Independent effects of emotional arousal and reward anticipation on episodic memory formation.

Events that elicit emotional arousal or are associated with reward are more likely remembered. Emotional arousal activates the amygdala and the central noradrenergic system, whereas reward anticipation results in an activity in the mesocorticolimbic dopaminergic system. The activation of both pathways enhances memory formation in the hippocampus where their effects are based on similar neural substrates, e.g. tagging of active hippocampal synapses. Moreover, emotional arousal and reward anticipation both enhance attention, which can also affect memory formation. In addition, both neuromodulators interact on the cellular level. Therefore, we tested in the current functional magnetic resonance imaging study whether simultaneously occurring emotional arousal and reward anticipation might have interacting effects on memory formation. We did not find evidence for such an interaction, neither on the behavioral nor on the neural level. Our results further suggest that reward anticipation enhances memory formation rather by an increase in anticipation-related arousal-reflected in activity in the dorsal anterior cingulate cortex-and not dopaminergic midbrain activity. Accompanying behavioral experiments indicated that the effect of reward anticipation on memory is (i) caused at least to some extent by anticipating the speeded response to obtain the reward and not by the valance of the outcome and (ii) can be observed already immediately after encoding, i.e. before consolidation.

The Assimilation of Novel Information into Schemata and Its Efficient Consolidation.

Schemata enhance memory formation for related novel information. This is true even when this information is neutral with respect to schema-driven expectations. This assimilation of novel information into schemata has been attributed to more effective organizational processing that leads to more referential connections with the activated associative schema network. Animal data suggest that systems consolidation of novel assimilated information is also accelerated. In the current study, we used both multivariate and univariate fMRI analyses to provide further support for these proposals and to elucidate the neural underpinning of these processes. Twenty-eight participants (5 male) overlearned fictitious schemata for 7 weeks and then encoded novel related and control facts in the scanner. These facts were retrieved both immediately and 2 weeks later, also in the scanner. Our results conceptually replicate previous findings with respect to enhanced vmPFC-hippocampus coupling during encoding of novel related information and point to a prior knowledge effect that is distinct from situations where novel information is experienced as congruent or incongruent with a schema. Moreover, the combination of both multivariate and univariate results further specified the proposed contributions of the vmPFC, precuneus and angular gyrus network to the more efficient encoding of schema-related information. In addition, our data provide further evidence for more efficient systems consolidation of such novel schema-related and potentially assimilated information.SIGNIFICANCE STATEMENT Our prior knowledge in a certain domain, often termed schema, heavily influences whether and how we form memories for novel information that can be related to them. The results of the current study show how a ventromedial prefrontal-precuneal-angular network contributes to the more efficient encoding of novel related information. Furthermore, the observed increase in prefrontal-hippocampal coupling during this process points to a critical distinction from the previously described mechanisms supporting the encoding of information that is experienced as congruent with schema-driven expectations. In addition, we find further support for the proposal based on animal data that prior knowledge enhances also the consolidation of schema-related information.

Sex Differences and Exogenous Estrogen Influence Learning and Brain Responses to Prediction Errors.

Animal studies show marked sex differences as well as effects of estrogen (E2) in the mesocorticolimbic dopaminergic (DA) pathways, which play a critical role in reward processing and reinforcement learning and are also implicated in drug addiction. In this computational pharmacological fMRI study, we investigate the effects of both factors, sex and estrogen, on reinforcement learning and the dopaminergic system in humans; 67 male and 64 naturally cycling female volunteers, the latter in their low-hormone phase, were randomly assigned, double-blind, to take E2 or placebo. They completed a reinforcement learning task in the MRI scanner for which we have previously shown reward prediction error (RPE)-related activity to be dopaminergic. We found RPE-related brain activity to be enhanced in women compared with men and to a greater extent when E2 levels were elevated in both sexes. However, both factors, female sex and E2, slowed adaptation to RPEs (smaller learning rate). This discrepancy of larger RPE-related activity yet smaller learning rates can be explained by organizational sex differences and activational effects of circulating E2, which both affect DA release differently to DA receptor binding capacities.

Category-sensitive incidental reinstatement in medial temporal lobe subregions during word recognition.

