Action prediction modulates self-other integration in joint action.

People often coordinate actions with others, requiring an adjustable amount of self-other integration between actor's and co-actor's actions. Previous research suggests that such self-other integration (indexed by the joint Simon effect) is enhanced by agent similarity of the co-actor (e.g., high in intentionality). In this study, we aimed to extend this line of research by testing whether experiencing agency over a co-actor's actions (vicarious agency) and/or action prediction strengthens the joint Simon effect. For this purpose, we manipulated experienced agency by varying the experienced control over a co-actor's actions (Experiment 1), and action prediction regarding the co-actor's actions (Experiment 2). Vicarious agency could effectively be induced, but did not modulate the size of the joint Simon effect. The joint Simon effect was decreased when the co-actor's actions were unpredictable (vs. predictable) during joint task performance. These findings suggest social agency can be induced and effectively measured in joint action. Action prediction can act as an effective agency cue modulating the amount of self-other integration in joint action.

Macroscopic information-based taste representations in insular cortex are shaped by stimulus concentration.

Taste processing is an essential ability in all animals signaling potential harm or benefit of ingestive behavior. However, current evidence for cortical taste representations remains contradictory. To address this issue, high-resolution functional MRI (fMRI) and multivariate pattern analysis were used to characterize taste-related informational content in human insular cortex, which contains primary gustatory cortex. Human participants judged pleasantness and intensity of low- and high-concentration tastes (salty, sweet, sour, and bitter) in two fMRI experiments on two different days to test for task- and concentration-invariant taste representations. We observed patterns of fMRI activity within insular cortex narrowly tuned to specific tastants consistently across tasks in all participants. Fewer patterns responded to more than one taste category. Importantly, changes in taste concentration altered the spatial layout of putative taste-specific patterns with distinct, almost nonoverlapping patterns for each taste category at different concentration levels. Together, our results point at macroscopic representations in human insular cortex as a complex function of taste category and concentration rather than representations based solely on taste identity.

Reinstatement of Cortical Outcome Representations during Higher-Order Learning.

Naturalistic learning scenarios are characterized by infrequent experience of external feedback to guide behavior. Higher-order learning mechanisms like second-order conditioning (SOC) may allow stimuli that were never experienced together with reinforcement to acquire motivational value. Despite its explanatory potential for real-world learning, surprisingly little is known about the neural mechanism underlying such associative transfer of value in SOC. Here, we used multivariate cross-session, cross-modality searchlight classification on functional magnetic resonance imaging data obtained from humans during SOC. We show that visual first-order conditioned stimuli (CS) reinstate cortical patterns representing previously paired gustatory outcomes in the lateral orbitofrontal cortex (OFC). During SOC, this OFC region showed increased functional covariation with amygdala, where neural pattern similarity between second-order CS and outcomes increased from early to late stages of SOC. Our data suggest a mechanism by which motivational value is conferred to stimuli that were never paired with reinforcement.

Audio-visual synchrony and spatial attention enhance processing of dynamic visual stimulation independently and in parallel: A frequency-tagging study.

The neural processing of a visual stimulus can be facilitated by attending to its position or by a co-occurring auditory tone. Using frequency-tagging, we investigated whether facilitation by spatial attention and audio-visual synchrony rely on similar neural processes. Participants attended to one of two flickering Gabor patches (14.17 and 17 Hz) located in opposite lower visual fields. Gabor patches further "pulsed" (i.e. showed smooth spatial frequency variations) at distinct rates (3.14 and 3.63 Hz). Frequency-modulating an auditory stimulus at the pulse-rate of one of the visual stimuli established audio-visual synchrony. Flicker and pulsed stimulation elicited stimulus-locked rhythmic electrophysiological brain responses that allowed tracking the neural processing of simultaneously presented Gabor patches. These steady-state responses (SSRs) were quantified in the spectral domain to examine visual stimulus processing under conditions of synchronous vs. asynchronous tone presentation and when respective stimulus positions were attended vs. unattended. Strikingly, unique patterns of effects on pulse- and flicker driven SSRs indicated that spatial attention and audiovisual synchrony facilitated early visual processing in parallel and via different cortical processes. We found attention effects to resemble the classical top-down gain effect facilitating both, flicker and pulse-driven SSRs. Audio-visual synchrony, in turn, only amplified synchrony-producing stimulus aspects (i.e. pulse-driven SSRs) possibly highlighting the role of temporally co-occurring sights and sounds in bottom-up multisensory integration.

