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Communications biology 5(1), 1297 (2022). doi:10.1038/s42003-022-04244-5, Identifying associations between interindividual variability in brain structure and behaviour requires large cohorts, multivariate methods, out-of-sample validation and, ideally, out-of-cohort replication. Moreover, the influence of nature vs nurture on brain-behaviour associations should be analysed. We analysed associations between brain structure (grey matter volume, cortical thickness, and surface area) and behaviour (spanning cognition, emotion, and alertness) using regularized canonical correlation analysis and a machine learning framework that tests the generalisability and stability of such associations. The replicability of brain-behaviour associations was assessed in two large, independent cohorts. The load of genetic factors on these associations was analysed with heritability and genetic correlation. We found one heritable and replicable latent dimension linking cognitive-control/executive-functions and positive affect to brain structural variability in areas typically associated with higher cognitive functions, and with areas typically associated with sensorimotor functions. These results revealed a major axis of interindividual behavioural variability linking to a whole-brain structural pattern., Published by Springer Nature, London

Social interactions are severely impaired in major depression and social anxiety. Social interactions associated with fairness have been studied using the Ultimatum Game (UG). In the UG, the responder receives an offer from a proposer about how to divide a sum of money. If the responder accepts the offer, both accumulate the money. If the responder rejects the offer, both accumulates nothing. The UG is comprised by fair (the responder is offered between 40-50% of the total amount of the offer), medium (the responder is offered between 27-33%) and unfair offers (the responder is offered between 18-23%). Previous studies have reported that at least two event-related potentials (ERPs) are modulated by fairness during the UG: the Medial Frontal Negativity (MFN) and the Late Positive Potential/P300 (LPP/P300). To our knowledge, there are no studies analysing ERPs in the UG in major depression and/or social anxiety. We aimed to study the MFN, the LPP/P300, the behavior and the emotions experienced during the UG in healthy volunteers (Control group, n = 72) and volunteers with symptoms of major depression and/or social anxiety (MD/SA group, n = 63). As expected, we found that the rejection of offers increased as the unfairness increased. Also, the medium offers were associated with longer reaction times than unfair offers, and in turn unfair offers were associated with longer reaction times than fair offers. In addition, participants reported less positive emotions and more negative emotions as the unfairness increased. Interestingly, in comparison with the Control group, the MD/SA group reported feeling more sadness in all offers, and specially in medium and unfair offers. The MFN was associated with more negative mean amplitudes in medium and unfair offers than in fair offers. This component would be modulated by the negative emotional/motivational impact caused by unfairness. Another plausible interpretation is that the volunteers would expect fair offers during the task, and that the unexpected medium and unfair offers would be associated with error predictions that would evoke the MFN. Interestingly, our results showed a borderline main effect of group in the MFN, suggesting that this component was associated with more negative mean amplitudes in the MD/SA group in comparison with the Control group, across all offers. This effect would be associated with enhanced negative emotions experienced during all levels of fairness during the UG in the MD/SA group, in comparison to controls. In addition, the LPP/P300 was associated with more positive mean amplitudes in fair offers in comparison with unfair offers, and with more positive mean amplitudes in unfair offers in comparison with medium offers. This result would indicate that fair offers would be associated with more arousal than unfair and medium offers, and that in turn unfair offers would be associated with more arousal than medium offers. An alternative interpretation is that the LPP/P300 would be modulated by the conflict associated with the decision-making of each level of fairness. In this line, the LPP/P300 would be more positive in fair, less conflictive offers in comparison with unfair and medium offers. In turn, this component would be more positive in unfair offers in comparison with medium offers, given that the medium offers are the most conflicting. Of note, the LPP/P300 was associated with more negative mean amplitudes in the MD/SA group in comparison with the Control group across all offers. This result could be related to less arousal and/or motivation in the MD/SA group in comparison with the Control group. Alternatively, this effect could be related to less attentional resources available to allocate to the task in the MD/SA group in comparison with controls. The lack of attentional resources in the MD/SA group could be due to the activation of other cognitive processes, such as rumination, which would compete for the cognitive resources available. Another interpretation is that this effect could be related to higher levels of conflict experienced during all offers by the MD/SA group. We aim to contribute to the understanding of social functioning and the neural basis associated with these processes in major depression and social anxiety. Las interacciones sociales se encuentran severamente afectadas en la depresión mayor y en la ansiedad social. Ciertos procesos relacionados a interacciones sociales justas e injustas se han estudiado utilizando el Ultimatum Game (UG). Durante el UG, el responder recibe ofertas de un proposer acerca de cómo dividir una cantidad de dinero. Si el responder acepta la oferta, ambos acumulan el dinero. Si el responder rechaza la oferta, ninguno acumulan nada. Durante el UG hay ofertas justas (al responder le ofrecen entre el 40-50% del total), medias (le ofrecen 27-33%) e injustas (le ofrecen 18-23%). Se ha reportado que al menos dos potenciales relacionados a eventos (ERPs, por la sigla en inglés para Event-Related Potentials) son modulados por la justicia durante el UG: el Medial Frontal Negativity (MFN) y el Late Positive Potential/P300 (LPP/P300). A nuestro conocimiento, no hay estudios que analicen ERPs durante el UG en depresión mayor y/o ansiedad social. Este