During associative retrieval, the brain reinstates neural representations that were present during encoding. The human medial temporal lobe (MTL), with its subregions hippocampus (HC), perirhinal cortex (PRC), and parahippocampal cortex (PHC), plays a central role in neural reinstatement. Previous studies have given compelling evidence for reinstatement in the MTL during explicitly instructed associative retrieval. High-confident recognition may be similarly accompanied by recollection of associated information from the encoding context. It is unclear, however, whether high-confident recognition memory elicits reinstatement in the MTL even in the absence of an explicit instruction to retrieve associated information. Here, we addressed this open question using high-resolution fMRI. Twenty-eight male and female human volunteers engaged in a recognition memory task for words that they had previously encoded together with faces and scenes. Using complementary univariate and multivariate approaches, we show that MTL subregions including the PRC, PHC, and HC differentially reinstate category-sensitive representations during high-confident word recognition, even though no explicit instruction to retrieve the associated category was given. This constitutes novel evidence that high-confident recognition memory is accompanied by incidental reinstatement of associated category information in MTL subregions, and supports a functional model of the MTL that emphasizes content-sensitive representations during both encoding and retrieval.

Competition between Associations in Memory.

If two associations share an item, one may be remembered at the expense of the other (BC recalled but not AB). Here, we identify the neural processes by which this competition materializes and is resolved. We analyzed fMRI signal while participants studied sets of pairs that reliably induced pair-to-pair associative interference, but which participants could not fully resolve. Precuneus activity tracked retrieval of previous pairs during study of later overlapping pairs. This retrieval apparently produced interference by diverting study resources from the currently displayed pair. However, when activity in ventromedial prefrontal cortex, as well as anterior subregions of the hippocampus, was present while the earlier pair had been studied, interference was reversed, and both pairs were likely to be recalled. Angular gyrus and mid-frontal activity were related to interference resolution once the participant had seen both pairs. Taken together, associations compete via precuneus-mediated competitive retrieval, but ventromedial prefrontal cortex may neutralize this by ensuring that when the earlier association is remembered while studying the later pair, memories of the two pairs can overcome interference likely via activity in mid-frontal cortex and angular gyrus.

Emotional arousal impairs association memory: roles of prefrontal cortex regions.

The brain processes underlying impairing effects of emotional arousal on associative memory were previously attributed to two dissociable routes using high-resolution fMRI of the MTL (Madan et al. 2017). Extrahippocampal MTL regions supporting associative encoding of neutral pairs suggested unitization; conversely, associative encoding of negative pairs involved compensatory hippocampal activity. Here, whole-brain fMRI revealed prefrontal contributions: dmPFC was more involved in hippocampal-dependent negative pair learning and vmPFC in extrahippocampal neutral pair learning. Successful encoding of emotional memory associations may require emotion regulation/conflict resolution (dmPFC), while neutral memory associations may be accomplished by anchoring new information to prior knowledge (vmPFC).

Dopaminergic Modulation of Human Intertemporal Choice: A Diffusion Model Analysis Using the D2-Receptor Antagonist Haloperidol.

The neurotransmitter dopamine is implicated in diverse functions, including reward processing, reinforcement learning, and cognitive control. The tendency to discount future rewards over time has long been discussed in the context of potential dopaminergic modulation. Here we examined the effect of a single dose of the D2 receptor antagonist haloperidol (2 mg) on temporal discounting in healthy female and male human participants. Our approach extends previous pharmacological studies in two ways. First, we applied combined temporal discounting drift diffusion models to examine choice dynamics. Second, we examined dopaminergic modulation of reward magnitude effects on temporal discounting. Hierarchical Bayesian parameter estimation revealed that the data were best accounted for by a temporal discounting drift diffusion model with nonlinear trialwise drift rate scaling. This model showed good parameter recovery, and posterior predictive checks revealed that it accurately reproduced the relationship between decision conflict and response times in individual participants. We observed reduced temporal discounting and substantially faster nondecision times under haloperidol compared with placebo. Discounting was steeper for low versus high reward magnitudes, but this effect was largely unaffected by haloperidol. Results were corroborated by model-free analyses and modeling via more standard approaches. We previously reported elevated caudate activation under haloperidol in this sample of participants, supporting the idea that haloperidol elevated dopamine neurotransmission (e.g., by blocking inhibitory feedback via presynaptic D2 auto-receptors). The present results reveal that this is associated with an augmentation of both lower-level (nondecision time) and higher-level (temporal discounting) components of the decision process.SIGNIFICANCE STATEMENT Dopamine is implicated in reward processing, reinforcement learning, and cognitive control. Here we examined the effects of a single dose of the D2 receptor antagonist haloperidol on temporal discounting and choice dynamics during the decision process. We extend previous studies by applying computational modeling using the drift diffusion model, which revealed that haloperidol reduced the nondecision time and reduced impulsive choice compared with placebo. These findings are compatible with a haloperidol-induced increase in striatal dopamine (e.g., because of a presynaptic mechanism). Our data provide novel insights into the contributions of dopamine to value-based decision-making and highlight how comprehensive model-based analyses using sequential sampling models can inform the effects of pharmacological modulation on choice processes.

