Thomas Dietl

Neural Bases of Cognitive ERPs: More than Phase Reset

Up to now, two conflicting theories have tried to explain the genesis of averaged event-related potentials (ERPs): Whereas one hypothesis claims that ERPs originate from an event-related activation of neural assemblies distinct from background dynamics, the other hypothesis states that ERPs are produced by phase resetting of ongoing oscillatory activity. So far, this question has only been addressed for early ERP components. Late ERP components, however, are generally thought to represent superimposed activities of several anatomically distinct brain areas. Thus, the question of which mechanism underlies the genesis of late ERP components cannot be easily answered based on scalp recordings. In contrast, two well-investigated late ERP components recorded invasively from within the human medial temporal lobe (MTL) in epilepsy patients, the so-called MTL-P300 and the anterior MTL-N400 (AMTL-N400), are based on single source activity. Hence, we investigated whether the MTL-P300 and the AMTL-N400 are based on an event-related activity increase, a phase reset of ongoing oscillatory activity or both. ERPs were recorded from the hippocampus and rhinal cortex in subjects performing a visual oddball paradigm and a visual word recognition paradigm. With wavelet techniques, stimulus-related phase-locking and power changes were analyzed in a frequency range covering 2 to 48 Hz. We found that the MTLP300 is accompanied by both phase reset and power increase and that both effects overlap partly in time. In contrast, the AMTL-N400 is initially associated with phase locking without power increase and only later during the course of the AMTL-N400 we observed an additional power increase. In conclusion, both aspects, event-related activation of neural assemblies and phase resetting of ongoing activity seem to be involved in the generation of late ERP components as recorded in cognitive tasks. Therefore, separate analysis of event-related power and phase-locking changes might reveal specific insights into the mechanisms underlying different cognitive functions.

Aggressive behavior of epilepsy patients in the course of levetiracetam add-on therapy: report of 33 mild to severe cases

Levetiracetam (LEV) was shown to be very efficacious and well tolerated as add-on therapy for refractory epilepsy. Here we report 33 patients with longstanding histories of epilepsy who experienced aggressive episodes during LEV therapy. This corresponds to 3.5% of LEV-treated patients as compared with less than 1% of patients not on LEV. Among these cases, 24 showed only moderate, partly transient irritability, with 10 patients requiring reduction or discontinuation of LEV. More strikingly, 9 patients displayed severe symptoms of aggression with physical violence and, in 2 cases, the need for psychiatric emergency treatment. One patient developed additional psychotic symptoms. We suggest that, specifically in patients with a previous history of aggression, behavioral tolerability of LEV should be carefully monitored.

Sensory gating of auditory evoked and induced gamma band activity in intracranial recordings

Oscillatory activity in the gamma band range (30-50 Hz) and its functional relation to auditory evoked potentials (AEPs) is yet poorly understood. In the current study, we capitalized on the advantage of intracranial recordings and studied gamma band activity (GBA) in an auditory sensory gating experiment. Recordings were obtained from the lateral surface of the temporal lobe in 34 epileptic patients undergoing presurgical evaluation. Two kinds of activity were differentiated: evoked (phase locked) and induced (not phase locked) GBA. In 18 patients, an intracranial P50 was observed. At electrodes with maximal P50, evoked GBA occurred with a similar peak latency as the P50. However, the intensities of P50 and evoked GBA were only modestly correlated, suggesting that the intracranial P50 does not represent a subset of evoked GBA. The peak frequency of the intracranial evoked GBA was on average relatively low (approximately 25 Hz) and is, therefore, probably not equivalent to extracranially recorded GBA which has normally a peak frequency of approximately 40 Hz. Induced GBA was detected in 10 subjects, nearly exclusively in the region of the superior temporal lobe. The induced GBA was increased after stimulation for several hundred milliseconds and encompassed frequencies up to 200 Hz. Single-trial analysis revealed that induced GBA occurred in relatively short bursts (mostly <<100 ms), indicating that the duration of the induced GBA in the averages originates from summation effects. Both types of gamma band activity showed a clear attenuation with stimulus repetition.

