A key role of the hippocampal P3 in the attentional blink.

The attentional blink (AB) refers to an impaired identification of target stimuli (T2), which are presented shortly after a prior target (T1) within a rapid serial visual presentation (RSVP) stream. It has been suggested that the AB is related to a failed transfer of T2 into working memory and that hippocampus (HC) and entorhinal cortex (EC) are regions crucial for this transfer. Since the event-related P3 component has been linked to inhibitory processes, we hypothesized that the hippocampal P3 elicited by T1 may impact on T2 processing within HC and EC. To test this hypothesis, we reanalyzed microwire data from 21 patients, who performed an RSVP task, during intracranial recordings for epilepsy surgery assessment (Reber et al., 2017). We identified T1-related hippocampal P3 components in the local field potentials (LFPs) and determined the temporal onset of T2 processing in HC/EC based on single-unit response onset activity. In accordance with our hypothesis, T1-related single-trial P3 amplitudes at the onset of T2 processing were clearly larger for unseen compared to seen T2-stimuli. Moreover, increased T1-related single-trial P3 peak latencies were found for T2[unseen] versus T2[seen] trials in case of lags 1 to 3, which was in line with our predictions. In conclusion, our findings support inhibition models of the AB and indicate that the hippocampal P3 elicited by T1 plays a central role in the AB.

What is mind blanking: A conceptual clarification.

The investigation of so-called mind blanking has been recently established in the context of mind wandering research. Unfortunately, the description of the term 'mind blanking' and its experimental assessment are often ambiguous. More specifically, two distinct phenomena have been conceptually blended and both characterized using the term 'mind blanking' in experimental studies: the absence of task-focus and thought, versus complete lack of conscious experiences. At least in part, this confusion can be traced back to the writings of William James, who referred to 'thought' as a superordinate term to address different conscious experiences. Applying the technique of so-called experience sampling, experimental studies, up to now, probably assessed the absence of thought, but not a complete lack of conscious experiences. There is no clear evidence yet for instances of the latter phenomenon occurring during non-pathological waking state. Possibly, such evidence could be revealed in the future using a conceptually more refined experience sampling.

Reduced past-oriented mind wandering in left compared to right medial temporal lobe epilepsy.

Mind wandering refers to a shift of attention away from a task at hand to task-unrelated thoughts. Several groups have shown increased activation of the left medial temporal lobe (MTL) before and during spontaneous thoughts suggesting that the left MTL may play a crucial role in mind wandering. Due to its relevance for long-term memory, we further hypothesized that the left MTL is particularly involved in mind wandering towards the past. Accordingly, we predicted a reduced propensity to mind wander and less past-oriented mind wandering in patients with left MTL epilepsies. To this end, we experimentally investigated mind wandering in 89 in-patients undergoing diagnostic evaluation of their putative epileptic disorder. Patients performed a sustained attention to response task with embedded experience sampling probes aiming to assess occurrence, meta-awareness and temporal orientation (past/present/future) of mind-wandering episodes. We did not find significant differences in the propensity to mind wander between patient subgroups. However, the left MTL epilepsy subgroup showed significantly reduced past-oriented mind wandering compared to right MTL epilepsies, as well as a trend towards diminished past-oriented mind wandering compared to idiopathic epilepsies. Possibly due to compensatory mechanisms, the right MTL epilepsy subgroup showed significantly increased past-oriented mind wandering compared to extratemporal epilepsies and patients with syncopes. These behavioural findings point to a rejection of the hypothesis that the amount of time engaged in mind wandering crucially depends on the left MTL. However, our data do support the idea that the left MTL is particularly involved in mind wandering towards the past.

No evidence for spontaneous cross-frequency phase-phase coupling in the human hippocampus.

Cross-frequency phase-phase coupling (PPC) has been suggested to play a role in cognitive processing and, in particular, in memory consolidation during sleep. Controversial results have been reported regarding the existence of spontaneous phase-phase coupling in the hippocampus. Here, we investigated this phenomenon in intracranial EEG recordings from the human hippocampus acquired during waking state and different sleep stages. We estimated the strength of interactions between different pairs of frequency bands and evaluated the statistical significance of findings using surrogates that build on different null hypotheses. Indications for spontaneous phase-phase coupling were only observed when testing with less rigorous surrogates. When requiring that all four surrogate tests be passed, however, there were no significant indications for phase-phase coupling. In conclusion, we did not detect evidence for spontaneous cross-frequency phase-phase coupling in the human hippocampus.

