Successful Memory Formation Research Articles

Top-down modulation of hippocampal encoding activity as measured by high-resolution functional MRI

Memory formation is known to be critically dependent upon the medial temporal lobe (MTL). Despite this well-characterized role, it remains unclear whether and how MTL encoding processes are affected by top-down goal states. Here, we examined the manner in which task demands at encoding affect MTL activity and its relation to subsequent memory performance. Participants were scanned using high-resolution neuroimaging of the MTL while engaging in two incidental encoding tasks: one that directed participants’ attention to stimulus distinctiveness, and the other requiring evaluation of similarities across stimuli. We hypothesized that attending to distinctiveness would lead to the formation of more detailed memories and would more effectively engage the hippocampal circuit than attending to similarity. In line with our hypotheses, higher rates of subsequent recollection were observed for stimuli studied under the Distinctiveness than Similarity task. Critically, within the hippocampus, CA1 and the subiculum demonstrated an interaction between memory performance and task such that a significant subsequent memory effect was found only when task goals required attention to stimulus distinctiveness. To this end, robust engagement of the hippocampal circuit may underlie the observed behavioral benefits of attending to distinctiveness. Taken together, these findings advance understanding of the effects of top-down intentional information on successful memory formation across subregions of the MTL.

A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy

Functional magnetic resonance imaging has demonstrated reorganization of memory encoding networks within the temporal lobe in temporal lobe epilepsy, but little is known of the extra-temporal networks in these patients. We investigated the temporal and extra-temporal reorganization of memory encoding networks in refractory temporal lobe epilepsy and the neural correlates of successful subsequent memory formation. We studied 44 patients with unilateral temporal lobe epilepsy and hippocampal sclerosis (24 left) and 26 healthy control subjects. All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words with subsequent out-of-scanner recognition assessments. A blocked analysis was used to investigate activations during encoding and neural correlates of subsequent memory were investigated using an event-related analysis. Event-related activations were then correlated with out-of-scanner verbal and visual memory scores. During word encoding, control subjects activated the left prefrontal cortex and left hippocampus whereas patients with left hippocampal sclerosis showed significant additional right temporal and extra-temporal activations. Control subjects displayed subsequent verbal memory effects within left parahippocampal gyrus, left orbitofrontal cortex and fusiform gyrus whereas patients with left hippocampal sclerosis activated only right posterior hippocampus, parahippocampus and fusiform gyrus. Correlational analysis showed that patients with left hippocampal sclerosis with better verbal memory additionally activated left orbitofrontal cortex, anterior cingulate cortex and left posterior hippocampus. During face encoding, control subjects showed right lateralized prefrontal cortex and bilateral hippocampal activations. Patients with right hippocampal sclerosis showed increased temporal activations within the superior temporal gyri bilaterally and no increased extra-temporal areas of activation compared with control subjects. Control subjects showed subsequent visual memory effects within right amygdala, hippocampus, fusiform gyrus and orbitofrontal cortex. Patients with right hippocampal sclerosis showed subsequent visual memory effects within right posterior hippocampus, parahippocampal and fusiform gyri, and predominantly left hemisphere extra-temporal activations within the insula and orbitofrontal cortex. Correlational analysis showed that patients with right hippocampal sclerosis with better visual memory activated the amygdala bilaterally, right anterior parahippocampal gyrus and left insula. Right sided extra-temporal areas of reorganization observed in patients with left hippocampal sclerosis during word encoding and bilateral lateral temporal reorganization in patients with right hippocampal sclerosis during face encoding were not associated with subsequent memory formation. Reorganization within the medial temporal lobe, however, is an efficient process. The orbitofrontal cortex is critical to subsequent memory formation in control subjects and patients. Activations within anterior cingulum and insula correlated with better verbal and visual subsequent memory in patients with left and right hippocampal sclerosis, respectively, representing effective extra-temporal recruitment.

Active avoidance learning in zebrafish (Danio rerio)—The role of sensory modality and inter-stimulus interval

The zebrafish (Danio rerio) promises to meet the growing need of a high throughput model in the fields of gerontological and neurobehavioral research by possessing highly conserved anatomy and physiology with vertebrates, while having low maintenance costs. Here we further explore the conditions of active avoidance learning in zebrafish. Two pairs of distinct aversive conditioning experiments using shuttle boxes were designed to compare the effects of sensory modality and conditioned-unconditioned stimulus interval (CS–US interval) upon memory formation and retention. We found that olfactory conditioning with phenylethyl alcohol as a CS was significantly more likely to produce a successful outcome than with a visual CS. Likewise a 10s CS–US interval yielded significantly more successful memory formation than a 15s interval. These conditions may further facilitate the use of zebrafish to explore the genetic and neuronal base of active avoidance learning and its neuropharmacological improvement.

