Sex-related hemispheric lateralization of amygdala function in emotionally influenced memory: an FMRI investigation

The amygdala appears necessary for enhanced long-term memory associated with emotionally arousing events. Recent brain imaging investigations support this view and indicate a sex-related hemispheric lateralization exists in the amygdala relationship to memory for emotional material. This study confirms and further explores this finding. Healthy men and women underwent functional Magnetic Resonance Imaging (fMRI) while viewing a series of standardized slides that were rated by the subjects as ranging from emotionally neutral to highly arousing. Two weeks later, memory for the slides was assessed in an incidental recognition test. The results demonstrate a significantly stronger relationship in men than in women between activity of the right hemisphere amygdala and memory for those slides judged as arousing, and a significantly stronger relationship in women than in men between activity of the left hemisphere amygdala and memory for arousing slides. An ANOVA confirmed a significant interaction between sex and hemisphere regarding amygdala function in memory. These results provide the strongest evidence to date of a sex-related hemispheric lateralization of amygdala function in memory for emotional material. Furthermore, they underscore the view that investigations of neural mechanisms underlying emotionally influenced memory must anticipate, and begin to account for, the apparently substantial influence of sex.     

Sex-related developmental differences in the lateralized activation of the prefrontal cortex and amygdala during perception of facial affect

The lateralization of cognitive abilities is influenced by a number of factors, including handedness, sex, and developmental maturation. To date, a small number of studies have examined sex differences in the lateralization of cognitive and affective functions, and in only few of these have the developmental trajectories of these lateralized differences been mapped from childhood through early adulthood. In the present study, a cross-sectional design was used with healthy children (n=7), adolescents (n= 12), and adults (n= 10) who underwent functional magnetic resonance imaging (fMRI) during a task that required perceiving fearful faces. Males and females differed in the asymmetry of activation of the amygdala and prefrontal cortex across the three age groups. For males, activation within the dorsolateral prefrontal cortex was bilateral in children, right lateralized in adolescents, and bilateral in adults, whereas females showed a monotonic relationship with age, with older females showing more bilateral activation than younger ones. In contrast, amygdala activation was similar for both sexes, with bilateral activation in children, right-lateralized activation in adolescents, and bilateral activation in adults. These results suggest that males and females show different patterns of lateralized cortical and subcortical brain activation across the period of development from childhood through early adulthood.     

Identification of genes expressed in the amygdala during the formation of fear memory

In this study we describe changes of gene expression that occur in the basolateral complex of the mouse amygdala (BLA) during the formation of fear memory. Through the combination of a behavioral training scheme with polymerase chain reaction-based expression analysis (subtractive hybridization and virtual Northern analysis) we were able to identify various gene products that are increased in expression after Pavlovian fear conditioning and are of potential significance for neural plasticity and information storage in the amygdala. In particular, a key enzyme of monoamine metabolism, aldehyde reductase, and the protein sorting and ubiquitination factor Praja1, showed pronounced and learning-specific induction six hours after fear conditioning training. Aldehyde reductase and Praja1, including a novel alternatively spliced isoform termed Praja1a, were induced in the BLA depending on the emotional stimulus presented and showed different expression levels in response to associative conditioning, training stress, and experience of conditioned fear. Stress and fear were further found to induce various signal transduction factors (transthyretin, phosphodiesterase1, protein kinase inhibitor-alpha) and structural reorganization factors (e.g., E2-ubiquitin conjugating enzyme, neuroligin1, actin, UDP-galactose transporter) during training. Our results show that the formation of Pavlovian fear memory is associated with changes of gene expression in the BLA, which may contribute to neural plasticity and the processing of information about both conditioned and unconditioned fear stimuli.     

Myosin II motor activity in the lateral amygdala is required for fear memory consolidation

Learning induces dynamic changes to the actin cytoskeleton that are required to support memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during learning and memory are poorly understood. Myosin II motors are highly expressed in actin-rich growth structures including dendritic spines, and we have recently shown that these molecular machines mobilize F-actin in response to synaptic stimulation and learning in the hippocampus. In this study, we report that Myosin II motors in the rat lateral amygdala (LA) are essential for fear memory formation. Pretraining infusions of the Myosin II inhibitor, blebbistatin (blebb), disrupted long term memory, while short term memory was unaffected. Interestingly, both post-training and pretesting infusions had no effect on memory formation, indicating that Myosin II motors operate during or shortly after learning to promote memory consolidation. These data support the idea that Myosin II motor-force generation is a general mechanism that supports memory consolidation in the mammalian CNS.     