Probing emotional recognition memory: how different response formats affect response behaviour.

Receiver-operating characteristic curves from confidence ratings and remember/know (R/K) judgments are often used to estimate the contribution of familiarity and recollection to recognition memory. Both coming with specific advantages and disadvantages, which could be reduced by their combination. Little is known how the combination of both methods impacts response behaviour. This could be particularly important for emotional memory research, which is susceptible to variation in meta-mnemonic processes. We obtained reference performance indices from the two methods, instructing individuals to give confidence ratings or R/K judgments in one step. Against these, we contrasted R/K judgments in a two-step format and two combined formats, confidence ratings followed by R/K judgments and vice versa. Regarding reference formats, confidence ratings resulted in more liberal response criteria and false alarm rates than R/K judgments. Two-step R/K judgments and confidence ratings followed by R/K judgments resulted in patterns similar to one-step R/K judgments. Reversing the order resulted in more liberal response biases, higher hit and false alarms rates. Recollection and familiarity were unaffected by response formats. Valence effects did not vary with response formats. The present results suggest that confidence ratings followed by R/K judgments provide the advantages of both without biasing response behaviour.

[Diagnostic work with the conflict axis of the OPD-CA: Empirical results on inpatients and outpatients]. / Diagnostische Arbeit mit dem Befundbogen der Konfliktachse der OPD-KJ: Empirische Ergebnisse an stationären und ambulanten Patient_innen.

Diagnostic work with the conflict axis of the OPD-CA: Empirical results on inpatients and outpatients Abstract. In recent years, the Operationalized Psychodynamic Diagnostics (OPD-CA) is increasingly being used in child and adolescent psychiatry and psychotherapy. This article presents the conflict axis of the OPD-CA, which contains an operationalization of seven psychodynamic conflicts and the processing modes assigned to them. It describes empirical comparisons of the conflict axis ratings and the structure rating in a group of outpatient and inpatient children and adolescents (total N = 186, 12.7 years, 54 % female). The findings in the total sample show that diagnosis-specific gender differences are disappearing, and that male and female patients have largely similar intrapsychic development-impairing conflicts. Patients in inpatient treatment in a child and adolescent psychiatry institution, however, more often show a self-conflict and, as expected, have a lower structural level than patients of the same age in outpatient psychotherapy. The number of highly stressful events before the start of therapy is also significantly higher in this group, which may have contributed to the structural deficits. For outpatients, there is a strikingly higher level of guilt and identity conflicts. In both samples, the mode of processing the conflicts is largely passive. Based on these findings, possible implications for therapeutic practice are discussed.

Dopamine Enhances Item Novelty Detection via Hippocampal and Associative Recall via Left Lateral Prefrontal Cortex Mechanisms.

The involvement of fronto-striatal circuits in item and associative memory retrieval as well as in the stabilization of memories by retrieval practice suggests that both retrieval and re-encoding of stored memories might rely on dopaminergic mechanisms in humans. We tested these hypotheses in a placebo-controlled pharmacological fMRI study using 2 mg of the D2 antagonist haloperidol administered acutely before a cued associative recall task of previously encoded picture-word pairs in 53 healthy humans of both sexes. The cued associative recall was moreover repeated 3 d later outside the scanner without pharmacological intervention. Dopaminergic modulation significantly improved associative recall performance and recognition accuracy of verbal items. Moreover, we observed a significant dopamine effect on re-encoding in terms of increased specificity of associative memories from the first to the second cued associative recall. Better association memory under haloperidol was linked with higher activity in the left lateral prefrontal cortex and right parietal cortex, suggesting that dopamine facilitates associative retrieval through increased recruitment of frontoparietal monitoring processes. In contrast, improved recognition of verbal items under haloperidol was reflected by enhanced novelty detection in the hippocampus and increased activity in saliency networks. Together, these results show distinct but concomitant positive effects of dopamine on associative recall and item recognition and suggest that the specificity of associative recall through re-encoding mechanisms is likewise augmented by dopamine.SIGNIFICANCE STATEMENT Although the neurotransmitter dopamine has been linked with learning and memory for a long time, dopaminergic effects on item recognition in humans were demonstrated only recently. The involvement of fronto-striatal monitoring processes in association retrieval suggests that associative memory might be particularly affected by dopamine. Moreover, fronto-striatal dopaminergic signals have been hypothesized to determine the updating and re-encoding of previously retrieved memories. We here demonstrate clear facilitative effects of dopamine on associative recall and item recognition mediated by prefrontal and hippocampal mechanisms respectively. Additionally, effects on re-encoding were reflected by increased specificity of associative memories. These results augment our understanding of dopaminergic processes in episodic memory retrieval and offer new perspectives on memory impairments in dopamine-related disorders and their treatment.