An fMRI study of episodic encoding across the lifespan: Changes in subsequent memory effects are evident by middle-age

Although it is well-documented that there are age differences between young and older adults in neural activity associated with successful memory formation (positive subsequent memory effects), little is known about how this activation differs across the lifespan, as few studies have included middle-aged adults. The present study investigated the effect of age on neural activity during episodic encoding using a cross-sectional lifespan sample (20–79 years old, N=192) from the Dallas Lifespan Brain Study. We report four major findings. First, in a contrast of remembered vs. forgotten items, a decrease in neural activity occurred with age in bilateral occipito-temporo-parietal regions. Second, when we contrasted forgotten with remembered items (negative subsequent memory), the primary difference was found between middle and older ages. Third, there was evidence for age equivalence in hippocampal regions, congruent with previous studies. Finally, low-memory-performers showed negative subsequent memory differences by middle age, whereas high memory performers did not demonstrate these differences until older age. Taken together, these findings delineate the importance of a lifespan approach to understanding neurocognitive aging and, in particular, the importance of a middle-age sample in revealing different trajectories.

Reward Modulation of Hippocampal Subfield Activation during Successful Associative Encoding and Retrieval

Emerging evidence suggests that motivation enhances episodic memory formation through interactions between medial-temporal lobe (MTL) structures and dopaminergic midbrain. In addition, recent theories propose that motivation specifically facilitates hippocampal associative binding processes, resulting in more detailed memories that are readily reinstated from partial input. Here, we used high-resolution fMRI to determine how motivation influences associative encoding and retrieval processes within human MTL subregions and dopaminergic midbrain. Participants intentionally encoded object associations under varying conditions of reward and performed a retrieval task during which studied associations were cued from partial input. Behaviorally, cued recall performance was superior for high-value relative to low-value associations; however, participants differed in the degree to which rewards influenced memory. The magnitude of behavioral reward modulation was associated with reward-related activation changes in dentate gyrus/CA(2,3) during encoding and enhanced functional connectivity between dentate gyrus/CA(2,3) and dopaminergic midbrain during both the encoding and retrieval phases of the task. These findings suggests that, within the hippocampus, reward-based motivation specifically enhances dentate gyrus/CA(2,3) associative encoding mechanisms through interactions with dopaminergic midbrain. Furthermore, within parahippocampal cortex and dopaminergic midbrain regions, activation associated with successful memory formation was modulated by reward across the group. During the retrieval phase, we also observed enhanced activation in hippocampus and dopaminergic midbrain for high-value associations that occurred in the absence of any explicit cues to reward. Collectively, these findings shed light on fundamental mechanisms through which reward impacts associative memory formation and retrieval through facilitation of MTL and ventral tegmental area/substantia nigra processing.

IC‐P‐091: Successful associative memory formation and retrieval in healthy older adults is associated with hippocampal subfield activation

IC‐P‐091: Successful associative memory formation and retrieval in healthy older adults is associated with hippocampal subfield activation

P3‐211: Successful associative memory formation and retrieval in healthy older adults is associated with hippocampal subfield activation

P3‐211: Successful associative memory formation and retrieval in healthy older adults is associated with hippocampal subfield activation

Context memory in Korsakoff's syndrome.

Memory for contextual information and target-context integration are crucial for successful episodic memory formation and are impaired in patients with Korsakoff’s syndrome. In this paper we review the evidence for the notion that a context memory deficit makes an important contribution to the amnesia in these patients. First, we focus on anterograde memory for contextual (spatial and temporal) information. Next, the use of contextual cues in memory retrieval is examined and their role in retrograde amnesia and confabulation. Evidence on the role of contextual cues and associations in working memory is discussed in relation to the underlying neurocognitive mechanisms and their dissociation from long-term encoding. Finally, we focus on implicit learning of contextual information in Korsakoff patients. It can be concluded that Korsakoff patients are impaired in the explicit processing of contextual information and in target-context binding, both in long-term (retrograde and anterograde) memory and in working memory. These results extend the context memory deficit hypothesis. In contrast, implicit contextual learning is relatively preserved in these patients. These findings are discussed in relation to evidence of dysfunction of the extended diencephalic-hippocampal memory circuit in Korsakoff’s syndrome.