The role of attention and relatedness in emotionally enhanced memory

Examining the positive and negative pictures separately revealed that emotionally enhanced memory (EEM) for positive pictures was mediated by attention, with no significant influence of emotional arousal, whereas the reverse was true of negative pictures. Consistent with this finding, in Experiment 2 EEM for negative pictures was found even when task emphasis was manipulated so that equivalent attention was allocated to negative and neutral pictures. The results show that attention and semantic relatedness contribute to EEM, with the extent varying with emotional valence. Negative emotion can influence memory independently of these 2 factors.     

Age-related neural activity during allocentric spatial memory

Age-related decline in allocentric (viewer-independent) spatial memory is seen across species. We employed a virtual reality analogue of the Morris Water Maze to study the effect of healthy ageing on neural activity during allocentric spatial memory using functional magnetic resonance imaging. Voxel-based morphometry was used to ascertain hippocampal volumetric integrity. A widespread neural network comprising frontal, parietal, occipital, thalamic, and cerebellar regions was activated in young and older adults, but only young adults significantly activated bilateral hippocampus and left parahippocampus, as well as right frontal pole and dorso-lateral prefrontal cortex (DLPFC) during encoding and right DLPC during retrieval. Hippocampal grey matter volume was unchanged in older adults; however, prefrontal and parahippocampal functional attenuation was accompanied by volumetric reduction. We conclude that the decline in allocentric spatial memory with age is associated with attenuated hippocampal function, as well as compromised function and structure of prefrontal and parahippocampal regions.     

Persistent activity in the prefrontal cortex during working memory

The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions.     

Quantitative difference in the experience of state-trait anxiety in emotionally disturbed and normal children

In order to investigate the state-trait anxiety distinction in emotionally disturbed and normal children, the responses of 120 emotionally disturbed children and 126 normal children to the State-Trait Anxiety Inventory for Children (Spielberger, 1973) were factor analyzed separately. For the emotionally disturbed group two A-State and two A-Trait factors were found with the A-State factors accounting for significantly more of the variance than did A-Trait factors. For the normal group four A-State and two A-Trait factors were found, but there was not a significant difference between the amount of variance accounted for by A-State and A-Trait factors. Results were discussed as supporting the state-trait distinction and as having several implications for future research on anxiety.     

A specific role for the human amygdala in olfactory memory

The medial temporal lobe is known to play a role in the processing of olfaction and memory. The specific contribution of the human amygdala to memory for odors has not been addressed, however. The role of this region in memory for odors was assessed in patients with unilateral amygdala damage due to temporal lobectomy (n = 20; 11 left, 9 right), one patient with selective bilateral amygdala damage, and in 20 age-matched normal controls. Fifteen odors were presented, followed 1 h later by an odor-name matching test and an odor-odor recognition test. Signal detection analyses showed that both unilateral groups were impaired in their memory for matching odors with names, these patients were not significantly impaired on odor-odor recognition. Bilateral amygdala damage resulted in severe impairment in both odor-name matching as well as in odor-odor recognition memory. Importantly, none of the patients were impaired on an auditory verbal learning task, suggesting that these findings reflect a specific impairment in olfactory memory, and not merely a more general memory deficit. Taken together, the data provide neuropsychological evidence that the human amygdala is essential for olfactory memory.     

The central amygdala nucleus via corticotropin-releasing factor is necessary for time-limited consolidation processing but not storage of contextual fear memory

The central nucleus of the amygdala (CeA) is traditionally portrayed in fear conditioning as the key neural output that relays conditioned information established in the basolateral amygdala complex to extra-amygdalar brain structures that generate emotional responses. However, several recent studies have questioned this serial processing view of the amygdalar fear conditioning circuit by showing an influence of the CeA on memory consolidation. We previously reported that inhibition of endogenous CeA secretion of corticotropin-releasing factor (CRF) at the time of contextual training effectively impaired fear memory consolidation. However, the time-dependent range of CeA CRF secretion in facilitating consolidation processing has not been examined. Therefore, to address this issue, we performed CeA site-specific microinjections of CRF antisense oligonucleotides (CRF ASO) at several post-training time intervals. Rats microinjected with CRF ASO at post-training intervals up to 24-h subsequently exhibited significant impairments in contextual freezing retention in contrast to animals treated 96-h after training. To further establish the validity of the results, CeA fiber-sparing lesions were made at two distinct post-training periods (24-h and 96-h), corresponding respectively to the temporal intervals when CeA CRF ASO administration disrupted or had no significant effects on memory consolidation. Similar to the CeA CRF ASO results, CeA lesions made 24-h, but not 96-h, after training induced significant freezing deficits in the retention test. In conclusion, the current results demonstrate: (1) an extended involvement of CeA CRF in contextual memory consolidation and (2) that contextual fear memory storage is not dependent on a functional CeA.     

