SignificanceLocus coeruleus (LC) integrity in cognitively normal older adults is a potentially important preclinical marker in dementia. Our study establishes a link between variability in LC integrity and cognitive decline related to noradrenergic modulation in old age. We find that in older adults, reduced LC integrity explains lower memory performance. This effect was more pronounced for memory related to negative events, and accompanied by increased pupil diameter size in response to negative events. The study provides a strong motivation for future research investigating the role of LC integrity in healthy, as well as in pathological, aging.

Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes with the strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.

Adolescents are prone to social influence from peers, with implications for development, both adaptive and maladaptive. Here, using a computer-based paradigm, we replicate a cross-sectional effect of more susceptibility to peer influence in a large dataset of adolescents 14 to 24 years old. Crucially, we extend this finding by adopting a longitudinal perspective, showing that a within-person susceptibility to social influence decreases over a 1.5 year follow-up time period. Exploiting this longitudinal design, we show that susceptibility to social influences at baseline predicts an improvement in peer relations over the follow-up period. Using a Bayesian computational model, we demonstrate that in younger adolescents a greater tendency to adopt others’ preferences arises out of a higher uncertainty about their own preferences in the paradigmatic case of delay discounting (a phenomenon called ‘preference uncertainty’). This preference uncertainty decreases over time and, in turn, leads to a reduced susceptibility of one’s own behaviour to an influence from others. Neuro-developmentally, we show that a measure of myelination within medial prefrontal cortex, estimated at baseline, predicts a developmental decrease in preference uncertainty at follow-up. Thus, using computational and neural evidence, we reveal adaptive mechanisms underpinning susceptibility to social influence during adolescence.

Compulsive behavior is enacted under a belief that a specific act controls the likelihood of an undesired future event. Compulsive behaviors are widespread in the general population despite having no causal relationship with events they aspire to influence. In the current study, we tested whether there is an increased tendency to assign value to aspects of a task that do not predict an outcome (i.e., outcome-irrelevant learning) among individuals with compulsive tendencies. We studied 514 healthy individuals who completed self-report compulsivity, anxiety, depression, and schizotypal measurements, and a well-established reinforcement-learning task (i.e., the two-step task). As expected, we found a positive relationship between compulsivity and outcome-irrelevant learning. Specifically, individuals who reported having stronger compulsive tendencies (e.g., washing, checking, grooming) also tended to assign value to response keys and stimuli locations that did not predict an outcome. Controlling for overall goal-directed abilities and the co-occurrence of anxious, depressive, or schizotypal tendencies did not impact these associations. These findings indicate that outcome-irrelevant learning processes may contribute to the expression of compulsivity in a general population setting. We highlight the need for future research on the formation of non-veridical action−outcome associations as a factor related to the occurrence and maintenance of compulsive behavior.

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Positive self-beliefs are important for well-being, and are influenced by how others evaluate us during social interactions. Mechanistic accounts of self-beliefs have mostly relied on associative learning models. These account for choice behaviour but not for the explicit beliefs that trouble socially anxious patients. Neither do they speak to selfschemas, which underpin vulnerability according to psychological research. Here, we compared belief-based and associative computational models of social-evaluation, in individuals that varied in fear of negative evaluation (FNE), a core symptom of social anxiety. We used a novel analytic approach, 'clinically informed model-fitting', to determine the influence of FNE symptom scores on model parameters. We found that high-FNE participants learn more easily from negative feedback about themselves, manifesting in greater self-negative learning rates. Crucially, we provide evidence that this bias is underpinned by an overall reduced belief about self-positive attributes. The study population could be characterized equally well by belief-based or associative models, however large individual differences in model likelihood indicated that some individuals relied more on an associative (model-free), while others more on a belief-guided strategy. Our findings have therapeutic importance, as positive belief activation may be used to specifically modulate learning.

Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14–24 y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.

A better memory for negative emotional events is often attributed to a conjoint impact of increased arousal and noradrenergic modulation. A decline in noradrenergic modulation (NA) during ageing is well documented but its impact on memory function during ageing is unclear. Using pupil diameter (PD) as a proxy for noradrenergic modulation, we examined age differences in memory for negative events in younger (18-30 years) and older (62-83 years) adults based upon a segregation of early arousal to negative events, and later retrieval related PD responses. In keeping with the hypothesis of reduced age-related NA influences, older adults showed attenuated induced PD responses to negative emotional events. The findings highlight a likely contribution of noradrenergic modulation to negative emotional memory, mediated via arousal that may be compromised with ageing.