Heterogeneous profiles of coupled sleep oscillations in human hippocampus.

Cross-frequency coupling of sleep oscillations is thought to mediate memory consolidation. While the hippocampus is deemed central to this process, detailed knowledge of which oscillatory rhythms interact in the sleeping human hippocampus is lacking. Combining intracranial hippocampal and non-invasive electroencephalography from twelve neurosurgical patients, we characterized spectral power and coupling during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Hippocampal coupling was extensive, with the majority of channels expressing spectral interactions. NREM consistently showed delta-ripple coupling, but ripples were also modulated by slow oscillations (SOs) and sleep spindles. SO-delta and SO-theta coupling, as well as interactions between delta/theta and spindle/beta frequencies also occurred. During REM, limited interactions between delta/theta and beta frequencies emerged. Moreover, oscillatory organization differed substantially between i) hippocampus and scalp, ii) sites along the anterior-posterior hippocampal axis, and iii) individuals. Overall, these results extend and refine our understanding of hippocampal sleep oscillations.

Theta Phase Synchronization between the Human Hippocampus and Prefrontal Cortex Increases during Encoding of Unexpected Information: A Case Study.

Events that violate predictions are thought to not only modulate activity within the hippocampus and PFC but also enhance communication between the two regions. Scalp and intracranial EEG studies have shown that oscillations in the theta frequency band are enhanced during processing of contextually unexpected information. Some theories suggest that the hippocampus and PFC interact during processing of unexpected events, and it is possible that theta oscillations may mediate these interactions. Here, we had the rare opportunity to conduct simultaneous electrophysiological recordings from the human hippocampus and PFC from two patients undergoing presurgical evaluation for pharmacoresistant epilepsy. Recordings were conducted during a task that involved encoding of contextually expected and unexpected visual stimuli. Across both patients, hippocampal-prefrontal theta phase synchronization was significantly higher during encoding of contextually unexpected study items, relative to contextually expected study items. Furthermore, the hippocampal-prefrontal theta phase synchronization was larger for contextually unexpected items that were later remembered compared with later forgotten items. Moreover, we did not find increased theta synchronization between the PFC and rhinal cortex, suggesting that the observed effects were specific to prefrontal-hippocampal interactions. Our findings are consistent with the idea that theta oscillations orchestrate communication between the hippocampus and PFC in support of enhanced encoding of contextually deviant information.

Memory encoding-related anterior hippocampal potentials are modulated by deep brain stimulation of the entorhinal area.

BACKGROUND: Deep brain stimulation (DBS) of the human entorhinal area using 50 Hz pulses has revealed conflicting results regarding memory performance. Moreover, its impact on memory-related hippocampal potentials has not yet been investigated. METHODS: We recorded data from seven epilepsy patients implanted with depth electrodes in the entorhinal cortex, hippocampus, amygdala, and parahippocampal cortex. Entorhinal DBS (bipolar, biphasic 50 Hz pulses, on- and off-cycles of 15 s) was applied with low amplitude (0.1 mA) to resemble physiologic conditions. During DBS on- and off-periods, patients learned noun-color associations that were later tested. RESULTS: During entorhinal DBS we observed more positive deflections of event-related potentials (ranging from 700 to 950 ms) in the anterior hippocampus for the on- vs. off-condition. We detected no effects in the amygdala, mid hippocampus and parahippocampal cortex. On the behavioral level, no differences in memory performance (item and source memory) were apparent in the on- vs. off-condition, neither across all trials nor across patients. DISCUSSION: Our findings indicate that entorhinal DBS with low amplitude has an impact on memory encoding-related potentials within the anterior hippocampus, but not on memory performance per se.

Prediction of memory formation based on absolute electroencephalographic phases in rhinal cortex and hippocampus outperforms prediction based on stimulus-related phase shifts.

