially from multipolar foramen ovale electrodes in 19 patients with unilateral TLE undergoing presurgical evaluation.
RESULTS: The primary epileptogenic area was correctly lateralized in 16 of the 19 investigated patients. The misclassification of the
side of seizure onset in three patients might be attributed to the larger distance between the foramen ovale electrodes and the mesial
temporal structures as compared to intrahippocampal depth electrodes. CONCLUSIONS: Our results confirm the previous findings
and provide further evidence for the usefulness of nonlinear time-series analysis for the characterization of the spatiotemporal
dynamics of the primary epileptogenic area in mesial temporal lobe epilepsy.
 
 
 

Eur J Neurosci 1998 Feb;10(2):786-9
Seizure prediction by non-linear time series analysis of brain electrical activity.
Elger CE, Lehnertz K

Brain electrical activity of 16 patients with temporal lobe epilepsy, recorded intracranially during seizure-free intervals as well as
during transitions to the seizure state, was analysed using methods derived from the theory of non-linear dynamics. Long-lasting
and marked changes towards low-dimensional system states were found to occur specifically up to 25 min prior to epileptic
seizures and allow to predict the occurrence of individual seizures in time. These findings reflect a continuous increase in the
degree of synchronicity, and thus open a window for the study of mechanisms generating seizures in humans.
This offers new possibilities for therapeutic interventions.
 

Physica D 1998, 121, 65-74
A fast general purpose algorithm for the computation of auto- and cross-correlation integrals from single channel data
Widman G, Lehnertz K, Jansen P, Meyer W, Burr W, Elger CE

We developed an optimized algorithm that allows computation of auto- and cross-correlation integrals from single channel
time series without restricting the range of hypersphere radii and embedding dimensions. Optimization was achieved by
eliminating any multiple computation of subsets entering the distance function in the time delay reconstruction of the phase
space repeatedly for increasing embedding dimensions; this is most effective when using the maximum norm. Compared to
more naive implementations an improvement of 2-3 was achieved, depending on the type of workstation, the operating system,
and the compiler. An additional optimization for 80x86 assembly language allows to run the algorithm on a standard personal
computer as fast as on a workstation. In contrast to other implementations, the execution speed of this algorithm is nearly
unaffected by the type of underlying data. Thus, it is optimal for real-time analyses.

NeuroReport 1998, 9, 3375-3378
Limbic ERPs predict verbal memory after left-sided hippocampectomy
Grunwald T, Lehnertz K, Helmstaedter C, Kutas M, Pezer N, Kurthen M, van Roost D, Elger CE

Surgical removal of the dominant medial temporal lobe regions runs a considerable risk of verbal memory deficit
which may be compensated for postoperatively by corresponding regions in the non-dominant medial temporal lobe.
We examined this possibility by recording event-related potentials (ERPs) to words from the medial temporal lobes of
patients with left-sided temporal lobe epilepsy (TLE) undergoing presurgical evaluation. N400 amplitudes in the
right anterior medial temporal lobe predicted the postoperative verbal recall performance of individual patients with
surprising accuracy, indicating that intracranial recordings can be used to quantify the functional capacities of the right
hemisphere that can compensate for the verbal memory deficits after loss of medial temporal lobe structures
in the left hemisphere.

Epilepsia 1999, 40, 303-306
Prediction of postoperative seizure control by hippocampal event-related potentials.
Grunwald T, Lehnertz K, Pezer N, Kurthen M, Van Roost D, Schramm J, Elger CE

PURPOSE: In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial
temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event-related potentials
(ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process,
we examined whether ERPs can help to improve the prediction of postoperative seizure control.
METHODS: We recorded ERPs to words from bilateral intrahippocaampal electrodes by using a visual word-recognition
paradigm in 70 patients with unilateral hippocampal pathology and related these measurements to seizure outcome after
temporal lobe surgery.
RESULTS: Words elicited N400 potentials, which were reduced in amplitude on repetition on the side contralateral to
hippocampal sclerosis. This contralateral repetition effect, however, was significantly diminished in the group of patients
who experienced seizure recurrence after the operation. Contralateral repetition effects thus permitted correct prediction of
postoperative seizure control in 94% of all patients.
CONCLUSIONS: Recording ERPs to words within the medial temporal lobes can improve the prediction of postoperative
seizure control. Reduced repetition effects contralateral to the side of hippocampal sclerosis may indicate bilateral
epileptogenicity.
 

