Rapid CommunicationLocus coeruleus neuromodulation of memories encoded during negative or unexpected action outcomes
Introduction
Adaptive behavior relies on the ability to encode and remember information associated with sub-optimal or unexpected performance outcomes. Autonomic arousal contributes to this process by signaling erroneous action outcomes (Ullsperger et al., 2010, Wessel et al., 2011) and facilitating learning when task demands fluctuate unpredictably (Raizada and Poldrack, 2007, Yu and Dayan, 2005). Such behaviorally relevant events activate the locus coeruleus (LC), a small brainstem nucleus that serves as the primary supplier of norepinephrine (NE) to the neocortex, (Berridge & Waterhouse, 2003), which in turn initiates a central orienting response that helps reallocate attentional resources to adjust and optimize task performance (Aston-Jones and Bloom, 1981, Aston-Jones and Cohen, 2005, Aston-Jones et al., 1997, Bouret and Sara, 2005; Clayton et al., 2004). This framework is supported by evidence showing that neurophysiological markers of LC activity, including increased pupil dilation (Critchley et al., 2005, Rajkowski et al., 1993) and a greater P3 component of event-related potentials (Nieuwenhuis, Aston-Jones, & Cohen, 2005), accompany salient action outcomes, such as errors. In light of these convergent findings, it has been proposed that LC activity promotes both error perception (Ullsperger et al., 2010) and learning during unexpected uncertainty (Yu & Dayan, 2005).
The LC–NE system also augments memory encoding and consolidation of arousing stimuli, particularly during stress (McGaugh & Roozendaal, 2002). Exposure to acute stressors elevates the stress hormones NE and cortisol which each selectively strengthen memory for events associated with their release (Schwabe, Joëls, Roozendaal, Wolf, & Oitzl, 2011). For instance, neuroimaging studies have demonstrated that LC activity increases during successful encoding of emotionally arousing images (Sterpenich et al., 2006) and neutral images encoded under stress (Qin, Hermans, van Marle, & Fernández, 2012). Given the importance of LC neuromodulation in both behavioral adjustments and memory, it is possible that the LC interacts with higher brain regions to promote memory of information associated with salient performance feedback. To our knowledge, no previous study has tested this hypothesis in humans.
The goal of the present study was to determine whether feedback-related functional interactions between the LC and rest of the brain predicted subsequent memory for photo-objects associated with specific performance outcomes. To this end, we used functional magnetic resonance imaging (fMRI) to examine LC functional connectivity during the feedback period of a monetary incentive delay (MID) task (e.g., Knutson et al., 2000, Mather and Schoeke, 2011). Approximately 25 min prior to task-related scanning, a cold pressor stressor (CPS) was used to induce stress, as measured by an increase in the stress hormone cortisol that peaks approximately 15–30 min after stressor onset (Dickerson & Kemeny, 2004). Given evidence that the LC responds to both reward and punishment (Bouret and Sara, 2004, Sara and Segal, 1991), we modeled brain activity during positive and negative feedback periods. Previous research suggests that positive outcomes relate to dopamine release (Adcock, Thangavel, Whitfield-Gabrieli, Knutson, & Gabrieli, 2006), whereas memory for aversive events has been consistently linked to activity in central nodes within the LC–NE system, including the amygdala (Murty et al., 2012, Sterpenich et al., 2006), insula (Rasch et al., 2009), and LC itself (Knutson et al., 2000). Thus, we hypothesized that enhanced functional connectivity between the LC and aversive-related memory processing regions would predict subsequent memory for pictures encoded in negative but not positive feedback trials. Motivated by evidence that the LC also promotes learning during unexpected uncertainty (Yu & Dayan, 2005), we also examined whether patterns of LC activity following low certainty responses (i.e., reaction times that occurred closest to a dynamic response deadline) were associated with memory of pictures in those trials.
