Electrophysiological correlates of face and object perception: A comparative analysis of 2D laboratory and virtual reality conditions.

Human face perception is a specialized visual process with inherent social significance. The neural mechanisms reflecting this intricate cognitive process have evolved in spatially complex and emotionally rich environments. Previous research using VR to transfer an established face perception paradigm to realistic conditions has shown that the functional properties of face-sensitive neural correlates typically observed in the laboratory are attenuated outside the original modality. The present study builds on these results by comparing the perception of persons and objects under conventional laboratory (PC) and realistic conditions in VR. Adhering to established paradigms, the PC- and VR modalities both featured images of persons and cars alongside standard control images. To investigate the individual stages of realistic face processing, response times, the typical face-sensitive N170 component, and relevant subsequent components (L1, L2; pre-, post-response) were analyzed within and between modalities. The between-modality comparison of response times and component latencies revealed generally faster processing under realistic conditions. However, the obtained N170 latency and amplitude differences showed reduced discriminative capacity under realistic conditions during this early stage. These findings suggest that the effects commonly observed in the lab are specific to monitor-based presentations. Analyses of later and response-locked components showed specific neural mechanisms for identification and evaluation are employed when perceiving the stimuli under realistic conditions, reflected in discernible amplitude differences in response to faces and objects beyond the basic perceptual features. Conversely, the results do not provide evidence for comparable stimulus-specific perceptual processing pathways when viewing pictures of the stimuli under conventional laboratory conditions.

Induced oscillatory brain responses under virtual reality conditions in the context of repetition priming.

In the human electroencephalogram (EEG), induced oscillatory responses in various frequency bands are regarded as valuable indices to examine the neural mechanisms underlying human memory. While the advent of virtual reality (VR) drives the investigation of mnemonic processing under more lifelike settings, the joint application of VR and EEG methods is still in its infancy (e.g., due to technical limitations impeding the signal acquisition). The objective of the present EEG study was twofold. First, we examined whether the investigation of induced oscillations under VR conditions yields equivalent results compared to standard paradigms. Second, we aimed at obtaining further insights into basic memory-related brain mechanisms in VR. To these ends, we relied on a standard implicit memory design, namely repetition priming, for which the to-be-expected effects are well-documented for conventional studies. Congruently, we replicated a suppression of the evoked potential after stimulus onset. Regarding the induced responses, we observed a modulation of induced alphaband in response to a repeated stimulus. Importantly, our results revealed a repetition-related suppression of the high-frequency induced gammaband response (>30 Hz), indicating the sharpening of a cortical object representation fostering behavioral priming effects. Noteworthy, the analysis of the induced gammaband responses required a number of measures to minimize the influence of external and internal sources of artefacts (i.e., the electrical shielding of the technical equipment and the control for miniature eye movements). In conclusion, joint VR-EEG studies with a particular focus on induced oscillatory responses offer a promising advanced understanding of mnemonic processing under lifelike conditions.

SHAP value-based ERP analysis (SHERPA): Increasing the sensitivity of EEG signals with explainable AI methods.

Conventionally, event-related potential (ERP) analysis relies on the researcher to identify the sensors and time points where an effect is expected. However, this approach is prone to bias and may limit the ability to detect unexpected effects or to investigate the full range of the electroencephalography (EEG) signal. Data-driven approaches circumvent this limitation, however, the multiple comparison problem and the statistical correction thereof affect both the sensitivity and specificity of the analysis. In this study, we present SHERPA - a novel approach based on explainable artificial intelligence (XAI) designed to provide the researcher with a straightforward and objective method to find relevant latency ranges and electrodes. SHERPA is comprised of a convolutional neural network (CNN) for classifying the conditions of the experiment and SHapley Additive exPlanations (SHAP) as a post hoc explainer to identify the important temporal and spatial features. A classical EEG face perception experiment is employed to validate the approach by comparing it to the established researcher- and data-driven approaches. Likewise, SHERPA identified an occipital cluster close to the temporal coordinates for the N170 effect expected. Most importantly, SHERPA allows quantifying the relevance of an ERP for a psychological mechanism by calculating an "importance score". Hence, SHERPA suggests the presence of a negative selection process at the early and later stages of processing. In conclusion, our new method not only offers an analysis approach suitable in situations with limited prior knowledge of the effect in question but also an increased sensitivity capable of distinguishing neural processes with high precision.