Facilitation of memory by contextual cues in patients with diencephalic or medial temporal lobe dysfunction

Item-context binding is crucial for successful episodic memory formation, and binding deficits have been suggested to underlie episodic-memory deficits. Here, our research investigated the facilitation of cued recall and recognition memory by contextual cues in 20 patients with Korsakoff's amnesia, 20 unilateral medial-temporal lobectomy (MTL) patients and 36 healthy controls. In a computerized task participants had to learn 40 nouns that were randomly combined with a photograph of an everyday scene. Korsakoff patients showed a general memory deficit in both the cued recall and the recognition condition. A less severe memory impairment was found in the patients with medial-temporal lobectomy. Contextual cues facilitated cued recall to an equal extent in unilateral temporal lobectomy patients and healthy controls. However, no facilitation was observed in Korsakoff patients, suggesting an impairment in item-context binding during cued recall tasks. In contrast to the presumed exclusive dependency of recognition memory on item information, all groups equally profited from the contextual cues in recognition tasks. Our findings show that unilateral lesions as with MTL result in normal binding of context and item information, while bilateral dysfunction of the hippocampal-diencephalic system results in impaired context and item binding.

P.1.020 Forced swim stress enhances the survival of new dentate gyrus neurons in rat through a glucocorticoid receptor-dependent mechanism

Adaptive and coping behaviours such as immobility in the forced swim (FS) retest are dependent on successful memory formation during initial training/tests. It has been suggested that stressful learning paradigms such as Morris water maze learning lead to enhanced survival of newly born neurons in the dentate gyrus (DG) and that these newly generated neurons may be involved in long-term memory formation. We have previously identified a signaling pathway, involving activation of ERK1/2 (extracellular signal-regulated kinase1/2), MSK1 (mitogen- and stress-activated kinase1), and Elk-1 (ets-domain- containing protein1) signaling molecules and activated within DG granule neurons following FS, which results in distinct epigenetic changes and induction of immediate early genes (IEGs; e.g. c-Fos/Egr-1) and the consolidation of the adaptive behavioural immobility response [1,2]. Glucocorticoid hormones, released as part of the stress response and acting via glucocorticoid receptors (GRs), enhance signaling through the ERK1/2/MSK1-Elk-1 pathway and thereby increase the impact on epigenetic and gene expression mechanisms. We aimed to determine if this signaling pathway leading to IEG induction is activated specifically in young adult-born dentate neurons following FS. Rats were injected twice daily for 5 days with BrdU to label new neurons. One, six or twelve weeks after BrdU treatment the rats were forced to swim (15 min, 25°C-water), before being killed 1h later and tissue analyzed by immunofluorescence. FS-induced c-Fos was observed at all time points but there was no co-localization of the IEG with BrdU. Next, given that experiences during the first 1−2 weeks of a young adult-born DG neuron's life is important for its survival [3], we studied whether FS would promote neuronal survival. Rats were injected with BrdU for 5 days and split into groups: control and FS groups. The FS group underwent a 15-min FS challenge one week after the BrdU injections, whereas the control group remained in their home cages. Four weeks after the initial FS test both groups (i.e. control group and FS group) underwent another FS procedure and killed 1h later. The FS group, which had undergone a FS challenge four weeks previously, showed significantly more immobility behavior compared with controls (n = 8, p<0.01, Students t-test), indicating that they had remembered the initial FS test. No co-localization of c-Fos with BrdU was found in either group. The number of BrdU-positive neurons was higher in the dentate gyrus of the FS group (19.6±2.1 neurons, n = 8) than in control animals (12.0±1.1 neurons, n=4) (p<0.03, Student's t-test). To investigate a role of GRs in the survival-promoting effect of FS we pre-treated rats with the GR antagonist RU486 before the initial FS challenge. RU486 impaired the behavioural immobility response in the 4-week retest (n = 7/group; p<0.01, post-hoc Bonferroni test) and abolished the FS-evoked increase in neuronal survival compared with the vehicle-pre-treated group (n = 5/control group, 7/FS group; p<0.001, post-hoc Bonferroni test). Thus, a single FS challenge promotes the survival of new adult-born DG granule neurons, which requires GR activation at the time of the stressful challenge and which may contribute to the formation of long-term memories of the FS event.

