Emotional arousal lingers in time to bind discrete episodes in memory.

Temporal stability and change in neutral contexts can transform continuous experiences into distinct and memorable events. However, less is known about how shifting emotional states influence these memory processes, despite ample evidence that emotion impacts non-temporal aspects of memory. Here, we examined if emotional stimuli influence temporal memory for recent event sequences. Participants encoded lists of neutral images while listening to auditory tones. At regular intervals within each list, participants heard emotional positive, negative, or neutral sounds, which served as "emotional event boundaries" that divided each sequence into discrete events. Temporal order memory was tested for neutral item pairs that either spanned an emotional sound or were encountered within the same auditory event. Encountering a highly arousing event boundary led to faster response times for items encoded within the next event. Critically, we found that highly arousing sounds had different effects on binding ongoing versus ensuing sequential representations in memory. Specifically, highly arousing sounds were significantly more likely to enhance temporal order memory for ensuing information compared to information that spanned those boundaries, especially for boundaries with negative valence. These findings suggest that within aversive emotional contexts, fluctuations in arousal help shape the temporal organisation of events in memory.

Dynamic emotional states shape the episodic structure of memory.

Human emotions fluctuate over time. However, it is unclear how these shifting emotional states influence the organization of episodic memory. Here, we examine how emotion dynamics transform experiences into memorable events. Using custom musical pieces and a dynamic emotion-tracking tool to elicit and measure temporal fluctuations in felt valence and arousal, our results demonstrate that memory is organized around emotional states. While listening to music, fluctuations between different emotional valences bias temporal encoding process toward memory integration or separation. Whereas a large absolute or negative shift in valence helps segment memories into episodes, a positive emotional shift binds sequential representations together. Both discrete and dynamic shifts in music-evoked valence and arousal also enhance delayed item and temporal source memory for concurrent neutral items, signaling the beginning of new emotional events. These findings are in line with the idea that the rise and fall of emotions can sculpt unfolding experiences into memories of meaningful events.

Subliminal backdoors to forgetting emotional memories.

Weakening negative memories often requires first remembering those events. To bypass this distressing process, Zhu et al. elicited forgetting by subliminally reactivating negative memories near in time to retrieval suppression of unrelated memories. Casting an amnesic shadow over harmful, reactivated memories thereby brings new therapeutic possibilities, and questions, to light.

Tag and capture: how salient experiences target and rescue nearby events in memory.

The long-term fate of a memory is not exclusively determined by the events occurring at the moment of encoding. Research at the cellular, circuit, and behavioral levels is beginning to reveal how neurochemical activations in the moments surrounding an event can retroactively and proactively rescue weak memory for seemingly mundane experiences. We review emerging evidence showing enhancement of weakly formed memories encoded minutes to hours before or after a related motivationally relevant experience. We discuss proposed neurobiological mechanisms for strengthening weak memories formed in temporal proximity to a strong event, and how this knowledge could be leveraged to improve memory for information that is prone to forgetting.

Survival of the salient: Aversive learning rescues otherwise forgettable memories via neural reactivation and post-encoding hippocampal connectivity.

The effects of aversive events on memory are complex and go beyond the simple enhancement of threatening information. Negative experiences can also rescue related but otherwise forgettable details encoded close in time. Here, we used functional magnetic resonance imaging (fMRI) in healthy young adults to examine the brain mechanisms that support this retrograde memory effect. In a two-phase incidental encoding paradigm, participants viewed different pictures of tools and animals before and during Pavlovian fear conditioning. During Phase 1, these images were intermixed with neutral scenes, which provided a unique 'context tag' for this specific phase of encoding. A few minutes later, during Phase 2, new pictures from one category were paired with a mild shock (threat-conditioned stimulus; CS+), while pictures from the other category were not shocked. FMRI analyses revealed that, across-participants, individuals who showed aversive learning-related retroactive memory benefits for Phase 1 CS+ items were also more likely to exhibit three brain effects: first, greater spontaneous reinstatement of the Phase 1 context when participants viewed conceptually-related CS+ items in Phase 2; second, greater successful encoding-related VTA/SN and LC activation for Phase 2 CS+ items; and third, learning-dependent increases in post-encoding hippocampal functional coupling with CS+ category-selective cortex. These biases in hippocampal-cortical connectivity also mediated the relationship between VTA/SN aversive encoding effects and across-participant variability in the retroactive memory benefit. Collectively, our findings suggest that both online and offline brain mechanisms may enable threatening events to preserve memories that acquire new significance in the future.

