Emotional Memory Task Research Articles

Age-related Differences in Mu Rhythm During Emotional Destination Memory Task.

Destination memory defined as the ability to remember to whom we addressed a piece of information is found to be impaired in normal aging. Theories of affect development and research findings have shown that emotional charging improves performance on memory tasks, and also that Mu rhythm is desynchronized as an index of mirror neuron activation during such tasks. In this paper, we sought to investigate the differences in Mu rhythm during an emotional destination memory task, between younger and older adults. 16 cognitively normal older adults, recruited from Alzheimer's disease day center and 16 young adults, recruited via advertisements, participated in this experimental study. We investigated destination memory of emotionally charged faces (Emotional Destination Memory, EDM) while applying electroencephalograph (EEG) in real time in young versus older adults. We measured Mu rhythm in frontal, fronto-temporal and central areas. EEG data has been pre-processed, segmented in non-overlapping epochs, and independent component analysis (ICA) has been conducted to reject artifacts. Results showed that young adults performed better than older adults in remembering facts associated with angry faces. Also, different neurophysiological activation was found, with older adults showing Mu suppression in frontal and fronto-temporal regions, specifically in F3, F7 and F8 electrodes, in contrast with young adults who showed Mu enhancement. Regarding within group differences, it was found that in the older adults group, electrodes F8 and central C3 were the most activated, while in the young adults group, C3 was the most activated electrode. The findings suggest better behavioral performance of young adults as a result of better cognitive state and adaptive bias. On a neurophysiological level, it is suggested that older adults employ Mu suppression, thus possible activation of mirror neurons, as a compensatory mechanism while mirroring properties are not spontaneously activated in young adults.

Somatization Symptoms Regulate Emotional Memory Bias in Adolescents With Major Depressive Disorder.

Objective: Somatization symptoms are commonly comorbid with depression. Furthermore, people with depression and somatization have a negative memory bias. We investigated the differences in emotional memory among adolescent patients with depressive disorders, with and without functional somatization symptoms (FSS).Methods: We recruited 30 adolescents with depression and FSS, 38 adolescents with depression but without FSS, and 38 healthy participants. Emotional memory tasks were conducted to evaluate the emotional memory of the participants in the three groups. The clinical symptoms were evaluated using the Hamilton Depression Rating Scale (HDRS) and the Children's Somatization Inventory (CSI).Results: The valence ratings and recognition accuracy rates for positive and neutral images of adolescent patients were significantly lower than those of the control group (F = 12.208, P < 0.001; F = 6.801, P < 0.05; F = 14.536, P < 0.001; F = 6.306, P < 0.05, respectively); however, the recognition accuracy rate for negative images of adolescent patients of depression without FSS was significantly lower than that of patients with FSS and control group participants (F = 10.316, P < 0.001). These differences persisted after controlling for HDRS scores. The within-group analysis revealed that patients of depression with FSS showed significantly higher recognition accuracy rates for negative images than the other types (F = 5.446, P < 0.05). The recognition accuracy rate for negative images was positively correlated with CSI scores (r = 0.352, P < 0.05).Conclusion: Therefore, emotional memory impairment exists in adolescent patients of depression and FSS are associated with negative emotional memory retention.

Training Emotion Recognition Accuracy: Results for Multimodal Expressions and Facial Micro Expressions.

Nonverbal emotion recognition accuracy (ERA) is a central feature of successful communication and interaction, and is of importance for many professions. We developed and evaluated two ERA training programs—one focusing on dynamic multimodal expressions (audio, video, audio-video) and one focusing on facial micro expressions. Sixty-seven subjects were randomized to one of two experimental groups (multimodal, micro expression) or an active control group (emotional working memory task). Participants trained once weekly with a brief computerized training program for three consecutive weeks. Pre-post outcome measures consisted of a multimodal ERA task, a micro expression recognition task, and a task about patients' emotional cues. Post measurement took place approximately a week after the last training session. Non-parametric mixed analyses of variance using the Aligned Rank Transform were used to evaluate the effectiveness of the training programs. Results showed that multimodal training was significantly more effective in improving multimodal ERA compared to micro expression training or the control training; and the micro expression training was significantly more effective in improving micro expression ERA compared to the other two training conditions. Both pre-post effects can be interpreted as large. No group differences were found for the outcome measure about recognizing patients' emotion cues. There were no transfer effects of the training programs, meaning that participants only improved significantly for the specific facet of ERA that they had trained on. Further, low baseline ERA was associated with larger ERA improvements. Results are discussed with regard to methodological and conceptual aspects, and practical implications and future directions are explored.