2D-dwell-time analysis with simulations of ion-channel gating using high-performance computing.

Single-channel patch-clamp recordings allow observing the action of a single protein complex in real time and hence the deduction of the underlying conformational changes in the ion-channel protein. Commonly, recordings are modeled using hidden Markov chains, connecting open and closed states in the experimental data with protein conformations. The rates between states denote transition probabilities that could be modified by membrane voltage or ligand binding. Modeling algorithms have to deal with limited recording bandwidth and a very noisy background. It was previously shown that the fit of two-dimensional (2D)-dwell-time histograms with simulations is very robust in that regard. Errors introduced by the low-pass filter or noise cancel out to a certain degree when comparing experimental and simulated data. In addition, the topology of models (that is, the chain of open and closed states) could be inferred from 2D-histograms. However, the 2D-fit was never applied to its full potential. A major reason may be the extremely time-consuming and often unreliable fitting process, due to the stochastic variability in the simulations. We have now solved these issues by introducing a message-passing interface (MPI) allowing massive parallel computing on a high-performance computing (HPC) cluster and obtaining ensemble solutions. With ensembles, we have demonstrated how important ranked solutions are for difficult tasks related to a noisy background, fast gating events beyond the corner frequency of the low-pass filter, and topology estimation of the underlying Markov model. Finally, we have shown that, by combining the objective function of the 2D-fit with the deviation of the current amplitude distributions, automatic determination of the current level of the conducting state is possible, even with an apparent current reduction due to low-pass filtering. Making use of an HPC cluster, the power of 2D-dwell-time analysis can be used to its fullest with minor input of the experimenter.

Addressing the role of PKD3 in the T cell compartment with knockout mice.

BACKGROUND: The Protein kinase D3 (PKD3) has been implicated in signal transduction downstream of the T cell receptor (TCR). However, its role for the activation of primary T lymphocytes has not been elucidated so far. METHODS: Expression of PKD isoforms in primary murine T cells was determined by RT-PCR and SDS-Page. A germline PKD3-knockout mouse line was analyzed for its immune response to OVA/alum intraperitoneal immunization. Phenotyping of the T cell compartment ex vivo as well as upon stimulation in vitro was performed by flow cytometry. Additionally, cytokine expression was assessed by flow cytometry, RT-PCR and Luminex technology. RESULTS: PKD expression in T cells is modulated by TCR stimulation, leading to a rapid down-regulation on mRNA and on protein level. PKD3-deficient mice respond to immunization with enhanced T follicular helper cell generation. Furthermore, peripheral PKD3-deficient CD4+ T cells express more interleukin-2 than wild type CD4+ T cells upon TCR stimulation ex vivo. However, purified naïve CD4+ T cells do not differ in their phenotype upon differentiation in vitro from wild type T cells. Moreover, we observed a shift towards an effector/memory phenotype of splenic T cells at steady state, which might explain the contradictory results obtained with pan-T cells ex vivo and naïve-sorted T cells. CONCLUSION: While PKD3-deficiency in vivo in mice leads to a skewing of the T cell compartment towards a more activated phenotype, this kinase seems to be dispensable for naïve CD4+ T cell differentiation in vitro. Video Abstract.

The kinase PKCα selectively upregulates interleukin-17A during Th17 cell immune responses.

Transforming growth-factor ß (TGFß) has been implicated in T helper 17 (Th17) cell biology and in triggering expression of interleukin-17A (IL-17A), which is a key Th17 cell cytokine. Deregulated TGFß receptor (TGFßR) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGFßR pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C α (PKCα) as a signaling intermediate specific to the Th17 cell subset in the activation of TGFßRI. We have shown that PKCα physically interacts and functionally cooperates with TGFßRI to promote robust SMAD2-3 activation. Furthermore, PKCα-deficient (Prkca(-/-)) cells demonstrated a defect in SMAD-dependent IL-2 suppression, as well as decreased STAT3 DNA binding within the Il17a promoter. Consistently, Prkca(-/-) cells failed to mount appropriate IL-17A, but not IL-17F, responses in vitro and were resistant to induction of Th17-cell-dependent experimental autoimmune encephalomyelitis in vivo.

The steady-state visual evoked potential (SSVEP) reflects the activation of cortical object representations: evidence from semantic stimulus repetition.

