Gateway to the study of the amygdala and emotion.

The study of the amygdala and its role in the processing of emotions has become a common focus in neuroscience. The modern expansion of research in this area is partly due to the discovery of a subcortical pathway for the transmission of emotional information and the experimental paradigm that was developed to study it. Groundbreaking experiments during the 90s utilized anatomical, neurophysiological, and behavioral lesion studies in a rodent animal model to uncover the neural circuitry of a simple emotional memory. These studies demonstrated the essential role of a specific monosynaptic pathway in emotional memory, using traditional tools and behavioral methods. The development of an animal model with a simple and appropriate classical conditioning paradigm made experimental investigations into the neural basis of emotion tenable and available to a generation of neuroscientists. These tools and a focus on the amygdala's neural connections and their essential role in emotional memory were a driving force in the explosion of research regarding the amygdala and emotion.

Fear, learning, and the amygdala: a personal reflection in honor of Joseph LeDoux.

In honor of Joseph LeDoux's retirement from an illustrious career in science, I offer a personal reflection on how my graduate training experiences in his lab shaped my subsequent career trajectory and the development of my views on human amygdala function and the scientific enterprise. I discuss the values of openness to scientific exploration and of multi-methodological integration, both of which distinguished his laboratory over the years. I highlight the unique historical context in which the lab's foundational discoveries on the emotional brain occurred and the importance of embracing new technologies to advance an understanding of brain-behavior relationships in affective neuroscience.

A study of somatization symptoms and low-frequency amplitude fluctuations of emotional memory in adolescent depression.

Studies have revealed that somatization symptoms are associated with emotional memory in adolescents with depressive disorders. This study investigated somatization symptoms and emotional memory among adolescents with depressive disorders using low-frequency amplitude fluctuations (ALFF). Participants were categorized into the somatization symptoms (FSS) group, non-FSS group and healthy control group (HC). The correctness of negative picture re-recognition was higher in the FFS and HC group than in the non-FSS group. The right superior occipital gyrus and right inferior temporal gyrus were significantly larger in the FSS group than those in the non-FSS and HC groups. Additionally, the ALFF in the superior occipital and inferior temporal gyrus were positively correlated with CSI score. Furthermore, the ALFF values in the temporal region positively correlated with correct negative image re-recognition. The negative image re-recognition rate was positively correlated with the ALFF in the left and right middle occipital gyri. These findings indicated that somatization symptoms in adolescent depression are associated with the superior occipital gyrus and inferior temporal gyrus. Notably, somatization symptoms play a role in memory bias within depressive disorders, with middle occipital and inferior temporal gyri potentially serving as significant brain regions.

Why Pimping Works: The Neurophysiology of Emotional Memories.

A time-honored medical ritual that combines emotion and cognition into a seamless consolidation of lucid memories is a feared teaching method in medical education. The resulting neurophysiology is explained from a neurosurgeon's perspective - equal parts guilt and dread as a prescription for an improved and sustained trainee fund of knowledge. Much of the available literature published with regard to pimping explores its pedagogy and use in medical practice. This review aims to explore the neurobehavioral and biological aspects of pimping in why it remains a popular teaching model. We describe the neuromodulatory process of integrating emotions and memory as observed during pimping. Additionally, we explore the neuronal pathways and circuits involved in memory encoding, consolidation, and retrieval. Finally, we explored the effects of this methodology as it is currently used in the United States medical education system.

The effects of shared, depression-specific, and anxiety-specific internalizing symptoms on negative and neutral episodic memories following post-learning sleep.

