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Contains fulltext : 69742.pdf (publisher's version ) (Open Access), Theta oscillations in the medial temporal lobe (MTL) of mammals are involved in various functions such as spatial navigation, sensorimotor integration, and cognitive processing. While the theta rhythm was originally assumed to originate in the medial septum, more recent studies suggest autonomous theta generation in the MTL. Although coherence between entorhinal and hippocampal theta activity has been found to influence memory formation, it remains unclear whether these two structures can generate theta independently. In this study we analyzed intracranial electroencephalographic (EEG) recordings from 22 patients with unilateral hippocampal sclerosis undergoing presurgical evaluation prior to resection of the epileptic focus. Using a wavelet-based, frequency-band-specific measure of phase synchronization, we quantified synchrony between 10 different recording sites along the longitudinal axis of the hippocampal formation in the non-epileptic brain hemisphere. We compared EEG synchrony between adjacent recording sites (i) within the entorhinal cortex, (ii) within the hippocampus, and (iii) between the hippocampus and entorhinal cortex. We observed a significant interregional gap in synchrony for the delta and theta band, indicating the existence of independent delta/theta rhythms in different subregions of the human MTL. The interaction of these rhythms could represent the temporal basis for the information processing required for mnemonic encoding and retrieval.

Contains fulltext : 70662.pdf (publisher's version ) (Closed access), Two step theories of memory formation assume that an initial learning phase is followed by a consolidation stage. Memory consolidation has been suggested to occur predominantly during sleep. Very recent findings, however, suggest that important steps in memory consolidation occur also during waking state but may become saturated after some time awake. Sleep, in this model, specifically favors restoration of synaptic plasticity and accelerated memory consolidation while asleep and briefly afterwards. To distinguish between these different views, we recorded intracranial electroencephalograms from the hippocampus and rhinal cortex of human subjects while they retrieved information acquired either before or after a "nap" in the afternoon or on a control day without nap. Reaction times, hippocampal event-related potentials, and oscillatory gamma activity indicated a temporal gradient of hippocampal involvement in information retrieval on the control day, suggesting hippocampal-neocortical information transfer during waking state. On the day with nap, retrieval of recent items that were encoded briefly after the nap did not involve the hippocampus to a higher degree than retrieval of items encoded before the nap. These results suggest that sleep facilitates rapid processing through the hippocampus but is not necessary for information transfer into the neocortex per se.

Contains fulltext : 70951.pdf (publisher's version ) (Closed access), PURPOSE: Functional magnetic resonance imaging (fMRI) is being used increasingly for language dominance assessment in the presurgical work-up of patients with pharmacoresistant epilepsy. However, the interpretation of bilateral fMRI-activation patterns is difficult. Various studies propose fMRI-lateralization index (LI) thresholds between +/-0.1 and +/-0.5 for discrimination of atypical from typical dominant patients. This study examines if these thresholds allow identifying atypical dominant patients with sufficient safety for presurgical settings. METHODS: 65 patients had a tight comparison, fully controlled semantic decision fMRI-task and a Wada-test for language lateralization. According to Wada-test, 22 were atypical language dominant. In the remaining, Wada-test results were compatible with unilateral left dominance. We determined fMRI-LI for two frontal and one temporo-parietal functionally defined, protocol-specific volume of interest (VOI), and for the least lateralized of these VOIs ("low-VOI") in each patient. RESULTS: We find large intra-individual LI differences between functionally defined VOIs irrespective of underlying type of language dominance (mean LI difference 0.33+/-0.35, range 0-1.6; 15% of patients have inter-VOI-LI differences >1.0). Across atypical dominant patients fMRI-LI in the Broca's and temporo-parietal VOI range from -1 to +1, in the "remaining frontal" VOI from -0.93 to 1. The highest low-VOI-LI detected in atypical dominant patients is 0.84. CONCLUSIONS: Large intra-individual inter-VOI-LI differences and strongly lateralized fMRI-activation in patients with Wada-test proven atypical dominance question the value of the proposed fMRI-thresholds for presurgical language lateralization. Future studies have to develop strategies allowing the reliable identification of atypical dominance with fMRI. The low-VOI approach may be useful.