Absolute (i.e. measured) rhinal and hippocampal phase values are predictive for memory formation. It has been an open question, whether the capability of mediotemporal structures to react to stimulus presentation with phase shifts may be similarly indicative of successful memory formation. We analysed data from 27 epilepsy patients implanted with depth electrodes in the hippocampus and entorhinal cortex, who performed a continuous word recognition task. Electroencephalographic phase information related to the first presentation of repeatedly presented words was used for prediction of subsequent remembering vs. forgetting applying a support vector machine. The capability to predict successful memory formation based on stimulus-related phase shifts was compared to that based on absolute phase values. Average hippocampal phase shifts were larger and rhinal phase shifts were more accumulated for later remembered compared to forgotten trials. Nevertheless, prediction based on absolute phase values clearly outperformed phase shifts and there was no significant increase in prediction accuracies when combining both measures. Our findings indicate that absolute rhinal and hippocampal phases and not stimulus-related phase shifts are most relevant for successful memory formation. Absolute phases possibly affect memory formation via influencing neural membrane potentials and thereby controlling the timing of neural firing.

Prediction of successful memory encoding based on single-trial rhinal and hippocampal phase information.

Mediotemporal EEG characteristics are closely related to long-term memory formation. It has been reported that rhinal and hippocampal EEG measures reflecting the stability of phases across trials are better suited to distinguish subsequently remembered from forgotten trials than event-related potentials or amplitude-based measures. Theoretical models suggest that the phase of EEG oscillations reflects neural excitability and influences cellular plasticity. However, while previous studies have shown that the stability of phase values across trials is indeed a relevant predictor of subsequent memory performance, the effect of absolute single-trial phase values has been little explored. Here, we reanalyzed intracranial EEG recordings from the mediotemporal lobe of 27 epilepsy patients performing a continuous word recognition paradigm. Two-class classification using a support vector machine was performed to predict subsequently remembered vs. forgotten trials based on individually selected frequencies and time points. We demonstrate that it is possible to successfully predict single-trial memory formation in the majority of patients (23 out of 27) based on only three single-trial phase values given by a rhinal phase, a hippocampal phase, and a rhinal-hippocampal phase difference. Overall classification accuracy across all subjects was 69.2% choosing frequencies from the range between 0.5 and 50Hz and time points from the interval between -0.5s and 2s. For 19 patients, above chance prediction of subsequent memory was possible even when choosing only time points from the prestimulus interval (overall accuracy: 65.2%). Furthermore, prediction accuracies based on single-trial phase surpassed those based on single-trial power. Our results confirm the functional relevance of mediotemporal EEG phase for long-term memory operations and suggest that phase information may be utilized for memory enhancement applications based on deep brain stimulation.

The role of phase synchronization in memory processes.

In recent years, studies ranging from single-unit recordings in animals to electroencephalography and magnetoencephalography studies in humans have demonstrated the pivotal role of phase synchronization in memory processes. Phase synchronization - here referring to the synchronization of oscillatory phases between different brain regions - supports both working memory and long-term memory and acts by facilitating neural communication and by promoting neural plasticity. There is evidence that processes underlying working and long-term memory might interact in the medial temporal lobe. We propose that this is accomplished by neural operations involving phase-phase and phase-amplitude synchronization. A deeper understanding of how phase synchronization supports the flexibility of and interaction between memory systems may yield new insights into the functions of phase synchronization in general.

Using state-trace analysis to dissociate the functions of the human hippocampus and perirhinal cortex in recognition memory.

