Coupling of gamma band activity to sleep spindle oscillations - a combined EEG/MEG study.

Sleep spindles are crucial to memory consolidation. Cortical gamma oscillations (30-100 Hz) are considered to reflect processing of memory in local cortical networks. The temporal and regulatory relationship between spindles and gamma activity might therefore provide clues into how sleep strengthens cortical memory representations. Here, combining EEG with MEG recordings during sleep in healthy humans (n = 12), we investigated the temporal relationships of cortical gamma band activity, always measured by MEG, during fast (12-16 Hz) and slow (8-12 Hz) sleep spindles detected in the EEG or MEG. Time-frequency distributions did not show a consistent coupling of gamma to the spindle oscillation, although activity in the low gamma (30-40 Hz) and neighboring beta range (<30 Hz) was generally increased during spindles. However, more fine-grained analyses of cross-frequency interactions revealed that both low and high gamma power (30-100 Hz) was coupled to the phase of slow and fast EEG spindles, importantly, with this coupling at a fixed phase only for the oscillations within an individual spindle, but with variable phase across spindles. We did not observe any coupling of gamma activity for spindles detected solely in the MEG and not in parallel EEG recordings, raising the possibility that these are more local spindles of different quality. Similar to fast spindle activity, low gamma band power followed a ~0.025 Hz infraslow rhythm during sleep whose frequency, however, was significantly faster than that of spindle activity. Our findings suggest a general function of fast and slow spindles that by spanning larger cortical networks might serve to synchronize gamma band activity occurring in more local but distributed networks. Thereby, spindles might help linking local memory processing between distributed networks.

Oscillatory MEG gamma band activity dissociates perceptual and conceptual aspects of visual object processing: a combined repetition/conceptual priming study.

We used a combined repetition/conceptual priming task to investigate attenuations of induced gamma-band activity (iGBA) due to prior experience. We hypothesized that distinguishable iGBA suppression effects can be related to the processing of (a) perceptual aspects, and (b) conceptual aspects of cortical object representations. Participants were asked to perform a semantic classification task with pictures of real world objects and their semantically corresponding words, using a design that isolated distinct levels of the neural suppression effect. By means of volumetric source analysis we located stimulus domain-specific iGBA repetition suppression effects (60-90 Hz) in temporal, parietal, and occipital areas of the human cortex. In contrast, domain-unspecific iGBA repetition suppression, corresponding to conceptual priming, was restricted to left temporal brain regions. We propose that the selective involvement of left temporal areas points to the activation of conceptual representations, whereas more posterior temporal, parietal, and occipital areas probably reflect perceptual aspects of higher-order visual object processing.

Evaluation of Accuracy and Reliability of a Mobile Screening Audiometer in Normal Hearing Adults.

Quantifying hearing thresholds via mobile self-assessment audiometric applications has been demonstrated repeatedly with heterogenous results regarding the accuracy. One important limitation of several of these applications has been the lack of appropriate calibration of their core technical components (sound generator and headphones). The current study aimed at evaluating accuracy and reliability of a calibrated application (app) for pure-tone screening audiometry by self-assessment on a tablet computer: Audimatch app installed on Apple iPad 4 in combination with Sennheiser HDA-280 headphones. In a repeated-measures design audiometric thresholds collected by the app were compared to those obtained by standardized automated audiometry and additionally test-retest reliability was evaluated. Sixty-eight participants aged 19-65 years with normal hearing were tested in a sound-attenuating booth. An equivalence test revealed highly similar hearing thresholds for the app compared with standardized automated audiometry. A test-retest reliability analysis within each method showed a high correlation coefficient for the app (Spearman rank correlation: rho = 0.829) and for the automated audiometer (rho = 0.792). The results imply that the self-assessment of audiometric thresholds via a calibrated mobile device represents a valid and reliable alternative for stationary assessment of hearing loss thresholds, supporting the potential usability within the area of occupational health care.