Eur J Neurosci 1999, 11, 1899-1906
Limbic P300s in temporal lobe epilepsy with and without Ammon's horn sclerosis.
Grunwald T, Beck H, Lehnertz K, Blumcke I, Pezer N, Kutas M, Kurthen M, Karakas HM,
Van Roost D, Wiestler OD, Elger CE

Limbic P300 potentials can be recorded within the mesial temporal lobes of patients with temporal lobe epilepsy (TLE).
To delineate possible mechanisms of their generation and pathological alteration, we analysed limbic P300s in 55 TLE
patients with and 29 without Ammon's horn sclerosis (AHS) and correlated their amplitudes with neuronal cell counts in 30 histopathological specimens. Limbic P300 amplitudes were reduced on the side of the epileptogenic focus only in patients
with AHS. Moreover, in AHS patients, limbic P300 latencies were prolonged bilaterally; and in patients with left-sided AHS, amplitudes were reduced bilaterally. Both findings suggest bilateral functional deficits in TLE with unilateral AHS.
Limbic P300 areas correlated significantly with neuronal densities of dentate gyrus granule cells but not hippocampal
pyramidal cells in the CA1-4 (cornu ammonis) subfields. This finding points to a potential mechanism for the bilateral effects of unilateral AHS as both dentate gyri exhibit strong reciprocal contralateral connectivity.

Schweizer Archiv f. Neurologie und Psychiatrie, 150, 72-78, 1999
Nichtlineare EEG-Analysen
Lehnertz K, Widman G, Andrzejak R, Arnhold J, Elger CE

The theory of nonlinear dynamics provides new concepts and powerful algorithms to analyze EEG time series. Due to its high
versatility, nonlinear time series analysis currently is being successfully applied in a variety of disciplines including neurology and
psychiatry. In epileptology, the extraction of nonlinear measures from the intracranially recorded EEG promises to be important
for clinical practice. Besides an immense reduction of the information content of long-lasting EEG recordings previous studies
have shown that these measures allow (a) to localize focal areas in different cerebral regions even during the interictal state,
(b) to investigate the influence of anticonvulsive drugs, (c) to analyze spatio-temporal interactions between focal and non-focal
brain areas and (d) to detect features predictive of imminent seizure activity. Nonlinear EEG-analysis provides new and
supplementary information upon the epileptogenic process and thus contributes to an improved presurgical evaluation.
 

Rev. Neurol. (Paris), 155 (6­7), 454­456, 1999
Is it possible to anticipate seizure onset by non-linear analysis of intracerebral EEG in human
partial epilepsies ?
Lehnertz K, Widman G, Andrzejak R, Arnhold J, Elger CE

Detection of electrophysiological features preceding and indicative of imminent seizures in patients with epilepsy would be a
major breakthrough with immense scientific and clinical implications. The definition of a "pre­ictal state" several minutes
prior to seizure onset would open a new time window for studying mechanisms of seizure generation as well as for possible therapeutic
interventions. In this review we present recent findings from nonlinear time series analysis of intracranially
recorded EEG that may allow to forecast seizure onset in patients with partial epilepsy.
 

Brain Res, 836, 156-163, 1999
Reduced signal complexity of intracellular recordings: a precursor for epileptiform activity?
Widman G, Bingmann D, Lehnertz K, Elger CE

Recent studies have shown that time windowed extraction of nonlinear parameters like an effective correlation dimension from
intracranially recorded EEG of epileptic patients often allows to detect and identify an unequivocal "pre-ictal phase" preceding an
epileptic seizure. In another study, however, such an anticipation could not be made. These conflicting findings may indicate that
observed changes in nonlinear parameters probably depend on the type of elementary mechanisms underlying epileptic processes
and/or the spatial distribution of neurons primarily involved in generation of epileptiform discharges. To test the existence of such
dependencies, the transition from normal to epileptiform activity (EA) of CA3-neurons in hippocampal slices was analyzed in four
epilepsy models, using a time windowed computation of an effective correlation dimension. Indeed, in xanthine and penicillin
models, signal complexity in intracellular recordings was reduced before manifestation of paroxysmal depolarization shifts (PDS),
whereas a preceding loss of complexity was missing in low-magnesium and veratridine models. These findings indicate that
interictal-like EA is predictable only in some epilepsy models.