Shedding light on emotional perception: Interaction of brightness and semantic content in extrastriate visual cortex.

The rapid extraction of affective cues from the visual environment is crucial for flexible behavior. Previous studies have reported emotion-dependent amplitude modulations of two event-related potential (ERP) components - the N1 and EPN - reflecting sensory gain control mechanisms in extrastriate visual areas. However, it is unclear whether both components are selective electrophysiological markers of attentional orienting toward emotional material or are also influenced by physical features of the visual stimuli. To address this question, electrical brain activity was recorded from seventeen male participants while viewing original and bright versions of neutral and erotic pictures. Bright neutral scenes were rated as more pleasant compared to their original counterpart, whereas erotic scenes were judged more positively when presented in their original version. Classical and mass univariate ERP analysis showed larger N1 amplitude for original relative to bright erotic pictures, with no differences for original and bright neutral scenes. Conversely, the EPN was only modulated by picture content and not by brightness, substantiating the idea that this component is a unique electrophysiological marker of attention allocation toward emotional material. Complementary topographic analysis revealed the early selective expression of a centro-parietal positivity following the presentation of original erotic scenes only, reflecting the recruitment of neural networks associated with sustained attention and facilitated memory encoding for motivationally relevant material. Overall, these results indicate that neural networks subtending the extraction of emotional information are differentially recruited depending on low-level perceptual features, which ultimately influence affective evaluations.

Visual, auditory and tactile stimuli compete for early sensory processing capacities within but not between senses.

We investigated whether unattended visual, auditory and tactile stimuli compete for capacity-limited early sensory processing across senses. In three experiments, we probed competitive audio-visual, visuo-tactile and audio-tactile stimulus interactions. To this end, continuous visual, auditory and tactile stimulus streams ('reference' stimuli) were frequency-tagged to elicit steady-state responses (SSRs). These electrophysiological oscillatory brain responses indexed ongoing stimulus processing in corresponding senses. To induce competition, we introduced transient frequency-tagged stimuli in same and/or different senses ('competitors') during reference presentation. Participants performed a separate visual discrimination task at central fixation to control for attentional biases of sensory processing. A comparison of reference-driven SSR amplitudes between competitor-present and competitor-absent periods revealed reduced amplitudes when a competitor was presented in the same sensory modality as the reference. Reduced amplitudes indicated the competitor's suppressive influence on reference stimulus processing. Crucially, no such suppression was found when a competitor was presented in a different than the reference modality. These results strongly suggest that early sensory competition is exclusively modality-specific and does not extend across senses. We discuss consequences of these findings for modeling the neural mechanisms underlying intermodal attention.

Entering into a self-regulated learning mode prevents detrimental effects of feedback removal on memory.

Incentives can decrease performance by undermining intrinsic motivation. How such an interplay of external reinforcers and internal self-regulation influences memory processes, however, is less known. Here, we investigated their interaction on memory performance while learning the meaning of new-words from their context. Specifically, participants inferred congruent meanings of new-words from semantic context (congruent trials) or lack of congruence (incongruent trials), while receiving external feedback in the first or second half of trials only. Removing feedback during learning of congruent word meanings lowered subsequent recognition rates a day later, whereas recognition remained high in the group, which received feedback only in the second half. In contrast, feedback did not substantially alter recognition rates for learning that new-words had no congruent meanings. Our findings suggest that external reinforcers can selectively impair memories if internal self-regulated processes are not already established, but whether they do so depends on what is being learned (specific word-meanings vs. unspecific incongruence). This highlights the relevance of self-regulated learning in education to support stable memory formation.

