Biomedical subjects

K Lehnertz

Publications and source records attributed to K Lehnertz.

At least 19 recordsLinked to original sources

PubMed2000

Spatial distribution of neuronal complexity loss in neocortical lesional epilepsies.

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 long-lasting 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.

Adolescent↗

PubMed2000

Nonlinear EEG analysis and its potential role in epileptology.

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.

Brain Mapping↗

PubMed1999

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors.

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.

Adult↗

PubMed1999

Real-time tracking of memory formation in the human rhinal cortex and hippocampus.

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.

Adult↗

PubMed1999

Reduced signal complexity of intracellular recordings: a precursor for epileptiform activity?

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.

Electroencephalography↗

PubMed1999

Non-linear 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 non-linear dynamics provides new concepts and powerful algorithms to analyze such time series. However, different influencing factors render the use of non-linear 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. Non-linear measures extracted from the intra-cranially recorded EEG allow (a) localization of epileptogenic areas in 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 non-linear 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 non-linear time series analysis to brain electrical activity offers new information about the dynamics of the underlying neuronal networks.

Electroencephalography↗

PubMed1999

Limbic P300s in temporal lobe epilepsy with and without Ammon's horn sclerosis.

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.

Adolescent↗

PubMed1999

Prediction of postoperative seizure control by hippocampal event-related potentials.

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.

Adolescent↗

PubMed1999

Is it possible to anticipate seizure onset by non-linear analysis of intracerebral EEG in human partial epilepsies?

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 "pre-ictal 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.

Animals↗

PubMed1998

Limbic ERPs predict verbal memory after left-sided hippocampectomy.

Surgical removal of the dominant medial temporal lobe regions runs a considerable risk of verbal memory deficits 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.

Adolescent↗

PubMed1998

Verbal novelty detection within the human hippocampus proper.

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.

Adolescent↗

PubMed1998

Properties of advanced headmodelling and source reconstruction for the localization of epileptiform activity.

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.

Adult↗

PubMed1998

Seizure prediction by non-linear time series analysis of brain electrical activity.

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.

Adolescent↗

PubMed1998

Neuronal complexity loss in interictal EEG recorded with foramen ovale electrodes predicts side of primary epileptogenic area in temporal lobe epilepsy: a replication study.

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.

Adult↗

PubMed1997

Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy.

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.

Adult↗

PubMed1997

Neuronal complexity loss in temporal lobe epilepsy: effects of carbamazepine on the dynamics of the epileptogenic focus.

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.

Adult↗

PubMed1997

Human temporal lobe potentials in verbal learning and memory processes.

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.

Adolescent↗

PubMed1997

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

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.

Adolescent↗