Sleep-related hippocampo-cortical interplay during emotional memory recollection

Emotional events are usually better remembered than neutral ones. This effect is mediated in part by a modulation of the hippocampus by the amygdala. Sleep plays a role in the consolidation of declarative memory. We examined the impact of sleep and lack of sleep on the consolidation of emotional (negative and positive) memories at the macroscopic systems level. Using functional MRI (fMRI), we compared the neural correlates of successful recollection by humans of emotional and neutral stimuli, 72 h after encoding, with or without total sleep deprivation during the first post-encoding night. In contrast to recollection of neutral and positive stimuli, which was deteriorated by sleep deprivation, similar recollection levels were achieved for negative stimuli in both groups. Successful recollection of emotional stimuli elicited larger responses in the hippocampus and various cortical areas, including the medial prefrontal cortex, in the sleep group than in the sleep deprived group. This effect was consistent across subjects for negative items but depended linearly on individual memory performance for positive items. In addition, the hippocampus and medial prefrontal cortex were functionally more connected during recollection of either negative or positive than neutral items, and more so in sleeping than in sleep-deprived subjects. In the sleep-deprived group, recollection of negative items elicited larger responses in the amygdala and an occipital area than in the sleep group. In contrast, no such difference in brain responses between groups was associated with recollection of positive stimuli. The results suggest that the emotional significance of memories influences their sleep-dependent systems-level consolidation. The recruitment of hippocampo-neocortical networks during recollection is enhanced after sleep and is hindered by sleep deprivation. After sleep deprivation, recollection of negative, potentially dangerous, memories recruits an alternate amygdalo-cortical network, which would keep track of emotional information despite sleep deprivation.     

Human hippocampal neurons predict how well word pairs will be remembered

What is the neuronal basis for whether an experience is recalled or forgotten? In contrast to recognition, recall is difficult to study in nonhuman primates and rarely is accessible at the single neuron level in humans. We recorded 128 medial temporal lobe (MTL) neurons in patients implanted with intracranial microelectrodes while they encoded and recalled word paired associates. Neurons in the amygdala, entorhinal cortex, and hippocampus showed altered activity during encoding (9%), recall (22%), and both task phases (23%). The responses of hippocampal neurons during encoding predicted whether or not subjects later remembered the pairs successfully. Entorhinal cortex neuronal activity during retrieval was correlated with recall success. These data provide support at the single neuron level for MTL contributions to encoding and retrieval, while also suggesting there may be differences in the level of contribution of MTL regions to these memory processes.     

The Effects of a Distracting N-Back Task on Recognition Memory Are Reduced by Negative Emotional Intensity

Memory performance is usually impaired when participants have to encode information while performing a concurrent task. Recent studies using recall tasks have found that emotional items are more resistant to such cognitive depletion effects than non-emotional items. However, when recognition tasks are used, the same effect is more elusive as recent recognition studies have obtained contradictory results. In two experiments, we provide evidence that negative emotional content can reliably reduce the effects of cognitive depletion on recognition memory only if stimuli with high levels of emotional intensity are used. In particular, we found that recognition performance for realistic pictures was impaired by a secondary 3-back working memory task during encoding if stimuli were emotionally neutral or had moderate levels of negative emotionality. In contrast, when negative pictures with high levels of emotional intensity were used, the detrimental effects of the secondary task were significantly attenuated.     

Cognitive neuroscience of emotional memory

Emotional events often attain a privileged status in memory. Cognitive neuroscientists have begun to elucidate the psychological and neural mechanisms underlying emotional retention advantages in the human brain. The amygdala is a brain structure that directly mediates aspects of emotional learning and facilitates memory operations in other regions, including the hippocampus and prefrontal cortex. Emotion-memory interactions occur at various stages of information processing, from the initial encoding and consolidation of memory traces to their long-term retrieval. Recent advances are revealing new insights into the reactivation of latent emotional associations and the recollection of personal episodes from the remote past.     