Orienting response and frontal midline theta activity: a somatosensory spectral perturbation study

OBJECTIVE Brain electric activity in the theta frequency band has been associated with the encoding of new, and the retrieving of previously stored, information. We studied the time course of stimulus-to-stimulus changes of theta activity under repetitive somatosensory stimulation. MATERIALS AND METHODS Twelve healthy subjects participated in the study. Repetitive electric stimuli, grouped into 48 stimulus trains, were applied to the left index finger. The stimulus trains contained 27 stimuli (0.9 Hz, 2.5 times sensory threshold). Each stimulus train of 30 s was followed by a stimulus-free break of 30 s. This stimulation paradigm allowed the separate estimation of effects for each position of the stimulus in the train and an analysis of stimulus-to-stimulus changes. Multichannel EEG recordings allowed a topographic analysis of the event-related spectral perturbation effects in the theta frequency band. The brain electric novelty response triggered by the stimulus train onset was analyzed by 3 methods: (1) event-related potentials; (2) event-related power spectra for the investigation of spectral perturbation effects on theta activity; and (3) an approach to break down the stimulus-induced theta activity into phase-locked activity and effects on the spontaneous, ongoing theta activity using digital filtering. RESULTS The main findings are a frontal midline activation in the theta band with the beginning of the stimulus train, which habituates during the subsequent stimulation cycles, as well as evidence that distinct effects of the first stimulus on the ongoing, non-phase-locked, theta activity exist.

Recognition of famous faces in the medial temporal lobe An invasive ERP study

Objective: To investigate the involvement of the rhinal cortex and the hippocampus in the processing of famous faces in contrast to nonfamous faces using intracranial event-related potentials (ERPs), and to analyze repetition effects for famous and nonfamous faces. Methods: ERPs were elicited by pictures of famous and nonfamous faces and recorded from rhinal and hippocampal sites of intracranial electrodes in 10 presurgical patients with unilateral medial temporal lobe epilepsy. Famous and nonfamous faces were presented twice and mixed with distorted faces serving as targets. There was no instruction for an overt discrimination between famous and nonfamous faces. In contrast to nonfamous faces, famous faces stimulate processes related with access and retrieval of semantic memory. Results: All faces evoked anterior medial temporal lobe N400-like (AMTL-N400) potentials in the rhinal cortex and P600-like potentials in the hippocampus. The AMTL-N400 and the hippocampal P600 amplitudes were larger for famous faces than for nonfamous faces. Mean amplitudes of the first and second presentation of famous faces suggest a repetition effect for the rhinal sites; however, they are significant only in the later signal components. No repetition effect was found for nonfamous faces and for potentials from the hippocampus. Conclusion: The anterior medial temporal lobe N400 and the hippocampal P600 may be related to the access and retrieval of person-specific semantic memory.

Processing of famous faces and medial temporal lobe event-related potentials: a depth electrode study.

The present study aims at analyzing the modulation of two types of event-related potentials originating from the human medial temporal lobe, the rhinal AMTL-N400 and the hippocampal P600 by the processing of famous faces. Therefore, we used a face recognition paradigm in which subjects had to discriminate the faces of famous persons from the faces of non-famous persons. Eleven patients with unilateral medial temporal lobe epilepsy undergoing intrahippocampal depth electrode recording for presurgical evaluation participated in this study. Event-related potentials (ERP) were recorded while a sequence of famous and non-famous faces was presented to the patients. The presentation of each face was repeated. The faces evoked N400-like potentials (anterior medial temporal lobe N400, AMTL-N400) in the rhinal cortex and P600-like potentials in the hippocampus. ERPs elicited by famous faces were contrasted with ERPs elicited by non-famous faces. The first presentation of famous faces elicited an enhanced AMTL-N400 and an enhanced hippocampal P600 in comparison to the second presentations of the famous faces or the (first and second presentation of the) non-famous faces. This findings are discussed in terms of associative semantic memory processes and the retrieval of person-specific information from long-term memory stores triggered by the processing of famous faces.

