Schizophrenia is characterized by marked communication dysfunctions encompassing potential impairments in the processing of social-abstract and non-social-concrete information, especially in everyday situations where multiple modalities are present in the form of speech and gesture. To date, the neurobiological basis of these deficits remains elusive. In a functional magnetic resonance imaging (fMRI) study, 17 patients with schizophrenia or schizoaffective disorder, and 18 matched controls watched videos of an actor speaking, gesturing (unimodal), and both speaking and gesturing (bimodal) about social or non-social events in a naturalistic way. Participants were asked to judge whether each video contains person-related (social) or object-related (non-social) information. When processing social-abstract content, patients showed reduced activation in the medial prefrontal cortex (mPFC) only in the gesture but not in the speech condition. For non-social-concrete content, remarkably, reduced neural activation for patients in the left postcentral gyrus and the right insula was observed only in the speech condition. Moreover, in the bimodal conditions, patients displayed improved task performance and comparable activation to controls in both social and non-social content. To conclude, patients with schizophrenia displayed modality-specific aberrant neural processing of social and non-social information, which is not present for the bimodal conditions. This finding provides novel insights into dysfunctional multimodal communication in schizophrenia, and may have potential therapeutic implications.

The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network". We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during the anticipation and perception of agoraphobia-specific stimuli.

Dysfunctional social communication is one of the most stable characteristics in patients with schizophrenia that also affects quality of life. Interpreting abstract speech and integrating nonverbal modalities is particularly affected. Considering the impact of communication on social life but failure to treat communication dysfunctions with usual treatment, we will investigate the possibility to improve verbal and non-verbal communication in schizophrenia by applying a multimodal speech-gesture training (MSG training). Here we describe the newly developed MSG training program and the study design for the first clinical investigation. The intervention contains perceptive rating (match/mismatch of sentence and gesture) and memory tasks (n-back tasks), imitation and productive tasks (e.g., SG fluency-similar to verbal fluency where words are accompanied by gesture). In addition, we offer information about gesture as meta-learning element as well as homework for reasons of transfer to everyday life as part of every session. In the MSG training intervention, we offer eight sessions (60 min each) of training. The first pilot study is currently conducted as a single-center, randomized controlled trial of speech-gesture intervention versus wait-list control with a follow-up. Outcomes are measured through pre-post-fMRI and standardized psychological questionnaires comparing two subject groups (30 patients with schizophrenia and 30 healthy controls). Patients and healthy controls are randomized in two intervention groups (with 20 being in the wait-training group and 10 in the training-follow-up group). With our study design we will be able to demonstrate the beneficial effect of the MSG training intervention on behavioral and neural levels.

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

Syntax, the grammatical structure of sentences, is a fundamental aspect of language. It remains debated whether reduced syntactic complexity is unique to schizophrenia spectrum disorder (SSD) or whether it is also present in major depressive disorder (MDD). Furthermore, the association of syntax (including syntactic complexity and diversity) with language-related neuropsychology and psychopathological symptoms across disorders remains unclear. Thirty-four SSD patients and thirty-eight MDD patients diagnosed according to DSM-IV-TR as well as forty healthy controls (HC) were included and tasked with describing four pictures from the Thematic Apperception Test. We analyzed the produced speech regarding its syntax delineating measures for syntactic complexity (the total number of main clauses embedding subordinate clauses) and diversity (number of different types of complex sentences). We performed cluster analysis to identify clusters based on syntax and investigated associations of syntactic, to language-related neuropsychological (verbal fluency and verbal episodic memory), and psychopathological measures (positive and negative formal thought disorder) using network analyses. Syntax in SSD was significantly reduced in comparison to MDD and HC, whereas the comparison of HC and MDD revealed no significant differences. No associations were present between speech measures and current medication, duration and severity of illness, age or sex; the single association accounted for was education. A cluster analysis resulted in four clusters with different degrees of syntax across diagnoses. Subjects with less syntax exhibited pronounced positive and negative symptoms and displayed poorer performance in executive functioning, global functioning, and verbal episodic memory. All cluster-based networks indicated varying degrees of domain-specific and cross-domain connections. Measures of syntactic complexity were closely related while syntactic diversity appeared to be a separate node outside of the syntactic network. Cross-domain associations were more salient in more complex syntactic production.