Sublethal effects of nine insecticides on Drosophila suzukii and its major pupal parasitoid Trichopria drosophilae.

BACKGROUND: Although the pupal parasitoid Trichopria drosophilae is used in conservative and augmentative biocontrol of Drosophila suzukii infestations, current pest management strategies mostly rely on multiple insecticide applications. In this context, the aim of the study was to investigate the baseline toxicity of nine insecticides on D. suzukii larvae and their multiple sublethal effects (LC10 ) on immature stages of the pest feeding on contaminated diet and T. drosophilae developing within the intoxicated host. RESULTS: Chlorpyriphos and azadirachtin showed the lowest and the highest LC10 , the values of which were 9.78 × 1013 and 1.46 × 103 times lower than their recommended label field rate, respectively. Among tested insecticides, imidacloprid, malathion and dimethoate were the only treatments that did not affect the juvenile development time of D. suzukii, while spinosad and the organophosphates chlorpyriphos and dimethoate did not influence fly pupal size. No sublethal effects were recorded on T. drosophilae degree of infestation (DI) and juvenile development time. On the contrary, cyazypyr and dimethoate negatively affected the success of parasitism (SP) and the number of progeny of the pupal parasitoid, in association with malathion for the first parameter and spinosad for the fertility. Compared to the untreated control, more female progeny emerged following azadirachtin exposure, while dimethoate caused the opposite effect. Imidacloprid, lambda-cyhalothrin and spinetoram decreased hind tibia length of emerged parasitoids. CONCLUSION: This study provides new insights on the (eco)toxicological profile of nine insecticides and new information needed to support the deployment of T. drosophilae in the field within the sustainable management techniques against D. suzukii. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Rapid processing of neutral and angry expressions within ongoing facial stimulus streams: Is it all about isolated facial features?

Our visual system extracts the emotional meaning of human facial expressions rapidly and automatically. Novel paradigms using fast periodic stimulations have provided insights into the electrophysiological processes underlying emotional content extraction: the regular occurrence of specific identities and/or emotional expressions alone can drive diagnostic brain responses. Consistent with a processing advantage for social cues of threat, we expected angry facial expressions to drive larger responses than neutral expressions. In a series of four EEG experiments, we studied the potential boundary conditions of such an effect: (i) we piloted emotional cue extraction using 9 facial identities and a fast presentation rate of 15 Hz (N = 16); (ii) we reduced the facial identities from 9 to 2, to assess whether (low or high) variability across emotional expressions would modulate brain responses (N = 16); (iii) we slowed the presentation rate from 15 Hz to 6 Hz (N = 31), the optimal presentation rate for facial feature extraction; (iv) we tested whether passive viewing instead of a concurrent task at fixation would play a role (N = 30). We consistently observed neural responses reflecting the rate of regularly presented emotional expressions (5 Hz and 2 Hz at presentation rates of 15 Hz and 6 Hz, respectively). Intriguingly, neutral expressions consistently produced stronger responses than angry expressions, contrary to the predicted processing advantage for threat-related stimuli. Our findings highlight the influence of physical differences across facial identities and emotional expressions.

Explicitly versus implicitly driven temporal expectations: No evidence for altered perceptual processing due to top-down modulations.