Science,  285 (5433), 1582-1585, SEP 3 1999
Real-time tracking of memory formation in the human rhinal cortex and hippocampus
Fernandez G, Effern A, Grunwald T, Pezer N, Lehnertz K, Dumpelmann M, Van Roost D, Elger CE

A fundamental question about human memory is which brain structures are involved, and when, in transforming experiences into
memories. This experiment sought to identify neural correlates of memory formation with the use of intracerebral electrodes
implanted in the brains of patients with temporal Lobe epilepsy. Event-related potentials (ERPs) were recorded directly from the
medial temporal Lobe (MTL) as the patients studied single words. ERPs elicited by words subsequently recalled in a memory test
were contrasted with ERPs elicited by unrecalled words. Memory formation was associated with distinct but interrelated ERP
differences within the rhinal cortex and the hippocampus, which arose after about 300 and 500 milliseconds, respectively. These
findings suggest that declarative memory formation is dissociable into subprocesses and sequentially organized within the MTL.
 

Int. J. Psychophysiol., 34, 45-52, 1999
Lehnertz K
Nonlinear time series analysis of intracranial EEG recordings in patients with epilepsy -- an overview.

Deterministic chaos offers a striking explanation for apparently irregular behavior, a characteristic feature of brain electrical activity.
The framework of the theory of nonlinear dynamics provides new concepts and powerful algorithms to analyze such time series.
However, different influencing factors render the use of nonlinear measures in a strict sense problematic. Nevertheless, if interpreted with care,
particularly the correlation dimension or the Lyapunov-exponents provide a means to reliably characterize different states of normal and
pathological brain function. This overview summarizes recent findings applying this concept in the field of epileptology that promise to be
important for clinical practice. Nonlinear measures extracted from the intracranially recorded EEG allow (a) localization of epileptogenic areas
n different cerebral regions even during seizure-free intervals, (b) investigation of the influence of anticonvulsive drugs and (c) detection of features
predictive of imminent seizure activity. Moreover, particularly the dimensional complexity proves a valuable parameter reflecting spatially
distributed neuronal activity during verbal learning and memory processes. Specific changes in time of this nonlinear measure allow the
prediction of memory performance and, in addition, represent an estimate of the recruitment potency in the anterior mesial temporal lobes.
Thus, the application of nonlinear time series analysis to brain electrical activity offers new information about the dynamics of the underlying
neuronal networks.

Proc Natl Acad Sci U S A 1999 Oct 12;96(21):12085-12089
Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors.
Grunwald T, Beck H, Lehnertz K, Blumcke I, Pezer N, Kurthen M, Fernandez G, Van Roost D, Heinze HJ, Kutas M, Elger CE

Studies in rodents and nonhuman primates have linked the activity of N-methyl-D-aspartate (NMDA) receptors within the hippocampus to
animals' performance on memory-related tasks. However, whether these receptors are similarly essential for human memory is still an open question.
Here we present evidence suggesting that hippocampal NMDA receptors, most likely within the CA1 region, do participate in human verbal memory
processes. Words elicit a negative event-related potential (ERP) peaking around 400 ms within the anterior mesial temporal lobe (AMTL-N400).
Ketamine, an NMDA-receptor antagonist, reduces the amplitude of the AMTL-N400 (in contrast to other hippocampal potentials) on initial presentation,
eliminates the typical AMTL-N400 amplitude reduction with repetition, and leads to significant memory impairment. Of the various hippocampal subfields,
only the density of CA1 neurons correlates with the word-related ERPs that are reduced by ketamine. Altogether, our behavioral, anatomical, and electrophysiological results indicate that hippocampal NMDA receptors are involved in human memory.

Physica D, 134, 419-430, 1999
A robust method for detecting interdependencies: application to intracranially recorded EEG
Arnhold J, Grassberger P, Lehnertz K, Elger CE

We present a measure for characterizing statistical relationships between  two time sequences. In contrast to commonly used
measures like cross-correlations, coherence and mutual information, the proposed measure is non-symmetric and
provides information about the direction of interdependence. It is closely related to recent attempts to detect generalized synchronization.
However, we do not assume a strict functional relationship between the two time sequences and try to define the measure so as to be
robust against noise, and to detect also weak interdependences. We apply our measure to intracranially recorded electroencephalograms
of patients suffering from severe epilepsies.
 