Emotional memory bias is a common characteristic of internalizing symptomatology and is enhanced during sleep. The current study employs bifactor S-1 modeling to disentangle depression-specific anhedonia, anxiety-specific anxious arousal, and the common internalizing factor, general distress, and test whether these internalizing symptoms interact with sleep to influence memory for emotional and neutral information. Healthy adults (N = 281) encoded scenes featuring either negative objects (e.g., a vicious looking snake) or neutral objects (e.g., a chipmunk) placed on neutral backgrounds (e.g., an outdoor scene). After a 12-hour period of daytime wakefulness (n = 140) or nocturnal sleep (n = 141), participants judged whether objects and backgrounds were the same, similar, or new compared with what they viewed during encoding. Participants also completed the mini version of the Mood and Anxiety Symptom Questionnaire. Higher anxious arousal predicted worse memory across all stimuli features, but only after a day spent being awake-not following a night of sleep. No significant effects were found for general distress and anhedonia in either the sleep or wake condition. In this study, internalizing symptoms were not associated with enhanced emotional memory. Instead, memory performance specifically in individuals with higher anxious arousal was impaired overall, regardless of emotional valence, but this was only the case when the retention interval spanned wakefulness (i.e., not when it spanned sleep). This suggests that sleep may confer a protective effect on general memory impairments associated with anxiety.

Exogenous glucocorticoids to improve extinction learning for post-traumatic stress disorder patients with hypothalamic-pituitary-adrenal-axis dysregulation: a study protocol description.

Background: Trauma-focused treatments for post-traumatic stress disorder (PTSD) are effective for many patients. However, relapse may occur when acquired extinction memories fail to generalize beyond treatment contexts. A subgroup of PTSD patients - potentially with substantial exposure to early-life adversity (ELA) - show dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which results in lower cortisol levels. Glucocorticoids, including cortisol, appear to facilitate strength and generalization of emotional memories.Objective: We describe the protocol of an integrated PTSD study. We investigate (A) associations between HPA-axis dysregulation, ELA, epigenetic markers, and PTSD treatment outcome (observational study); and (B) effects of exogenous glucocorticoids on strength and generalization of extinction memories and associated neural mechanisms [pharmacological intervention study with functional magnetic resonance imaging (fMRI)]. The objective is to provide proof of concept that PTSD patients with HPA-axis dysregulation often experienced ELA and may show improved strength and generalization of extinction learning after glucocorticoid administration.Method: The observational study (n = 160 PTSD group, n = 30 control group) assesses ELA, follow-up PTSD symptoms, epigenetic markers, and HPA-axis characteristics (salivary cortisol levels during low-dose dexamethasone suppression test and socially evaluated cold-pressor test). The pharmacological intervention study (n = 80 PTSD group, with and without HPA-axis dysregulation) is a placebo-controlled fMRI study with a crossover design. To investigate strength and generalization of extinction memories, we use a differential fear acquisition, extinction, and extinction recall task with spatial contexts within a virtual environment. Prior to extinction learning, 20 mg hydrocortisone or placebo is administered. During next-day recall, strength of the extinction memory is determined by recovery of skin conductance and pupil dilation differential responding, whereas generalization is assessed by comparing responses between different spatial contexts.Conclusion: The integrated study described in the current protocol paper could inform a personalized treatment approach in which these PTSD patients may receive glucocorticoids as a treatment enhancer in trauma-focused therapies.Trial registration: The research project is registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database, https://eudract.ema.europa.eu/, EudraCT number 2020-000712-30.

This protocol reports a proof-of-concept study for glucocorticoids as an enhancer for PTSD treatment.The study examines whether glucocorticoids enhance the strength and generalization of extinction memory.A further aim is to identify HPA-axis-related PTSD subgroups that may particularly benefit.

Coping with the experience of frustration throughout life: Sex- and age-specific effects of early life stress on the susceptibility to reward devaluation.

Early life stress may lead to lifelong impairments in psychophysiological functions, including emotional and reward systems. Unpredicted decrease in reward magnitude generates a negative emotional state (frustration) that may be involved with susceptibility to psychiatric disorders. We evaluated, in adolescents and adult rats of both sexes, whether maternal separation (MS) alters the ability to cope with an unexpected reduction of reward later in life. Litters of Wistar rats were divided into controls (non handled - NH) or subjected to MS. Animals were trained to find sugary cereal pellets; later the amount was reduced. Increased latency to reach the reward-associated area indicates higher inability to regulate frustration. The dorsal hippocampus (dHC) and basolateral amygdala (BLA) were evaluated for protein levels of NMDA receptor subunits (GluN2A/GluN2B), synaptophysin, PSD95, SNAP-25 and CRF1. We found that adult MS males had greater vulnerability to reward reduction, together with decreased GluN2A and increased GluN2B immunocontent in the dHC. MS females and adolescents did not differ from controls. We concluded that MS enhances the response to frustration in adult males. The change in the ratio of GluN2A and GluN2B subunits in dHC could be related to a stronger, more difficult to update memory of the aversive experience.