Topography and morphology of heart action-related EEG potentials

Joint ECG and EEG measurements were performed in 22 healthy subjects under standardized laboratory conditions. Averaged EEG potentials were computed using the R-peaks in the ECG as reference events. Spatio-temporal potential patterns of heart action-related EEG activity were obtained from 26 scalp channels. A heart action-related positive potential was found, peaking over the parietal scalp regions. Its independence from the cardiac electrical field, the source of an EEG artifact that may be confounded with heart action-related brain potentials, is demonstrated. The potential reaches its maximum amplitude of about 0.5 microV at a latency of about 500 ms after the R-peak. Its topography, with peak amplitudes at the parietal electrode locations, is different from the topography of potentials observed in the few comparable experimental studies published so far. This suggests the presence of somatosensory-evoked components in heart action-related potentials and indicates that a renewed discussion of the underlying neuronal processes is necessary.

Persistent severe amnesia due to seizure recurrence after unilateral temporal lobectomy.

Anterograde amnesia is a severely disabling state which has been reported as a consequence of bilateral mesiotemporal lesions in humans. In the present paper, recurrent epileptic seizures after temporal lobectomy are described as a rare cause of severe amnesia in two patients. Diffusion-weighted MRI in one patient showed cytotoxic edema during a nonconvulsive status epilepticus and subsequent progressive hippocampal atrophy within the following month. In the other patient, repeated conventional MRI revealed no structural abnormalities in the contralateral temporal lobe.

Phase-locking characteristics of limbic P3 responses in hippocampal sclerosis.

Amplitudes of the P3 recorded invasively from the medial temporal lobe (MTL-P3) have been reported to be reduced on the side of a mediotemporal epileptogenic focus. This reduction has been attributed to the massive cell loss within the hippocampus associated with hippocampal sclerosis. It has remained unclear how functional connectivity between the hippocampus and rhinal cortex, as well as within the hippocampus, is altered in hippocampal sclerosis. To investigate this issue, we analyzed to what extent stimulus-related phase-locking and power changes within the low-frequency range (2-30 Hz) and within the gamma band (32-48 Hz), as well as rhinal-hippocampal phase synchronization contribute to the averaged MTL-P3 potentials. Event-related responses were recorded via bilateral depth electrodes in epilepsy patients with unilateral hippocampal sclerosis, who performed a visual oddball experiment. On the contralateral (nonsclerotic) side, successful target detection was associated with an increase of power and phase locking of hippocampal activity in both the low-frequency range and in the gamma range. Besides, there were rhinal-hippocampal synchronization enhancements in the theta and gamma range. On the ipsilateral (sclerotic) side, the event-related power increase in the low-frequency range had almost disappeared, a finding likely to be explained by the loss of principle neurons. However, low-frequency phase-locking, rhinal-hippocampal synchronization, as well as event-related power changes in the gamma range persisted ipsilaterally, although there were differences in temporal and spectral characteristics. These findings support the hypothesis that functional connectivity between hippocampus and rhinal cortex, as well as intrahippocampal connectivity, are partially preserved in hippocampal sclerosis.

Hippocampus proper distinguishes between identified and unidentified real-life visual objects: an intracranial ERP study.

Converging evidence indicates that the medial temporal lobe participates not only in memory but also in visual object processing. We investigated hippocampal contributions to visual object identification by recording event-related potentials directly from within the hippocampus during a visual object identification task with spatially filtered pictures of real objects presented at different levels of filtering. Hippocampal responses differentiated between identified and unidentified visual objects within a time window of 200-900 ms after stimulus presentation: identified objects elicited a small negative component peaking around 300 ms (hippocampal-N300) and a large positive component, around 650 ms (hippocampal-P600), while the N300 was increased and the P600 was reduced in amplitude in response to unidentified objects. These findings demonstrate that the hippocampus proper contributes to the identification of visual objects discriminating from the very early between identified and unidentified meaningful visual objects.