Actin polymerization in lateral amygdala is essential for fear memory formation

Actin polymerization is involved in key neuronal functions such as intracellular trafficking and morphogenesis. In this study, we examined the role of actin polymerization in lateral amygdala (LA) in fear conditioning memory formation. Microinfusion of cytochalasin D, an actin polymerization inhibitor, into rat LA immediately before fear conditioning training impaired the formation of long-term fear memory (LTM) but not short-term fear memory (STM). Microinfusion of cytochalasin D into rat LA immediately after fear conditioning impaired LTM. Cytochalasin D had no effect on fear conditioning memory retrieval when injected immediately before LTM test. These results show that actin cytoskeleton rearrangement is essential for fear memory consolidation.     

条件性恐惧提取消退的性别差异

基于记忆再巩固理论的提取消退范式能够有效地削弱非适应性恐惧记忆。性别差异是个体差异性研究的关键变量, 但在提取消退范式的研究中仍然比较少见关于性别差异的探索。因此本研究以立体几何图形作为条件刺激, 腕部电击作为非条件刺激, 皮肤电反应为恐惧反应指标, 探究提取消退范式在恐惧消退效果上是否存在性别差异。结果表明, 在恐惧自发恢复测试中, 提取消退范式的所有被试都成功抑制了恐惧复发, 但恐惧重建测试中只有女性被试抑制了恐惧复发。这说明, 提取消退范式在抑制恐惧自发恢复方面效果显著, 在恐惧重建上女性的消退效果显著优于男性。     

Processing and storage in working memory span

Two experiments are reported that address theoretical assumptions as to the nature of working memory involved in working memory span tasks (Daneman & Carpenter, 1980). Experiment 1 used a version of the sentence span task, and Experiment 2 combined arithmetic verification with recall of presented words. In each experiment, working memory processing span was assessed independently of temporary storage span prior to their combination. Combined task performance under high demand for each component resulted in substantial residual performance for both task elements, particularly in Experiment 2. The results do not challenge the utility of the sentence span task as a measure of on-line cognition, but they raise concerns as to how resource might be allocated to processing and storage elements of the task within a single flexible resource pool, or between different resources of a multiple component working memory system. Although both models lack predictive power regarding resource allocation in these tasks, the multiple resource model appears to offer the better account.     

Neural correlates of inefficient filtering of emotionally neutral distractors from working memory in trait anxiety

Research has indicated that highly trait-anxious (HTA) individuals exhibit a specific deficit in filtering threat-related distractors from visual–spatial working memory (WM). Prior demonstrations of impaired inhibition control in HTA individuals have mainly focused on tasks that required the inhibition of prepotent response tendencies. Studies on the suppression of emotionally neutral distractors from WM in trait anxiety have also been minimal. In this article, we present a study on the manifestation of general inefficient filtering of neutral distractors during visual–spatial WM maintenance stages in HTA individuals. Female participants performed a visual–spatial WM task while event-related potentials were recorded. They were made to remember the orientations of red rectangles within half of the screen and to ignore all salient green rectangles. As predicted, no significant main effect of group and no interaction between group and condition were found in the N2pc component, suggesting that group differences did not manifest in the initial process of object individuation. During the subsequent WM maintenance phase, HTA individuals were highly inefficient at filtering the irrelevant items from WM, as reflected not only by parallel late contralateral delay activity (CDA; 450 to 900 ms) amplitudes for the distractor condition and the four red items, but also by a smaller filtering efficiency score in the HTA group than in the low-trait-anxiety group. Extending previous studies, our findings verify a general filtering impairment in HTA individuals for task-irrelevant salient distractors during a WM maintenance phase.     

The amygdala is involved in the modulation of long-term memory, but not in working or short-term memory

Rats with cannulae implanted in the junction between the central and the basolateral nuclei of the amygdala were trained in one-trial step-down inhibitory avoidance and tested at 3 s for working memory (WM) or 1.5 or 24 h later for short-term memory (STM) and long-term memory (LTM), respectively. Several drugs were infused 6 min prior to training in the animals in which WM was measured or 0 min posttraining in those in which STM and LTM were measured: the glutamate receptor antagonists CNQX (0.5 microg) and AP5 (5.0 microg), the indirect GABA A receptor antagonist picrotoxin (0.08 microg), the cholinergic muscarinic receptor blocker scopolamine (2. 0 microg), norepinephrine (0.3 microg), the protein kinase C inhibitor staurosporin (1.0 microg), or the calcium/calmodulin dependent protein kinase II inhibitor Kn-62 (3.5 ng). None of the drugs had any effect on either WM or STM. All had, as previously shown, strong effects on LTM: picrotoxin and norepinephrine enhanced it, and CNQX, AP5, scopolamine, Kn-62, and staurosporin inhibited it. The results do not support the idea that memory of this task is formed in the amygdala; they indicate that the amygdala is not involved in WM or STM processing and support the idea that the amygdala modulates LTM storage processes carried out elsewhere.     

