Despite attempts to unify the different theoretical accounts of the mismatch negativity (MMN), there is still an ongoing debate on the neurophysiological mechanisms underlying this complex brain ...response. On one hand, neuronal adaptation to recurrent stimuli is able to explain many of the observed properties of the MMN, such as its sensitivity to controlled experimental parameters. On the other hand, several modeling studies reported evidence in favor of Bayesian learning models for explaining the trial-to-trial dynamics of the human MMN. However, direct comparisons of these two main hypotheses are scarce, and previous modeling studies suffered from methodological limitations. Based on reports indicating spatial and temporal dissociation of physiological mechanisms within the timecourse of mismatch responses in animals, we hypothesized that different computational models would best fit different temporal phases of the human MMN. Using electroencephalographic data from two independent studies of a simple auditory oddball task (n = 82), we compared adaptation and Bayesian learning models' ability to explain the sequential dynamics of auditory deviance detection in a time-resolved fashion. We first ran simulations to evaluate the capacity of our design to dissociate the tested models and found that they were sufficiently distinguishable above a certain level of signal-to-noise ratio (SNR). In subjects with a sufficient SNR, our time-resolved approach revealed a temporal dissociation between the two model families, with high evidence for adaptation during the early MMN window (from 90 to 150-190 ms post-stimulus depending on the dataset) and for Bayesian learning later in time (170-180 ms or 200-220ms). In addition, Bayesian model averaging of fixed-parameter models within the adaptation family revealed a gradient of adaptation rates, resembling the anatomical gradient in the auditory cortical hierarchy reported in animal studies.
We argue that many of the crises currently afflicting science can be associated with a present failure of science to sufficiently embody its own values. Here, we propose a response beyond mere crisis ...resolution based on the observation that an ethical framework of flourishing derived from the Buddhist tradition aligns surprisingly well with the values of science itself. This alignment, we argue, suggests a recasting of science from a competitively managed activity of knowledge production to a collaboratively organized moral practice that puts kindness and sharing at its core. We end by examining how Flourishing Science could be embodied in academic practice, from individual to organizational levels, and how that could help to arrive at a flourishing of scientists and science alike.
Attribution of responsibility for the causes of suffering is one of the main factors that influence responses to individuals in distress. While the role of attributional processes on prosocial ...motivation has been widely investigated in social psychology, only few attempts have been made to characterize their behavioural and neurophysiological underpinnings. This is partly due to the lack of stimuli that can facilitate within-subject experimental designs. To overcome this problem, we created a set of stimuli consisting of videos depicting people in different situations of distress. Each video is paired with short stories that aim to manipulate the perceived degree of responsibility of the main character.
To validate the stimuli, we investigated the effect of different context-video pairs on self-report measures of participants’ subjective experience. We found that different contexts preceding the same video can influence blame and responsibility judgments, affective responses and willingness to help.
In a complementary analysis, we replicated previous findings on the influence of empathy and responsibility on willingness to help, showing how the latter is mediated by moral judgments.
Finally, we observed a general increase in responses times when videos were paired with responsible contexts. We provide interpretations of this finding that can relate attribution accounts to prominent theories in moral psychology.
Overall, this study highlights the possibility of expanding existing theories on prosocial motivation by implementing a set of stimuli that includes multiple scenarios and allows for the collection of third person measures in within-subject designs.
Within western social psychology and neuroscience, compassion is described as being conditioned by cost-benefit appraisals, such as the attribution of responsibility for the causes of suffering. ...Buddhist traditions maintain the possibility of cultivating and embodying unconditioned and universal forms of compassion. Whereas a growing body of empirical literature suggests that Buddhist-inspired compassion-based programs foster prosociality and well-being in healthy and clinical populations, there is no evidence that such compassionate disposition toward others can become unconditioned from moral judgment. To address this question, we collected and integrated self-report and behavioral data from expert Buddhist practitioners and trained novices using a previously validated within-subject experiment that manipulates contextual information to influence moral judgment toward suffering others and a newly designed approach-avoidance task. We found that context manipulation impacted responsibility and blame attribution in both groups and that experts' reported willingness to help was higher and less influenced by context, compared to novices. Partial correlation networks highlighted a negative relationship between blame attribution and willingness to help in novices, but not in expert practitioners. Self-reported willingness to help was correlated to reaction times when approaching suffering stimuli. Approach behavior was modulated by context in novice, but not in experts. This study provides initial evidence of a dissociation between moral attributions and prosocial attitude in expert Buddhist practitioners and challenges established evolutionary accounts of compassion in western psychology.
Public Significance Statement
This study provides initial evidence for a dissociation between moral judgment and prosocial attitude in expert Buddhist practitioners. Findings are in line with Buddhist theories on compassion and contemplative training and expand established theories in social psychology.