proyecto tuvo como objetivo estudiar el MFN, el LPP/P300, el comportamiento y las emociones experimentadas durante el UG en personas sin historia de trastornos mentales (grupo Control, n = 72) y personas con síntomas de depresión mayor y/o ansiedad social (grupo MD/SA, n = 63). Como era esperado, la tasa de rechazo aumentó a medida que aumentaba la injusticia. Además, los tiempos de reacción fueron mayores en las ofertas medias en comparación a las injustas, y mayores en las ofertas injustas en comparación a las justas. Asimismo, los participantes reportaron más emociones negativas y menos emociones positivas a medida que aumentaba la injusticia. Cabe señalar que el grupo MD/SA reportó mayores niveles de tristeza en todas las ofertas, y especialmente en las ofertas medias e injustas. Además, el MFN se asoció a una amplitud media más negativa en las ofertas medias e injustas en comparación a las justas, lo que reflejaría el impacto emocional/motivacional negativo causado por la injusticia. Otra explicación posible es que los voluntarios esperarían recibir ofertas justas durante el UG, y que las ofertas medias e injustas inesperadas se asociarían a un error de predicción que modularía el MFN. Cabe destacar que se encontró una tendencia en el efecto principal de grupo en el MFN, sugiriendo que, en todas las ofertas, el MFN estaría asociado a una amplitud media más negativa en el grupo MD/SA en comparación al grupo Control. Este efecto estaría relacionado con emociones negativas acentuadas durante todas las ofertas en el grupo MD/SA en comparación al grupo Control. Asimismo, el LPP/P300 se asoció a una amplitud media más positiva durante ofertas justas en comparación a injustas, y con una amplitud media más positiva durante ofertas injustas en comparación a medias. Este resultado indicaría que las ofertas justas se asociarían con mayores niveles de arousal en comparación a las ofertas injustas y medias, y que las ofertas injustas se asociarían a mayores niveles de arousal que las ofertas medias. Una explicación alternativa es que el LPP/P300 sería modulado por el nivel de conflicto en la toma de decisiones. En este sentido, el LPP/P300 aparecería más positivo en las ofertas justas, que son las menos conflictivas, en comparación a ofertas injustas y medias. A su vez, el LPP/P300 se asociaría a amplitudes medias más negativas en las ofertas medias, dado que son las más conflictivas, en comparación a justas e injustas. Cabe resaltar que el LPP/P300 se asoció con una amplitud media más negativa en el grupo MD/SA que en el grupo Control en todas las ofertas. Este resultado podría estar asociado a menores niveles de arousal y/o motivación en el grupo MD/SA en comparación al grupo Control. Alernativamente, este efecto podría estar asociado a menores recursos atencionales disponibles para asignar a la tarea en el grupo MD/SA en comparación al grupo Control. Esto podría deberse a la actividad de otros procesos cognitivos que consumirían recursos cognitivos, como por ejemplo, rumia. Otra interpretación es que este efecto podría deberse a mayores niveles de conflicto experimentado en todas las ofertas en el grupo MD/SA. Esperamos contribuir al entendimiento del funcionamiento social y de las bases neurales asociadas a estos procesos en la depresión mayor y la ansiedad social.

Cooperation upholds life in organized societies, but its neurobiological mechanisms remain unresolved. Recent theoretical analyses have contrasted cooperation by its fast versus slower modes of decision making. This raises the question of the neural timescales involved in the integration of decision-related information, and of the participating neural circuits. Using time-resolved electroencephalography (EEG) methods, we characterized relevant neural signatures of feedback processing at the iterated prisoner’s dilemma (iPD), an economic task that addresses cooperation-based exchange between social agents. We then probed the ability of relevant EEG signals to indicate subsequent decision-making, and inspected game and behavioral conditions under which they do so - including timing. Participants played against an assumed co-player, and the neural activation at the game feedback stage was analyzed via event-related potential (ERP) and spectrotemporal analysis methods. As expected from value-based decision-making studies, ERPs were increased by cooperation, including the feedback-related negativity (FRN) and the P3. In addition, we report a late potential (LP) lateralized to left frontal regions, which was also modulated by cooperation. Slow-wave, delta-band activity associated to the LP component (termed ‘LP-delta’) was also found to be reduced for mutual versus one-sided cooperation feedback. We then addressed individually which of these feedback signals related to subsequent cooperation and when. Crucially, the FRN, P3 and LP-delta components were modulated by choice at the next round, although involvement of each component was contingent upon the current outcome type. Immediately after one-sided cooperation (‘sucker’s payoff’), differential signaling indicating future decision-making occurred at the relatively early FRN, decreasing in amplitude for player choices not to cooperate at the next round. For outcomes where the player did not cooperate at the co-player expense, P3 increases were associated with subsequent cooperation by the player. Following mutual cooperation rounds, and at a relatively late stage of feedback processing, modulations by forthcoming decision were found in the form of LP-delta desynchronizations that were prospective of further cooperation. We note that the decision to cooperate in the game can be based on predicting different aspects of the prospective interaction given the past realized outcome (e.g. whether ‘to sustain’ mutual cooperation or ‘to retaliate’ if it is one-sided). The results support information integration for cooperation decision-making at the iPD, beginning at different timescales and circuits, by such updating context. The specific case of verifying a partner’s cooperation entailed a shorter reciprocation response which was predictable by feedback signal changes at the immediately preceding trial. A neurally informed account of fast-mode dual-process mechanisms, and involvement of predictive coding principles in guiding cooperation with a partner at the iPD, are discussed. Highlights *FRN, P3 and late delta-band asymmetric frontal activity encode cooperation feedback *Decision to cooperate in iterated prisoner’s dilemma indicated by prior round signals *Speed of reciprocating partner’s cooperation correlates with single-trial activity