Learning the statistical regularities of environmental events is a powerful tool for enhancing performance. However, it remains unclear whether this often implicit type of behavioral facilitation can be proactively modulated by explicit knowledge about temporal regularities. Only recently, Menceloglu and colleagues (Attention, Perception & Psychophysics, 79(1), 169-179, 2017) tested for differences between implicit versus explicit statistical learning of temporal regularities by using a within-paradigm manipulation of metacognitive temporal knowledge. The authors reported that temporal expectations were enhanced if participants had explicit knowledge about temporal regularities. Here, we attempted to replicate and extend their results, and to provide a mechanistic framework for any effects by means of computational modelling. Participants performed a letter-discrimination task, with target letters embedded in congruent or incongruent flankers. Temporal predictability was manipulated block-wise, with targets occurring more often after either a short or a long delay period. During the delay a sound was presented in half of the trials. Explicit knowledge about temporal regularities was manipulated by changing instructions: Participants received no information (implicit), information about the most likely cue-target delay (explicit), or received 100% valid cues on each trial (highly explicit). We replicated previous effects of target-flanker congruence and sound presence. However, no evidence was found for an effect of explicit knowledge on temporal expectations using Bayesian statistics. Concordantly, computational modelling suggested that explicit knowledge may only influence non-perceptual processing such as response criteria. Together, our results indicate that explicit metacognitive knowledge does not necessarily alter sensory representations or temporal expectations but rather affects response strategies.

Saccadic eye movements do not trigger a joint Simon effect.

Although the joint Simon task (JST) has been investigated for more than a decade, its cause is still unclear. According to ideomotor views of action control, action effects are a commonly cited explanation. However, action effects are usually confounded with the actions producing such effects. We combined a JST with eye tracking and asked participants to respond by performing specific saccades. Saccades were followed by visual feedback (central vs. lateral feedback), serving as the action effect. This arrangement allowed us to isolate actions from action effects and, also to prevent each actor from seeing the reciprocal actions of the other actor. In this saccadic JST, we found a significant compatibility effect in the individual setting. The typical enhanced compatibility effect in the joint setting of the JST was absent with central action feedback and even when lateralized visual action feedback was provided. Our findings suggest that the perception of action effects alone might not be sufficient to modulate compatibility effects for eye movements. The presence of a compatibility effect in the individual setting shows the specific requirements of a saccadic compatibility task - the requirement to perform prosaccades to compatible and antisaccades to incompatible target locations. The lack of a difference between compatibility effects in joint and individual settings and the lack of a modulation of the compatibility effect through lateralized visual action feedback shows that the finding of a joint Simon effect that has frequently been reported for manual responses is absent for saccadic responses.

Strain and schedule-dependent differences in the acquisition, maintenance and extinction of intravenous cannabinoid self-administration in rats.

Cannabinoids have been reported to sustain self-administration in laboratory animals; however, genetic differences and environmental factors critical in the initiation and retention of such behaviour are yet to be defined. This study investigated the acquisition, maintenance and extinction of self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 (6.25-25 microg/kg/inf) in Long Evans, Lister Hooded and Sprague-Dawley rats under a continuous schedule of reinforcement and two different response-like operanda, nose-poking and lever-pressing. Results showed that Long Evans and Lister Hooded, but not Sprague Dawley, rats acquired and retained stable cannabinoid self-administration behaviour under both modus operandi, as defined by significant differences between responding in the active versus the inactive hole/lever. In rats developing firm self-administration, substitution of saline for WIN 55,212-2 extinguished the responding, supporting the notion that cannabinoids may serve as a positive reinforcer in laboratory animals. Nevertheless, significant differences among strains and responding modalities were observed in the percentage of acquisition, amount of drug intake during maintenance and timing of extinction. In addition, no significant strain differences were found in motor response to WIN 55,212-2 (0.3 and 3.0 mg/kg), thus excluding that strain differences observed during cannabinoid self-administration could be related to different cannabinoid-induced locomotor effects.

Two novel and one known mutation of the TGFBR2 gene in Marfan syndrome not associated with FBN1 gene defects.