Mid-Latency Auditory Evoked Potentials Differentially Predict Sedation and Drug Level Under Opioid and Hypnotic Agents.

Background: Auditory-evoked brain potentials (AEPs) are widely used to assess depth of the sedative component of general anesthesia. Depth of sedation as induced by hypnotic drugs (e.g., propofol) is characterized by a gradual decline of mid-latency cortical AEPs (10-50 ms). Using the decline of mid-latency AEPs as a reliable index for sedation requires its robustness against confounding pharmaceutical influences, e.g., analgesic opioids such as remifentanil. Critically, in this context the following two questions remained unresolved so far: First, it is unclear whether opioids directly affect mid-latency AEPs. Second, high doses of opioids decrease arousal, but it is unknown whether opioid-induced sedation is reflected by the diminution of mid-latency AEPs. We hypothesized that opioids affect mid-latency AEPs and that these effects rely on different mechanisms compared to hypnotic agents. Methods: To address both questions, we performed a series of experiments under the participation of healthy human volunteers. We measured AEPs and quantified participants' sedation state by a standardized rating scale during stepwise increase of different pharmaceutical agents (remifentanil, propofol or placebo). Results: Our results revealed a decline of mid-latency AEPs during remifentanil medication. This decrease was predicted by drug dose, rather than sedation level. In contrast, attenuation of the mid-latency AEPs during propofol was predicted by sedation level and was not related to hypnotic drug dose. We did not find any drug-induced changes of brainstem AEPs (1-10 ms). Conclusion: As remifentanil reduced mid-latency AEPs without inducing strong sedation levels, a decrease of this evoked brain component does not constitute an unequivocal index for the depth of sedation. These results challenge the use of mid-latency AEPs as a reliable marker of depth of the sedative component of anesthesia if hypnotic drugs are combined with opioids.

Neuronal mechanisms of repetition priming in occipitotemporal cortex: spatiotemporal evidence from functional magnetic resonance imaging and electroencephalography.

Repeated stimulus presentation (priming) is generally associated with a reduction in neuronal firing, macroscopically mirrored by a decrease in oscillatory electrophysiological markers as well as reduced hemodynamic responses. However, these repetition effects seem to be dependent on stimulus familiarity. We investigate the spatiotemporal correlates of repetition priming in cortical word-recognition networks and their modulation by stimulus familiarity (i.e., words vs pseudowords). Event-related functional magnetic resonance imaging results show reduced activation for repeated words in occipitotemporal cortical regions. Electroencephalogram recordings reveal a significant reduction of induced gamma-band responses (GBRs) between 200 and 350 ms after stimulus onset, accompanied by a decrease in phase synchrony between electrode positions. Pseudoword repetition, in contrast, leads to an activation increase in the same areas, to increased GBRs, and to an increased phase coupling. This spatiotemporal repetition by stimulus type interaction suggests that qualitatively distinct mechanisms are recruited during repetition priming of familiar and unfamiliar stimuli. Repetition of familiar stimuli leads to a "sharpening" of extrastriate object representations, whereas the repetition of unfamiliar stimuli results in the "formation" of a novel cortical network by means of synchronized oscillatory activity. In addition to isolating these mechanisms, the present study provides the first evidence for a possible link between induced electrophysiological and hemodynamic measures of brain activity.

Lexical memory search during N400: cortical couplings in auditory comprehension.

In this study, we applied partial-directed EEG-coherence analysis to assess regional changes in neuronal couplings and information transfer related to semantic processing. We tested the hypothesis whether (and which) processing differences between spoken words and pseudowords are reflected by changes in cortical networks within the time window of a specific event related potential (ERP) component, the N400. Fourteen native speaking German subjects performed a lexical decision paradigm, while being confronted sequentially with two-syllabic nouns and phonologically legal pseudowords. Using ERP analysis, we defined the time window of the N400 effect, known to reflect semantic processing, and, subsequently, we examined the coupling differences. Lexico-semantic memory search appears to be subserved by a network between temporal, parietal and frontal areas, particularly restricted to the left hemisphere.