Fear and Favoritism in the Time of COVID-19

Does fear cause us to “circle the wagons” and favor those in our in-group? Or does fear of the “other” cause us to recognize our common humanity and become more charitable to those we might otherwise consider outsiders? The measurement of this effect is confounded by the fact that some groups respond more strongly to fear than others. We run an online experiment on a nationally representative sample in South Korea in which we induce fear via the autobiographical emotional memory task method and examine the impact on donations to either an in-group charity (the Korean Red Cross) or one that caters to an out-group (the Korea Support Center for Foreign Workers). We find that, while the reported level of fear is negatively correlated with donations to the out-group, the induced fear caused by the experimental intervention is positively correlated with donations to the out-group. We also find that the fear effect depends on political views, media exposure, and social preferences. We confirm our experimental results by looking at how regional attitudes toward out-groups have shifted over time and compare those changes to the average level of reported fear during the COVID-19 pandemic. Places that report the most fear of COVID-19 also have had the greatest increases in prosocial attitudes toward out-groups.

The G protein-coupled estrogen receptor (GPER) regulates recognition and aversively–motivated memory in male rats

Estrogens, particularly 17β-estradiol (estradiol, E2), regulate memory formation. E2 acts through its intracellular receptors, estrogen receptors (ER) ERα and ERβ, as well as a recently identified G protein-coupled estrogen receptor (GPER). Although the effects of E2 on memory have been investigated, studies examining the effects of GPER stimulation are scarce. Selective GPER agonism improves memory in ovariectomized female rats, but little information is available regarding the effects of GPER stimulation in male rodents. The aim of the present study was to investigate the effects of the GPER agonist, G1, on consolidation and reconsolidation of inhibitory avoidance (IA) and object recognition (OR) memory in male rats. Animals received vehicle, G1 (15, 75, 150 µg/kg; i.p.), or the GPER antagonist G15 (100 µg/kg; i.p.) immediately after training, or G1 (150 µg/kg; i.p.) 3 or 6 h after training. To investigate reconsolidation, G1 was administered immediately after IA retention Test 1. Results indicated that G1 administered immediately after training at the highest dose enhanced both OR and IA memory consolidation, while GPER blockade immediately after training impaired OR. No effects of GPER stimulation were observed when G1 was given 3 or 6 h after training or after Test 1. The present findings provide evidence that GPER is involved in the early stages of memory consolidation in both neutral and emotional memory tasks in male adult rats.

Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial

Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d′, an index of the detectability of working memory signals) and response bias were evaluated in the context of task-related brain activations. Subjects with more severe PTSD showed both greater tolcapone-mediated improvements in d′ and larger tolcapone-mediated reductions in liberally-biased responding for fearful stimuli. FMRI revealed that tolcapone augmented activity within bilateral frontoparietal control regions during the decision phase of the task. Specifically, tolcapone increased cortical responses to fearful relative to neutral stimuli in higher severity PTSD subjects, and reduced cortical responses to fearful stimuli for lower severity PTSD subjects. Moreover, tolcapone modulated prefrontal connectivity with areas overlapping the default mode network. These findings suggest that enhancing cortical dopamine tone may represent an approach to remediating cognitive and affective dysfunction in individuals with more severe PTSD symptoms.

Language modulation on emotional valence tasks in preschoolers

Language plays a crucial role in developing emotions. Diverse investigations studied the relationship between different components of emotional understanding and language skills. Specifically, we want to find out if this modulation is uniform or if there are variations in the different components of emotional understanding. The goals of this study were to compare the responses to tasks with different cognitive demands and different emotional information processing modalities and to demonstrate any variations in function to the language performance. For it, this paper analysed the responses to tasks with an emotional and neutral valence of preschool children grouped by different language performances. The children performed three tasks related to different emotional understanding components (video and images emotional appraisal, and an emotional memory task) and a language test that evaluated different language skills in a single sample of participants. Language skills are associated with different emotional appraisal task performances but only for dynamic visual stimuli and emotional valences (positive and negative). According to the type of stimulus used, the differences in emotional processing tasks’ performance align with the literature about using dynamic and ecological stimuli for studies with children. Language comprehension would play an essential role in assessing dynamic emotional stimuli, while other language skills would not affect the assessment of static or neutral dynamic stimuli during preschool.