Self-initiated movements are accompanied by an efference copy, a motor command sent from motor regions to the sensory cortices, containing a prediction of the movement's sensory outcome. Previous studies have proposed pre-motor event-related potentials (ERPs), including the readiness potential (RP) and its lateralized sub-component (LRP), as potential neural markers of action feedback prediction. However, it is not known how specific these neural markers are for voluntary (active) movements as compared to involuntary (passive) movements, which produce much of the same sensory feedback (tactile, proprioceptive) but are not accompanied by an efference copy. The goal of the current study was to investigate how active and passive movements are distinguishable from premotor electroencephalography (EEG), and to examine if this change of neural activity differs when participants engage in tasks that differ in their expectation of sensory outcomes. Participants made active (self-initiated) or passive (finger moved by device) finger movements that led to either visual or auditory stimuli (100 ms delay), or to no immediate contingency effects (control). We investigated the time window before the movement onset by measuring pre-movement ERPs time-locked to the button press. For RP, we observed an interaction between task and movement. This was driven by movement differences in the visual and auditory but not the control conditions. LRP conversely only showed a main effect of movement. We then used multivariate pattern analysis to decode movements (active vs. passive). The results revealed ramping decoding for all tasks from around -800 ms onwards up to an accuracy of approximately 85% at the movement. Importantly, similar to RP, we observed lower decoding accuracies for the control condition than the visual and auditory conditions, but only shortly (from -200 ms) before the button press. We also decoded visual vs. auditory conditions. Here, task is decodable for both active and passive conditions, but the active condition showed increased decoding shortly before the button press. Taken together, our results provide robust evidence that pre-movement EEG activity may represent action-feedback prediction in which information about the subsequent sensory outcome is encoded.

The brain can adapt its expectations about the relative timing of actions and their sensory outcomes in a process known as temporal recalibration. This might occur as the recalibration of timing between the sensory (e.g. visual) outcome and (1) the motor act (sensorimotor) or (2) tactile/proprioceptive information (inter-sensory). This fMRI recalibration study investigated sensorimotor contributions to temporal recalibration by comparing active and passive conditions. Subjects were repeatedly exposed to delayed (150 ms) or undelayed visual stimuli, triggered by active or passive button presses. Recalibration effects were tested in delay detection tasks, including visual and auditory outcomes. We showed that both modalities were affected by visual recalibration. However, an active advantage was observed only in visual conditions. Recalibration was generally associated with the left cerebellum (lobules IV, V and vermis) while action related activation (active > passive) occurred in the right middle/superior frontal gyri during adaptation and test phases. Recalibration transfer from vision to audition was related to action specific activations in the cingulate cortex, the angular gyrus and left inferior frontal gyrus. Our data provide new insights in sensorimotor contributions to temporal recalibration via the middle/superior frontal gyri and inter-sensory contributions mediated by the cerebellum.

The approach to apply multivariate pattern analyses based on neuro imaging data for outcome prediction holds out the prospect to improve therapeutic decisions in mental disorders. Patients suffering from panic disorder with agoraphobia (PD/AG) often exhibit an increased perception of bodily sensations. The purpose of this investigation was to assess whether multivariate classification applied to a functional magnetic resonance imaging (fMRI) interoception paradigm can predict individual responses to cognitive behavioral therapy (CBT) in PD/AG.

A high frequency of outgroup contact-as experienced by urban dwellers and migrants-possibly increases schizophrenia risk. This risk might be further amplified by genetic and environmental risk factors, such as the A-allele of rs1006737 within the calcium voltage-gated channel subunit alpha1 C gene and childhood interpersonal trauma (CIT). Both have been related to ventral anterior cingulate cortex (vACC) functioning. We investigated vACC functioning, during ingroup and outgroup emotion perception in relation to rs1006737 and CIT. Group membership was manipulated through a minimal group paradigm. Thus, in our functional magnetic resonance imaging study, a group of healthy Caucasian participants (n = 178) viewed video-recorded facial emotions (happy vs angry) of actors artificially assigned to represent the ingroup or the outgroup. Rs1006737 and CIT were related to brain activation for group and emotion specific processing. The group-emotion interaction in the vACC showed reduced sensitivity to emotional valence for outgroup member processing. Specifically for the angry outgroup condition, we found a gene by environment interaction in vACC activity. We speculate that the increased schizophrenia risk in migrants and urban dwellers could therefore be facilitated via this pathophysiological pathway.