Pupil-linked arousal signals track the temporal organization of events in memory.

Everyday life unfolds continuously, yet we tend to remember past experiences as discrete event sequences or episodes. Although this phenomenon has been well documented, the neuromechanisms that support the transformation of continuous experience into distinct and memorable episodes remain unknown. Here, we show that changes in context, or event boundaries, elicit a burst of autonomic arousal, as indexed by pupil dilation. Event boundaries also lead to the segmentation of adjacent episodes in later memory, evidenced by changes in memory for the temporal duration, order, and perceptual details of recent event sequences. These subjective and objective changes in temporal memory are also related to distinct temporal features of pupil dilations to boundaries as well as to the temporal stability of more prolonged pupil-linked arousal states. Collectively, our findings suggest that pupil measures reflect both stability and change in ongoing mental context representations, which in turn shape the temporal structure of memory.

Isometric exercise facilitates attention to salient events in women via the noradrenergic system.

The locus coeruleus (LC) regulates attention via the release of norepinephrine (NE), with levels of tonic LC activity constraining the intensity of phasic LC responses. In the current fMRI study, we used isometric handgrip to modulate tonic LC-NE activity in older women and in young women with different hormone statuses during the time period immediately after the handgrip. During this post-handgrip time, an oddball detection task was used to probe how changes in tonic arousal influenced functional coordination between the LC and a right frontoparietal network that supports attentional selectivity. As expected, the frontoparietal network responded more to infrequent target and novel sounds than to frequent sounds. Across participants, greater LC-frontoparietal functional connectivity, pupil dilation, and faster oddball detection were all positively associated with LC MRI structural contrast from a neuromelanin-sensitive scan. Thus, LC structure was related to LC functional dynamics and attentional performance during the oddball task. We also found that handgrip influenced pupil and attentional processing during a subsequent oddball task. Handgrip decreased subsequent tonic pupil size, increased phasic pupil responses to oddball sounds, speeded oddball detection speed, and increased frontoparietal network activation, suggesting that inducing strong LC activity benefits attentional performance in the next few minutes, potentially due to reduced tonic LC activity. In addition, older women showed a similar benefit of handgrip on frontoparietal network activation as younger women, despite showing lower frontoparietal network activation overall. Together these findings suggest that a simple exercise may improve selective attention in healthy aging, at least for several minutes afterwards.

Echoes of Emotions Past: How Neuromodulators Determine What We Recollect.

We tend to re-live emotional experiences more richly in memory than more mundane experiences. According to one recent neurocognitive model of emotional memory, negative events may be encoded with a larger amount of sensory information than neutral and positive events. As a result, there may be more perceptual information available to reconstruct these events at retrieval, leading to memory reinstatement patterns that correspond with greater memory vividness and sense of recollection for negative events. In this commentary, we offer an alternative perspective on how emotion may influence such sensory cortex reinstatement that focuses on engagement of the noradrenergic (NE) and dopaminergic (DA) systems rather than valence. Specifically, we propose that arousal-related locus coeruleus-norepinephrine (LC-NE) system activation promotes the prioritization of the most salient features of an emotional experience in memory. Thus, a select few details may drive lower-level sensory cortical activity and a stronger sense of recollection for arousing events. By contrast, states of high behavioral activation, including novelty-seeking and exploration, may recruit the DA system to broaden the scope of cognitive processing and integrate multiple event aspects in memory. These more integrated memory representations may be reflected in higher-order cortical reinstatement at retrieval. Thus, the balance between activation in these neuromodulatory systems at encoding, rather than the valence of the event, may ultimately determine the quality of emotional memory recollection and neural reinstatement.

Transcending time in the brain: How event memories are constructed from experience.