Human emotion and memory: interactions of the amygdala and hippocampal complex

The amygdala and hippocampal complex, two medial temporal lobe structures, are linked to two independent memory systems, each with unique characteristic functions. In emotional situations, these two systems interact in subtle but important ways. Specifically, the amygdala can modulate both the encoding and the storage of hippocampal-dependent memories. The hippocampal complex, by forming episodic representations of the emotional significance and interpretation of events, can influence the amygdala response when emotional stimuli are encountered. Although these are independent memory systems, they act in concert when emotion meets memory.     

Neural repetition effects in the medial temporal lobe complex are modulated by previous encoding experience

It remains an intriguing question why the medial temporal lobe (MTL) can display either attenuation or enhancement of neural activity following repetition of previously studied items. To isolate the role of encoding experience itself, we assessed neural repetition effects in the absence of any ongoing task demand or intentional orientation to retrieve. Experiment 1 showed that the hippocampus and surrounding MTL regions displayed neural repetition suppression (RS) upon repetition of past items that were merely attended during an earlier study phase but this was not the case following re-occurrence of items that had been encoded into working memory (WM). In this latter case a trend toward neural repetition enhancement (RE) was observed, though this was highly variable across individuals. Interestingly, participants with a higher degree of neural RE in the MTL complex displayed higher memory sensitivity in a later, surprise recognition test. Experiment 2 showed that massive exposure at encoding effected a change in the neural architecture supporting incidental repetition effects, with regions of the posterior parietal and ventral-frontal cortex in addition to the hippocampus displaying neural RE, while no neural RS was observed. The nature of encoding experience therefore modulates the expression of neural repetition effects in the MTL and the neocortex in the absence of memory goals.     

The hippocampus is coupled with the default network during memory retrieval but not during memory encoding

The brain's default mode network (DMN) is activated during internally-oriented tasks and shows strong coherence in spontaneous rest activity. Despite a surge of recent interest, the functional role of the DMN remains poorly understood. Interestingly, the DMN activates during retrieval of past events but deactivates during encoding of novel events into memory. One hypothesis is that these opposing effects reflect a difference between attentional orienting towards internal events, such as retrieved memories, vs. external events, such as to-be-encoded stimuli. Another hypothesis is that hippocampal regions are coupled with the DMN during retrieval but decoupled from the DMN during encoding. The present fMRI study investigated these two hypotheses by combining a resting-state coherence analysis with a task that measured the encoding and retrieval of both internally-generated and externally-presented events. Results revealed that the main DMN regions were activated during retrieval but deactivated during encoding. Counter to the internal orienting hypothesis, this pattern was not modulated by whether memory events were internal or external. Consistent with the hippocampal coupling hypothesis, the hippocampus behaved like other DMN regions during retrieval but not during encoding. Taken together, our findings clarify the relationship between the DMN and the neural correlates of memory retrieval and encoding.     

Uncovering camouflage: amygdala activation predicts long-term memory of induced perceptual insight

What brain mechanisms underlie learning of new knowledge from single events? We studied encoding in long-term memory of a unique type of one-shot experience, induced perceptual insight. While undergoing an fMRI brain scan, participants viewed degraded images of real-world pictures where the underlying objects were hard to recognize ("camouflage"), followed by brief exposures to the original images ("solution"), which led to induced insight ("Aha!"). A week later, the participants' memory was tested; a solution image was classified as "remembered" if detailed perceptual knowledge was elicited from the camouflage image alone. During encoding, subsequently remembered images were associated with higher activity in midlevel visual cortex and medial frontal cortex, but most pronouncedly, in the amygdala, whose activity could be used to predict which solutions will remain in long-term memory. Our findings extend the known roles of amygdala in memory to include promotion of long-term memory of the sudden reorganization of internal representations.     