A recurring issue in neuroscience concerns evidence as to whether two or more brain regions implement qualitatively different functions. Here we introduce the application of state-trace analysis to measures of neural activity, illustrating how this analysis can furnish compelling evidence for qualitatively different functions, even when the precise "neurometric" mapping between function and brain measure is unknown. In doing so, we address a long-standing debate about the brain systems supporting human memory: whether the hippocampus and the perirhinal cortex, two key components of the medial temporal lobe memory system, provide qualitatively different contributions to recognition memory. An alternative account has been that both regions support a single shared function, such as memory strength, with the apparent dissociations obtained by previous neuroimaging studies merely reflecting different, nonlinear neurometric mappings across regions. To adjudicate between these scenarios, we analyze intracranial electroencephalographic data obtained directly from human hippocampus and perirhinal cortex during a recognition paradigm and apply state-trace analysis to responses evoked by the retrieval cue as a function of different types of memory judgment. Assuming only that the neurometric mapping in each region is monotonic, any unidimensional theory (such as the memory-strength account) will produce a monotonic state trace. Critically, results showed a nonmonotonic state trace; that is, activity levels in the two regions did not show the same relative ordering across memory conditions. This nonmonotonic state trace demonstrates that there are at least two different functions implemented across the hippocampus and perirhinal cortex, allowing formal rejection of a single-process account of medial temporal lobe contributions to recognition memory.

Neural communication patterns underlying conflict detection, resolution, and adaptation.

In an ever-changing environment, selecting appropriate responses in conflicting situations is essential for biological survival and social success and requires cognitive control, which is mediated by dorsomedial prefrontal cortex (DMPFC) and dorsolateral prefrontal cortex (DLPFC). How these brain regions communicate during conflict processing (detection, resolution, and adaptation), however, is still unknown. The Stroop task provides a well-established paradigm to investigate the cognitive mechanisms mediating such response conflict. Here, we explore the oscillatory patterns within and between the DMPFC and DLPFC in human epilepsy patients with intracranial EEG electrodes during an auditory Stroop experiment. Data from the DLPFC were obtained from 12 patients. Thereof four patients had additional DMPFC electrodes available for interaction analyses. Our results show that an early θ (4-8 Hz) modulated enhancement of DLPFC γ-band (30-100 Hz) activity constituted a prerequisite for later successful conflict processing. Subsequent conflict detection was reflected in a DMPFC θ power increase that causally entrained DLPFC θ activity (DMPFC to DLPFC). Conflict resolution was thereafter completed by coupling of DLPFC γ power to DMPFC θ oscillations. Finally, conflict adaptation was related to increased postresponse DLPFC γ-band activity and to θ coupling in the reverse direction (DLPFC to DMPFC). These results draw a detailed picture on how two regions in the prefrontal cortex communicate to resolve cognitive conflicts. In conclusion, our data show that conflict detection, control, and adaptation are supported by a sequence of processes that use the interplay of θ and γ oscillations within and between DMPFC and DLPFC.

Selective processing of buildings and faces during working memory: the role of the ventral striatum.

The ventral striatum seems to play an important role during working memory (WM) tasks when irrelevant information needs to be filtered out. However, the concrete neural mechanisms underlying this process are still unknown. In this study, we investigated these mechanisms in detail. Eighteen healthy human participants were presented with multiple items consisting of faces or buildings. They either had to maintain two or four items from one category (low- and high-memory-load condition), or two from one category and suppress (filter out) two items from the other category (distraction condition). Striatal activity was increased in the distraction as compared with the high-load condition. Activity in category-specific regions in the inferior temporal cortex [fusiform face area (FFA) and parahippocampal place area (PPA)] was reduced when items from the other category needed to be selectively maintained. Furthermore, functional connectivity analysis showed significant reduction of striatal-PPA correlations during selective maintenance of faces. However, striatal-FFA connectivity was not reduced during maintenance of buildings vs. faces, possibly because face stimuli are more salient. Taken together, our results suggest that the ventral striatum supports selective WM maintenance by reduced gating of task-irrelevant activity via attenuating functional connectivity without increasing task-relevant activity correspondingly.

Intracranial electroencephalography power and phase synchronization changes during monaural and binaural beat stimulation.