Contains fulltext : 53560.pdf (publisher's version ) (Closed access), Little is known about the neural mechanisms underlying top-down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task. In the study phase subjects were required to respond to either pictures or words that were presented superimposed on each other. In the repetition phase only words were presented that were new, previously attended or ignored, or picture names that were derived from previously attended or ignored pictures. Relative to new words we found repetition priming for previously attended words. Previously ignored words showed a reduced priming effect, and there was no significant priming for pictures repeated as picture names. Brain imaging data showed that neural priming of words in the left prefrontal cortex (LIPFC) and left fusiform gyrus (LOTC) was affected by attention, semantic compatibility of superimposed stimuli during study and cross-modal priming. Neural priming reduced for words in the LIPFC and for words and pictures in the LOTC if stimuli were previously ignored. Previously ignored words that were semantically incompatible with a superimposed picture during study induce increased neural priming compared to semantically compatible ignored words (LIPFC) and decreased neural priming of previously attended pictures (LOTC). In summary, top-down control induces dissociable effects on neural priming by attention, cross-modal priming and semantic compatibility in a way that was not evident from behavioral results.

Contains fulltext : 51962.pdf (publisher's version ) (Closed access), The functional deficits associated with hippocampal sclerosis during declarative memory formation are largely unknown. In this study, we analyzed intracranial event-related potentials recorded from the medial temporal lobes of nine epilepsy patients performing a word memorization task. We used frequency-specific wavelet analysis to assess stimulus-related changes in power and intertrial phase coherence. Statistical analysis revealed a significant decrease of stimulus-induced power in the delta and theta range on the side of pathology. No significant differences in phase locking were observed. Findings indicate a reduced availability of recruitable neural assemblies not only in the hippocampus but also in the rhinal cortex during memory formation. Network functions related to the timing of neural responses to the stimulus appear to be preserved.

Contains fulltext : 52262.pdf (publisher's version ) (Open Access), In contrast to classical findings that the medial temporal lobe (MTL) specifically underlies long-term memory, previous data suggest that MTL structures may also contribute to working memory (WM). However, the neural mechanisms by which the MTL supports WM have remained unknown. Here, we exploit intracranial EEG to identify WM-specific sustained activity patterns with the highest temporal and spatial resolution currently available in humans. Using a serial Sternberg paradigm, we found a positive shift of the direct current (DC) potential and a long-lasting decrease in MTL gamma-band activity during maintenance of a single item, reflective of a sustained reduction in neural activity. Maintenance of an increasing number of items elicited an incrementally negative shift of the DC potential and an increase in MTL gamma-band activity. In addition, the paradigm was conducted in healthy control subjects using functional magnetic resonance imaging. This confirmed that our results were not caused by pathological processes within the MTL, and that this region was indeed specifically activated during the task. Our results thus provide direct evidence for sustained neural activity patterns during working memory maintenance in the MTL, and show that these patterns depend on WM load.

Contains fulltext : 50124.pdf (publisher's version ) (Closed access), PURPOSE: To determine whether language functional magnetic resonance imaging (fMRI) before epilepsy surgery can be similarly interpreted in patients with greatly different performance levels. METHODS: An fMRI paradigm using a semantic decision task with performance control and a perceptual control task was applied to 226 consecutive patients with drug-resistant localization-related epilepsy during their presurgical evaluations. The volume of activation and lateralization in an inferior frontal and a temporoparietal area was assessed in correlation with individual performance levels. RESULTS: We observed differential effects of task performance on the volume of activation in the inferior frontal and the temporoparietal region of interest, but performance measures did not correlate with the lateralization of activation. CONCLUSIONS: fMRI, as applied here, in patients with a wide range of cognitive abilities, can be interpreted regarding language lateralization in a similar way.

Contains fulltext : 50341.pdf (publisher's version ) (Closed access), Lesion and imaging studies have demonstrated that encoding and retrieval of declarative memories, i.e. consciously accessible events and facts, depend on operations within the rhinal cortex and the hippocampus, two substructures of the medial temporal lobe. Analysis of intracranially recorded EEG in presurgical epilepsy patients revealed that successful memory formation is accompanied within one second by a transient enhancement and later decrease of Rhinal-hippocampal phase synchronization in the gamma range, as well as enhanced connectivity in the low-frequency range. In these studies, words with a high frequency of occurrence were used as stimulus material. Here, we re-examined these effects in another group of 10 presurgical epilepsy patients, this time not only for high-frequency, but also for low-frequency words. For successfully memorized compared to later forgotten high-frequency words we again observed an early phase coupling and later decoupling within the gamma range, as well as enhanced coupling within the sub-gamma range. However, for remembered as compared to forgotten low-frequency words clear synchronization increases were only observed for the delta band, but not for the gamma band. Our data suggest, that broadband Rhinal-hippocampal coupling including the gamma range only occurs, when significant semantic associations are processed within rhinal cortex, as is the case for high-frequency words.