Our daily lives unfold continuously, yet when we reflect on the past, we remember those experiences as distinct and cohesive events. To understand this phenomenon, early investigations focused on how and when individuals perceive natural breakpoints, or boundaries, in ongoing experience. More recent research has examined how these boundaries modulate brain mechanisms that support long-term episodic memory. This work has revealed that a complex interplay between hippocampus and prefrontal cortex promotes the integration and separation of sequential information to help organize our experiences into mnemonic events. Here, we discuss how both temporal stability and change in one's thoughts, goals, and surroundings may provide scaffolding for these neural processes to link and separate memories across time. When learning novel or familiar sequences of information, dynamic hippocampal processes may work both independently from and in concert with other brain regions to bind sequential representations together in memory. The formation and storage of discrete episodic memories may occur both proactively as an experience unfolds. They may also occur retroactively, either during a context shift or when reactivation mechanisms bring the past into the present to allow integration. We also describe conditions and factors that shape the construction and integration of event memories across different timescales. Together these findings shed new light on how the brain transcends time to transform everyday experiences into meaningful memory representations.

Arousal increases neural gain via the locus coeruleus-norepinephrine system in younger adults but not in older adults.

In younger adults, arousal amplifies attentional focus to the most salient or goal-relevant information while suppressing other information. A computational model of how the locus coeruleus-norepinephrine (LC-NE) system can implement this increased selectivity under arousal and an fMRI study comparing how arousal affects younger and older adults' processing indicate that the amplification of salient stimuli and the suppression of non-salient stimuli are separate processes, with aging affecting suppression without impacting amplification under arousal. In the fMRI study, arousal increased processing of salient stimuli and decreased processing of non-salient stimuli for younger adults. In contrast, for older adults, arousal increased processing of both low and high salience stimuli, generally increasing excitatory responses to visual stimuli. Older adults also showed decline in LC functional connectivity with frontoparietal networks that coordinate attentional selectivity. Thus, among older adults, arousal increases the potential for distraction from non-salient stimuli.

Age differences in selective memory of goal-relevant stimuli under threat.

When faced with threat, people often selectively focus on and remember the most pertinent information while simultaneously ignoring any irrelevant information. Filtering distractors under arousal requires inhibitory mechanisms, which take time to recruit and often decline in older age. Despite the adaptive nature of this ability, relatively little research has examined how both threat and time spent preparing these inhibitory mechanisms affect selective memory for goal-relevant information across the life span. In this study, 32 younger and 31 older adults were asked to encode task-relevant scenes, while ignoring transparent task-irrelevant objects superimposed onto them. Threat levels were increased on some trials by threatening participants with monetary deductions if they later forgot scenes that followed threat cues. We also varied the time between threat induction and a to-be-encoded scene (i.e., 2 s, 4 s, 6 s) to determine whether both threat and timing effects on memory selectivity differ by age. We found that age differences in memory selectivity only emerged after participants spent a long time (i.e., 6 s) preparing for selective encoding. Critically, this time-dependent age difference occurred under threatening, but not neutral, conditions. Under threat, longer preparation time led to enhanced memory for task-relevant scenes and greater memory suppression of task-irrelevant objects in younger adults. In contrast, increased preparation time after threat induction had no effect on older adults' scene memory and actually worsened memory suppression of task-irrelevant objects. These findings suggest that increased time to prepare top-down encoding processes benefits younger, but not older, adults' selective memory for goal-relevant information under threat. (PsycINFO Database Record

Locus Coeruleus Activity Strengthens Prioritized Memories Under Arousal.