The auditory mismatch negativity (MMN) is a well characterized event-related potential component which has gained recent attention in theoretical models describing the impact of various styles of ...mindfulness meditation on attentional processes and perceptual inference. Previous findings highlighted a distinct modulation of the MMN amplitude by different meditation practices and degrees of expertise. In the present study, we attempted to replicate results from the recent literature with a data sample that allowed for increased statistical power compared to previous experiments. Relying on traditional frequentist analysis, we found no effect of focused attention and open monitoring meditation on the auditory MMN amplitude compared to a control condition (silent movie) in expert or novice practitioners (all p > 0.17), providing a non-replication of our previous work (Fucci et al. 2018). Using a Bayesian approach, we found strong evidence against an interaction effect on the MMN amplitude between expertise groups and meditation practices (BF01 = 11.0), strong evidence against effects of either meditation practices compared to the control condition (BF01 between 11.9 and 16.1) and moderate evidence against an effect of expertise during meditation (BF01 between 5.3 and 7.9). On the other hand, we replicated previous evidence of increased alpha oscillatory power during meditation practices compared to a control state (p < 0.001). We discuss our null findings in relation to factors that could undermine the replicability of previous research on this subject, namely low statistical power, use of flexible analysis methods and a possible publication bias leading to a misrepresentation of the available evidence.
•We attempted to replicate previous findings on the effect of different meditation styles on the auditory MMN.•We found no effect of meditation on the auditory MMN using frequentist analysis.•Bayesian analysis yields moderate to strong evidence against effects of meditation practice and expertise.•Null findings are discussed in relation to factors undermining research replicability.
•Novice meditators can be trained to report their phenomenological experience.•Self-reports are associated with history of practice, not with desirable responding.•Balance between focused attention ...(FA) and open monitoring (OM) practices predicts the ability to dissociate them.•Daily practice of FA predicts the felt stability of long sessions.•Total practice of OM predicts phenomenological proficiency.
Empirical descriptions of the phenomenology of meditation states rely on practitioners’ ability to provide accurate information on their experience. We present a meditation training protocol that was designed to equip naive participants with a theoretical background and experiential knowledge that would enable them to share their experience. Subsequently, novices carried on with daily practice during several weeks before participating in experiments. Using a neurophenomenological experiment designed to explore two different meditation states (focused attention and open monitoring), we found that self-reported phenomenological ratings (i) were sensitive to meditation states, (ii) reflected meditation dose and fatigue effects, and (iii) correlated with behavioral measures (variability of response time). Each of these effects was better predicted by features of participants’ daily practice than by desirable responding. Our results provide evidence that novice practitioners can reliably report their experience along phenomenological dimensions and warrant the future investigation of this training protocol with a longitudinal design.
De part sa mise en pratique considérable dans des conditions cliniques, l’étude neuroscientifique de la méditation de pleine conscience a vu un développement rapide ces deux dernières décennies. ...Malgré des preuves de modifications de l’activité et de la structure du cerveau, les mécanismes neuronaux et cognitifs sous tendant les pratiques méditatives sont encore peu connus. Dans le présent travail nous avons testé l’hypothèse que la méditation de pleine conscience implique un changement dans la cognition de l’expérience vécue, impactant de ce fait la formation des habitudes mentales. Pour cela nous avons étudié la relation entre la phénoménologie de différents styles de méditation, chez des pratiquants experts et novices, et des marqueurs neurophysiologiques de l’apprentissage perceptuel (i.e. négativité de discordance auditive) et de l’attention dans des conditions neutres et émotionnelles.Nous avons trouvé qu’un style de méditation non-duel augmente la vigilance sensorielle et réduit l’apprentissage perceptuel comparé à une pratique d’attention focalisée. Par ailleurs, nous avons démontré que l’apprentissage perceptuel auditif n’est pas influencé par une menace non prédictible, à part pour des sujets naturellement plus anxieux ; un effet qui pourrait être diminué par la méditation de pleine conscience. Nous avons aussi identifié des composants de la réponse évoquée auditive comme potentiels corrélats neuraux des processus de vigilance à l‘œuvre lors des états de pleine conscience. Enfin, nous avons mis en évidence, chez des pratiquants experts, un lien direct entre la régulation émotionnelle et des changements de l’expérience subjective.Au final, le travail actuel enrichit le dialogue entre les neurosciences cognitives et les modèles phénoménologiques de la méditation en apportant des preuves sur les possibles mécanismes neurocognitifs sous-tendant les pratiques méditatives et leur expertise