Auditory stimulation with monaural or binaural auditory beats (i.e. sine waves with nearby frequencies presented either to both ears or to each ear separately) represents a non-invasive approach to influence electrical brain activity. It is still unclear exactly which brain sites are affected by beat stimulation. In particular, an impact of beat stimulation on mediotemporal brain areas could possibly provide new options for memory enhancement or seizure control. Therefore, we examined how electroencephalography (EEG) power and phase synchronization are modulated by auditory stimulation with beat frequencies corresponding to dominant EEG rhythms based on intracranial recordings in presurgical epilepsy patients. Monaural and binaural beat stimuli with beat frequencies of 5, 10, 40 and 80 Hz and non-superposed control signals were administered with low amplitudes (60 dB SPL) and for short durations (5 s). EEG power was intracranially recorded from mediotemporal, temporo-basal and temporo-lateral and surface sites. Evoked and total EEG power and phase synchronization during beat vs. control stimulation were compared by the use of Bonferroni-corrected non-parametric label-permutation tests. We found that power and phase synchronization were significantly modulated by beat stimulation not only at temporo-basal, temporo-lateral and surface sites, but also at mediotemporal sites. Generally, more significant decreases than increases were observed. The most prominent power increases were seen after stimulation with monaural 40-Hz beats. The most pronounced power and synchronization decreases resulted from stimulation with monaural 5-Hz and binaural 80-Hz beats. Our results suggest that beat stimulation offers a non-invasive approach for the modulation of intracranial EEG characteristics.

Memory consolidation by replay of stimulus-specific neural activity.

Memory consolidation transforms initially labile memory traces into more stable representations. One putative mechanism for consolidation is the reactivation of memory traces after their initial encoding during subsequent sleep or waking state. However, it is still unknown whether consolidation of individual memory contents relies on reactivation of stimulus-specific neural representations in humans. Investigating stimulus-specific representations in humans is particularly difficult, but potentially feasible using multivariate pattern classification analysis (MVPA). Here, we show in healthy human participants that stimulus-specific activation patterns can indeed be identified with MVPA, that these patterns reoccur spontaneously during postlearning resting periods and sleep, and that the frequency of reactivation predicts subsequent memory for individual items. We conducted a paired-associate learning task with items and spatial positions and extracted stimulus-specific activity patterns by MVPA in a simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) study. As a first step, we investigated the amount of fMRI volumes during rest that resembled either one of the items shown before or one of the items shown as a control after the resting period. Reactivations during both awake resting state and sleep predicted subsequent memory. These data are first evidence that spontaneous reactivation of stimulus-specific activity patterns during resting state can be investigated using MVPA. They show that reactivation occurs in humans and is behaviorally relevant for stabilizing memory traces against interference. They move beyond previous studies because replay was investigated on the level of individual stimuli and because reactivations were not evoked by sensory cues but occurred spontaneously.

Hippocampal control of repetition effects for associative stimuli.

Recent findings suggest that repetition effects interact with episodic memory processes that are putatively supported by the hippocampus. Thus, the formation or refinement of episodic memories may be related to a modulating signal from the hippocampus to the neocortex which leads to sparser or more extended stimulus representations (repetition suppression or enhancement), depending on the type of stimulus and the brain site. This framework suggests that hippocampal activity during the initial presentation of a stimulus correlates with the magnitude of repetition effects. Here, we tested this hypothesis in an fMRI study in which associations between faces and buildings were presented twice. BOLD responses showed repetition suppression in fusiform face area (FFA) and parahippocampal place area (PPA), most likely due to a refinement of existing category representations. Hippocampal activity during the first presentations was correlated with the amount of repetition suppression, in particular in the FFA. Repetition enhancement effects were observed on BOLD responses in posterior parietal cortex, possibly related to the formation of new representations of associative stimuli. The magnitude of parietal BOLD repetition effects depended on successful memory formation. These findings suggest that both repetition enhancement and repetition suppression effects are influenced by a modulating signal from the hippocampus.

Insights into the time course of mind wandering during task execution.

Our minds tend to wander, sometimes with little control. Despite this phenomenon, that can affect our ability to perform everyday tasks gaining much interest, relatively little is understood about the actual time course of MW across an experimental task. With this in mind, we collated data from two previously reported studies investigating the effect of auditory beat stimulation on MW. Taking experience sampling probes intermittently dispersed throughout a sustained-attention-to-response task (SART), we re-evaluated responses to theta monaural beat stimulation, as well as to two control conditions (silence (headphones only) and a sine wave control tone). The experience sampling probes were binned into shorter intervals of approximately five minutes duration, chronologically as they appeared within the paradigm. Experience sampling probes assayed whether MW had occurred, with or without meta-awareness, and lastly in which temporal orientation (past/present/future). By applying this somewhat temporally better resolved approach, we were able to examine the time course of attentional fluctuations related to MW during the execution of the SART, as well as interactions arising from the auditory beat stimulation. As anticipated, MW increased during task execution, most prominently at the beginning of the experiment. We also observed that levels of meta-awareness declined over time. Moreover, the temporal evolution of meta-awareness and past-orientation appeared to depend on the stimulation condition. These data demonstrate that time-on-task is a crucial factor in measuring MW, during the performance of an attentional task.