Light-Dependent Effects of Prefrontal rTMS on Emotional Working Memory.

Growing evidence suggests that colored light exposure can affect several brain functions in addition to conscious visual perception. Blue as compared to green light has especially been shown to enhance alertness and vigilance, as well as cognitive functions. However, the role of light exposure in studies using non-invasive brain stimulation remains unclear. Here, we examined the impact of light on cognitive-emotional effects of prefrontal repetitive transcranial magnetic stimulation (rTMS). In a randomized within-subjects design, twenty participants (12 males, 26 ± 4 years) were exposed to blue or green light prior and concomitant to active or sham rTMS (1Hz, 15min, 110% of the resting motor threshold), applied over the right dorsolateral prefrontal cortex (DLPFC). In each condition, an emotional working memory task (EMOBACK) was presented pre- and post-intervention. Stimuli of the EMOBACK task were positive, negative and neutral words. Our results revealed valence-specific stimulation effects in dependence of colored light exposure. More specifically, task accuracy was significantly increased for positive stimuli under blue light and for negative stimuli under green light exposure. Our findings highlight the importance of state-dependency in studies using non-invasive brain stimulation and show blue light exposure to be a potential adjunctive technique to rTMS for enhancing cognitive-emotional modulation.

Ketamine specifically reduces cognitive symptoms in depressed patients: An investigation of associated neural activation patterns

Major depressive disorder (MDD) is characterized by heterogeneous cognitive, affective and somatic symptoms. Hence, the investigation of differential treatment effects on these symptoms as well as the identification of symptom specific biomarkers might crucially contribute to the development of individualized treatment strategies.We here aimed to examine symptom specific responses to treatment with ketamine, which repeatedly demonstrated rapid antidepressant effects in severe MDD. Additionally, we investigated working memory (WM) related brain activity associated with changes in distinct symptoms in order to identify specific response predictors. In a sample of 47 MDD patients receiving a single sub-anesthetic dose of ketamine, we applied a three-factor solution of the Beck Depression Inventory (BDI) to detect symptom specific changes 24 h post-infusion. A subsample of 16 patients underwent additional fMRI scanning during an emotional working memory task prior to ketamine treatment. Since functional aberrations in the default mode network (DMN) as well as in the dorsolateral prefrontal cortex (DLPFC) have been associated with impaired cognitive and emotional processing in MDD, we investigated neural activity in these regions.Our results showed that ketamine differentially affects MDD symptoms, with the largest symptom reduction in the cognitive domain. WM related neuroimaging results indicated that a more pronounced effect of ketamine on cognitive symptoms is predicted by lower DMN deactivation and higher DLPFC activation. Findings thereby not only indicate that ketamine's antidepressant efficacy is driven by a pro-cognitive mechanism, but also suggest that this might be mediated by increased potential for adaptive adjustment in the circumscribed brain regions.

The impact of emotions on stereotyping in workplace selection: The role of certainty appraisals

AbstractAn appraisal tendency approach was adopted to explore the influence of emotional certainty on stereotyping and judgment in a workplace context. Across two studies, participants completed an emotional memory task designed to induce emotions representing two different levels of emotional certainty (certain versus uncertain). They then reviewed interview footage, a résumé, and qualifying criteria before rating a hypothetical job candidate’s personality and employability. Study 1 revealed that emotions high in certainty (compared to uncertainty) led to more favorable personality and employability ratings for attractive compared to unattractive candidates. Study 2 produced the same pattern of results for younger (compared to older) candidates. We conclude that certainty appraisals associated with temporary, incidental emotions are a useful predictor of the likelihood that stereotypes will be applied during decision making.