Inferior frontal gyrus involvement during search and solution in verbal creative problem solving: A parametric fMRI study.

In verbal creative problems like compound remote associates (CRAs), the solution is semantically distant and there is no predefined path to the solution. Therefore, people first search through the space of possible solutions before retrieving the correct semantic content by extending their search space. We assume that search and solution are both part of a semantic control process which involves the inferior frontal gyrus (IFG). Furthermore, we expect the degree of relevant semantic control areas like the IFG to depend on how much the search space needs to be extended, i.e. how semantically distant the solution is. To demonstrate this, we created a modified CRA paradigm which systematically modulates the semantic distance from the first target word to the solution via priming. We show that brain areas (left IFG and middle temporal gyrus) associated with semantic control are already recruited during search. In addition, BOLD response in the left angular gyrus linearly correlates with search space extension. Hence, there is evidence that this process already takes place during search. Furthermore, bilateral IFG (pars orbitalis and triangularis) also correlates with search space extension but during solution. We discuss the role of the IFG in accessing semantically distant information during verbal creative problem solving.

Verbal insight revisited: fMRI evidence for early processing in bilateral insulae for solutions with AHA! experience shortly after trial onset.

In insight problem solving solutions with AHA! experience have been assumed to be the consequence of restructuring of a problem which usually takes place shortly before the solution. However, evidence from priming studies suggests that solutions with AHA! are not spontaneously generated during the solution process but already relate to prior subliminal processing. We test this hypothesis by conducting an fMRI study using a modified compound remote associates paradigm which incorporates semantic priming. We observe stronger brain activity in bilateral anterior insulae already shortly after trial onset in problems that were later solved with than without AHA!. This early activity was independent of semantic priming but may be related to other lexical properties of attended words helping to reduce the amount of solutions to look for. In contrast, there was more brain activity in bilateral anterior insulae during solutions that were solved without than with AHA!. This timing (after trial start/during solution) x solution experience (with/without AHA!) interaction was significant. The results suggest that (a) solutions accompanied with AHA! relate to early solution-relevant processing and (b) both solution experiences differ in timing when solution-relevant processing takes place. In this context, we discuss the potential role of the anterior insula as part of the salience network involved in problem solving by allocating attentional resources.

Test-retest reliability of the emotional enhancement of memory.

Emotionally arousing stimuli are usually better remembered than neutral ones. This effect can be observed immediately after encoding and becomes more robust after a period of consolidation. The magnitude of this effect in an individual has been treated in various research contexts implicitly as reliable and temporally stable. However, we recently observed in 69 participants that an individual's memory advantage for negative over neutral stimuli, whether immediate or delayed, was very weakly correlated with the advantage measured after 3.5 years, albeit with slightly different memory paradigms. In the current study, we tested whether the test-retest reliability of these emotional memory effects might be larger if the temporal lapse between tests was shorter (10 weeks) and more similar memory tests were used. We observed that the better memory for emotional stimuli is highly replicable on the group level. However, the retest reliability on the individual level was very low. We replicated these findings by re-analysing data from a previous study where female participants took emotional memory tests at two different points of their menstrual cycle. We conclude, therefore, that the individual emotional enhancement of memory is not stable or that it cannot be measured reliably with the standard emotional memory paradigm.

Retrieval Demands Adaptively Change Striatal Old/New Signals and Boost Subsequent Long-Term Memory.