Contains fulltext : 50730.pdf (publisher's version ) (Closed access), It is well recognized that the incidence of atypical language lateralization is increased in patients with focal epilepsy. The hypothesis that shifts in language dominance are particularly likely when epileptic lesions are located in close vicinity to the so-called language-eloquent areas rather than in more remote brain regions such as the hippocampus has been challenged by recent studies. This study was undertaken to assess the effect of lesions in different parts of the left hemisphere, lesions present during language acquisition, on language lateralization. We investigated 84 adult patients with drug-resistant focal epilepsy with structural lesions and 45 healthy control subjects with an established functional MRI language paradigm. Out of the 84 patients 43 had left hippocampal sclerosis, 13 a left frontal lobe lesion and 28 a left temporal-lateral lesion. All these lesions were likely to have been present during the first years of life during language acquisition. To assess the lateralization of cerebral language representation globally as well as regionally, we calculated lateralization indices derived from activations in four regions of interest (i.e. global, inferior frontal, temporo-parietal and remaining prefrontal). Patients with left hippocampal sclerosis showed less left lateralized language representations than all other groups of subjects (P < 0.005). This effect was independent of the factor of region, indicating that language lateralization was generally affected by a left hippocampal sclerosis. Patients with left frontal lobe or temporal-lateral lesions displayed the same left lateralization of language-related activations as the control subjects. Thus, the hippocampus seems to play an important role in the establishment of language dominance. Possible underlying mechanisms are discussed.

Contains fulltext : 51286.pdf (publisher's version ) (Closed access), Asymmetry is a common phenomenon in higher organisms. In humans, the cortical representation of language exhibits a high degree of asymmetry with a prevalence of about 90% of left hemispheric dominance, the underlying mechanisms of which are largely unknown. Another sign that exhibits a form of lateralization is the scalp hair-whorl direction, which is either clockwise or anti-clockwise. The scalp hair-whorl develops from the same germ layer as the nervous system, the ectoderm, between the 10th and 16th week in utero and has been shown to be associated with various neurodevelopmental disorders. Here, we use an established fMRI paradigm to examine the association of a solely biological marker of asymmetry, hair-whorl direction and language lateralization. We show that the mechanism that influences hair-whorl direction and handedness [Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 1651, 269-276.] also affects cerebral language dominance.

Contains fulltext : 50571.pdf (publisher's version ) (Closed access), Cognitive functions not only depend on the localization of neural activity, but also on the precise temporal pattern of activity in neural assemblies. Synchronization of action potential discharges provides a link between large-scale EEG recordings and cellular plasticity mechanisms. Here, we focus on the role of neuronal synchronization in different frequency domains for the subsequent stages of memory formation. Recent EEG studies suggest that synchronized neural activity in the gamma frequency range (around 30-100 Hz) plays a functional role for the formation of declarative long-term memories in humans. On the cellular level, gamma synchronization between hippocampal and parahippocampal regions may induce LTP in the CA3 region of the hippocampus. In order to encode spatial locations or sequences of multiple items and to guarantee a defined temporal order of memory processing, synchronization in the gamma frequency range has to be accompanied by a stimulus-locked phase reset of ongoing theta oscillations. Simultaneous gamma- and theta-dependent plasticity leads to complex learning rules required for realistic declarative memory formation. Subsequently, consolidation of declarative memories may occur via replay of newly acquired patterns in so-called sharp wave-ripple complexes, predominantly during slow-wave sleep. These irregular bursts induce longer lasting forms of synaptic plasticity in output regions of the hippocampus and in the neocortex. In summary, synchronization of neural assemblies in different frequency ranges induces specific forms of cellular plasticity during subsequent stages of memory formation.

Contains fulltext : 50340.pdf (publisher's version ) (Closed access), Compared with waking state attention, volition and semantic processing play a minor role during sleep. Thus, investigating declarative memory formation during sleep may allow us to isolate mnemonic core processes. The most feasible approach to memory formation during sleep is the analysis of dream memories. Lesion and imaging studies have demonstrated that encoding of declarative memories, i.e. consciously accessible events and facts, depends on operations within the rhinal cortex and the hippocampus, two substructures of the medial temporal lobe. Successful memory formation is accompanied by a transient rhinal-hippocampal interaction. Consequently, the ability to memorize dreams may be related to mediotemporal connectivity. Therefore, we recorded EEG during sleep from rhinal and hippocampal depth electrodes implanted in 12 epilepsy patients (eight women, mean age 41.1 +/- 6.4 years). They were awakened during rapid eye movement sleep (REM) and asked to recall their dream. Via coherence analyses we show that rhinal-hippocampal connectivity values are approximately twice as large for patients with good dream recall versus those patients with poor recall. This suggests that rhinal-hippocampal connectivity is a key factor in determining declarative memory formation.

Contains fulltext : 47942.pdf (publisher's version ) (Closed access), 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.