Comparing the Short and Long-Term Effects of Acute Moderate-Intensity Exercise on Mnemonic Similarity and Emotional Memory Tasks

Mounting research has linked acute moderate-intensity exercise with changes indiscrimination of similar events – i.e., mnemonic memory. Conversely, few studies have compared performance in tasks associated to each type of memory(mnemonic similarity and emotional) and less have evaluatedperformance several days after exercise sessions. Thirty-five undergraduate students were randomly distributed in three groups that differed in the assigned duration of the moderate-intensity exercise session.Weestablished first the moderate-intensityexercise program by calculating the VO2max 50%. Two-to-five days later, participantsengaged in the exercise condition to which they were assigned, followed by a five-minute rest period. Immediately after, all participantswere exposed to the training phase of both memory tasks. The first retrieval phase was tested 45 minutes afterencoding phase was completed. Subsequent retrieval phases were conducted 24, 48, and 168 hours post-training. Exercise of long duration in creased discrimination performance in images of low similarity. Comparison of the effects of exercise on discrimination of the three types of images that the emotional-memory task entailsshowed improved performance only for aversive and neutral images. Exercise improves discrimination of low similarity images, with better overall performance after a longer exercise session. This finding adds to previous reports that have found analogous effects using other memory tasks.It also supports the notion that acute effects due to exercise are specifically related to hippocampal functionality and its ability to separate patterns. Finally, maintenance of emotional information across time suggest a different mechanism,independent of pattern-separation processing.

Task MRI-Based Functional Brain Network of Major Depression.

This chapter will focus on task magnetic resonance imaging (MRI) to understand the biological mechanisms and pathophysiology of brain in major depressive disorder (MDD), which would have minor alterations in the brain function. Therefore, the functional study, such as task MRI functional connectivity, would play a crucial role to explore the brain function in MDD. Different kinds of tasks would determine the alterations in functional connectivity in task MRI studies of MDD. The emotion-related tasks are linked with alterations in anterior cingulate cortex, insula, and default mode network. The emotional memory task is linked with amygdala-hippocampus alterations. The reward-related task would be related to the reward circuit alterations, such as fronto-straital. The cognitive-related tasks would be associated with frontal-related functional connectivity alterations, such as the dorsolateral prefrontal cortex, anterior cingulate cortex, and other frontal regions. The visuo-sensory characteristics of tasks might be associated with the parieto-occipital alterations. The frontolimbic regions might be major components of task MRI-based functional connectivity in MDD. However, different scenarios and tasks would influence the representations of results.

Fear and Favoritism in the Time of COVID-19

Does fear cause us to "circle the wagons" and favor those in our in-group? Or does fear of the "other" cause us to recognize our common humanity and become more charitable to those we might otherwise consider outsiders? The measurement of this effect is confounded by the fact that some groups respond more strongly to fear than others. We run an online experiment on a nationally representative sample in South Korea in which we induce fear via the autobiographical emotional memory task method and examine the impact on donations to either an in-group charity (the Korean Red Cross) or one that caters to an out-group (the Korea Support Center for Foreign Workers). We find that, while the reported level of fear is negatively correlated with donations to the out-group, the induced fear caused by the experimental intervention is positively correlated with donations to the out-group. We also find that the fear effect depends on political views, media exposure, and social preferences. We confirm our experimental results by looking at how regional attitudes toward out-groups have shifted over time and compare those changes to the average level of reported fear during the COVID-19 pandemic. Places that report the most fear of COVID-19 also have had the greatest increases in prosocial attitudes toward out-groups.

Functional indicators of a decline in the noradrenergic locus coeruleus in ageing

AbstractBackgroundPostmortem studies show that the locus coeruleus (LC), the major source of cortical noradrenergic projections, exhibits evidence of neurodegeneration early in Alzheimer’s disease (AD). Indeed, the noradrenergic system is more affected than the dopaminergic or cholinergic ones. Albeit to a smaller extent, neuronal loss in the LC is also seen in cognitively normal older adults, which can in some cases reflect the earliest stages of AD neuropathology before cognitive changes are clinically detectable. These postmortem findings have been corroborated in recent years by in vivo assessments of LC integrity using anatomical MRI (magnetic resonance imaging) approaches. Before measurable neuronal loss occurs, functional LC decline should be observable. I will present the results of a series of studies involving pupillometry, high‐resolution fMRI (functional) as well as cognitive paradigms targeting noradrenergic function, which investigated whether a decline in LC function can be detected in cognitively normal older adults.MethodWe examined LC function during an emotional memory task known to rely on the noradrenergic system in 22 healthy younger adults (18‐30 years) and 22 healthy older adults (62‐83 years) with pupillometry (a proxy for LC function) (Study 1), as well as 22 healthy younger adults (20‐31 years) and 28 healthy older adults (65‐84 years), using high resolution fMRI (Study 2).ResultOur studies reveal both, a) evidence for a decline in functional LC responses with ageing (Figure 1, pupillometric data), as well as, b) evidence for no decline in functional LC responses in older adults (in pupillometry and fMRI). Specifically, reduced LC responses with ageing were observed in experimental conditions that allowed for a more selective assessment of LC function, independent of the engagement of other brain areas, underlining the need for a careful selection of cognitive paradigms when investigating functional indicators of LC decline.ConclusionOur results show that fMRI and pupillometry are promising methods for assessing changes in LC function in ageing and early AD. We provide recommendations for cognitive paradigms, experimental setups as well as data analysis methods for researchers interested in assessing functional changes in the noradrenergic system in AD and other disorders.