Section snippets
2.1 Sample
Twenty-one male participants (age: M = 23.63, SD = 3.95; range = 18–31) underwent scan sessions on two separate days, and were randomly assigned to the stress or control condition on their first day. Scanning was conducted between 2 and 5 p.m. when cortisol levels are relatively stable. Participants also refrained from eating, caffeine intake, and exercise for at least 1 h and sleeping for at least 2 h prior to arrival. All participants provided written informed consent approved by the University of
3.1 Reaction time results
The adaptive response deadline algorithm produced a mean RT hit rate of 60.12% (SD = 2.23%). Since the CPS failed to induce stress, RT performance values and memory data were collapsed across both experimental sessions. We performed two separate 2 × 3 × 2 repeated-measures ANOVAs for RT and memory performance with Feedback (hit or miss), Money (lose, none or win) and Certainty (high or low) modeled as within-subjects factors. The results (in milliseconds) revealed that participants responded faster
4. Discussion
To our knowledge, our results provide the first human evidence that LC functional connectivity with the left anterior insula and DLPFC are associated with later memory for stimuli encoded during negative or uncertain action outcomes, respectively. Our findings support current theories positing a link between noradrenergic activity and action outcomes by showing that LC functional coupling may be a common neural mechanism underlying both the monitoring and encoding of negative or surprising
Acknowledgments
We thank Zara Abrams and Jiancheng Zhuang, Ph.D., for their assistance with scanning participants. We also thank Dr. Keren and colleagues (2009) for providing us with their standard-space LC mask. This project was funded by federal NIH Grants R01AG038043 and K02AG032309.
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2022, Trends in Cognitive SciencesCitation Excerpt :The effect is deceptively simple: by boosting activity patterns in a widespread fashion, those regions with an intermediate level of activity can now cross a nonlinear barrier that drastically increases their firing rate (known as a ‘bifurcation’ in dynamical systems theory [43]). In other words, neurons that are already partially active (i.e., processing glutamatergic inputs) can now ‘stand out’ from the background activity [44] and, hence, have an impact on the evolving spatiotemporal brain state that controls a diverse set of brain states, including cognitive function [45,46], memory encoding [47,48], perceptual learning [49,50], motor performance [51], and perceptual awareness [38,52,53]. There is now empirical evidence to support this relatively global effect of the LC on whole-brain dynamics in both rodents [10] and humans [18,19,38,54–57].
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2021, NeuropsychologiaCitation Excerpt :For example, there is evidence that items associated with outcomes of monetary reward were remembered more accurately than those with outcomes of monetary punishment (Eppinger et al., 2010), and that the memory enhancement was modulated by the amount of monetary reward associated with the items (Madan et al., 2012; Mason et al., 2017). A similar effect on memories by reward outcomes has been found in the memory enhancement of objects associated with feedbacks of receiving rewards, as well as avoiding punishments (Clewett et al., 2014; Mather and Schoeke, 2011). These findings suggest that memories are enhanced by outcomes of social and monetary rewards.
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2020, Neuroscience and Biobehavioral ReviewsCitation Excerpt :This may be related to the wiring properties of LC-NE system: LC projections to the frontal cortex are more numerous, fire faster, are more excitable, and contain more glutamate receptors than projections to other regions of the cortex (Chandler et al., 2014a). Increased functional coupling between LC and the frontal cortex was associated with better behavioral performance in the monetary incentive delay task (Clewett et al., 2014), suggesting that the LC-NE system monitors behavioral outcomes and triggers memory processes to modify subsequent behavior. Different terms have been employed to refer to the role of LC in brain function and behavior: a switch in the trade-off between exploitation and exploration, a brain reset signal, a learning signal or a temporal filter.
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2017, Behavioural Brain ResearchCitation Excerpt :This, in turn, further interacts with the influence of NE on longer-term memory processes and leads to enhanced memory for arousing information [30]. Indeed, whether an event is remembered or not depends on modulations in the strength of communication across synapsis and the modulation of NE release following arousing information [31]. In this regard, genetic variations linked to NE has been shown to influence LC activity and convergent evidence suggests that a gene variant, the so-called ADRA2b, is associated with higher levels of intercellular NE availability [32].