Contains fulltext : 49136.pdf (publisher's version ) (Closed access), We analyzed intracranial electroencephalographic (EEG) recordings from the medial temporal lobes of 12 epilepsy patients during a continuous word recognition paradigm, contrasting trials of correctly recognized repeated words (hits) and correctly identified new words (correct rejections). Using a wavelet-based analysis, we investigated how power changes and phase clustering in different frequency bands contribute to the averaged event-related potentials (ERPs). In addition, we analyzed the actual mean phases of the different oscillations. Our analyses yielded the following results: (1) power changes contributed significantly only to the late components of the ERPs (>400 ms) (2) earlier ERP components were produced by a stimulus-related broad-band phase and amplitude reset of ongoing oscillatory activity about 190 ms after stimulus onset that involved not only the theta band, but also covered alpha and lower beta band frequencies (3) phase and amplitude reset occurred during an epoch of increased phase entrainment over time that lasted for about two oscillation periods for all involved frequencies and was more pronounced for correct rejections than for hits. The broad-band phase and amplitude reset was observed for both hits and correct rejections, and therefore, did not appear to support a specific cognitive function, but rather to act as a general facilitating factor for the processes involved in this memory task. Further analyses of synchronization between oscillations and power changes in different frequency bands revealed a task-dependent modulation of gamma activity by the entrained theta cycle, a mechanism potentially related to memory encoding and retrieval in the rhinal cortex and hippocampus, respectively.

Contains fulltext : 47737.pdf (publisher's version ) (Closed access), Evidence for a response-control-related kind of declarative memory during deep propofol anesthesia has recently been reported. Connectivity within the mediotemporal lobe (MTL), and in particular rhinal-hippocampal synchronization within the gamma band, has been shown to be crucial for declarative memory formation. Thus, we analyzed EEG recordings obtained from the scalp, as well as directly from within the hippocampus and from the anterior parahippocampal gyrus, which is covered by rhinal cortex, in patients with unilateral temporal lobe epilepsy during propofol anesthesia, which preceded electrode explantation. For the gamma band a power decrease starting with induction of anesthesia was observed at scalp position Cz, but a power increase was detected at MTL locations. In contrast to prior results for sleep recordings, rhinal-hippocampal coherence did not decrease within the gamma band at deeper levels of anesthesia. These findings may represent an indirect electrophysiological correlate of partially intact declarative memory formation during deep propofol sedation. Furthermore, we investigated how well the plasma propofol level, as well as different stages of anesthesia including the burst suppression phase, could be monitored by different spectral as well as by nonlinear EEG measures. We observed that conventional spectral power measures, most prominently those recorded from mediotemporal locations, are most closely correlated with the plasma propofol level, whereas different stages of anesthesia can be distinguished best by nonconventional spectral as well as nonlinear measures.

Contains fulltext : 47978.pdf (publisher's version ) (Closed access), PURPOSE: The determination of language dominance as part of the presurgical workup of patients with pharmacoresistant epilepsies has experienced fundamental changes. With the introduction of noninvasive functional magnetic resonance imaging (fMRI), the number of patients receiving intracarotid amobarbital procedures (IAPs) for assessment of language dominance has decreased considerably. However, recent studies show that because of methodologic limitations of fMRI, IAP remains an important tool for language lateralization. The current study examines whether unilateral instead of bilateral IAP is an adequate way to apply IAP with reduced invasiveness. METHODS: We retrospectively examine the predictive value of unilateral IAP for the results of bilateral IAP based on a sample of 75 patients with various types of language dominance. Target parameters are the prediction of the language-dominant hemisphere and the identification of patients with atypical language dominance. For language assessment based on unilateral IAP, we introduce the measure hemispheric language capacity (HLC). RESULTS: Unilateral IAP performed on the side of intended surgery quantifies language capacity contralateral to the intended surgery. It detects atypical (bilateral or right) language dominance in the majority of patients. Experience with a separate series of 107 patients requiring presurgical language lateralization shows that in >80%, bilateral IAPs are redundant. CONCLUSIONS: Unilateral IAP is principally sufficient for language lateralization in the presurgical evaluation of patients with pharmacoresistant epilepsies. Necessity of bilateral IAP is restricted to few indications (e.g., callosotomy). In times of noninvasive language lateralization, we propose unilateral IAP as the method of choice for the verification of doubtful (bilateral) fMRI activation patterns.

Contains fulltext : 49135.pdf (Publisher’s version ) (Closed access), 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.