We applied high-density EEG to examine steady-state visual evoked potentials (SSVEPs) during a perceptual/semantic stimulus repetition design. SSVEPs are evoked oscillatory cortical responses at the same frequency as visual stimuli flickered at this frequency. In repetition designs, stimuli are presented twice with the repetition being task irrelevant. The cortical processing of the second stimulus is commonly characterized by decreased neuronal activity (repetition suppression). The behavioral consequences of stimulus repetition were examined in a companion reaction time pre-study using the same experimental design as the EEG study. During the first presentation of a stimulus, we confronted participants with drawings of familiar object images or object words, respectively. The second stimulus was either a repetition of the same object image (perceptual repetition; PR) or an image depicting the word presented during the first presentation (semantic repetition; SR)-all flickered at 15 Hz to elicit SSVEPs. The behavioral study revealed priming effects in both experimental conditions (PR and SR). In the EEG, PR was associated with repetition suppression of SSVEP amplitudes at left occipital and repetition enhancement at left temporal electrodes. In contrast, SR was associated with SSVEP suppression at left occipital and central electrodes originating in bilateral postcentral and occipital gyri, right middle frontal and right temporal gyrus. The conclusion of the presented study is twofold. First, SSVEP amplitudes do not only index perceptual aspects of incoming sensory information but also semantic aspects of cortical object representation. Second, our electrophysiological findings can be interpreted as neuronal underpinnings of perceptual and semantic priming.

Behavioral realism and lifelike psychophysiological responses in virtual reality by the example of a height exposure.

Virtual reality (VR) is increasingly gaining importance as a valuable methodical tool for psychological research. The greatest benefit of using VR is generating rich, complex and vivid, but still highly controllable settings. As VR has been found to elicit lifelike psychophysiological and emotional responses, we examined by means of a height exposure whether VR resembles physical reality to the necessary degree to constitute a suitable framework for investigating real-life behavior in a controlled experimental context. As hypothesized, participants behaved in VR exactly as would be appropriate in a real environment: Being exposed to great height, participants walked significantly slower across a virtual steel girder construction protruding from a high-rise building as compared to participants who traversed the very same construction on the ground level. In the height condition, this realistic behavior could be predicted on basis of the participants' trait anxiety. Aligned with the behavioral responses, they showed realistic psychophysiological responses, i.e., an elevated heart rate when exposed to height. Interestingly, participants of the height condition reported a greater sense of presence, which indicates that emotions have an elevating effect on presence. As a conclusion, our findings provide further evidence that VR evokes lifelike responses at both behavioral and psychophysiological level and therefore increases ecological validity of psychological experiments.

Virtual reality experiences promote autobiographical retrieval mechanisms: Electrophysiological correlates of laboratory and virtual experiences.

Recent advancements in memory research indicate that virtual reality (VR) experiences are more vividly memorized as compared to conventional laboratory events. In contrast to the latter, VR experiences are highly immersive, simulating the multimodality, vividness and inclusiveness of real-life experiences. Therefore, VR might enable researchers to identify memory processes underlying events which participants have actually experienced, in contrast to conventional on-screen experiences. To differentiate the electrophysiological correlates of memory processes underlying VR experiences as compared to conventional laboratory experiences, participants watched videos either in a PC condition or in a VR condition, followed by an unannounced recognition memory test. As hypothesized, we replicated the well-established theta old/new effect for the PC condition, but remarkably, this effect was absent in the VR condition. Additionally, the latter was accompanied by significantly lower alpha activity as compared to the PC condition. As increases in theta-band responses are related to top-down control on, and memory load during retrieval, the observed theta responses might rather relate to retrieval effort than to retrieval success per se. Congruently, higher alpha activity measured over occipital sensor areas in the PC condition reflect visually guided search processes within episodic memory. The VR condition comes in with lower alpha activity, reflecting immediate and effortless memory access. Hence, our findings indicate that the retrieval of VR experiences promotes autobiographical  retrieval mechanisms, whereas recalling conventional laboratory events comes in with higher effort, which might not reflect the mechanisms of everyday memory.

Vaccine against peanut allergy based on engineered virus-like particles displaying single major peanut allergens.