Recent models posit that bursts of locus ceruleus (LC) activity amplify neural gain such that limited attention and encoding resources focus even more on prioritized mental representations under arousal. Here, we tested this hypothesis in human males and females using fMRI, neuromelanin MRI, and pupil dilation, a biomarker of arousal and LC activity. During scanning, participants performed a monetary incentive encoding task in which threat of punishment motivated them to prioritize encoding of scene images over superimposed objects. Threat of punishment elicited arousal and selectively enhanced memory for goal-relevant scenes. Furthermore, trial-level pupil dilations predicted better scene memory under threat, but were not related to object memory outcomes. fMRI analyses revealed that greater threat-evoked pupil dilations were positively associated with greater scene encoding activity in LC and parahippocampal cortex, a region specialized to process scene information. Across participants, this pattern of LC engagement for goal-relevant encoding was correlated with neuromelanin signal intensity, providing the first evidence that LC structure relates to its activation pattern during cognitive processing. Threat also reduced dynamic functional connectivity between high-priority (parahippocampal place area) and lower-priority (lateral occipital cortex) category-selective visual cortex in ways that predicted increased memory selectivity. Together, these findings support the idea that, under arousal, LC activity selectively strengthens prioritized memory representations by modulating local and functional network-level patterns of information processing.SIGNIFICANCE STATEMENT Adaptive behavior relies on the ability to select and store important information amid distraction. Prioritizing encoding of task-relevant inputs is especially critical in threatening or arousing situations, when forming these memories is essential for avoiding danger in the future. However, little is known about the arousal mechanisms that support such memory selectivity. Using fMRI, neuromelanin MRI, and pupil measures, we demonstrate that locus ceruleus (LC) activity amplifies neural gain such that limited encoding resources focus even more on prioritized mental representations under arousal. For the first time, we also show that LC structure relates to its involvement in threat-related encoding processes. These results shed new light on the brain mechanisms by which we process important information when it is most needed.

The Ebb and Flow of Experience Determines the Temporal Structure of Memory.

Everyday life consists of a continuous stream of information, yet somehow we remember the past as distinct episodic events. Prominent models posit that event segmentation is driven by erroneous predictions about how current experiences are unfolding. Yet this perspective fails to explain how memories become integrated or separated in the absence of prior knowledge. Here, we propose that contextual stability dictates the temporal organization of events in episodic memory. To support this view, we summarize new findings showing that neural measures of event organization index how ongoing changes in external contextual cues and internal representations of time influence different forms of episodic memory.

Arousal amplifies biased competition between high and low priority memories more in women than in men: The role of elevated noradrenergic activity.

Recent findings indicate that emotional arousal can enhance memory consolidation of goal-relevant stimuli while impairing it for irrelevant stimuli. According to one recent model, these goal-dependent memory tradeoffs are driven by arousal-induced release of norepinephrine (NE), which amplifies neural gain in target sensory and memory processing brain regions. Past work also shows that ovarian hormones modulate activity in the same regions thought to support NE's effects on memory, such as the amygdala, suggesting that men and women may be differentially susceptible to arousal's dual effects on episodic memory. Here, we aimed to determine the neurohormonal mechanisms that mediate arousal-biased competition processes in memory. In a competitive visuo-attention task, participants viewed images of a transparent object overlaid on a background scene and explicitly memorized one of these stimuli while ignoring the other. Participants then heard emotional or neutral audio-clips and provided a subjective arousal rating. Hierarchical generalized linear modeling (HGLM) analyses revealed that greater pre-to-post task increases in salivary alpha-amylase (sAA), a biomarker of noradrenergic activity, was associated with significantly greater arousal-enhanced memory tradeoffs in women than in men. These sex-dependent effects appeared to result from phasic and background noradrenergic activity interacting to suppress task-irrelevant representations in women but enhancing them in men. Additionally, in naturally cycling women, low ovarian hormone levels interacted with increased noradrenergic activity to amplify memory selectivity independently of emotion-induced arousal. Together these findings suggest that increased noradrenergic transmission enhances preferential consolidation of goal-relevant memory traces according to phasic arousal and ovarian hormone levels in women.

Higher locus coeruleus MRI contrast is associated with lower parasympathetic influence over heart rate variability.

The locus coeruleus (LC) is a key node of the sympathetic nervous system and suppresses parasympathetic activity that would otherwise increase heart rate variability. In the current study, we examined whether LC-MRI contrast reflecting neuromelanin accumulation in the LC was associated with high-frequency heart rate variability (HF-HRV), a measure reflecting parasympathetic influences on the heart. Recent evidence indicates that neuromelanin, a byproduct of catecholamine metabolism, accumulates in the LC through young and mid adulthood, suggesting that LC-MRI contrast may be a useful biomarker of individual differences in habitual LC activation. We found that, across younger and older adults, greater LC-MRI contrast was negatively associated with HF-HRV during fear conditioning and spatial detection tasks. This correlation was not accounted for by individual differences in age or anxiety. These findings indicate that individual differences in LC structure relate to key cardiovascular parameters.