Physica D, 140, 257-266, 2000
Nonlinear denoising of transient signals with application to event related potentials
Effern A, Lehnertz K, Schreiber T, David P, Elger C E

We present a new wavelet-based method for the denoising of event-related potentials (ERPs), employing techniques recently developed for
the paradigm of deterministic chaotic systems. The denoising scheme has been constructed to be appropriate for short and transient time
sequences using circular state space embedding. Its effectiveness was successfully tested on simulated signals as well as on ERPs recorded
from within a human brain. The method enables the study of individual ERPs against strong ongoing brain electrical activity.
 

Physikalische Blätter, 56, April, 2000, 27-32
Chaos im Kopf? Nichtlineare Dynamik und Epilepsie
Arnhold J, Grassberger P, Lehnertz K

Ungefähr ein Prozent der Weltbevölkerung – in der Bundesrepublik sind es ca. 600000 Menschen – leidet an Epilepsie, einer Erkrankung
des Zentralnervensystems. Obwohl viele Betroffene mit Medikamenten oder einem chirurgischen Eingriff am Gehirn gut behandelbar sind, ist
diese Erkrankung dennoch ein wichtiges gesundheitspolitisches Problem. Im Folgenden beschreiben wir Ansätze, die mit Hilfe neuester
Erkenntnisse aus der Theorie der nichtlinearen Dynamik – der „Chaostheorie“ – die Diagnostik und Therapie dieser Erkrankung
verbessern sollen.

Physica D, 144, 358-369, 2000
Mean phase coherence as a measure for phase synchronization and its application to the EEG of epilepsy patients.
Mormann F, Lehnertz K, David P, Elger CE

We apply the concept of phase synchronization of chaotic and/or noisy systems and the statistical distribution of the relative
instantaneous phases to electroencephalograms (EEGs) recorded from patients with temporal lobe epilepsy.
Using the mean phase coherence as a statistical measure for phase synchronization, we observe characteristic spatial and temporal
shifts in synchronization that appear to be strongly related to pathological activity. In particular, we observe distinct
differences in the degree of synchronization between recordings from seizure-free intervals and those before an impending seizure,
indicating an altered state of brain dynamics prior to seizure activity.
 
 

Epilepsia, 41, 811-817, 2000
Spatial distribution of neuronal complexity loss in neocortical epilepsies.
Widman G, Lehnertz K, Urbach H, Elger CE

Purpose: Nonlinear EEG analysis is valuable in characterizing the spatiotemporal dynamics of the epileptogenic process in mesial
temporal lobe epilepsy. We examined the ability of the measure neuronal complexity loss (L*) to characterize the primary epileptogenic
area of neocortical lesional epilepsies during the interictal state.
Methods: Spatial distribution of L* (L* map) was extracted from electrocorticograms (n = 52) recorded during presurgical assessment
via subdural 64-contact grid electrodes covering lesions in either frontal, parietal, or temporal neocortex in 15 patients. The exact location
of recording contacts on the brain surface was identified by matching a postimplant lateral x-ray of the skull with a postoperatively
obtained sagittal MRI scan. Reprojecting L* maps onto the subject's brain surface allowed us to compare the spatial distribution of
L* with the resection range of the extended lesionectomy.
Results: In each of the six patients who became seizure-free, maximum values of L* were restricted to recording sites coinciding with
the area of resection. In contrast, L* maps of most patients who had no benefit from the resection indicated a more widespread extent
or the existence of additional, probably autonomous, foci. The mean of L* values obtained from recording sites outside the area of
resection correctly distinguished 13 patients (86.7 %) with respect to seizure outcome.
Conclusions: Relevant information obtained from longlasting interictal electrocorticographic recordings can be compressed to a single
L* map that contributes to a spatial characterization of the primary epileptogenic area. In neocortical lesional epilepsies, L* allows for
identification and characterization of epileptogenic activity and thus provides an additional diagnostic tool for presurgical assessment.
 