BACKGROUND: Peanut allergy is a severe and increasingly frequent disease with high medical, psychosocial, and economic burden for affected patients and wider society. A causal, safe, and effective therapy is not yet available. OBJECTIVE: We sought to develop an immunogenic, protective, and nonreactogenic vaccine candidate against peanut allergy based on virus-like particles (VLPs) coupled to single peanut allergens. METHODS: To generate vaccine candidates, extracts of roasted peanut (Ara R) or the single allergens Ara h 1 or Ara h 2 were coupled to immunologically optimized Cucumber Mosaic Virus-derived VLPs (CuMVtt). BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to alum. Immunotherapy consisted of a single subcutaneous injection of CuMVtt coupled to Ara R, Ara h 1, or Ara h 2. RESULTS: The vaccines CuMVtt-Ara R, CuMVtt-Ara h 1, and CuMVtt-Ara h 2 protected peanut-sensitized mice against anaphylaxis after intravenous challenge with the whole peanut extract. Vaccines did not cause allergic reactions in sensitized mice. CuMVtt-Ara h 1 was able to induce specific IgG antibodies, diminished local reactions after skin prick tests, and reduced the infiltration of the gastrointestinal tract by eosinophils and mast cells after oral challenge with peanut. The ability of CuMVtt-Ara h 1 to protect against challenge with the whole extract was mediated by IgG, as shown via passive IgG transfer. FcγRIIb was required for protection, indicating that immune complexes with single allergens were able to block the allergic response against the whole extract, consisting of a complex allergen mixture. CONCLUSIONS: Our data suggest that vaccination using single peanut allergens displayed on CuMVtt may represent a novel therapy against peanut allergy with a favorable safety profile.

Electrophysiological correlates of gist perception: a steady-state visually evoked potentials study.

Gist perception refers to perceiving the substance or general meaning of a scene. To investigate its neuronal mechanisms, we used the steady-state visually evoked potential (SSVEP) method-an evoked oscillatory cortical response at the same frequency as a visual stimulus flickered at this frequency. Two neighboring stimuli were flickered at different frequencies f1 and f2, for example, a drawing of a sun on the left side of the screen flickering at 8.6 Hz and the drawing of a parasol on the right side of the screen flickering at 12 Hz. SSVEPs enabled us to separate the responses to the two distinct stimuli by extracting oscillatory brain responses at f1 and f2. Additionally, it allowed to investigate intermodulation frequencies, that is, the brain's response at a linear combination of f1 and f2 (here at f1 + f2 = 20.6 Hz) as an indicator of processing shared aspects of the input, that is, gist perception (here: a beach scene). We recorded high-density EEG of 18 participants. Results revealed clear and separable neuronal oscillations at f1 and f2. Additionally, occipital electrodes showed increased amplitudes at the intermodulation frequency in related as compared to unrelated pairs. The increase in intermodulation frequency was associated with bilateral temporal and parietal lobe activation, probably reflecting the interaction of local object representations as a basis for activating the gist network. The study demonstrates that SSVEPs are an excellent method to unravel mechanisms underlying the processing within multi-stimulus displays in the context of gist perception.

The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.

Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology. This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases.

Memory entrainment by visually evoked theta-gamma coupling.

The wake human brain constantly encodes novel information and integrates them into existing neuronal representations. It is posited that the formation of new memory traces is orchestrated by the synchronization of neuronal activity in the theta rhythm (3-8 Hz), theta coupled gamma activity (40-120 Hz), and decreases in the alpha rhythm (8-12 Hz). Critically, given the correlative nature of neurophysiological recordings, the functional relevance of oscillatory processes is not well understood. Here, we experimentally enhanced memory formation processes by a rhythmic visual stimulation at an individual theta frequency, in contrast to the stimulation at an individual alpha frequency. This memory entrainment effect was not explained by theta power per se, but was driven by a visually evoked theta-gamma coupling pattern. This underlines the functional role of the theta rhythm and the theta-gamma neuronal code in human episodic memory. The entrainment of mnemonic network mechanisms by a visual stimulation technique provides a proof of concept that visual pacemakers can entrain complex cognitive processes in the wake human brain.

Alterations in oscillatory cortical activity indicate changes in mnemonic processing during continuous item recognition.