Differential functional response in the posteromedial cortices and hippocampus to stimulus repetition during successful memory encoding

The reduction of neural activity in response to repeated stimuli, repetition suppression, is one of the most robust experience-related cortical dynamics known to cognitive neuroscience. Functional magnetic resonance imaging (fMRI) studies during episodic memory encoding have demonstrated repetition suppression in the hippocampus and this reduction has been linked to successful memory formation. An emerging body of functional imaging evidence suggests that the posteromedial cortex, in addition to the medial temporal lobes, may have a pivotal role in successful episodic memory. This area typically deactivates during initial memory encoding, but its functional changes in response to repetitive encoding remain poorly specified. Here, we investigate the repetition-related changes in the posteromedial cortex as well as the hippocampus while the participants underwent an fMRI experiment involving repetitive encoding of face-name pairs. During the first encoding trial of face-name pairs, significant activation in the hippocampus was observed. The second and third encoding trials demonstrated a repetition suppression effect in the hippocampus, indicated by a stepwise decrease of activation. In contrast, the posteromedial cortex demonstrated significant deactivation during the initial encoding trial of face-name pairs. The second and third encoding trials demonstrated a stepwise decrease of deactivation, repetition enhancement, with activity at or above baseline levels in the final encoding trial. These findings demonstrate that hippocampus repetition suppression as well as posteromedial repetition enhancement is related to successful encoding processes and are discussed in relation to the default mode hypothesis as well as potential implications for understanding late-life amnestic disorders.

Event-Related Nociceptive Arousal Enhances Memory Consolidation for Neutral Scenes

The superior memory for emotional events has been attributed to the beneficial effects of noradrenaline released into the amygdala attributable to arousal. Noradrenaline mediates the effects of different hormones and neurotransmitters, including adrenal stress hormones on consolidation (McGaugh, 2004; Roozendaal et al., 2009). The majority of human fMRI studies of the enhancement of emotional memories contrasted successful encoding of emotionally arousing and neutral stimuli (LaBar and Cabeza, 2006; Murty et al., 2010). Recently, it was highlighted that emotional stimuli elicit not only arousal but also intensify cognitive processes that contribute to the enhanced memory. In particular, the enhanced use of selective attention as well as the greater distinctiveness and semantic relatedness of emotional stimuli influence memory formation (Talmi et al., 2007a). The present study aimed to explore the effects of arousal on memory formation independent of these cognitive factors in an event-related manner. Arousal was induced by the application of a nociceptive stimulus briefly after the presentation of neutral scenes. The results show a purely arousal-driven memory enhancement for the neutral scenes that differs in critical aspects from the superior memory for emotional stimuli. In particular, the enhancement was only evident after consolidation and exclusively based on an increase in item familiarity but not recollection. Moreover, successful memory formation for stimuli followed by arousal was correlated with activity in the parahippocampal cortex but not the amygdala, as is the case for emotional stimuli.

The Relationship between Brain Oscillations and BOLD Signal during Memory Formation: A Combined EEG–fMRI Study

Previous studies demonstrated that increases in the theta frequency band with concomitant decreases in the alpha/beta frequency band indicate successful memory formation. However, little is known about the brain regions and the cognitive processes that underlie these encoding-related oscillatory memory effects. We investigated this relationship using simultaneous EEG-fMRI recordings in humans during long-term memory encoding. In line with prior studies, we demonstrate that a decrease in beta power and an increase in theta power positively predict subsequent recall. In fMRI, stronger activity in the left inferior prefrontal cortex and the right parahippocampal gyrus correlated with successful memory formation. EEG source localization revealed that the subsequent memory effect in the beta band was localized in the left inferior prefrontal cortex, whereas the effect in the theta band was localized in medial temporal lobe regions. Trial-by-trial correlations between EEG and BOLD activity showed that beta power correlated negatively with left inferior prefrontal cortex activity. This correlation was more pronounced for items that could later be successfully recalled compared to items later forgotten. Based on these findings, we suggest that beta oscillations in the left inferior prefrontal cortex indicate semantic encoding processes, whereas theta oscillations in the medial temporal lobe reflect the binding of an item to its spatiotemporal context.

Decoding episodic memory in ageing: a Bayesian analysis of activity patterns predicting memory.