Semantic structures facilitate threat memory integration throughout the medial temporal lobe and medial prefrontal cortex.

Emotional experiences can profoundly impact our conceptual model of the world, modifying how we represent and remember a host of information even indirectly associated with that experienced in the past. Yet, how a new emotional experience infiltrates and spreads across pre-existing semantic knowledge structures (e.g., categories) is unknown. We used a modified aversive sensory preconditioning paradigm in fMRI (n = 35) to investigate whether threat memories integrate with a pre-established category to alter the representation of the entire category. We observed selective but transient changes in the representation of conceptually related items in the amygdala, medial prefrontal cortex, and occipitotemporal cortex following threat conditioning to a simple cue (geometric shape) pre-associated with a different, but related, set of category exemplars. These representational changes persisted beyond 24 h in the hippocampus and perirhinal cortex. Reactivation of the semantic category during threat conditioning, combined with activation of the hippocampus or medial prefrontal cortex, was predictive of subsequent amygdala reactivity toward novel category members at test. This provides evidence for online integration of emotional experiences into semantic categories, which then promotes threat generalization. Behaviorally, threat conditioning by proxy selectively and retroactively enhanced recognition memory and increased the perceived typicality of the semantic category indirectly associated with threat. These findings detail a complex route through which new emotional learning generalizes by modifying semantic structures built up over time and stored in memory as conceptual knowledge.

Insights from EEG analysis of evoked memory recalls using deep learning for emotion charting.

Affect recognition in a real-world, less constrained environment is the principal prerequisite of the industrial-level usefulness of this technology. Monitoring the psychological profile using smart, wearable electroencephalogram (EEG) sensors during daily activities without external stimuli, such as memory-induced emotions, is a challenging research gap in emotion recognition. This paper proposed a deep learning framework for improved memory-induced emotion recognition leveraging a combination of 1D-CNN and LSTM as feature extractors integrated with an Extreme Learning Machine (ELM) classifier. The proposed deep learning architecture, combined with the EEG preprocessing, such as the removal of the average baseline signal from each sample and extraction of EEG rhythms (delta, theta, alpha, beta, and gamma), aims to capture repetitive and continuous patterns for memory-induced emotion recognition, underexplored with deep learning techniques. This work has analyzed EEG signals using a wearable, ultra-mobile sports cap while recalling autobiographical emotional memories evoked by affect-denoting words, with self-annotation on the scale of valence and arousal. With extensive experimentation using the same dataset, the proposed framework empirically outperforms existing techniques for the emerging area of memory-induced emotion recognition with an accuracy of 65.6%. The EEG rhythms analysis, such as delta, theta, alpha, beta, and gamma, achieved 65.5%, 52.1%, 65.1%, 64.6%, and 65.0% accuracies for classification with four quadrants of valence and arousal. These results underscore the significant advancement achieved by our proposed method for the real-world environment of memory-induced emotion recognition.

Consolidation of emotional memory during waking rest depends on trait anxiety.

A short period of eyes-closed waking rest improves long-term memory for recently learned information, including declarative, spatial, and procedural memory. However, the effect of rest on emotional memory consolidation remains unknown. This preregistered study aimed to establish whether post-encoding rest affects emotional memory and how anxiety levels might modulate this effect. Participants completed a modified version of the dot-probe attention task that involved reacting to and encoding word stimuli appearing underneath emotionally negative or neutral photos. We tested the effect of waking rest on memory for these words and pictures by manipulating the state that participants entered just after this task (rest vs. active wake). Trait anxiety levels were measured using the State-Trait Anxiety Inventory and examined as a covariate. Waking rest improved emotional memory consolidation for individuals high in trait anxiety. These results suggest that the beneficial effect of waking rest on memory extends into the emotional memory domain but depends on individual characteristics such as anxiety.

Probing the content of affective semantic memory following caregiving-related early adversity.

