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Contains fulltext : 122905.pdf (publisher's version ) (Open Access)

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 : 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 : 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.