Contains fulltext : 58754.pdf (publisher's version ) (Open Access), 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 s

Contains fulltext : 57192.pdf (publisher's version ) (Closed access), Using event-related fMRI, we scanned young healthy subjects while they memorized real-world photographs and subsequently tried to recognize them within a series of new photographs. We confirmed that activity in the medial temporal lobe (MTL) and inferior prefrontal cortex correlates with declarative memory formation as defined by the subsequent memory effect, stronger responses to subsequently remembered than forgotten items. Additionally, we confirmed that activity in specific regions within the parietal lobe, anterior prefrontal cortex, anterior cingulate and cerebellum correlate with recognition memory as measured by the conventional old/new effect, stronger responses for recognized old items (hits) than correctly identified new items (correct rejections). To obtain a purer measure of recognition success, we introduced two recognition effects by comparing brain responses to hits and old items misclassified as new (misses). The positive recognition effect (hits > misses) revealed prefrontal, parietal and cerebellar contributions to recognition, and in line with electrophysiological findings, the negative recognition effect (hits < misses) revealed an anterior medial temporal contribution. Finally, by inclusive masking, we identified temporal and cerebellar brain areas that support both declarative memory formation and retrieval. For matching operations during recognition, these areas may re-use representations formed and stored locally during encoding.

Contains fulltext : 58755.pdf (publisher's version ) (Closed access)

Contains fulltext : 59134.pdf (publisher's version ) (Closed access), Our event-related functional MRI (efMRI) study investigates whether visual advance information (AI) affects rather perceptual or central response-related processing areas. Twelve subjects were required to make a go/no-go decision to a conjunction of a specific color and motion direction. The stimuli were preceded by a cue, providing 100% valid advance information about motion direction. Partial and full advance information (PAI and FAI) predicted possible targets, respectively, certain nontargets, neutral cues (NAI) gave no prediction. The time between cue and stimulus (stimulus onset asynchrony, SOA) was varied. A response benefit was found after PAI as compared with NAI. The benefit was small with a short SOA (150 ms), increased with intermediate SOA (450 ms) and sustained with long SOA (750 ms). Perceptual and central processing areas were more active with increasing SOA, but only central response-related processing areas were selectively modulated by cue information. In particular, supplementary motor area and bilateral inferior parietal lobe were more active with PAI than with NAI. If comparing NAI with FAI, more errors were made and activity was larger in central processing areas. Our results suggest that, depending on the processing time, cues providing perceptual information modulate central response-related processes.

Contains fulltext : 59327.pdf (publisher's version ) (Closed access)

Item does not contain fulltext, BACKGROUND: fMRI is becoming a standard tool for the presurgical lateralization and mapping of brain areas involved in language processing. However, its within-subject reproducibility has yet to be fully explored. OBJECTIVE: To evaluate within-test and test-retest reliability of language fMRI in consecutive patients undergoing evaluation for epilepsy surgery. METHODS: Thirty-four unselected patients were investigated once (within-test reliability) and 12 patients twice (test-retest reliability). The imaging series consisted of an alternating 25-second synonym judgment condition with a 25-second letter-matching condition repeated 15 times. Reproducibility of activation maps of the first and second half of session 1 or activation maps of sessions 1 and 2 was evaluated by comparing one global and three regional lateralization indexes (Broca's area, remaining prefrontal cortex, temporoparietal area) and on a voxel-by-voxel basis (intraclass correlation coefficient, percentage overlap, correlation of t-values). RESULTS: Global and regional language lateralization was achieved with high reliability within and across sessions. Reproducibility was evenly distributed across both hemispheres but not within each hemisphere. Frontal activations were more reliable than temporoparietal ones. Depending on the statistical threshold chosen, the voxel-by-voxel analysis revealed a mean overlap of activations derived from the first and second investigation of up to 48.9%. CONCLUSION: Language fMRI proved sufficiently reliable for the determination of global and regional lateralization of language representation in individual unselected patients with epilepsy.

Item does not contain fulltext, Today, much evidence exists that sensory feature binding is accomplished by phase synchronization of induced neuronal gamma activity (30-80 Hz). Recent studies furthermore suggest that phase synchronization of induced gamma activity may represent a general mechanism enabling transient associations of neural assemblies and thus may play a central role in cortical information processing. Here, we describe findings indicating that synchronized gamma activity is moreover specifically involved in selective attention. While feature binding appears to depend primarily on induced gamma synchronization, attentional processes seem to involve both induced and evoked gamma oscillations. Yet it is still an open question, as to which top-down and bottom-up processes are associated with attentional modulation of gamma activity. A possible mechanism to project influences from attentional control structures to areas concerned with stimulus representation and vice versa, may be neuronal synchronization and the resulting firing rate changes of coincidence-detecting neurons in target areas.