TGF-beta-receptor 2 (TGFBR2) gene defects have been recently associated with Marfan syndrome (MFS) with prominent cardio-skeletal phenotype in patients with negative fibrillin-1 (FBN1) gene screening. Four mutations have been identified to date in five unrelated families. We screened TGFBR2 gene by direct automated sequencing in two adult patients diagnosed with MFS according to Ghent criteria, and in one girl clinically suspected as affected on the basis of a major cardiovascular criterion and skeletal involvement, all proven not to carry mutations in the exon-intron boundaries of FBN1 gene. We identified two novel and one known TGFBR2 gene mutations in the three unrelated probands. The D446N was identified in a 4-year-old girl with de novo disease characterized by severe cardiovascular disease and skeletal involvement. The M425V and R460H mutations were identified in two familial, autosomal dominant MFSs, both characterized by major cardio-skeletal signs and absence of major ocular signs. The mutation R460H has been recently reported in a family with thoracic aortic aneurysms and dissection. The three mutations are absent in 192 controls and affect evolutionarily conserved residues of the serine/threonine kinase domain (exon 5). Our data support the recently reported association between TGFBR2 gene and MFS without major ocular signs (MFS2). The number of genotyped cases however is too low to confirm that major ocular signs are characteristically absent in MFS2. Accordingly, all patients proven or suspected to be affected by MFS with negative FBN1 gene screening could benefit from rapid investigation of the TGFBR2 gene.

Pointing out mechanisms underlying joint action.

Recent studies have shown that spatial and feature-based attention can contribute to inducing a spatial compatibility effect in both the standard Simon task and the joint Simon task. Less work generally has been devoted to investigating how attention modulates spatial compatibility effects. In the present study, we aimed to explore whether indirectly manipulating the degree of attention necessary to respond to a compatible or an incompatible stimulus can modulate the spatial compatibility effect in a joint Simon task and elicit a compatibility effect in the individual go-no-go Simon task. To this end, we biased spatial attention to the compatible stimulus by asking participants to perform a pointing response always toward the compatible side, regardless of the stimulus location. Crucially, reaction times-recorded at gesture onset-showed a compatibility effect pattern in the individual condition and an additional modulation in the joint condition. These results show that the spatial attention intrinsic to action planning can affect both individual and joint Simon tasks.

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies.

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.

Concurrent visual and tactile steady-state evoked potentials index allocation of inter-modal attention: a frequency-tagging study.

We investigated effects of inter-modal attention on concurrent visual and tactile stimulus processing by means of stimulus-driven oscillatory brain responses, so-called steady-state evoked potentials (SSEPs). To this end, we frequency-tagged a visual (7.5Hz) and a tactile stimulus (20Hz) and participants were cued, on a trial-by-trial basis, to attend to either vision or touch to perform a detection task in the cued modality. SSEPs driven by the stimulation comprised stimulus frequency-following (i.e. fundamental frequency) as well as frequency-doubling (i.e. second harmonic) responses. We observed that inter-modal attention to vision increased amplitude and phase synchrony of the fundamental frequency component of the visual SSEP while the second harmonic component showed an increase in phase synchrony, only. In contrast, inter-modal attention to touch increased SSEP amplitude of the second harmonic but not of the fundamental frequency, while leaving phase synchrony unaffected in both responses. Our results show that inter-modal attention generally influences concurrent stimulus processing in vision and touch, thus, extending earlier audio-visual findings to a visuo-tactile stimulus situation. The pattern of results, however, suggests differences in the neural implementation of inter-modal attentional influences on visual vs. tactile stimulus processing.

Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1.

Late-stage neuropathological hallmarks of Alzheimer's disease (AD) are ß-amyloid (ßA) and hyperphosphorylated tau peptides, aggregated into plaques and tangles, respectively. Corresponding phenotypes have been mimicked in existing transgenic mice, however, the translational value of aggressive over-expression has recently been questioned. As controlled gene expression may offer animal models with better predictive validity, we set out to design a transgenic mouse model that circumvents complications arising from pronuclear injection and massive over-expression, by targeted insertion of human mutated amyloid and tau transgenes, under the forebrain- and neurone-specific CaMKIIα promoter, termed PLB1(Double). Crossing with an existing presenilin 1 line resulted in PLB1(Triple) mice. PLB1(Triple) mice presented with stable gene expression and age-related pathology of intra-neuronal amyloid and hyperphosphorylated tau in hippocampus and cortex from 6 months onwards. At this early stage, pre-clinical (18)FDG PET/CT imaging revealed cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain. Quantitative EEG analyses yielded heightened delta power during wakefulness and REM sleep, and time in wakefulness was already reliably enhanced at 6 months of age. These anomalies were paralleled by impairments in long-term and short-term hippocampal plasticity and preceded cognitive deficits in recognition memory, spatial learning, and sleep fragmentation all emerging at ∼12 months. These data suggest that prodromal AD phenotypes can be successfully modelled in transgenic mice devoid of fibrillary plaque or tangle development. PLB1(Triple) mice progress from a mild (MCI-like) state to a more comprehensive AD-relevant phenotype, which are accessible using translational tools such as wireless EEG and microPET/CT.