The striatum is a central part of the dopaminergic mesolimbic system and contributes both to the encoding and retrieval of long-term memories. In this regard, the co-occurrence of striatal novelty and retrieval success effects in independent studies underlines the structure's double duty and suggests dynamic contextual adaptation. To test this hypothesis and further investigate the underlying mechanisms of encoding and retrieval dynamics, human subjects viewed pre-familiarized scene images intermixed with new scenes and classified them as indoor versus outdoor (encoding task) or old versus new (retrieval task), while fMRI and eye tracking data were recorded. Subsequently, subjects performed a final recognition task. As hypothesized, striatal activity and pupil size reflected task-conditional salience of old and new stimuli, but, unexpectedly, this effect was not reflected in the substantia nigra and ventral tegmental area (SN/VTA), medial temporal lobe, or subsequent memory performance. Instead, subsequent memory generally benefitted from retrieval, an effect possibly driven by task difficulty and activity in a network including different parts of the striatum and SN/VTA. Our findings extend memory models of encoding and retrieval dynamics by pinpointing a specific contextual factor that differentially modulates the functional properties of the mesolimbic system.SIGNIFICANCE STATEMENT The mesolimbic system is involved in the encoding and retrieval of information but it is unclear how these two processes are achieved within the same network of brain regions. In particular, memory retrieval and novelty encoding were considered in independent studies, implying that novelty (new > old) and retrieval success (old > new) effects may co-occur in the striatum. Here, we used a common framework implicating the striatum, but not other parts of the mesolimbic system, in tracking context-dependent salience of old and new information. The current study, therefore, paves the way for a more comprehensive understanding of the functional properties of the mesolimbic system during memory encoding and retrieval.

Dark aerobic sulfide oxidation by anoxygenic phototrophs in anoxic waters.

Anoxygenic phototrophic sulfide oxidation by green and purple sulfur bacteria (PSB) plays a key role in sulfide removal from anoxic shallow sediments and stratified waters. Although some PSB can also oxidize sulfide with nitrate and oxygen, little is known about the prevalence of this chemolithotrophic lifestyle in the environment. In this study, we investigated the role of these phototrophs in light-independent sulfide removal in the chemocline of Lake Cadagno. Our temporally resolved, high-resolution chemical profiles indicated that dark sulfide oxidation was coupled to high oxygen consumption rates of ~9 µM O2 ·h-1 . Single-cell analyses of lake water incubated with 13 CO2 in the dark revealed that Chromatium okenii was to a large extent responsible for aerobic sulfide oxidation and it accounted for up to 40% of total dark carbon fixation. The genome of Chr. okenii reconstructed from the Lake Cadagno metagenome confirms its capacity for microaerophilic growth and provides further insights into its metabolic capabilities. Moreover, our genomic and single-cell data indicated that other PSB grow microaerobically in these apparently anoxic waters. Altogether, our observations suggest that aerobic respiration may not only play an underappreciated role in anoxic environments but also that organisms typically considered strict anaerobes may be involved.

Reduced associative memory for negative information: impact of confidence and interactive imagery during study.

Although item-memory for emotional information is enhanced, memory for associations between items is often impaired for negative, emotionally arousing compared to neutral information. We tested two possible mechanisms underlying this impairment, using picture pairs: 1) higher confidence in one's own ability to memorise negative information may cause participants to under-study negative pairs; 2) better interactive imagery for neutral pairs could facilitate associative memory for neutral pairs more than for negative pairs. Tested with associative recognition, we replicated the impairment of associative memory for negative pairs. We also replicated the result that confidence in future memory (judgments of learning) was higher for negative than neutral pairs. Inflated confidence could not explain the impairment of associative recognition memory: Judgements of learning were positively correlated with associative memory success for both negative and neutral pairs. However, neutral pairs were rated higher in their conduciveness to interactive imagery than negative pairs, and this difference in interactive imagery showed a robust relationship to the associative memory difference. Thus, associative memory reductions for negative information are not due to differences in encoding effort. Instead, interactive imagery may be less effective for encoding of negative than neutral pairs.

Dissociable contributions of the amygdala to the immediate and delayed effects of emotional arousal on memory.

