Prior Reward Conditioning Dampens Hippocampal and Striatal Responses during an Associative Memory Task.

Offering reward during encoding typically leads to better memory [Adcock, R. A., Thangavel, A., Whitfield-Gabrieli, S.,Knutson, B., & Gabrieli, J. D. E. Reward-motivated learning: Mesolimbic activation precedes memory formation. Neuron, 50, 507-517, 2006]. Whether such memory benefit persists when tested in a different task context remains, however, largely understudied [Wimmer, G. E., & Buechel, C. Reactivation of reward-related patterns from single past episodes supports memory-based decision making. Journal of Neuroscience, 36, 2868-2880, 2016]. Here, we ask whether reward at encoding leads to a generalized advantage across learning episodes, a question of high importance for any everyday life applications, from education to patient rehabilitation. Although we confirmed that offering monetary reward increased responses in the ventral striatum and pleasantness judgments for pictures used as stimuli, this immediate beneficial effect of reward did not carry over to a subsequent and different picture-location association memory task during which no reward was delivered. If anything, a trend for impaired memory accuracy was observed for the initially high-rewarded pictures as compared to low-rewarded ones. In line with this trend in behavioral performance, fMRI activity in reward (i.e., ventral striatum) and in memory (i.e., hippocampus) circuits was reduced during the encoding of new associations using previously highly rewarded pictures (compared to low-reward pictures). These neural effects extended to new pictures from same, previously highly rewarded semantic category. Twenty-four hours later, delayed recall of associations involving originally highly rewarded items was accompanied by decreased functional connectivity between the hippocampus and two brain regions implicated in value-based learning, the ventral striatum and the ventromedial PFC. We conclude that acquired reward value elicits a downward value-adjustment signal in the human reward circuit when reactivated in a novel nonrewarded context, with a parallel disengagement of memory-reward (hippocampal-striatal) networks, likely to undermine new associative learning. Although reward is known to promote learning, here we show how it may subsequently hinder hippocampal and striatal responses during new associative memory formation.

Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6- interleukin-10+ cytokine patterns in ST-elevation acute myocardial infarction.

RATIONALE: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6(+)) levels or very low-IL-6(-) levels. OBJECTIVE: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response. METHODS AND RESULTS: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6(+) STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6(-) STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6(+) STEMI and IL-6(-) STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6(+) STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1ß, and monokine induced by interferon-γ. IL-10 was increased both in IL-6(+) STEMI and IL-6(-) STEMI patients compared with controls. IL-6(+)IL-10(+) STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6(-)IL-10(+) STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death. CONCLUSIONS: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies.

Reward-enhanced encoding improves relearning of forgotten associations.

Research on human memory has shown that monetary incentives can enhance hippocampal memory consolidation and thereby protect memory traces from forgetting. However, it is not known whether initial reward may facilitate the recovery of already forgotten memories weeks after learning. Here, we investigated the influence of monetary reward on later relearning. Nineteen healthy human participants learned object-location associations, for half of which we offered money. Six weeks later, most of these associations had been forgotten as measured by a test of declarative memory. Yet, relearning in the absence of any reward was faster for the originally rewarded associations. Thus, associative memories encoded in a state of monetary reward motivation may persist in a latent form despite the failure to retrieve them explicitly. Alternatively, such facilitation could be analogous to the renewal effect observed in animal conditioning, whereby a reward-associated cue can reinstate anticipatory arousal, which would in turn modulate relearning. This finding has important implications for learning and education, suggesting that even when learned information is no longer accessible via explicit retrieval, the enduring effects of a past prospect of reward could facilitate its recovery.

Influence of reward motivation on human declarative memory.

Motivational relevance can prioritize information for memory encoding and consolidation based on reward value. In this review, we pinpoint the possible psychological and neural mechanisms by which reward promotes learning, from guiding attention to enhancing memory consolidation. We then discuss how reward value can spill-over from one conditioned stimulus to a non-conditioned stimulus. Such generalization can occur across perceptually similar items or through more complex relations, such as associative or logical inferences. Existing evidence suggests that the neurotransmitter dopamine boosts the formation of declarative memory for rewarded information and may also control the generalization of reward values. In particular, temporally-correlated activity in the hippocampus and in regions of the dopaminergic circuit may mediate value-based decisions and facilitate cross-item integration. Given the importance of generalization in learning, our review points to the need to study not only how reward affects later memory but how learned reward values may generalize to related representations and ultimately alter memory structure.

Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity.

Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity.

How musical training affects cognitive development: rhythm, reward and other modulating variables.

Musical training has recently gained additional interest in education as increasing neuroscientific research demonstrates its positive effects on brain development. Neuroimaging revealed plastic changes in the brains of adult musicians but it is still unclear to what extent they are the product of intensive music training rather than of other factors, such as preexisting biological markers of musicality. In this review, we synthesize a large body of studies demonstrating that benefits of musical training extend beyond the skills it directly aims to train and last well into adulthood. For example, children who undergo musical training have better verbal memory, second language pronunciation accuracy, reading ability and executive functions. Learning to play an instrument as a child may even predict academic performance and IQ in young adulthood. The degree of observed structural and functional adaptation in the brain correlates with intensity and duration of practice. Importantly, the effects on cognitive development depend on the timing of musical initiation due to sensitive periods during development, as well as on several other modulating variables. Notably, we point to motivation, reward and social context of musical education, which are important yet neglected factors affecting the long-term benefits of musical training. Further, we introduce the notion of rhythmic entrainment and suggest that it may represent a mechanism supporting learning and development of executive functions. It also hones temporal processing and orienting of attention in time that may underlie enhancements observed in reading and verbal memory. We conclude that musical training uniquely engenders near and far transfer effects, preparing a foundation for a range of skills, and thus fostering cognitive development.

Working memory load attenuates emotional enhancement in recognition memory.

Emotionally arousing stimuli are perceived and remembered better than neutral stimuli. Under threat, this negativity bias is further increased. We investigated whether working memory (WM) load can attenuate incidental memory for emotional images. Two groups of participants performed the N-back task with two WM load levels. In one group, we induced anxiety using a threat of shock paradigm to increase attentional processing of negative information. During task performance we incidentally and briefly flashed emotional distracter images which prolonged response times in both load conditions. A subsequent unannounced immediate recognition memory test revealed that when load at exposure had been low, recognition was better for negative items in both participant groups. This enhancement, however, was attenuated under high load, leaving performance on neutral items unchanged regardless of the threat of shock manipulation. We conclude that both in threat and in normal states WM load at exposure can attenuate immediate emotional memory enhancement.