Item does not contain fulltext, BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the second of two paired clicks but not in schizophrenia patients. To identify its neural correlates, we recorded electrical traces of sensory gating directly from the human hippocampus and neocortex. METHODS: Intracranial evoked potentials were recorded using hippocampal depth electrodes and subdural strip and grid electrodes in 32 epilepsy patients undergoing invasive presurgical evaluation. RESULTS: We found evidence of sensory gating only in the hippocampus, the temporo-parietal region (Brodmann's areas 22 and 2), and the prefrontal cortex (Brodmann's areas 6 and 24); however, whereas neocortical habituating responses to paired clicks were peaking around 50 msec, responses within the hippocampus proper had a latency of about 250 msec. CONCLUSIONS: Consistent with data from animal studies, our findings show that the hippocampus proper contributes to sensory gating, albeit during a time window following neocortical habituation processes. Thus, sensory gating may be a multistep process, with an early phase subserved by the temporo-parietal and prefrontal cortex and a later phase mediated by the hippocampus.

Item does not contain fulltext, Transient phase synchronization of EEG oscillations was reported to be essential for conscious brain activity. However, it has been argued that EEG synchrony is not the only necessary factor, but at least must be accompanied by a sufficient complexity of brain dynamics. Here, we propose that, besides complexity, EEG chaoticity may be another necessary condition for conscious brain functioning.

Item does not contain fulltext, The human medial temporal lobe (MTL) system mediates memories that can be consciously recollected. However, the specific natures of the individual contributions of its various subregions to conscious memory processes remain equivocal. Here we show a functional dissociation between the hippocampus proper and the parahippocampal region in conscious and unconscious memory as revealed by invasive recordings of limbic event-related brain potentials recorded during explicit and implicit word recognition: Only hippocampal and not parahippocampal neural activity exhibits a sensitivity to the implicit versus explicit nature of the recognition memory task. Moreover, only within the hippocampus proper do the neural responses to repeated words differ not only from those to new words but also from each other as a function of recognition success. By contrast parahippocampal (rhinal) responses are sensitive to repetition independent of conscious recognition. These findings thus demonstrate that it is the hippocampus proper among the MTL structures that is specifically engaged during conscious memory processes.

Contains fulltext : 135771.pdf (publisher's version ) (Open Access), In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly executed by one hemisphere. To search for neural correlates of hormonally mediated neural plasticity in humans, we thus conducted a functional magnetic resonance imaging study measuring brain activity related to a semantic decision task in the language domain. This was contrasted with a letter-matching task in the perceptual domain, in which we expected no steroid hormone-mediated effect. We investigated 12 young healthy women in a counterbalanced repeated-measure design during low-steroid menstruation and high-steroid midluteal phase. Steroid serum levels correlated with the volume and lateralization of particular brain activations related to the semantic task but not with brain activity related to the perceptual task. More specifically, bilateral superior temporal recruitment correlated positively with progesterone and medial superior frontal recruitment with both progesterone and estradiol serum levels, whereas activations in inferior and middle frontal cortex were unaffected by steroid levels. In contrast to these specific interactions, testosterone levels correlated nonselectively with overall activation levels by neural and/or vascular factor(s). In conclusion, our data demonstrate steroid hormone responsivity in the adult human brain by revealing neural plasticity in the language domain, which appears hormone, task, and region specific.

Item does not contain fulltext, The deficiency of declarative memory compared with waking state is an often overlooked characteristic of sleep. Here, we investigated whether rhinal-hippocampal coherence, an electrophysiological correlate of declarative memory formation, is significantly altered during sleep as compared with waking state. For this purpose, we analysed recordings of intracranial EEG activity during sleep obtained directly from within the medial temporal lobe in patients with unilateral temporal lobe epilepsy. We found a general reduction of rhinal-hippocampal EEG coherence during sleep compared with waking state, which was most pronounced within the upper gamma bands (average decrease up to 56%). The observed coherence changes clearly differ from findings reported for surface EEG data and thus appear to be specific for the medial temporal lobe. The decrease of rhinal-hippocampal EEG coherence from waking state towards sleep may yield an electrophysiological explanation for the sleep-related deficiency of declarative memory.

Item does not contain fulltext, Focal brain lesions such as cortical dysplasia and glioneural tumors generate epileptic activity and thus may be synaptically connected with normal cortex. To test this hypothesis, we compared event-related potentials recorded directly from the medial temporal lobe (MTL) and a dysplastic lesion in eight patients with intractable temporal lobe epilepsy. The P3 component, related to visual target detection, showed different peak latencies in four patients and a larger intralesional amplitude compared to established anterior-MTL-generators in two patients. Semantic processing was identified by the N400 component and showed a different latency in four patients and larger intralesional amplitudes in two patients. These results are compatible with the hypothesis that cortical lesions interact with synaptic pathways related to cognitive functions such as visual target detection, and verbal processing.

