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We recorded limbic event-related potentials (ERPs) with intrahippocampal depth electrodes in a more demanding verbal and an easier pictorial continuous recognition task in patients undergoing presurgical evaluations of their medical refractory mesial temporal lobe epilepsies (MTLE). In all cases depth electrodes were implanted because non-invasive studies could not demonstrate unilateral seizure-onset unequivocally. For the present study we only considered 24 patients who eventually were found to suffer from unilateral MTLE, in whom hippocampal sclerosis (HS) was confirmed histologically, and who were seizure-free post-operatively. We found that the rhinal anterior medial temporal lobe N400 (AMTL-N400) to first presentations of words but not to pictures was reduced in amplitude on the side of seizure origin. Our data suggest that limbic ERPs to words are more sensitive to the epileptogenic process than those to pictures. Thus, if limbic ERPs are recorded as part of invasive presurgical evaluations, verbal instead of pictorial recognition paradigms should be employed.

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The filtering of sensory information, also referred to as "sensory gating", is impaired in various neuropsychiatric diseases. In the auditory domain, sensory gating is investigated mainly as a response decrease of the auditory evoked potential component P50 from one click to the second in a double-click paradigm. In order to relate deficient sensory gating to anatomy, it is essential to identify the cortical structures involved in the generation of P50. However, the exact cerebral topography of P50 gating remains largely unknown. In a group of 17 patients with drug-resistant focal epilepsy, P50 was recorded invasively via subdural electrodes, and the topography of functionally indispensable ("eloquent") cortices was obtained by electrical stimulation mapping. These eloquent areas were involved in language, motor, and sensory functions. P50 could be identified in 13 patients in either temporal (n=8) or midfrontal sites (n=5). There were six occurrences (in five patients) of overlap of sites with maximal P50 responses and eloquent areas. Those were auditory (n=1), supplementary sensorimotor (n=3), primary motor (n=1), and supplementary negative motor (n=1). Results suggest that the early stage of sensory gating already involves a top-down modulation of sensory input by frontal areas.

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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.

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It is still a matter of debate at which time point faces are recognized as familiar, with some studies claiming a relatively early face recognition and others later effects of familiarity. The authors report on effects of famousness of depicted persons and stimulus repetition on intracranially recorded event-related potentials. Famousness resulted in an increased latency of the N200 component, as well as in an increased amplitude of a later long-lasting potential (N700). In contrast, repetition led to an increased amplitude of the N200 but no increase of its latency. They suppose that the recognition of faces becomes observable within the N200 latency range and that the increased N200 latency reflects a feature processing additional to the holistic face processing.

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In this report a patient with episodic depersonalization is described. As the depersonalization episodes had been attributed to partial seizures, this patient was treated with antiepileptic medication. However, clinical evaluation with long-term video/EEG revealed no evidence of seizure activity during the depersonalization episodes. On the other hand, further evaluation revealed findings that are frequently associated with focal epilepsy. In addition to episodic depersonalization, this patient had secondary generalized seizures. The relationship between episodic depersonalization, temporal lobe pathology, and epilepsy is discussed against the background of this case.

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Concrete words, whose meanings are readily imagined, are better remembered than abstract words. However, the neural correlates of this effect are poorly understood. Here, we investigated the effect of imageability on brain activity in the medial temporal lobe (MTL) processes underlying recognition memory. We recorded event-related potentials (ERPs) via depth electrodes from within the MTL in 14 patients with drug-resistant epilepsy. Patients performed a continuous word recognition task with words of high and low imageability (controlled for word frequency). Behaviorally, recognition performance was better for high, compared to low, imageable words. Two ERP components associated with recognition memory, the AMTL-N400 and the hippocampal late negative component, showed an old/new effect, but only the hippocampal P600 showed a main effect of imageability. We suggest that the hippocampal effect of imageability in recognition memory may be associated with conceptual or pictorial information processing of concrete words.

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Mismatch negativity (MMN) is elicited by discernible changes in an otherwise regular stream of auditory stimulation and reflects a pre-attentive detection mechanism. In the current study, auditory evoked potentials were recorded intracranially and electrode contacts sensitive for stimulus deviance were selected in order to further elucidate the contribution of different brain areas to MMN generation. Data were obtained from patients with frontal and temporal lobe epilepsy undergoing a presurgical evaluation by subdural and depth electrodes. In 13 of 29 patients under investigation an intracranial MMN could be observed, while in four other patients a response recovery of the N100 was revealed, mimicking an MMN. Most electrodes with an MMN signal were located in or close to the superior temporal lobe. In two patients an MMN was observed at electrode contacts over the lateral inferior frontal cortex and in one patient at a frontal interhemispheric electrode strip, giving evidence for a participation of the frontal gyrus in MMN generation. Current findings have, however, to be interpreted with caution owing to the placement and limited extension of the used electrode arrays.

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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.

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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 MTL-P300 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.

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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.

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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.

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