Humans integrate information communicated by speech and gestures. Functional magnetic resonance imaging (fMRI) studies suggest that the posterior superior temporal sulcus (STS) and adjacent gyri are relevant for multisensory integration. However, a connectivity model representing this essential combinatory process is still missing. Here, we used dynamic causal modeling for fMRI to analyze the effective connectivity pattern between middle temporal gyrus (MTG), occipital cortex (OC) and STS associated with auditory verbal, visual gesture-related, and integrative processing, respectively, to unveil the neural mechanisms underlying integration of intrinsically meaningful gestures (e.g., "Thumbs-up gesture") and corresponding speech. 20 participants were presented videos of an actor either performing intrinsic meaningful gestures in the context of German or Russian sentences, or speaking a German sentence without gesture, while performing a content judgment task. The connectivity analyses resulted in a winning model that included bidirectional intrinsic connectivity between all areas. Furthermore, the model included modulations of both connections to the STS (OC→STS; MTG→STS), and non-linear modulatory effects of the STS on bidirectional connections between MTG and OC. Coupling strength in the occipital pathway (OC→STS) correlated with gesture related advantages in task performance, whereas the temporal pathway (MTG→STS) correlated with performance in the speech only condition. Coupling between MTG and OC correlated negatively with subsequent memory performance for sentences of the Gesture-German condition. Our model provides a first step towards a better understanding of speech-gesture integration on network level. It corroborates the importance of the STS during audio-visual integration by showing that this region inhibits direct auditory-visual coupling.

Metaphoric (MP) co-speech gestures are commonly used during daily communication. They communicate about abstract information by referring to gestures that are clearly concrete (e.g., raising a hand for "the level of the football game is high"). To understand MP co-speech gestures, a multisensory integration at semantic level is necessary between abstract speech and concrete gestures. While semantic gesture-speech integration has been extensively investigated using functional magnetic resonance imaging, evidence from electroencephalography (EEG) is rare. In the current study, we set out an EEG experiment, investigating the processing of MP vs. iconic (IC) co-speech gestures in different contexts, to reveal the oscillatory signature of MP gesture integration. German participants (n = 20) viewed video clips with an actor performing both types of gestures, accompanied by either comprehensible German or incomprehensible Russian (R) speech, or speaking German sentences without any gestures. Time-frequency analysis of the EEG data showed that, when gestures were accompanied by comprehensible German speech, MP gestures elicited decreased gamma band power (50-70 Hz) between 500 and 700 ms in the parietal electrodes when compared to IC gestures, and the source of this effect was localized to the right middle temporal gyrus. This difference is likely to reflect integration processes, as it was reduced in the R language and no-gesture conditions. Our findings provide the first empirical evidence suggesting the functional relationship between gamma band oscillations and higher-level semantic processes in a multisensory setting.

Body orientation of gesture entails social-communicative intention, and may thus influence how gestures are perceived and comprehended together with auditory speech during face-to-face communication. To date, despite the emergence of neuroscientific literature on the role of body orientation on hand action perception, limited studies have directly investigated the role of body orientation in the interaction between gesture and language. To address this research question, we carried out an electroencephalography (EEG) experiment presenting to participants (n = 21) videos of frontal and lateral communicative hand gestures of 5 s (e.g., raising a hand), followed by visually presented sentences that are either congruent or incongruent with the gesture (e.g., "the mountain is high/low…"). Participants underwent a semantic probe task, judging whether a target word is related or unrelated to the gesture-sentence event. EEG results suggest that, during the perception phase of handgestures, while both frontal and lateral gestures elicited a power decrease in both the alpha (8-12 Hz) and the beta (16-24 Hz) bands, lateral versus frontal gestures elicited reduced power decrease in the beta band, source-located to the medial prefrontal cortex. For sentence comprehension, at the critical word whose meaning is congruent/incongruent with the gesture prime, frontal gestures elicited an N400 effect for gesture-sentence incongruency. More importantly, this incongruency effect was significantly reduced for lateral gestures. These findings suggest that body orientation plays an important role in gesture perception, and that its inferred social-communicative intention may influence gesture-language interaction at semantic level.

Predictive mechanisms are essential to successfully interact with the environment and to compensate for delays in the transmission of neural signals. However, whether and how we predict multisensory action outcomes remains largely unknown. Here we investigated the existence of multisensory predictive mechanisms in a context where actions have outcomes in different modalities. During fMRI data acquisition auditory, visual and auditory-visual stimuli were presented in active and passive conditions. In the active condition, a self-initiated button press elicited the stimuli with variable short delays (0-417ms) between action and outcome, and participants had to detect the presence of a delay for auditory or visual outcome (task modality). In the passive condition, stimuli appeared automatically, and participants had to detect the number of stimulus modalities (unimodal/bimodal). For action consequences compared to identical but unpredictable control stimuli we observed suppression of the blood oxygen level depended (BOLD) response in a broad network including bilateral auditory and visual cortices. This effect was independent of task modality or stimulus modality and strongest for trials where no delay was detected (undetected