Item does not contain fulltext, PURPOSE: To examine interictal EEG abnormalities in patients with psychogenic nonepileptic seizures (PNESs). METHODS: (a) Retrospective study of EEG reports of 187 consecutive patients with PNES seen at the Department of Epileptology, Bonn, Germany; (b) Blinded, multirater comparison of EEGs of all PNES patients with no other clinically recognizable cause of EEG disturbance (n = 50) and healthy controls (n = 50). RESULTS: Of 187 consecutive patients with PNESs, 57 patients had PNESs and epilepsy (PNES+E), and 130 patients, PNESs alone. The diagnosis of additional epilepsy was based on ictal (video-) EEG or on the critical assessment of all clinical data by an experienced epileptologist. Retrospective review of all available EEG reports showed that 92.9% of patients in the PNES+E and 53.8% in the PNES-only group had one or more abnormal EEGs (median number of EEGs per patient, three; range, one to 42). In the PNES-only group, EEG changes were nonspecific in 42.3% of patients. Only 50 of 130 patients with PNESs alone had no other clinically recognizable cause of EEG disturbance and entered the controlled study. In this study, 18% of patients and 10% of controls had abnormal EEGs. The frequency of epileptiform EEG changes was similar to that in previous population studies in both groups (2.0%). CONCLUSIONS: PNESs often occur in patients with organic brain disease. Even in patients with PNESs alone and no clinically recognizable cause of EEG disturbance, nonspecific abnormalities are found 1.8 times as often as in healthy controls. Interictal EEG changes are common in patients with PNESs and, in isolation, should not be interpreted as evidence of epilepsy.

Item does not contain fulltext, The attentional blink (AB) is an impairment of attention, which occurs when subjects have to report a target stimulus (T2) following a previous target (T1) with a short delay (up to 600 ms). Theories explaining the AB assume that processing of T2 is more vulnerable to decay or substitution, as long as attention is allocated to T1. Existing models of the AB, however, do not account for the fact that T2 detection accuracy reaches the minimum when T2 is presented after about 300 ms and not immediately following T1. Therefore, a new model is suggested, which is based on chronometrical considerations together with recent neurophysiological findings concerning the relation between the P3 event-related potential and the AB, the interaction between P3 and gamma oscillations, and the significance of the early evoked gamma band response. We hypothesize that suppression of the early gamma response to T2, accompanying the P3 related to T1, causes the AB.

Item does not contain fulltext, OBJECTIVE: To assess whether surgery to reduce or control epileptic seizures is safe and effective in patients known to have additional psychogenic seizures. DESIGN: We reviewed our computerized database of 1342 patients examined for epilepsy surgery and identified 13 patients with both epileptic and psychogenic seizures on whom postoperative outcome data were available. Data were gathered from the patients' records. Mean postoperative follow-up was 56 months. RESULTS: Epilepsy surgery led to clinically relevant improvements in 11 of 13 patients. Seven patients became free of epileptic and psychogenic seizures, 2 patients became free of epileptic seizures but continued to have infrequent psychogenic seizures, 1 patient reported more than an 80% improvement in epileptic seizure frequency and an abolishment of psychogenic attacks, and in 1 patient nondisabling epileptic seizures persisted at lower frequency but psychogenic seizures stopped. In 2 of 13 patients, epilepsy surgery failed to produce notable improvements. Although 1 patient became free of epileptic attacks and the other had fewer than 3 epileptic seizures per year, the severity or frequency of psychogenic seizures and pseudo-status epilepticus increased postoperatively. One of these patients had a preoperative diagnosis of somatization disorder; in the other, pathological illness behavior had been noted. CONCLUSION: A diagnosis of additional psychogenic seizures should not be considered an absolute contraindication to epilepsy surgery, although patients should undergo careful preoperative psychiatric evaluation.