Epilepsia, 41 (Suppl 3), S34-S38, 2000
Nonlinear EEG analysis and its potential role in epileptology
Elger CE, Widman G, Andrzejak R, Arnhold J, David P, Lehnertz K

Deterministic chaos offers a striking explanation for apparently irregular behavior of the brain that is evidenced in the EEG.
Recent developments in the physical-mathematical framework of the theory of nonlinear dynamics (colloquially often termed chaos theory)
provide new concepts and powerful algorithms to analyze such time series. Because of its high versatility, nonlinear time series analysis has
already gone beyond the physical sciences and, at present, is being successfully applied in a variety of disciplines, including cardiology,
neurology, psychiatry, and epileptology. However, it is well known that different influencing factors limit the use of nonlinear measures to
characterize EEG dynamics in a strict sense. Nevertheless, when interpreted with care, relative estimates of, e.g., the correlation dimension
or the Lyapunov exponents, can reliably characterize different states of normal and pathologic brain function. In epileptology, extraction of
nonlinear measures from the intracranially recorded EEG promises to be important for clinical practice. In addition to an immense reduction
of information content of long-lasting EEG recordings, previous studies have shown that these measures enable (a) localization of the primary
epileptogenic area in different cerebral regions during the interictal state, (b) investigations of antiepileptic drug effects, (c) analyses of
spatio-temporal interactions between the epileptogenic zone and other brain areas, and (d) detection of features predictive of imminent seizure activity.
Nonlinear time series analysis provides new and supplementary information about the epileptogenic process and thus contributes to an
improvement in presurgical evaluation.
 

Clin Neurophysiol. 111, 2255-2263, 2000
Single trial analysis of event related potentials: non-linear de-noising with wavelets
Effern A, Lehnertz K, Fernandez G, Grunwald T, David P, Elger CE

We present and apply a method for single trial analysis of event related potentials (ERPs) that combines techniques from non-linear time
series analysis with the wavelet transform. For this method, convincing results have already been achieved for simulated data as well as for
intracranially recorded ERPs (Physica D 140 (2000) 257). However, ERPs are affected by a variety of external and internal experimental
parameters, which makes the appropriate configuration of single trial analysis difficult. Thus, several pitfalls may occur in realistic applications.
In this paper, we applied the method of non-linear de-noising with wavelets to both intra- and extracranially recorded ERPs, and show
examples of how and where this single trial analysis can be used to obtain additional information on dynamic neural processes.
 

Psychophysiology, 37, 859-865, 2000
Time adaptive denoising of single trial event related potentials in wavelet domain
Effern A, Lehnertz K, Grunwald T, Fernandez G, David P, Elger CE

We present a new wavelet-based method for single trial analysis of transient and time variant event-related potentials (ERPs).
Expecting more accurate filter settings than achieved by other techniques (low-pass filter, a posteriori Wiener filter, time invariant wavelet filter),
ERPs were initially balanced in time. By simulation, better filter performance could be established for test signals contaminated with either
white noise or isospectral noise. To provide an example of real application, the method was applied to limbic P300 potentials (MTL-P300).
As a result, variance of single trial MTL-P300s decreased, without restricting the corresponding mean.
The proposed method can be regarded as an alternative for single-trial ERP analysis.
 

Physical Review E 62, 8380-8386, 2000
Kulback-Leibler and renormalized entropies: Applications to electroencephalograms of epilepsy patients
Quiroga RQ, Arnhold J, Lehnertz K, Grassberger P

Recently, "renormalized entropy'' was proposed as a novel measure of relative entropy
[P. Saparin et al., Chaos, Solitons and Fractals 4, 1907 (1994)] and applied to several physiological time sequences,
including electroencephalograms (EEGs) of patients with epilepsy. We show here that this measure is just a modified
Kulback-Leibler (KL) relative entropy, and it gives similar numerical results to the standard KL entropy. The latter
better distinguishes frequency contents of, e.g., seizure and background EEGs than renormalized entropy.
We thus propose that renormalized entropy might not be as useful as claimed by its proponents. In passing, we also make some
critical remarks about the implementation of these methods.