Patients with schizophrenia spectrum disorder often demonstrate impairments in action-outcome monitoring. Passivity phenomena and hallucinations, in particular, have been related to impairments of efference copy-based predictions which are relevant for the monitoring of outcomes produced by voluntary action. Frontal transcranial direct current stimulation has been shown to improve action-outcome monitoring in healthy subjects. However, whether transcranial direct current stimulation can improve action monitoring in patients with schizophrenia spectrum disorder remains unknown. We investigated whether transcranial direct current stimulation can improve the detection of temporal action-outcome discrepancies in patients with schizophrenia spectrum disorder. On 4 separate days, we applied sham or left cathodal/right anodal transcranial direct current stimulation in a randomized order to frontal (F3/F4), parietal (CP3/CP4) and frontoparietal (F3/CP4) areas of 19 patients with schizophrenia spectrum disorder and 26 healthy control subjects. Action-outcome monitoring was assessed subsequent to 10 min of sham/transcranial direct current stimulation (1.5 mA). After a self-generated (active) or externally generated (passive) key press, subjects were presented with a visual outcome (a dot on the screen), which was presented after various delays (0-417 ms). Participants had to detect delays between the key press and the visual consequence. Symptom subgroups were explored based on the presence or absence of symptoms related to a paranoid-hallucinatory syndrome. In general, delay-detection performance was impaired in the schizophrenia spectrum disorder compared to the healthy control group. Interaction analyses showed group-specific (schizophrenia spectrum disorder versus healthy control group) and symptom-specific (with/without relevant paranoid-hallucinatory symptoms) transcranial direct current stimulation effects. Post hoc tests revealed that frontal transcranial direct current stimulation improved the detection of long delays in active conditions and reduced the proportion of false alarms in undelayed trials of the passive condition in patients. The patients with no or few paranoid-hallucinatory symptoms benefited especially from frontal transcranial direct current stimulation in active conditions, while improvement in the patients with paranoid-hallucinatory symptoms was predominantly reflected in reduced false alarm rates in passive conditions. These data provide some first evidence for the potential utility of transcranial direct current stimulation in improving efference copy mechanisms and action-outcome monitoring in schizophrenia spectrum disorder. Current data indicate that improving efference copy-related processes can be especially effective in patients with no or few positive symptoms, while intersensory matching (i.e. task-relevant in passive conditions) could be more susceptible to improvement in patients with paranoid-hallucinatory symptoms.

Sensory action consequences are highly predictable and thus engage less neural resources compared to externally generated sensory events. While this has frequently been observed to lead to attenuated perceptual sensitivity and suppression of activity in sensory cortices, some studies conversely reported enhanced perceptual sensitivity for action consequences. These divergent findings might be explained by the type of action feedback, i.e., discrete outcomes vs. continuous feedback. Therefore, in the present study we investigated the impact of discrete and continuous action feedback on perceptual and neural processing during action feedback monitoring. During fMRI data acquisition, participants detected temporal delays (0-417 ms) between actively or passively generated wrist movements and visual feedback that was either continuously provided during the movement or that appeared as a discrete outcome. Both feedback types resulted in (1) a neural suppression effect (active

Social group membership modulates the neural processing of emotional facial expressions, which, in turn, recruits part of the neural production system. However, little is known about how mixed - and potentially conflicting - social identity cues affect this mechanism. In this study, we tested the hypothesis that incongruent cues of two group memberships (ethnic and experimentally created minimal groups) elicit conflict processing for neutral and, in particular, angry facial expressions. We further expected this interaction of ethnic group, minimal group and emotion to also modulate activation in an emotional production-perception network. Twenty-two healthy German subjects saw dynamic angry and neutral facial expressions, presented in short video clips during functional MRI scanning. All depicted actors belonged to an ethnic in- or outgroup (German or Turkish descent) as well as an ad hoc experimentally created minimal in- or outgroup. Additionally, subjects produced angry or neutral expressions themselves. The whole-brain interaction of ethnic group, minimal group and emotion revealed activity in the right parietal lobule and left cerebellum. Both showed strongest activation for angry faces with conflicting group memberships (e.g., 'ethnic outgroup/minimal ingroup'). In addition, a sub-region of the left cerebellum cluster was also activated for both perceiving and producing angry versus neutral expressions. These results suggest that incongruent group members displaying angry facial expressions elicit conflict processing. Group interaction effects in an emotional production-perception network further indicate stronger neural resonance for incongruent group members.