Cognitive science has demonstrated that we construct knowledge about the world by abstracting patterns from routinely encountered experiences and storing them as semantic memories. This preregistered study tested the hypothesis that caregiving-related early adversities (crEAs) shape affective semantic memories to reflect the content of those adverse interpersonal-affective experiences. We also tested the hypothesis that because affective semantic memories may continue to evolve in response to later-occurring positive experiences, child-perceived attachment security will inform their content. The sample comprised 160 children (ages 6-12 at Visit 1; 87F/73 M), 66% of whom experienced crEAs (n = 105). At Visit 1, crEA exposure prior to study enrollment was operationalized as parental-reports endorsing a history of crEAs (abuse/neglect, permanent/significant parent-child separation); while child-reports assessed concurrent attachment security. A false memory task was administered online ∼2.5 years later (Visit 2) to probe the content of affective semantic memories-specifically attachment schemas. Results showed that crEA exposure (vs. no exposure) was associated with a higher likelihood of falsely endorsing insecure (vs. secure) schema scenes. Attachment security moderated the association between crEA exposure and insecure schema-based false recognition. Findings suggest that interpersonal-affective semantic schemas include representations of parent-child interactions that may capture the quality of one's own attachment experiences and that these representations shape how children remember attachment-relevant narrative events. Findings are also consistent with the hypothesis that these affective semantic memories can be modified by later experiences. Moving forward, the approach taken in this study provides a means of operationalizing Bowlby's notion of internal working models within a cognitive neuroscience framework. RESEARCH HIGHLIGHTS: Affective semantic memories representing insecure schema knowledge (child needs + needs-not-met) may be more salient, elaborated, and persistent among youths exposed to early caregiving adversity. All youths, irrespective of early caregiving adversity exposure, may possess affective semantic memories that represent knowledge of secure schemas (child needs + needs-met). Establishing secure relationships with parents following early-occurring caregiving adversity may attenuate the expression of insecure semantic memories, suggesting potential malleability. Affective semantic memories include schema representations of parent-child interactions that may capture the quality of one's own attachment experiences and shape how youths remember attachment-relevant events.

Can neutral episodic memories become emotional? Evidence from facial expressions and subjective feelings.

Maladaptive emotional memories are a transdiagnostic feature of mental health problems. Therefore, understanding whether and how emotional memories can change might help to prevent and treat mental disorders. We tested whether neutral memories of naturalistic events can retroactively acquire positive or negative affect, in a preregistered three-day Modification of Valence in Episodes (MOVIE) paradigm. On Day 1, participants (N = 41) encoded memories of neutral movie scenes, representing lifelike naturalistic experiences. On Day 2, they retrieved each episode before viewing a happy, sad, or neutral scene from the same movie (yielding a within-subjects design with a neutral-negative, neutral-positive, and neutral-neutral condition). On Day 3, participants again retrieved each memory from Day 1. We assessed the affective tone of episodes through facial expressions of positive and negative affect (using facial electromyography, fEMG) and through self-reported feelings. Positive updating of neutral episodes led to increased expressions of positive affect, whereas negative updating led to increased self-reported negative feelings. These results suggest that complex neutral episodic memories can retroactively acquire an affective tone, but the effects were modest and inconsistent across affect readouts. Future research should investigate alternative approaches to updating emotional memories that produce more profound changes in the valence of memories.

Age-Differential Role of Gaze Reinstatement in Recognition Memory for Negative Visual Stimuli.

OBJECTIVES: Although research has shown that the replay of encoding-specific gaze patterns during retrieval, known as gaze reinstatement, facilitates memory retrieval, little is known about whether it differentially associates with the negativity preference in memory (defined as enhanced memory for negative stimuli relative to neutral stimuli in this study) among younger and older adults. The present study aims to address this research gap. METHODS: A total of 33 older adults (16 women; aged 58-69 years, M = 63.48, SD = 2.98) and 36 younger adults (10 women; aged 18-26 years, M = 20.39, SD = 1.57) completed a remember/know recognition memory task involving negative and neutral pictures. Their eye movements were tracked during both the memory encoding and retrieval phases. RESULTS: Younger and older adults had better memory for negative than neutral pictures. Older adults exhibited significantly stronger gaze reinstatement for negative than neutral stimuli, while this difference was nonsignificant in younger adults. Moreover, gaze reinstatement is positively linked to memory performance in both age groups. DISCUSSION: The results suggest that gaze reinstatement may play age-differential roles in the negativity preference of memory. Negative valence may enhance gaze reinstatement, which improves subsequent recognition memory, particularly among older adults. The finding contributes to a better understanding of the mechanisms underlying the negative preference for memory in different age groups.