Side effects of monaural beat stimulation during sustained mental work on mind wandering and performance measures.

Excessive mind wandering (MW) contributes to the development and maintenance of psychiatric disorders. Previous studies have suggested that auditory beat stimulation may represent a method enabling a reduction of MW. However, little is known about how different auditory stimulation conditions are subjectively perceived and whether this perception is in turn related to changes in subjective states, behavioral measures of attention and MW. In the present study, we therefore investigated MW under auditory beat stimulation and control conditions using experience sampling during a sustained attention to response task (SART). The subjective perception of the stimulation conditions, as well as changes in anxiety, stress and negative mood after versus before stimulation were assessed via visual-analog scales. Results showed that any auditory stimulation applied during the SART was perceived as more distracting, disturbing, uncomfortable and tiring than silence and was related to more pronounced increases of stress and negative mood. Importantly, the perception of the auditory conditions as disturbing was directly correlated with MW propensity. Additionally, distracting, disturbing and uncomfortable perceptions predicted negative mood. In turn, negative mood was inversely correlated with response accuracy for target stimuli, a behavioral indicator of MW. In summary, our data show that MW and attentional performance are affected by the adverse perception of auditory stimulation, and that this influence may be mediated by changes in mood.

Local category-specific gamma band responses in the visual cortex do not reflect conscious perception.

Which neural processes underlie our conscious experience? One theoretical view argues that the neural correlates of consciousness (NCC) reside in local activity in sensory cortices. Accordingly, local category-specific gamma band responses in visual cortex correlate with conscious perception. However, as most studies manipulated conscious perception by altering the amount of sensory evidence, it is possible that they reflect prerequisites or consequences of consciousness rather than the actual NCC. Here we directly address this issue by developing a new experimental paradigm in which conscious perception is modulated either by sensory evidence or by previous exposure of the images while recording intracranial EEG from the higher-order visual cortex of human epilepsy patients. A clear prediction is that neural processes directly reflecting conscious perception should be present regardless of how it comes about. In contrast, we observed that although subjective reports were modulated both by sensory evidence and by previous exposure, gamma band responses solely reflected sensory evidence. This result contradicts the proposal that local gamma band responses in the higher-order visual cortex reflect conscious perception.

Cross-frequency coupling supports multi-item working memory in the human hippocampus.

Recent findings indicate that the hippocampus supports not only long-term memory encoding but also plays a role in working memory (WM) maintenance of multiple items; however, the neural mechanism underlying multi-item maintenance is still unclear. Theoretical work suggests that multiple items are being maintained by neural assemblies synchronized in the gamma frequency range (25-100 Hz) that are locked to consecutive phase ranges of oscillatory activity in the theta frequency range (4-8 Hz). Indeed, cross-frequency coupling of the amplitude of high-frequency activity to the phase of slower oscillations has been described both in animals and in humans, but has never been linked to a theoretical model of a cognitive process. Here we used intracranial EEG recordings in human epilepsy patients to test pivotal predictions from theoretical work. First, we show that simultaneous maintenance of multiple items in WM is accompanied by cross-frequency coupling of oscillatory activity in the hippocampus, which is recruited during multi-item WM. Second, maintenance of an increasing number of items is associated with modulation of beta/gamma amplitude with theta band activity of lower frequency, consistent with the idea that longer cycles are required for an increased number of representations by gamma cycles. This effect cannot be explained by a difference in theta or beta/gamma power. Third, we describe how the precision of cross-frequency coupling predicts individual WM performance. These data support the idea that working memory in humans depends on a neural code using phase information.