Physical Review E 63, 036209, 2001
Nonlinear denoising using reference data.
Sternickel K, Effern A, Lehnertz K, Schreiber T, David P

We introduce a method to clean uncorrelated deterministic and stochastic noise components from time series.
It combines recently developed techniques for nonlinear projection with properties of the wavelet transform to
extract noise in state space. The method requires that time series are generated by a dynamical system which is
at least approximately deterministic and that they are recorded together with a reference signal.
Its efficiency was tested on both simulated signals and measured magnetic fields of the heart.
Convincing results are obtained even at low signal-to-noise ratios
 

Epilepsy Research, 44, 129-140, 2001
The epileptic process as nonlinear deterministic dynamics in a stochastic environment – an evaluation of mesial temporal lobe epilepsy.
Andrzejak RG, Widman G, Lehnertz K, Rieke C, David P, Elger CE

The theory of deterministic chaos addresses simple deterministic dynamics in which nonlinearity gives rise to
complex temporal behavior. Although biological neuronal networks such as the brain are highly complicated,
a number of  studies provide growing evidence that nonlinear time series analysis of brain electrical activity in
patients with epilepsy is capable of providing potentially useful diagnostic information. In the present study, this
analysis framework was extended by introducing a new measure, denoted ?? to discriminate between nonlinear
deterministic and linear stochastic dynamics. For the evaluation of  its discriminative power, ? was extracted from
intracranial multi-channel EEGs recorded during the interictal state in 25 patients with unilateral mesial temporal
lobe epilepsy. Pronounced indications of nonlinear determinism were found in recordings from within the primary
epileptogenic area while EEG signals from other sites mainly resembled linear stochastic dynamics. In all investigated
cases this differentiation allowed to retrospectively determine the side of the primary epileptogenic area in full
agreement with results of the presurgical workup.
 

J. Clin. Neurophysiol. 18, 209-222, 2001
Nonlinear EEG analysis in epilepsy: Its possible use for interical focus localization, seizure anticipation, and prevention.
Lehnertz K, Andrzejak RG, Arnhold J, Kreuz T, Mormann F, Rieke C, Widman G, Elger CE

Several recent studies emphasize the high value of nonlinear EEG analysis particularly for improved characterization of epileptic
brain states. In this review the authors report their work to increase insight into the spatial and temporal dynamics of the epileptogenic process.
Specifically, they discuss possibilities for seizure anticipation, which is one of the most challenging aspects of epileptology. Although there are
numerous studies exploring basic neuronal mechanisms that are likely to be associated with seizures, to date no definite information is available
regarding how, when, or why a seizure occurs. Nonlinear EEG analysis now provides strong evidence that the interictal–ictal state transition is
not an abrupt phenomenon. Rather, findings indicate that it is indeed possible to detect a preseizure phase. The unequivocal definition of such a
state with a sufficient length would enable investigations of basic mechanisms leading to seizure initiation in humans, and development of
adequate seizure prevention strategies. 

Hum Brain Mapp. 14, 251-260, 2001
Inferior temporal stream for word processing with integrated mnemonic function. 
Fernandez G, Heitkemper P, Grunwald T, Van Roost D, Urbach H, Pezer N, Lehnertz K, Elger CE.

The participation of the inferior temporal cortex in visual word perception and recognition raises several questions:
Is there a directed processing stream proceeding anteriorly by continuous cortical processing? How fast are words processed
within such an inferior temporal stream? Does this stream support implicit or explicit memory? To answer these questions,
we analyzed the spatio-temporal relationship of event-related potentials, recorded directly from the inferior temporal cortex in epilepsy
patients performing a continuous visual word recognition paradigm. Event-related potentials elicited an inferior temporal positivity in a
strip along the left collateral sulcus. This potential exhibited a linear (r = 0.74) peak latency progression from posterior to anterior
inferior temporal regions (approximately 15 cm/sec), indicating a directed, intracortical processing stream. Peak amplitudes and latencies
showed reliable old/new effects with smaller amplitudes and shorter latencies for old as opposed to new words.
Although the amplitude-old/new-effect occurred for all repeated words (e.g., implicit memory), the latency-old/new-effect occurred
for correctly recognized old words only (e.g., explicit recognition). These results seem to dissociate two distinct mnemonic processes.
The graded decrease of mean ITP peak amplitudes and latencies, however, does not allow us to exclude a single trace model as assumed
for explicit recognition memory based on familiarity (Mandler [1980]: Psychol Rev 87:252-271). Regardless whether there is a dissociation
between implicit and explicit memory in inferior temporal cortex or not, our findings are in accordance with an integrated inferior temporal
processing stream for words that performs continuously semantic and mnemonic operations supporting both implicit and explicit memory.