Normal ageing is associated with a decline in episodic memory, and neuroimaging studies in older adults have shown reduced activity in prefrontal cortex and other regions critical for memory function in the young. However, older adults also activate additional regions, suggesting a degree of functional reorganisation that has been attributed variously to detrimental and adaptive changes. Evaluation of these competing hypotheses depends critically upon inferences about the relative location and distribution of activity that are not well supported by current univariate or multivariate analyses. Here, we employed a recently developed model-based multivariate ‘decoding’ approach (Friston et al., 2008) to re-analyse a rich episodic encoding dataset and examine directly how the patterns of activity change in ageing. We assessed which spatial activity patterns, within lateral prefrontal cortex, best predict successful memory formation. Bayesian model comparison showed that the older adults had more distributed and bilateral (fragmented) predictive patterns of activity in anterior inferior frontal gyrus and middle frontal gyrus. With this direct multivariate test for changes in patterns of activity, we replicate and extend earlier findings of reduced prefrontal lateralisation in ageing. These findings extend conclusions based on conventional analyses, and support the notion that ageing alters the spatial deployment of neuronal activity, to render it less spatially coherent and regionally specific. This greater distribution of activity in older adults was also linked to poorer individual memory performance, suggesting that it reflects neural ageing, rather than adaptive compensatory responses.

Short-Term Duloxetine Administration Affects Neural Correlates of Mood-Congruent Memory

It is unknown how antidepressants reverse mood-congruent memory bias, a cognitive core factor causing and maintaining depression. Using a double-blind, placebo-controlled, cross-over design, we investigated the effect of a short-term treatment (14 days) with the dual reuptake inhibitor duloxetine on neural correlates of mood-congruent and mood-incongruent memory formation and retrieval in healthy volunteers who underwent a sad mood induction procedure. Duloxetine did not affect acute mood state or memory performance, but interacted with brain processes mediating mood-congruent memory. It decreased activity related to successful memory formation for mood-congruent and -incongruent items in a set of brain regions comprising the putamen and the middle frontal gyrus, as well as the middle and the anterior cingulate cortex. Duloxetine specifically increased amygdala activity related to successful memory retrieval for mood-incongruent items. Here we show that short-term administration of duloxetine affects the neural correlates of emotional memory formation and retrieval in a set of brain regions whose processing is related to affective state and its regulation. While duloxetine suppressed the neural correlates of emotional memory formation in general, it specifically enhanced amygdala processes associated with mood-incongruent memory retrieval. This pattern of results shows how an antidepressant may reduce emotional memory formation and reverse mood-congruent processing biases at retrieval.

Perirhinal and Parahippocampal Cortices Differentially Contribute to Later Recollection of Object- and Scene-Related Event Details

How the different elements of our experiences are encoded into episodic memories has remained one of the major questions in memory research. Although the pivotal role of the medial temporal lobe as a whole for memory formation is well established, much controversy surrounds the precise contributions of the subregions in the medial temporal lobe cortex (MTLC), most notably the perirhinal cortex (PrC) and the parahippocampal cortex (PhC). Although one prominent view links PrC processes with familiarity-based memory and PhC with recollection, an alternative organizing principle is the representational domain critical for successful memory performance (e.g., object- versus scene-related information). In this functional magnetic resonance imaging study, we directly compared successful source encoding during object versus scene imagery, holding perceptual input constant across the two representational domains. Although the hippocampus contributed to associative encoding of both object and scene information, our results revealed a clear double dissociation between PrC and PhC for object- versus scene-related source encoding. In particular, PrC, but not PhC, encoding activation predicted later source memory for the object imagery task, whereas PhC, but not PrC, encoding activation predicted later source memory for the scene imagery task. Interestingly, the transitional zone between PrC and posterior PhC contributed to both object and scene source encoding, possibly reflecting a gradient in domain preference along MTLC. In sum, these results strongly point to representational domain as a key factor determining the involvement of different MTLC subregions during successful episodic memory formation.

How mood challenges emotional memory formation: An fMRI investigation

Experimental mood manipulations and functional magnetic resonance imaging (fMRI) provide a unique opportunity for examining the neural correlates of mood-congruent memory formation. While prior studies in mood-disorder patients point to the medial temporal lobe in the genesis of mood-congruent memory (MCM) bias, the interaction between mood and emotional memory formation has not been investigated in healthy participants. In particular it remains unclear how regulatory structures in the pre-frontal cortex may be involved in mediating this phenomenon. In this study, event-related fMRI was performed on 20 healthy participants using a full-factorial, within-subjects repeated-measures design to examine how happy and sad moods impact memory for valenced stimuli (positive, negative and neutral words). Main effects of mood, stimulus valence and memory were examined as was activity related to successful memory formation during congruent and in-congruent moods. Behavioral results confirm an MCM bias while imaging results show amygdala and hippocampal engagement in a global mood and successful recall, respectively. MCM formation was characterized by increased activity during mood-congruent encoding of negative words in the orbito-frontal cortex (OFC) and for mood-incongruent processing of negative words in medial- and inferior-frontal gyri (MFG/IFG). These findings indicate that different pre-frontal regions facilitate mood-congruent and incongruent encoding of successfully recalled negative words at the time of learning, with OFC enhancing congruency and the left IFG and MFG helping overcome semantic incongruities between mood and stimulus valence.