Age-related positivity effect in emotional memory consolidation from middle age to late adulthood.

Background: While younger adults are more likely to attend to, process, and remember negative relative to positive information, healthy older adults show the opposite pattern. The current study evaluates when, exactly, this positivity shift begins, and how it influences memory performance for positive, negative, and neutral information. Methods: A total of 274 healthy early middle-aged (35-47), late middle-aged (48-59), and older adults (>59) viewed scenes consisting of a negative, positive, or a neutral object placed on a plausible neutral background, and rated each scene for its valence and arousal. After 12 h spanning a night of sleep (n = 137) or a day of wakefulness (n = 137), participants completed an unexpected memory test during which they were shown objects and backgrounds separately and indicated whether the scene component was the "same," "similar," or "new" to what they viewed during the study session. Results and conclusions: We found that both late middle-aged and older adults rated positive and neutral scenes more positively compared to early middle-aged adults. However, only older adults showed better memory for positive objects relative to negative objects, and a greater positive memory trade-off magnitude (i.e., remembering positive objects at the cost of their associated neutral backgrounds) than negative memory trade-off magnitude (i.e., remembering negative objects at the cost of their associated neutral backgrounds). Our findings suggest that while the positivity bias may not emerge in memory until older adulthood, a shift toward positivity in terms of processing may begin in middle age.

The interplay between memory control and emotion regulation.

Memory control (MC) and emotion regulation (ER) are critical cognitive functions for adapting to life's challenges, drawing significant research attention. Accumulating evidence suggests these processes are interrelated, yet a comprehensive discussion of their interplay remains lacking. We introduce an integrative framework exploring the mutual influence between MC and ER, composed of two interrelated branches: first, MC aids in ER through the retrieval of positive memories, intentional forgetting of undesirable content, and the adaptive updating of memory stores. Second, ER impacts MC by upregulating positivity and downregulating negativity in memories. The framework spotlights the need to harness MC-ER interplay for future research. Potential directions include utilizing MC to amplify ER capabilities, training ER skills to refine MC performance, and modulating the cognitive and neural overlapping of both processes to improve both functions. Delving into the MC-ER nexus advances understanding of the intricate emotion-memory relationship and holds great promise for developing novel behavioral interventions.

Effects of chronic haloperidol treatment on the expression of fear memory and fear memory extinction in the cued fear-conditioned rats.

AIM: Impairments in emotional memory are frequently observed in several mental disorders, highlighting their significance as potential therapeutic targets. Recent research on the cued fear conditioning model has elucidated the neural circuits involved in fear memory processing. However, contradictory findings have been reported concerning the role of dopamine and the impact of dopamine D2 receptor (D2R) antagonists. There is notably limited knowledge regarding the clinical utility of chronic D2R antagonist treatments. This study aimed to uncover how such treatments affect fear memory processing. METHODS: We utilized a cued fear conditioning rat model and conducted chronic haloperidol treatment for 14 days. Subsequently, to investigate the effect of chronic haloperidol treatment on fear-conditioned memory expression and extinction, we observed freezing behavior under exposure to a conditioned stimulus for 14 days. RESULTS: Chronic haloperidol treatment suppressed freezing time on the fear memory expression. In contrast, a single haloperidol administration enhanced the freezing time on fear memory expression and delayed extinction. CONCLUSION: The results of this study suggest that chronic administration of antipsychotic drugs affects fear memory processing differently from single-dose administration. This indicates that the effects of chronic D2R antagonist treatment are distinct from the nonspecific effects of the drugs. This study provides fundamental insights that may contribute to our understanding of therapeutic mechanisms for fear memory disorders related to D2R in the future.

Folie et Société: eroding the body-mind relationship via dysfunctional paternalistic systems.