The classification of repeating stimuli as either old or new is a general mechanism of everyday perception. However, the cortical mechanisms underlying this process are not fully understood. In general, mnemonic processes are thought to rely on changes in oscillatory brain activity across several frequencies as well as their interaction. Lower frequencies, mainly theta-band (3-7 Hz) and alpha-band (8-14 Hz) activity, are attributed to executive control and resource management, respectively; whereas recent studies revealed higher frequencies, e.g. gamma-band (> 25 Hz) activity, to reflect the activation of cortical object representations. Furthermore, low-frequency phase to high-frequency amplitude coupling (PAC) was recently found to coordinate the involved mnemonic networks. To further unravel the processes behind memorization of repeatedly presented stimuli, we applied a continuous item recognition task with up to five presentations per item (mean time between repetitions ~ 10 s) while recording high-density EEG. We examined spectral amplitude modulations as well as PAC. We observed theta amplitudes reaching a peak at second presentation, a reduction of alpha suppression after second presentation, decreased response time, as well as reduced theta-gamma PAC (3 to 7 to - 30 to 45 Hz) at frontal sites after third presentation. We conclude a shift from an explicit- to an implicit-like mnemonic processing, occurring around third presentation, with theta power to signify encoding of repetition-based episodic information and PAC as a neural correlate of the coordination of local neural networks.

Phase-Amplitude Coupling and Long-Range Phase Synchronization Reveal Frontotemporal Interactions during Visual Working Memory.

It has been suggested that cross-frequency phase-amplitude coupling (PAC), particularly in temporal brain structures, serves as a neural mechanism for coordinated working memory storage. In this magnetoencephalography study, we show that during visual working memory maintenance, temporal cortex regions, which exhibit enhanced PAC, interact with prefrontal cortex via enhanced low-frequency phase synchronization. Healthy human participants were engaged in a visual delayed match-to-sample task with pictures of natural objects. During the delay period, we observed increased spectral power of beta (20-28 Hz) and gamma (40-94 Hz) bands as well as decreased power of theta/alpha band (7-9 Hz) oscillations in visual sensory areas. Enhanced PAC between the phases of theta/alpha and the amplitudes of beta oscillations was found in the left inferior temporal cortex (IT), an area known to be involved in visual object memory. Furthermore, the IT was functionally connected to the prefrontal cortex by increased low-frequency phase synchronization within the theta/alpha band. Together, these results point to a mechanism in which the combination of PAC and long-range phase synchronization subserves enhanced large-scale brain communication. They suggest that distant brain regions might coordinate their activity in the low-frequency range to engage local stimulus-related processing in higher frequencies via the combination of long-range, within-frequency phase synchronization and local cross-frequency PAC. SIGNIFICANCE STATEMENT: Working memory maintenance, like other cognitive functions, requires the coordinated engagement of brain areas in local and large-scale networks. However, the mechanisms by which spatially distributed brain regions share and combine information remain primarily unknown. We show that the combination of long-range, low-frequency phase synchronization and local cross-frequency phase-amplitude coupling might serve as a mechanism to coordinate memory processes across distant brain areas. In this study, low-frequency phase synchronization between prefrontal and temporal cortex co-occurred with local cross-frequency phase-amplitude coupling to higher frequencies in the latter. By such means, ongoing working memory storage taking place in higher frequencies in temporal regions might be effectively coordinated by distant frontal brain regions through synchronized activity in the low-frequency range.

Coherence in general and personal semantic knowledge: functional differences of the posterior and centro-parietal N400 ERP component.

A growing body of scientific literature investigated the difference between general and personal semantic knowledge. In contrast to general world knowledge, personal semantics comprises highly individual knowledge about oneself. The present study aimed to differentiate processes of integration into personal as opposed to general semantic knowledge. For that purpose, participants were presented with pictures of themselves (Self-condition) or unknown persons (Other-condition) superimposed on a congruent or incongruent background. We hypothesized that self-referential processing is based on automatic retrieval of personal information as opposed to the processing of unknown persons, which requires voluntary, i.e., strategic, attention demanding processing. The topography of the N400 effect varied as a function of the type of semantic knowledge. We found a centro-parietal N400 effect within the Self-condition and a posterior effect within the Other-condition. The voluntary integration of facial expressions of unknown persons within the Other-condition was, furthermore, indexed by an N170 effect. The unresolved tension in personal semantics was reflected by the N500. Our study thus provides new impulses for interpretation of the N400's functional properties and extends our knowledge about the N500. Implications for the functional properties of the self as an organizational structure are discussed.