Transcriptomic and proteomic analysis in the cardiovascular setting: unravelling the disease?

Whole gene expression analysis through microarray technologies revolutionized the manner of identifying changes in biological events and complex diseases, such as cardiovascular settings. These new methodologies may scan up to 35 000 transcripts at once rather than screening a small amount of genes one at a time. The ability of microarrays to provide a broad insight into the disease process directly within the tissues provides a unique insight into the intracellular perturbations of the cell organization and function and sheds an entirely unique new perspective on the heart failure process. Commonalities and differences at the molecular level will identify critical pathways of pathogenesis, and response to therapy, or both: indeed, gene expression profiling holds tremendous promise for classifying clinical phenotypes, developing prognostic predictors and, most importantly, providing novel unbiased insights into the mechanisms underlying heart disease and, eventually, novel causative genes. On the contrary, established proteomic technologies, together with the new alternative strategies currently under evaluation (i.e. metabolomics), are now making possible the translation of data obtained on the bench to the daily clinical routine with the discovery of new diagnostic/prognostic biomarkers (such as troponin for ACS and BNP for congestive heart failure) and the identification of new therapeutic approaches for combating heart diseases. Finally, genomic studies (including transcriptomics) together with proteomics should not represent a challenge for who is going to win the final battle, but rather they should provide a setting in which together and in a complementary fashion the final fight against heart disease can be won.

Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 genes.

Barth syndrome is an X-linked recessive disorder caused by the tafazzin (TAZ) gene mutations and includes dilated cardiomyopathy (DCM) with left ventricular non-compaction, neutropenia, skeletal myopathy, abnormal mitochondria and 3-methylglutaconic aciduria. Dilated cardiomyopathy with left ventricular non-compaction transmitted as an autosomal dominant condition has also been associated with LIM domain-binding 3 (LDB3) gene defects. We describe a family in which the 12-year-old proband had left ventricular non-compaction and DCM. His mother had five miscarriages, two other sons who died in infancy, and a healthy son and daughter. The proband showed left ventricular non-compaction-DCM, skeletal myopathy, recurrent oral aphthous ulcers and cyclic neutropenia. The DCM progressively improved with age; medical therapy was discontinued at 5 years of age. At present, left ventricular function is normal and arrhythmias are absent. Magnetic resonance imaging documented left ventricular non-compaction. However, oral aphthous ulcers and cyclic neutropenia have recurred. In the proband we identified two novel mutations, one of maternal origin in the TAZ gene (p.[Glu202ValfsX15]) and one of paternal origin in the LDB3 gene (p.[Thr350Ile]). The mother, brother and father are healthy; although the latter two show prominent left ventricle trabeculation without dysfunction. Expression studies of TAZ and LDB3 genes were conducted in family members and controls. In the proband, brother and father, LDB3 expression was similar to control cases. TAZ and LDB3 expression progressively declined with age in control both blood and myocardial samples. However, an endomyocardial biopsy performed in the proband at 6 months of age, showed significantly lower TAZ and LDB3 expression than in age-matched myocardial controls. We believe that the clinical, genetic and expression data support the hypothesis that tafazzins are essential during fetal and early post-natal life.