Contributions of the amygdala to emotion processing: from animal models to human behavior

Research on the neural systems underlying emotion in animal models over the past two decades has implicated the amygdala in fear and other emotional processes. This work stimulated interest in pursuing the brain mechanisms of emotion in humans. Here, we review research on the role of the amygdala in emotional processes in both animal models and humans. The review is not exhaustive, but it highlights five major research topics that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory, emotional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation.     

Effects of Acute Methamphetamine on Emotional Memory Formation in Humans: Encoding vs Consolidation

Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies.     

Face pictures reduce behavioural, autonomic, endocrine and neural indices of stress and fear in sheep

Faces are highly emotive stimuli and we find smiling or familiar faces both attractive and comforting, even as young babies. Do other species with sophisticated face recognition skills, such as sheep, also respond to the emotional significance of familiar faces? We report that when sheep experience social isolation, the sight of familiar sheep face pictures compared with those of goats or inverted triangles significantly reduces behavioural (activity and protest vocalizations), autonomic (heart rate) and endocrine (cortisol and adrenaline) indices of stress. They also increase mRNA expression of activity-dependent genes (c-fos and zif/268) in brain regions specialized for processing faces (temporal and medial frontal cortices and basolateral amygdala) and for emotional control (orbitofrontal and cingulate cortex), and reduce their expression in regions associated with stress responses (hypothalamic paraventricular nucleus) and fear (central and lateral amygdala). Effects on face recognition, emotional control and fear centres are restricted to the right brain hemisphere. Results provide evidence that face pictures may be useful for relieving stress caused by unavoidable social isolation in sheep, and possibly other animal species, including humans. The finding that sheep, like humans, appear to have a right brain hemisphere involvement in the control of negative emotional experiences also suggests that functional lateralization of brain emotion systems may be a general feature in mammals.     

Amygdala-hippocampus dynamic interaction in relation to memory

Typically the term "memory" refers to the ability to consciously remember past experiences or previously learned information. This kind of memory is considered to be dependent upon the hippocampal system. However, our emotional state seems to considerably affect the way in which we retain information and the accuracy with which the retention occurs. The amygdala is the most notably involved brain structure in emotional responses and the formation of emotional memories. In this review we describe a system, composed of the amygdala and the hippocampus, that acts synergistically to form long-term memories of significantly emotional events. These brain structures are activated following an emotional event and cross-talk with each other in the process of consolidation. This dual activation of the amygdala and the hippocampus and the dynamics between them may be what gives emotionally based memories their uniqueness.     

Molecular mechanisms underlying emotional learning and memory in the lateral amygdala

Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The lateral nucleus of the amygdala (LA) is a crucial site of neural changes that occur during fear conditioning. Pharmacological manipulations of the LA, strategically timed with respect to training and testing, have shed light on the molecular events that mediate the acquisition of fear associations and the formation and maintenance of long-term memories of those associations. Similar mechanisms have been found to underlie long-term potentiation (LTP) in LA, an artificial means of inducing synaptic plasticity and a physiological model of learning and memory. Thus, LTP-like changes in synaptic plasticity may underlie fear conditioning. Given that the neural circuit underlying fear conditioning has been implicated in emotional disorders in humans, the molecular mechanisms of fear conditioning are potential targets for psychotherapeutic drug development.     

Task and content modulate amygdala-hippocampal connectivity in emotional retrieval

The ability to remember emotional events is crucial for adapting to biologically and socially significant situations. Little is known, however, about the nature of the neural interactions supporting the integration of mnemonic and emotional information. Using fMRI and dynamic models of effective connectivity, we examined regional neural activity and specific interactions between brain regions during a contextual memory retrieval task. We independently manipulated emotional context and relevance of retrieved emotional information to task demands. We show that retrieval of emotionally valenced contextual information is associated with enhanced connectivity from hippocampus to amygdala, structures crucially involved with encoding of emotional events. When retrieval of emotional information is relevant to current behavior, amygdala-hippocampal connectivity increases bidirectionally, under modulatory influences from orbitofrontal cortex, a region implicated in representation of affective value and behavioral guidance. Our findings demonstrate that both memory content and behavioral context impact upon large scale neuronal dynamics underlying emotional retrieval.     