This theoretical perspective examines the proposition of shared complex trauma between a parent and child, arising from blurred relational boundaries and societal oppression, leading to inequality both at home and within the larger paternalistic system of society. Specifically, the focus is on living within a paternalistic, authoritarian system where rules are unjust, demanding obedience and compliance without questioning the behaviors of the authority. Individuals growing up in these circumstances are subject to adverse and emotionally overwhelming experiences, which lead to the creation of emotional memory images (EMIs). The delusion in which the child is caught up becomes a reality for the child as time passes. This phenomenon is recognized in psychiatry as "Folie à deux" (the madness of two or more) at the micro level, and "Folie et Société" (the madness of society) on the macro level. Complex trauma, derived from a child's exposure to multiple adverse events, can erode the mind-body relationship, impacting both mental and physical health. These traumatic experiences in early childhood can manifest as body-focused disorders in adolescents, prevailing throughout adulthood if left unattended. This article provides a theoretical perspective on dealing with the dissociation and chronic stress related to oppressive and authoritarian family systems. The broader implications of this article include highlighting the psychophysiological underpinnings of complex trauma, the relationship of a highly oppressive paternalistic authoritarian system imposed on children and adolescents, and the role of Split-Second Unlearning as a therapeutic intervention to clear EMIs and improve overall health outcomes.

Targeting Histamine and Histamine Receptors for Memory Regulation: An Emotional Perspective.

Histamine has long been accepted as a pro-cognitive agent. However, lines of evidence have suggested that the roles of histamine in learning and memory processes are much more complex than previously thought. When explained by the spatial perspectives, there are many contradictory results. However, using emotional memory perspectives, we suspect that the histaminergic system may interplay with stress, reward inhibition, and attention to modulate emotional memory formation. The functional diversity of histamine makes it a viable target for clinical management of neuropsychiatric disorders. Here, we update the current knowledge about the functions of histamine in emotional memory and summarize the underlying molecular and neural circuit mechanisms. Finally, we review the main clinical studies about the impacts of histamine-related compounds on memory and discuss insights into future research on the roles of histamine in emotional memory. Despite the recent progress in histamine research, the histaminergic emotional memory circuits are poorly understood, and it is also worth verifying the functions of histamine receptors in a more spatiotemporally specific manner.

Norms for the Triana Test: A Story Recall Test Based on Emotional Material.

Background: The "Triana Test" is a novel story recall test based on emotional material with demonstrated accuracy in diagnosing mild cognitive impairment patients. Objective: This study aims to obtain normative data for the "Triana Test". Methods: A normative study was conducted at a university hospital in Spain. Partners of patients were systematically recruited if eligible (age ≥50, no memory complaints, and a total TMA-93 score at or above the 10th percentile). The "Triana Test" was administered and scored. For developing the normative data, a regression-based method was followed. Results: The final sample included 362 participants (median age = 66, range = 50-88; 64.9% females). A model including age and educational level better predicted the total scores. Combinations of these variables resulted in different 10th percentile scores. Conclusions: Norms for using the "Triana Test" are now available. The provided cutoffs for the 10th percentile will aid in the diagnosis of prodromal Alzheimer's disease.

Past Adversity Influencing Now (PAIN): perspectives on the impact of temporal language on the persistence of pain.

Persistent pain is a significant healthcare issue, often unresponsive to traditional treatments. We argue for incorporating non-biomedical perspectives in understanding pain, promoting more comprehensive solutions. This article explores how language, specifically time-related terms, may affect the persistence (stickiness) of pain. We delve into how language influences one's experience of the world, especially in understanding pain through spatial metaphors. Notably, time perceptions differ across languages and cultures and there is no absolute construct of temporal pain experience. In English, time is viewed linearly as past, present, and future. We introduce a framework called Past Adversity Influencing Now (PAIN) which includes various temporal phases of pain; Past Perfect, Past Imperfect, Present, Future Imperfect, and Future Perfect. We suggest that past negative memories (emotional memory images) can "trap" individuals in a "sticky" pain state. We speculate that the process of diagnosing pain as "chronic" may solidify this "stickiness", drawing from the ancient Greek idea of "logos", where pain communicates a message across time and space needing recognition. Our PAIN framework encourages examining pain through a temporal lens, guiding individuals towards a more positive future.