Patterns of brain-electrical activity during declarative memory performance in 10-month-old infants

This study of infant declarative memory concurrently examined brain-electrical activity and deferred imitation performance in 10-month-old infants. Continuous electroencephalogram (EEG) measures were collected throughout the activity-matched baseline, encoding (modeling) and retrieval (delayed test) phases of a within-subjects deferred imitation task. Infants were divided into two memory performance groups based on the exhibition of ordered-recall after a 24-h delay. Whereas no group differences were found in EEG collected during encoding, performance-group differences in EEG were present during retrieval. Infants who successfully displayed ordered-recall showed a pattern of increasing EEG from baseline to task at anterior temporal scalp locations, whereas infants showing no ordered-recall displayed no changes in EEG from baseline to task. These findings are discussed with respect to the biobehavioral developments underlying declarative memory abilities.     

Patterns of brain-electrical activity during declarative memory performance in 10-month-old infants

This study of infant declarative memory concurrently examined brain-electrical activity and deferred imitation performance in 10-month-old infants. Continuous electroencephalogram (EEG) measures were collected throughout the activity-matched baseline, encoding (modeling) and retrieval (delayed test) phases of a within-subjects deferred imitation task. Infants were divided into two memory performance groups based on the exhibition of ordered-recall after a 24-h delay. Whereas no group differences were found in EEG collected during encoding, performance-group differences in EEG were present during retrieval. Infants who successfully displayed ordered-recall showed a pattern of increasing EEG from baseline to task at anterior temporal scalp locations, whereas infants showing no ordered-recall displayed no changes in EEG from baseline to task. These findings are discussed with respect to the biobehavioral developments underlying declarative memory abilities.     

The basolateral amygdala modulates specific sensory memory representations in the cerebral cortex

Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1–28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cortex (A1) to the frequency of a conditioned stimulus (CS), and the greater the level of CS importance, the larger the area of representational gain [Weinberger, N. M. (2007). Associative representational plasticity in the auditory cortex: A synthesis of two disciplines. Learning & Memory, 14(1–2), 1–16]. The two lines of research suggest that BLA strengthening of memory might be accomplished in part by increasing the representation of an environmental stimulus. The present study investigated whether stimulation of the BLA can affect cortical memory representations. In male Sprague–Dawley rats studied under urethane general anesthesia, frequency receptive fields were obtained from A1 before and up to 75 min after the pairing of a tone with BLA stimulation (BLAstm: 100 trials, 400 ms, 100 Hz, 400 μA [±16.54]). Tone started before and continued after BLAstm. Group BLA/1.0 (n = 16) had a 1 s CS–BLAstm interval while Group BLA/1.6 (n = 5) has a 1.6 s interval. The BLA/1.0 group did develop specific tuning shifts toward and to the CS, which could change frequency tuning by as much as two octaves. Moreover, its shifts increased over time and were enduring, lasting 75 min. However, group BLA/1.6 did not develop tuning shifts, indicating that precise CS–BLAstm timing is important in the anesthetized animal. Further, training in the BLA/1.0 paradigm but stimulating outside of the BLA did not produce tuning shifts. These findings demonstrate that the BLA is capable of exerting highly specific, enduring, learning-related modifications of stimulus representation in the cerebral cortex. These findings suggest that the ability of the BLA to alter specific cortical representations may underlie, at least in part, the modulatory influence of BLA activity on strengthening long-term memory.     

Aversive memory reactivation engages in the amygdala only some neurotransmitters involved in consolidation

Consolidation refers to item stabilization in long-term memory. Retrieval renders a consolidated memory sensitive, and a "reconsolidation" process has been hypothesized to keep the original memory persistent. Some authors could not detect this phenomenon. Here we show that retrieved contextual fear memory is vulnerable to amnesic treatments and that the amygdala is critically involved. Cholinergic and histaminergic systems seem to modulate only consolidation, whereas cannabinoids are involved in both consolidation and reactivation. The lability of retrieved memory affords opportunities to treat disorders such as phobias, post-traumatic stress, or chronic pain, and these results help searching for appropriate therapeutic targets.