Ventromedial Prefrontal Cortex Activation Is Associated with Memory Formation for Predictable Rewards

During reinforcement learning, dopamine release shifts from the moment of reward consumption to the time point when the reward can be predicted. Previous studies provide consistent evidence that reward-predicting cues enhance long-term memory (LTM) formation of these items via dopaminergic projections to the ventral striatum. However, it is less clear whether memory for items that do not precede a reward but are directly associated with reward consumption is also facilitated. Here, we investigated this question in an fMRI paradigm in which LTM for reward-predicting and neutral cues was compared to LTM for items presented during consumption of reliably predictable as compared to less predictable rewards. We observed activation of the ventral striatum and enhanced memory formation during reward anticipation. During processing of less predictable as compared to reliably predictable rewards, the ventral striatum was activated as well, but items associated with less predictable outcomes were remembered worse than items associated with reliably predictable outcomes. Processing of reliably predictable rewards activated the ventromedial prefrontal cortex (vmPFC), and vmPFC BOLD responses were associated with successful memory formation of these items. Taken together, these findings show that consumption of reliably predictable rewards facilitates LTM formation and is associated with activation of the vmPFC.

Genetic variation of the α2b‐adrenoceptor affects neural correlates of successful emotional memory formation

Enhanced memory for emotionally charged events helps us to remember potentially vital information. There are large interindividual differences in emotional-memory enhancement, but little is known about their neurobiological basis. Recently, a functional deletion variant of the gene that codes for the α2b-adrenoceptor (ADRA2B) has been shown to affect memory for emotional experiences. Initial neuroimaging evidence linked this behavioral effect to increased amygdala activity, but its influence on successful memory processing remains unknown. Therefore, the aim of this study was to investigate the effect of the common deletion in the ADRA2B gene on neural activity related to specific mnemonic processing, successful memory formation, and retrieval. Twenty-three noncarriers (10 males) and 28 deletion carriers (13 males) with a mean age of 24 years were investigated while performing an emotional-learning task with sad and happy scenes. Functional magnetic resonance imaging was acquired both during memory formation and retrieval. Although there were no differences in memory performance between groups, the common deletion variant of ADRA2B was related to enhanced activity in the amygdala and inferior frontal gyrus during successful emotional memory formation, but not retrieval. Deletion carriers showed a larger differential response in these brain regions between later-remembered and later-forgotten stimuli than nondeletion carriers did. Our results demonstrate that the ADRA2B polymorphism influences emotional memory formation but not memory retrieval in the amygdala and left inferior frontal gyrus.

Rose or black-coloured glasses?: Altered neural processing of positive events during memory formation is a trait marker of depression

BackgroundValence-specific memory enhancement is one of the core cognitive functions that causes and maintains Major Depressive Disorder (MDD). While previous neuroimaging studies have elucidated the neural underpinnings of this emotional enhancement effect in depressed patients, this study aimed at detecting processing biases that are maintained throughout remission while patients were euthymic. MethodsFourteen medication-free women remitted from unipolar MDD and 14 matched controls were scanned while learning negative, positive, and neutral words, which were subsequently tested with free recall. ResultsThe two groups did not differ in memory performance and showed no neural differences during successful encoding of neutral or negative words. However, during successful encoding of positive words, patients exhibited a larger recruitment of a set of areas, comprising cingulate gyrus, right inferior- and left medial-frontal gyrus as well as the right anterior hippocampus/amygdala. LimitationsRestriction to female participants may limit the generalization of the findings. ConclusionFemale MDD patients in clinical remission exert greater neural recruitment of memory-related brain regions when successfully encoding positive words, suggesting that neural biases related to memory formation of positive information do not entirely normalize. Further research is needed to establish whether this processing bias during successful memory formation of positive information is predictive for future relapse thereby offering the possibility to develop more focused therapeutic interventions to specifically target these processes.