Dynamic behavior of the locus coeruleus during arousal-related memory processing in a multi-modal 7T fMRI paradigm.

A body of animal and human evidence points to the norepinephrine (NE) locus coeruleus (LC) system in modulating memory for arousing experiences, but whether the LC would recast its role along memory stages remains unknown. Sedation precluded examination of LC dynamics during memory processing in animals. Here, we addressed the contribution of the LC during arousal-associated memory processing through a unique combination of dedicated ultra-high-field LC-imaging methods, a well-established emotional memory task, online physiological and saliva alpha-amylase measurements in young adults. Arousal-related LC activation followed amygdala engagement during encoding. During consolidation and recollection, activation transitioned to hippocampal involvement, reflecting learning and model updating. NE-LC activation is dynamic, plays an arousal-controlling role, and is not sufficient but requires interactions with the amygdala to form adaptive memories of emotional experiences. These findings have implications for understanding contributions of LC dysregulation to disruptions in emotional memory formation, observed in psychiatric and neurocognitive disorders.

Effect of the NMDA receptor partial agonist, d-cycloserine, on emotional processing and autobiographical memory.

Studies suggest that d-cycloserine (DCS) may have antidepressant potential through its interaction with the glycine site of the N-methyl-D-aspartate receptor; however, clinical evidence of DCS's efficacy as a treatment for depression is limited. Other evidence suggests that DCS affects emotional learning which may also be relevant for the treatment of depression and anxiety. The aim of the present investigation was to assess the effect of DCS on emotional processing in healthy volunteers and to further characterise its effects on emotional and autobiographical memory. Forty healthy volunteers were randomly allocated to a single dose of 250 mg DCS or placebo in a double-blind design. Three hours later, participants performed an Emotional Test Battery [including Facial Expression Recognition Task (FERT), Emotional Categorisation Task (ECAT), Emotional Recall Task (EREC), Facial Dot-Probe Task (FDOT) and Emotional Recognition Memory Task (EMEM)] and an Autobiographical Memory Test (AMT). Also, participants performed the FERT, EREC and AMT tasks again after 24 h in order to assess longer lasting effects of a single dose of DCS. DCS did not significantly affect the FERT, EMEM and FDOT performance but significantly increased emotional memory and classification for positive words v. negative words. Also, DCS enhanced the retrieval of more specific autobiographical memories, and this effect persisted at 24 h. These findings support the suggestion that low-dose DCS increases specific autobiographical memory retrieval and positive emotional memory. Such effects make it an intriguing agent for further investigation in clinical depression, which is characterised by decreased autobiographical memory specificity and increased negative bias in memory recall. It also underscores the potential role of DCS as an adjunct to cognitive behavioural therapy in depression.

The Effect of Self-Reported REM Behavior Disorder Symptomology on Intrusive Memories in Post-Traumatic Stress Disorder

ABSTRACT Background: PTSD is characterised by severe sleep disturbances, which is increasingly recognised to in many cases consist of similar symptomology to sleep disorders such as REM Behaviour Disorder (RBD). The present study aimed to investigate whether different aspects of sleep quality influence intrusive memory development and whether PTSD status moderates this relationship. Participants and Methods: 34 PTSD, 52 trauma-exposed (TE) and 42 non-trauma exposed (NTE) participants completed an emotional memory task, where they viewed 60 images (20 positive, 20 negative and 20 neutral) and, two days later, reported how many intrusive memories they had of each valence category. Participants also completed three measures of sleep quality: the Pittsburgh Sleep Quality Index, the REM Behaviour Disorder Screening Questionnaire and total hours slept before each session. Results: The PTSD group reported poorer sleep quality than both TE and NTE groups on all three measures, and significantly more negative intrusive memories than the NTE group. Mediation analyses revealed that self-reported RBD symptomology before the second session mediated the relationship between PTSD status and intrusive memories. Follow-up moderation analyses revealed that self-reported RBD symptomology before the second session was only a significant predictor of intrusion in the PTSD group, though with a small effect size. Conclusions: These findings suggest that RBD symptomology is an indicator of consolidation of intrusive memories in PTSD but not trauma-exposed or healthy participants, which supports the relevance of characterising RBD in PTSD.