Cortical hypersynchrony predicts breakdown of sensory processing during loss of consciousness.

Intrinsic cortical dynamics modulates the processing of sensory information and therefore may be critical for conscious perception. We tested this hypothesis by electroencephalographic recording of ongoing and stimulus-related brain activity during stepwise drug-induced loss of consciousness in healthy human volunteers. We found that progressive loss of consciousness was tightly linked to the emergence of a hypersynchronous cortical state in the alpha frequency range (8-14 Hz). This drug-induced ongoing alpha activity was widely distributed across the frontal cortex. Stimulus-related responses to median nerve stimulation consisted of early and midlatency response components in primary somatosensory cortex (S1) and a late component also involving temporal and parietal regions. During progressive sedation, the early response was maintained, whereas the midlatency and late responses were reduced and eventually vanished. The antagonistic relation between the late sensory response and ongoing alpha activity held for constant drug levels on the single-trial level. Specifically, the late response component was negatively correlated with the power and long-range coherence of ongoing frontal alpha activity. Our results suggest blocking of intracortical communication by hypersynchronous ongoing activity as a key mechanism for the loss of consciousness.

Directed cortical information flow during human object recognition: analyzing induced EEG gamma-band responses in brain's source space.

The increase of induced gamma-band responses (iGBRs; oscillations >30 Hz) elicited by familiar (meaningful) objects is well established in electroencephalogram (EEG) research. This frequency-specific change at distinct locations is thought to indicate the dynamic formation of local neuronal assemblies during the activation of cortical object representations. As analytically power increase is just a property of a single location, phase-synchrony was introduced to investigate the formation of large-scale networks between spatially distant brain sites. However, classical phase-synchrony reveals symmetric, pair-wise correlations and is not suited to uncover the directionality of interactions. Here, we investigated the neural mechanism of visual object processing by means of directional coupling analysis going beyond recording sites, but rather assessing the directionality of oscillatory interactions between brain areas directly. This study is the first to identify the directionality of oscillatory brain interactions in source space during human object recognition and suggests that familiar, but not unfamiliar, objects engage widespread reciprocal information flow. Directionality of cortical information-flow was calculated based upon an established Granger-Causality coupling-measure (partial-directed coherence; PDC) using autoregressive modeling. To enable comparison with previous coupling studies lacking directional information, phase-locking analysis was applied, using wavelet-based signal decompositions. Both, autoregressive modeling and wavelet analysis, revealed an augmentation of iGBRs during the presentation of familiar objects relative to unfamiliar controls, which was localized to inferior-temporal, superior-parietal and frontal brain areas by means of distributed source reconstruction. The multivariate analysis of PDC evaluated each possible direction of brain interaction and revealed widespread reciprocal information-transfer during familiar object processing. In contrast, unfamiliar objects entailed a sparse number of only unidirectional connections converging to parietal areas. Considering the directionality of brain interactions, the current results might indicate that successful activation of object representations is realized through reciprocal (feed-forward and feed-backward) information-transfer of oscillatory connections between distant, functionally specific brain areas.

Semantic memory retrieval: cortical couplings in object recognition in the N400 window.

To characterize the regional changes in neuronal couplings and information transfer related to semantic aspects of object recognition in humans we used partial-directed EEG-coherence analysis (PDC). We examined the differences of processing recognizable and unrecognizable pictures as reflected by changes in cortical networks within the time-window of a determined event-related potential (ERP) component, namely the N400. Fourteen participants performed an image recognition task, while sequentially confronted with pictures of recognizable and unrecognizable objects. The time-window of N400 as indicative of object semantics was defined from the ERP. Differences of PDC in the beta-band between these tasks were represented topographically as patterns of electrical couplings, possibly indicating changing degrees of functional cooperation between brain areas. Successful memory retrieval of picture meaning appears to be supported by networks comprising left temporal and parietal regions and bilateral frontal brain areas.