Adaptation to delays between actions and sensory feedback is important for efficiently interacting with our environment. Adaptation may rely on predictions of action-feedback pairing (motor-sensory component), or predictions of tactile-proprioceptive sensation from the action and sensory feedback of the action (inter-sensory component). Reliability of temporal information might differ across sensory feedback modalities (e.g. auditory or visual), which in turn influences adaptation. Here, we investigated the role of motor-sensory and inter-sensory components on sensorimotor temporal recalibration for motor-auditory (button press-tone) and motor-visual (button press-Gabor patch) events. In the adaptation phase of the experiment, action-feedback pairs were presented with systematic temporal delays (0 ms or 150 ms). In the subsequent test phase, audio/visual feedback of the action were presented with variable delays. The participants were then asked whether they detected a delay. To disentangle motor-sensory from inter-sensory component, we varied movements (active button press or passive depression of button) at adaptation and test. Our results suggest that motor-auditory recalibration is mainly driven by the motor-sensory component, whereas motor-visual recalibration is mainly driven by the inter-sensory component. Recalibration transferred from vision to audition, but not from audition to vision. These results indicate that motor-sensory and inter-sensory components contribute to recalibration in a modality-dependent manner.

It has been widely assumed that internal forward models use efference copies to create predictions about the sensory consequences of our own actions. While these predictions have frequently been associated with a reduced blood oxygen level dependent (BOLD) response in sensory cortices, the timing and duration of the hemodynamic response for the processing of video feedback of self-generated (active) versus externally generated (passive) movements is poorly understood. In the present study, we tested the hypothesis that predictive mechanisms for self-generated actions lead to early and shorter neural processing compared with externally generated movements. We investigated active and passive movements using a custom-made fMRI-compatible movement device. Visual video feedback of the active and passive movements was presented in real time or with variable delays. Participants had to judge whether the feedback was delayed. Timing and duration of BOLD impulse response was calculated using a first (temporal derivative [TD]) and second-order (dispersion derivative [DD]) Taylor approximation. Our reanalysis confirmed our previous finding of reduced BOLD response for active compared to passive movements. Moreover, we found positive effects of the TD and DD in the supplementary motor area, cerebellum, visual cortices, and subcortical structures, indicating earlier and shorter hemodynamic responses for active compared to passive movements. Furthermore, earlier activation in the putamen for active compared to passive conditions was associated with reduced delay detection performance. These findings indicate that efference copy-based predictive mechanisms enable earlier processing of action feedback, which might have reduced the ability to detect short delays between action and feedback.

Bacteria associated with plants can enhance the plants' growth and resistance against phytopathogens. Today, growers aim to reduce the use of mineral fertilizers and pesticides. Since phytopathogens cause severe yield losses in crop production systems, biological alternatives gain more attention. Plant and also seed endophytes have the potential to influence the plant, especially seed-borne bacteria may express their beneficiary impact at initial plant developmental stages. In the current study, we assessed the endophytic seed microbiome of seven genetically diverse barley accessions by 16S rRNA gene amplicon sequencing and verified the in vitro plant beneficial potential of isolated seed endophytes. Furthermore, we investigated the impact of the barley genotype and its seed microbiome on the rhizosphere microbiome at an early growth stage by 16S rRNA gene amplicon sequencing.

Electrophysiological studies in rodents allow recording neural activity during threats with high temporal and spatial precision. Although fMRI has helped translate insights about the anatomy of underlying brain circuits to humans, the temporal dynamics of neural fear processes remain opaque and require EEG. To date, studies on electrophysiological brain signals in humans have helped to elucidate underlying perceptual and attentional processes, but have widely ignored how fear memory traces evolve over time. The low signal-to-noise ratio of EEG demands aggregations across high numbers of trials, which will wash out transient neurobiological processes that are induced by learning and prone to habituation. Here, our goal was to unravel the plasticity and temporal emergence of EEG responses during fear conditioning. To this end, we developed a new sequential-set fear conditioning paradigm that comprises three successive acquisition and extinction phases, each with a novel CS+/CS- set. Each set consists of two different neutral faces on different background colors which serve as CS+ and CS-, respectively. Thereby, this design provides sufficient trials for EEG analyses while tripling the relative amount of trials that tap into more transient neurobiological processes. Consistent with prior studies on ERP components, data-driven topographic EEG analyses revealed that ERP amplitudes were potentiated during time periods from 33-60 ms, 108-200 ms, and 468-820 ms indicating that fear conditioning prioritizes early sensory processing in the brain, but also facilitates neural responding during later attentional and evaluative stages. Importantly, averaging across the three CS+/CS- sets allowed us to probe the temporal evolution of neural processes: Responses during each of the three time windows gradually increased from early to late fear conditioning, while long-latency (460-730 ms) electrocortical responses diminished throughout fear extinction. Our novel paradigm demonstrates how short-, mid-, and long-latency EEG responses change during fear conditioning and extinction, findings that enlighten the learning curve of neurophysiological responses to threat in humans.