Item does not contain fulltext, OBJECTIVES: Patients with intractable epilepsy may benefit from epilepsy surgery especially if they have a radiologically demonstrable cerebral lesion. Dedicated magnetic resonance imaging (MRI) protocols as performed at epilepsy surgery centres can detect epileptogenic abnormalities with great sensitivity and specificity. However, many patients with epilepsy are investigated with standard MRI sequences by radiologist outside epilepsy centres ("non-experts"). This study was undertaken to compare standard MRI and epilepsy specific MRI findings in patients with focal epilepsy. METHODS: Comparison of results of standard MRI reported by "non-expert" radiologists, standard MRI evaluated by epilepsy "expert" radiologists, and epilepsy specific MRI read by "expert" radiologists in 123 consecutive patients undergoing epilepsy surgery evaluation between 1996 and 1999. Validation of radiological findings by correlation with postoperative histological examination. RESULTS: Sensitivity of "non-expert" reports of standard MRI reports for focal lesions was 39%, of "expert" reports of standard MRI 50%, and of epilepsy dedicated MRI 91%. Dedicated MRI showed focal lesions in 85% of patients with "non-lesional" standard MRI. The technical quality of standard MRI improved during the study period, but "non-expert" reporting did not. In particular, hippocampal sclerosis was missed in 86% of cases. Neuropathological diagnoses (n=90) were predicted correctly in 22% of "non-expert" standard MRI reports but by 89% of dedicated MRI reports. CONCLUSIONS: Standard MRI failed to detect 57% of focal epileptogenic lesions. Patients without MRI lesion are less likely to be considered candidates for epilepsy surgery. Patients with refractory epilepsy should be referred to an MRI unit with epileptological experience at an early point.

Item does not contain fulltext, This study investigated how different spectral and nonlinear EEG measures covaried with alpha power during auditory alpha biofeedback training, performed by 13 healthy subjects. We found a significant positive correlation of alpha power with the largest Lyapunov-exponent, pointing to an increased dynamical instability of the EEG accompanying alpha enhancement. Alpha power amplification, moreover, was significantly correlated with a decrease of spectral entropy within the alpha range. This outcome reflects a sharpening of the alpha peak during biofeedback training. The fact that the sharpening effect clearly preceded the increase of alpha amplitude could be exploited in future biofeedback settings.

Item does not contain fulltext, Delay to diagnosis was studied in 313 consecutive patients with psychogenic nonepileptic seizures (PNES). On average, patients with PNES were diagnosed 7.2 years after manifestation (SD 9.3 years). Younger age, interictal epileptiform potentials in the EEG, and anticonvulsant treatment were associated with longer delays. Other patient factors did not explain the great variability of the time to diagnosis, suggesting that physician factors contributed to delays.

Item does not contain fulltext, Markers of brain abnormalities in patients with psychogenic nonepileptic seizures (PNES) were studied to explore whether physical brain disorder is associated with an increased risk of PNES. Evidence of epileptiform EEG changes, MRI abnormalities, and neuropsychological (NPS) deficits was obtained from the records of 329 consecutive patients in whom the diagnosis of PNES was established at our center between 1991 and 2001. Two hundred six patients had PNES alone, and 123 PNES and epilepsy (PNES+E). In the PNES-only group, at least one marker of brain disorder was detected in 22.3% of patients (epileptiform potentials in 8.7%, MRI changes in 9.7%, NPS deficits in 9.7%). The actual prevalence of abnormalities is likely to be higher because 54.9% of the patients with only psychogenic seizures did not undergo MRI or neuropsychological testing. Evidence of brain abnormality was found more frequently in the PNES+E group (epileptiform potentials in 70.7%, MRI changes in 60.2%, NPS deficits in 52.8%). Although markers of brain abnormality were detected much less commonly in the PNES than in the PNES+E group, they were still found in a substantial proportion of patients with PNES alone. This suggests that physical brain disease plays a role in the development of PNES. Markers of physical abnormality were not more common in the right hemisphere.

Item does not contain fulltext, Spike-Wave Discharges (SWDs) occur spontaneously in the EEG of WAG/Rij rats. These SWDs are a model for human absence seizures. In order to examine whether non-linear analysis methods can contribute to the analysis of SWDs, we estimated the correlation dimension of the SWDs and compared the value to that of the phase-randomized signals

Item does not contain fulltext, To find a new measure from the EEG that quantifies the effects of anesthetics during surgery, the correlation dimension (CD) of the EEG of eight rats was estimated. To get informed about the anesthetic state, the noxious induced withdrawal reflex (NIWR) was measured, i.e. the force elicited by transcutaneous electrical stimulation of the hind paw. The algorithm of Grassberger and Procaccia (1983) to compute the CD was slightly modified and labeled as "dimensional complexity" (DC). The DC was estimated by applying a fit procedure to find the scaling region in the correlation integral. Experiments were performed under propofol infusion (30 à 40 mg.kg-1.h-1), with repeated bolus injections (3 mg) to induce periods of more profound anesthesia. The DC was compared to the Spectral Edge Frequency (SEF), a linear measure extracted from the power spectrum. The DC and SEF were correlated with the NIWR responses. The DC showed higher and more consistent correlations with the NIWR than the SEF. Correlation coefficients of NIWR and DC mainly varied between 0.6 and 0.8. Conclusion: New parameters from the field of non-linear dynamics can be an aiding tool in detecting effectual changes induced by anesthetics.