Transcranial Magnetic Stimulation of the Medial Prefrontal Cortex Decreases Emotional Memory Schemas.

Mood-congruent memory bias is a critical characteristic of depression, but the underlying neural mechanism is largely unknown. Negative memory schemas might enhance encoding and consolidation of negative experiences, thereby contributing to the genesis and perpetuation of depressive pathology. To investigate this relationship, we aimed to perturb medial prefrontal cortex (mPFC) processing, using neuronavigated transcranial magnetic stimulation (TMS) targeting the mPFC. Forty healthy volunteers first underwent a negative mood induction to activate negative schema processing after which they received either active inhibitory (N = 20) or control (N = 20) stimulation to the mPFC. Then, all participants performed the encoding of an emotional false memory task. Recall and recognition performance was tested the following morning. Polysomnographic data were recorded continuously during the night before and after encoding. We observed a significantly lower false recognition of negative critical lures following mPFC inhibition, but no differences in veridical memory. These findings were supported by reaction time data, showing a relative slower response to negative compared with positive critical lures. The current findings support previous causal evidence for a role of the mPFC in schema memory processing and further suggest a role of the mPFC in memory bias.

P.630 Amygdala functional connectivity in depressed bipolar patients as possible predictor of antidepressant response to chronobiological treatment

Adolescence is a developmental period in which depression and related mood syndromes often emerge, but few objective markers exist to guide diagnosis or predict symptoms. One potential mood marker is the functioning of frontoinsular networks, which undergo substantial development in adolescence and have been implicated in adult depression. To test this hypothesis, we used task-based neuroimaging to evaluate whether frontoinsular network dysfunction was linked to current and prospective mood health in adolescents.Adolescents (n = 40, 13–19 years of age) reporting varying levels of depressive symptom severity performed an emotional working memory task with neuroimaging. Next, teens completed a 2-week follow-up consisting of a daily diary report of negative affect and final report of depressive symptoms (n = 28 adherent). Analyses tested associations between task-related functional connectivity in frontoinsular networks and baseline or prospective measures of mood health over 2-week follow-up.Frontoinsular task response was associated with higher current depression severity (p = .049, ηp2 = .12), increases in future depression severity (p = .018, ηp2 = .23), and more intense and labile negative affect in daily life (ps = .015 to .040, ηp2 = .22 to .30). In particular, hypoconnectivity between insula and lateral prefrontal regions of the frontoparietal network was related to both baseline and prospective mood health, and hyperconnectivity between insula and midline or temporal regions of the default network was related to prospective mood health.These findings indicate that frontoinsular imbalances are related to both current depression and changes in mood health in the near future and suggest that frontoinsular markers may hold promise as translational tools for risk prediction.

A role for 5-HT4 receptors in human learning and memory.

5-HT4 receptor stimulation has pro-cognitive and antidepressant-like effects in animal experimental studies; however, this pharmacological approach has not yet been tested in humans. Here we used the 5-HT4 receptor partial agonist prucalopride to assess the translatability of these effects and characterise, for the first time, the consequences of 5-HT4 receptor activation on human cognition and emotion. Forty one healthy volunteers were randomised, double-blind, to a single dose of prucalopride (1 mg) or placebo in a parallel group design. They completed a battery of cognitive tests measuring learning and memory, emotional processing and reward sensitivity. Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task and increased the probability of choosing a symbol associated with a high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks. These findings are a translation of the memory enhancing effects of 5-HT4 receptor agonism seen in animal studies, and lend weight to the idea that the 5-HT4 receptor could be an innovative target for the treatment of cognitive deficits associated with depression and other neuropsychiatric disorders. Contrary to the effects reported in animal models, prucalopride did not reveal an antidepressant profile in human measures of emotional processing.