Paradoxical facilitation of working memory after basolateral amygdala damage

Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical functional facilitation effect.     

The neural substrates of memory suppression: a FMRI exploration of directed forgetting

The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes. We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items. Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory. For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control. Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes.     

The effect of negative and positive emotionality on associative memory: an FMRI study

In general, emotion is known to enhance memory processes. However, the effect of emotion on associative memory and the underling neural mechanisms remains largely unexplored. In this study, we explored brain activation during an associative memory task that involved the encoding and retrieval of word and face pairs. The word and face pairs consisted of either negative or positive words with neutral faces. Significant hippocampal activation was observed during both encoding and retrieval, regardless of whether the word was negative or positive. Negative and positive emotionality differentially affected the hemodynamic responses to encoding and retrieval in the amygdala, with increased responses during encoding negative word and face pairs. Furthermore, activation of the amygdala during encoding of negative word and neutral face pairs was inversely correlated with subsequent memory retrieval. These findings suggest that activation of the amygdala induced by negative emotion during encoding may disrupt associative memory performance.     

When more means less: neural activity related to unsuccessful memory encoding

The neural correlates of memory encoding have been studied by contrasting neural activity elicited by items at the time of learning according to whether they were later remembered or forgotten [1]. Previous studies have focused on regions where neural activity is greater for subsequently remembered items [2-8]. Here, we describe regions where activity is greater for subsequently forgotten items. In two experiments that employed the same incidental learning task, activity in an overlapping set of cortical regions (posterior cingulate, inferior and medial parietal, and dorsolateral prefrontal) was associated with failure on a subsequent memory test.     

Are Age Effects in Positivity Influenced by the Valence of Distractors?

An age-related ‘positivity’ effect has been identified, in which older adults show an information-processing bias towards positive emotional items in attention and memory. In the present study, we examined this positivity bias by using a novel paradigm in which emotional and neutral distractors were presented along with emotionally valenced targets. Thirty-five older and 37 younger adults were asked during encoding to attend to emotional targets paired with distractors that were either neutral or opposite in valence to the target. Pupillary responses were recorded during initial encoding as well as a later incidental recognition task. Memory and pupillary responses for negative items were not affected by the valence of distractors, suggesting that positive distractors did not automatically attract older adults’ attention while they were encoding negative targets. Additionally, the pupil dilation to negative items mediated the relation between age and positivity in memory. Overall, memory and pupillary responses provide converging support for a cognitive control account of positivity effects in late adulthood and suggest a link between attentional processes and the memory positivity effect.     

Remembering the Object You Fear: Brain Potentials during Recognition of Spiders in Spider-Fearful Individuals

In the present study we investigated long-term memory for unpleasant, neutral and spider pictures in 15 spider-fearful and 15 non-fearful control individuals using behavioral and electrophysiological measures. During the initial (incidental) encoding, pictures were passively viewed in three separate blocks and were subsequently rated for valence and arousal. A recognition memory task was performed one week later in which old and new unpleasant, neutral and spider pictures were presented. Replicating previous results, we found enhanced memory performance and higher confidence ratings for unpleasant when compared to neutral materials in both animal fearful individuals and controls. When compared to controls high animal fearful individuals also showed a tendency towards better memory accuracy and significantly higher confidence during recognition of spider pictures, suggesting that memory of objects prompting specific fear is also facilitated in fearful individuals. In line, spider-fearful but not control participants responded with larger ERP positivity for correctly recognized old when compared to correctly rejected new spider pictures, thus showing the same effects in the neural signature of emotional memory for feared objects that were already discovered for other emotional materials. The increased fear memory for phobic materials observed in the present study in spider-fearful individuals might result in an enhanced fear response and reinforce negative beliefs aggravating anxiety symptomatology and hindering recovery.