Neuronal Oscillations Indicate Sleep-dependent Changes in the Cortical Memory Trace.

Sleep promotes the consolidation of newly acquired associative memories. Here we used neuronal oscillations in the human EEG to investigate sleep-dependent changes in the cortical memory trace. The retrieval activity for object-color associations was assessed immediately after encoding and after 3 hr of sleep or wakefulness. Sleep had beneficial effects on memory performance and led to reduced event-related theta and gamma power during the retrieval of associative memories. Furthermore, event-related alpha suppression was attenuated in the wake group for memorized and novel stimuli. There were no sleep-dependent changes in retrieval activity for missed items or items retrieved without color. Thus, the sleep-dependent reduction in theta and gamma oscillations was specific for the retrieval of associative memories. In line with theoretical accounts on sleep-dependent memory consolidation, decreased theta may indicate reduced mediotemporal activity because of a transfer of information into neocortical networks during sleep, whereas reduced parietal gamma may reflect effects of synaptic downscaling. Changes in alpha suppression in the wake group possibly index reduced attentional resources that may also contribute to a lower memory performance in this group. These findings indicate that the consolidation of associative memories during sleep is associated with profound changes in the cortical memory trace and relies on multiple neuronal processes working in concert.

Visual cortical networks align with behavioral measures of context-sensitivity in early childhood.

This study investigates how visual cortical networks align with context-sensitivity, namely the relative focus on the object versus the background of a visual scene, in early childhood. Context-sensitivity was assessed by a picture description and a recognition memory task. To segregate object and background processing in the visual cortex in 5- and 7-year-old children, object and background were presented at different frequencies (12 Hz or 15 Hz), evoking disparate neuronal responses (steady state visually evoked potentials, SSVEPs) in the electroencephalogram. In younger compared to older children the background elicited higher SSVEPs. Visual cortical processing of object versus background was associated with behavioral measures for older but not for younger children. This relation was strongest for verbal descriptions and generalized to the cortical processing of abstract stimuli and object and background presented alone. Thus, visual cortical networks restructure and align with behavioral measures of context-sensitivity in early childhood.

Oscillatory EEG dynamics underlying automatic chunking during sentence processing.

Sentences are easier to remember than random word sequences, likely because linguistic regularities facilitate chunking of words into meaningful groups. The present electroencephalography study investigated the neural oscillations modulated by this so-called sentence superiority effect during the encoding and maintenance of sentence fragments versus word lists. We hypothesized a chunking-related modulation of neural processing during the encoding and retention of sentences (i.e., sentence fragments) as compared to word lists. Time-frequency analysis revealed a two-fold oscillatory pattern for the memorization of sentences: Sentence encoding was accompanied by higher delta amplitude (4Hz), originating both from regions processing syntax as well as semantics (bilateral superior/middle temporal regions and fusiform gyrus). Subsequent sentence retention was reflected in decreased theta (6Hz) and beta/gamma (27-32Hz) amplitude instead. Notably, whether participants simply read or properly memorized the sentences did not impact chunking-related activity during encoding. Therefore, we argue that the sentence superiority effect is grounded in highly automatized language processing mechanisms, which generate meaningful memory chunks irrespective of task demands.

The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity.

The protein kinase C (PKC) family of serine-threonine kinases plays a central role in T lymphocyte activation. Here, we identify NR2F6, a nuclear zinc-finger orphan receptor, as a critical PKC substrate and essential regulator of CD4(+) T cell activation responses. NR2F6 potently antagonized the ability of T helper 0 (Th0) and Th17 CD4(+) T cells to induce expression of key cytokine genes such as interleukin-2 (IL-2) and IL-17. Mechanistically, NR2F6 directly interfered with the DNA binding of nuclear factor of activated T cells (NF-AT):activator protein 1 (AP-1) but not nuclear factor kappaB (NF-kappa B) and, subsequently, transcriptional activity of the NF-AT-dependent IL-17A cytokine promoter. Consistent with our model, Nr2f6-deficient mice had hyperreactive lymphocytes, developed a late-onset immunopathology, and were hypersusceptible to Th17-dependent experimental autoimmune encephalomyelitis. Our study establishes NR2F6 as a transcriptional repressor of IL-17 expression in Th17-differentiated CD4(+) T cells in vitro and in vivo.