Emotional arousal enhances memory encoding and consolidation leading to better immediate and delayed memory. Although the central noradrenergic system and the amygdala play critical roles in both effects of emotional arousal, we have recently shown that these effects are at least partly independent of each other, suggesting distinct underlying neural mechanisms. Here we aim to dissociate the neural substrates of both effects in 70 female participants using an emotional memory paradigm to investigate how neural activity, as measured by fMRI, and a polymorphism in the α2B-noradrenoceptor vary for these effects. To also test whether the immediate and delayed effects of emotional arousal on memory are stable traits, we invited back participants who were a part of a large-scale behavioral memory study ∼3.5 yr ago. We replicated the low correlation of the immediate and delayed emotional enhancement of memory across participants (r = 0.16) and observed, moreover, that only the delayed effect was, to some degree, stable over time (r = 0.23). Bilateral amygdala activity, as well as its coupling with the visual cortex and the fusiform gyrus, was related to the preferential encoding of emotional stimuli, which is consistent with affect-biased attention. Moreover, the adrenoceptor genotype modulated the bilateral amygdala activity associated with this effect. The left amygdala and its coupling with the hippocampus was specifically associated with the more efficient consolidation of emotional stimuli, which is consistent with amygdalar modulation of hippocampal consolidation.

Dissociation of immediate and delayed effects of emotional arousal on episodic memory.

Emotionally arousing events are usually better remembered than neutral ones. This phenomenon is in humans mostly studied by presenting mixed lists of neutral and emotional items. An emotional enhancement of memory is observed in these studies often already immediately after encoding and increases with longer delays and consolidation. A large body of animal research showed that the more efficient consolidation of emotionally arousing events is based on an activation of the central noradrenergic system and the amygdala (Modulation Hypothesis; Roozendaal & McGaugh, 2011). The immediately superior recognition of emotional items is attributed primarily to their attraction of attention during encoding which is also thought to be based on the amygdala and the central noradrenergic system. To investigate whether the amygdala and noradrenergic system support memory encoding and consolidation via shared neural substrates and processes a large sample of participants (n = 690) encoded neutral and arousing pictures. Their memory was tested immediately and after a consolidation delay. In addition, they were genotyped in two relevant polymorphisms (α2B-adrenergic receptor and serotonin transporter). Memory for negative and positive emotional pictures was enhanced at both time points where these enhancements were correlated (immediate r = 0.60 and delayed test r = 0.46). Critically, the effects of emotional arousal on encoding and consolidation correlated only very low (negative r = 0.14 and positive r = 0.03 pictures) suggesting partly distinct underlying processes consistent with a functional heterogeneity of the central noradrenergic system. No effect of genotype on either effect was observed.

The Emergence of Knowledge and How it Supports the Memory for Novel Related Information.

Current theories suggest that memories for novel information and events, over time and with repeated retrieval, lose the association to their initial learning context. They are consolidated into a more stable form and transformed into semantic knowledge, that is, semanticized. Novel, related information can then be rapidly integrated into such knowledge, leading to superior memory. We tested these hypotheses in a longitudinal, 302-day, human functional magnetic resonance imaging study in which participants first overlearned and consolidated associative structures. This phase was associated with a shift from hippocampal- to ventrolateral prefrontal cortex (vlPFC)-mediated retrieval, consistent with semanticization. Next, participants encoded novel, related information whose encoding into the already acquired knowledge was orchestrated by the ventromedial prefrontal cortex. Novel related information exhibited reduced forgetting compared with novel control information, which corresponded to a faster shift from hippocampal- to vlPFC-mediated retrieval. In sum, the current results suggest that memory for novel information can be enhanced by anchoring it to prior knowledge via acceleration of the processes observed during semanticization.

Intrusions in episodic memory: reconsolidation or interference?

It would be profoundly important if reconsolidation research in animals and other memory domains generalized to human episodic memory. A 3-d-list-discrimination procedure, based on free recall of objects, with a contextual reminder cue (the testing room), has been thought to demonstrate reconsolidation of human episodic memory (as noted in a previous study). Our goal was to replicate the central result, a high intrusion rate during recall of the target list, and evaluate the reconsolidation account relative to an alternative account, based on state-dependent learning and interference. First, replication was not straightforward (Experiment 1). Second, using a very unique, highly salient context (Experiment 2), the method produced a qualitative replication, but it was small in magnitude. A critical assumption of the reconsolidation account, that the target list is reactivated and destabilized during re-exposure to the study context, was not supported (Experiment 3). Although troubling for the reconsolidation account, the findings can be easily accommodated by an alternative account that does not assume additional neurobiological processes underlying the destabilization of consolidated memories, instead explaining intrusion rates simply in terms of well-established cognitive effects, such as item-to-context binding and interference during retrieval.