Noradrenergic mechanisms of arousal's bidirectional effects on episodic memory.

Arousal's selective effects on cognition go beyond the simple enhancement of emotional stimuli, sometimes enhancing and other times impairing processing of proximal neutral information. Past work shows that arousal impairs encoding of subsequent neutral stimuli regardless of their top-down priority via the engagement of ß-adrenoreceptors. In contrast, retrograde amnesia induced by emotional arousal can flip to enhancement when preceding neutral items are prioritized in top-down attention. Whether ß-adrenoreceptors also contribute to this retrograde memory enhancement of goal-relevant neutral stimuli is unclear. In this pharmacological study, we administered 40mg of propranolol or 40mg of placebo to healthy young adults to examine whether emotional arousal's bidirectional effects on declarative memory relies on ß-adrenoreceptor activation. Following pill intake, participants completed an emotional oddball task in which they were asked to prioritize a neutral object appearing just before an emotional or neutral oddball image within a sequence of 7 neutral objects. Under placebo, emotional oddballs impaired memory for lower priority oddball+1 objects but had no effect on memory for high priority oddball-1 objects. Propranolol blocked this anterograde amnesic effect of arousal. Emotional oddballs also enhanced selective memory trade-offs significantly more in the placebo than drug condition, such that high priority oddball-1 objects were more likely to be remembered at the cost of their corresponding lower priority oddball+1 objects under arousal. Lastly, those who recalled more high priority oddball-1 objects preceding an emotional versus neutral oddball image showed greater increases in salivary alpha-amylase, a biomarker of noradrenergic system activation, across the task. Together these findings suggest that different noradrenergic mechanisms contribute to the anterograde and retrograde mnemonic effects of arousal on proximal neutral memoranda.

Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging.

Leading a mentally stimulating life may build up a reserve of neural and mental resources that preserve cognitive abilities in late life. Recent autopsy evidence links neuronal density in the locus coeruleus (LC), the brain's main source of norepinephrine, to slower cognitive decline before death, inspiring the idea that the noradrenergic system is a key component of reserve (Robertson, I. H. 2013. A noradrenergic theory of cognitive reserve: implications for Alzheimer's disease. Neurobiol. Aging. 34, 298-308). Here, we tested this hypothesis using neuromelanin-sensitive magnetic resonance imaging to visualize and measure LC signal intensity in healthy younger and older adults. Established proxies of reserve, including education, occupational attainment, and verbal intelligence, were linearly correlated with LC signal intensity in both age groups. Results indicated that LC signal intensity was significantly higher in older than younger adults and significantly lower in women than in men. Consistent with the LC-reserve hypothesis, both verbal intelligence and a composite reserve score were positively associated with LC signal intensity in older adults. LC signal intensity was also more strongly associated with attentional shifting ability in older adults with lower cognitive reserve. Together these findings link in vivo estimates of LC neuromelanin signal intensity to cognitive reserve in normal aging.

Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory.

Emotional arousal enhances perception and memory of high-priority information but impairs processing of other information. Here, we propose that, under arousal, local glutamate levels signal the current strength of a representation and interact with norepinephrine (NE) to enhance high priority representations and out-compete or suppress lower priority representations. In our "glutamate amplifies noradrenergic effects" (GANE) model, high glutamate at the site of prioritized representations increases local NE release from the locus coeruleus (LC) to generate "NE hotspots." At these NE hotspots, local glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. In contrast, arousal-induced LC activity inhibits less active representations via two mechanisms: 1) Where there are hotspots, lateral inhibition is amplified; 2) Where no hotspots emerge, NE levels are only high enough to activate low-threshold inhibitory adrenoreceptors. Thus, LC activation promotes a few hotspots of excitation in the context of widespread suppression, enhancing high priority representations while suppressing the rest. Hotspots also help synchronize oscillations across neural ensembles transmitting high-priority information. Furthermore, brain structures that detect stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during, or after encoding enhances synaptic plasticity at NE hotspots, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms promote selective attention and memory under arousal. GANE not only reconciles apparently contradictory findings in the emotion-cognition literature but also extends previous influential theories of LC neuromodulation by proposing specific mechanisms for how LC-NE activity increases neural gain.