Due to its widespread implementation in clinical settings, the neuroscientific study of mindfulness meditation has seen a rapid growth in the last two decades. Despite the evidence of changes in brain activity and structures, the neurocognitive mechanisms underlying meditation practices are largely unknown. In this work, we investigated the hypothesis that mindfulness meditation entails a cognitive stance towards experience which impacts the formation of mental habits. With this aim, we studied the relationship between the phenomenology of different styles of mindfulness meditation, in expert and novice practitioners, and neurophysiological markers of perceptual learning (i.e. auditory mismatch negativity) and attention in neutral and emotional settings. We found that a nondual style of mindfulness meditation increased sensory monitoring and reduced perceptual learning compared to a focused attention practice. Additionally, we demonstrated that auditory perceptual learning is not affected by unpredictable threat, except for individuals with high dispositional anxiety; an effect that might be downregulated by meditation states. Finally, we identified components of the auditory evoked response as putative neural correlates of monitoring processes during mindfulness practices and we highlighted a direct link between changes in subjective experience and emotion regulation in expert practitioners.Overall, the present work fosters the dialogue between cognitive neuroscience and phenomenological models of meditation and provides evidence of the possible neurocognitive mechanisms underlying meditation practices and expertise
FAM46C is a non-canonical poly(A) polymerase uniquely mutated in up to 20% of multiple myeloma (MM) patients, implying a tissue-specific tumor suppressor function. Here, we report that FAM46C ...selectively stabilizes mRNAs encoding endoplasmic reticulum (ER)-targeted proteins, thereby concertedly enhancing the expression of proteins that control ER protein import, folding, N-glycosylation, and trafficking and boosting protein secretion. This role requires the interaction with the ER membrane resident proteins FNDC3A and FNDC3B. In MM cells, FAM46C expression raises secretory capacity beyond sustainability, inducing ROS accumulation, ATP shortage, and cell death. FAM46C activity is regulated through rapid proteasomal degradation or the inhibitory interaction with the ZZ domain of the autophagic receptor p62 that hinders its association with FNDC3 proteins via sequestration in p62+ aggregates. Altogether, our data disclose a p62/FAM46C/FNDC3 circuit coordinating sustainable secretory activity and survival, providing an explanation for the MM-specific oncosuppressive role of FAM46C and uncovering potential therapeutic opportunities against cancer.
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•In myeloma cells, FAM46C boosts ER growth and Ig secretion beyond sustainability•The ER-expanding activity of FAM46C requires its interaction with FNDC3 proteins•FAM46C abundance is tightly regulated by UPS-operated proteolysis•p62 compensates for UPS insufficiency by sequestering FAM46C away from the ER
Fucci et al. show that the poly(A) polymerase FAM46C acts as a multiple myeloma-specific tumor suppressor, increasing secretory capacity and antibody production beyond sustainability via its interaction with endoplasmic reticulum transmembrane FNDC3 proteins. Moreover, its activity is restricted through proteasomal degradation or p62-dependent aggregation and sequestration from FNDC3 proteins.
Introduction: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. End-stage kidney disease ...patients on dialysis are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Vaccination on dialysis patients (DP) still remains challenging because of the variable response and a low seroconversion rate compared with healthy participants (HP). Therefore, it is urgently necessary to establish a different vaccination strategy for DP, in terms of the dose and administration time. Methods: Here, we report an observational prospective cohort study in which the immunogenic efficacies of SARS-CoV-2 vaccine BNT162b2 on DP and HP were evaluated by absolute quantification of IgG levels in the blood. Results: DP showed a delayed seroconversion after two vaccine doses, with a low absolute IgG levels compared to HP. While HP reached complete seroconversion within 10 days from the administration of a second dose, only 76% of DP were seropositive. After the booster dose, DP had a strongly improved seroconversion rate as well as antibody levels, reaching 97% seropositivity and 50 times enhancement on antibody levels. Discussion/Conclusion: These results prompt to suggest an additional vaccine dose in DP, reducing the interval of time from the second dose. Since limited data are available on immune response in DP overtime after three vaccine doses currently, our study is among the first reports demonstrating the improved seropositivity and IgG levels in DP after the booster vaccine dose.
The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory ...mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest structural diversity is observed.
To investigate the degree of conservation in cis-regulatory components that form the basis of Hox expression in the anterior nervous system, we have used assays for transcriptional activity in ascidians and vertebrates to compare and contrast regulatory potential. We identified four regulatory sequences located near the CiHox1, CiHox2 and CiHox4 genes of the ascidian Ciona intestinalis which direct neural specific domains of expression. Using functional assays in Ciona and vertebrate embryos in combination with sequence analyses of enhancer fragments located in similar positions adjacent to Hox paralogy group genes, we compared the activity of these four Ciona cis-elements with a series of neural specific enhancers from the amphioxus Hox1-3 genes and from mouse Hox paralogous groups 1-4.
This analysis revealed that Kreisler and Krox20 dependent enhancers critical in segmental regulation of the hindbrain appear to be specific for the vertebrate lineage. In contrast, neural enhancers that function as Hox response elements through the action of Hox/Pbx binding motifs have been conserved during chordate evolution. The functional assays reveal that these Hox response cis-elements are recognized by the regulatory components of different and extant species. Together, our results indicate that during chordate evolution, cis-elements dependent upon Hox/Pbx regulatory complexes, are responsible for key aspects of segmental Hox expression in neural tissue and appeared with urochordates after cephalochordate divergence.
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