Episodic Memory Encoding Research Articles

Reduced Prefrontal Activation in Pediatric Patients With Obsessive-Compulsive Disorder During Verbal Episodic Memory Encoding

Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. The semantic clustering strategy score (SCS) predicted VEM performance in HC (p< .001, R(2)= 0.635), but not in patients (p= .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p= .001, r= 0.635), but not in patients with OCD (p= .936, r= 0.017). Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD.

EEG oscillations during sleep and dream recall: state- or trait-like individual differences?

Dreaming represents a peculiar form of cognitive activity during sleep. On the basis of the well-known relationship between sleep and memory, there has been a growing interest in the predictive role of human brain activity during sleep on dream recall. Neuroimaging studies indicate that rapid eye movement (REM) sleep is characterized by limbic activation and prefrontal cortex deactivation. This pattern could explain the presence of emotional contents in dream reports. Furthermore, the morphoanatomical measures of amygdala and hippocampus predict some features of dream contents (bizarreness, vividness, and emotional load). More relevant for a general view of dreaming mechanisms, empirical data from neuropsychological and electroencephalographic (EEG) studies support the hypothesis that there is a sort of continuity between the neurophysiological mechanisms of encoding and retrieval of episodic memories across sleep and wakefulness. A notable overlap between the electrophysiological mechanisms underlying emotional memory formation and some peculiar EEG features of REM sleep has been suggested. In particular, theta (5–8 Hz) EEG oscillations on frontal regions in the pre-awakening sleep are predictive of dream recall, which parallels the predictive relation during wakefulness between theta activity and successful retrieval of episodic memory. Although some observations support an interpretation more in terms of an intraindividual than interindividual mechanism, the existing empirical evidence still precludes from definitely disentangling if this relation is explained by state- or trait-like differences.

Computational diversity in the hippocampus: a matter of components.

Computational diversity in the hippocampus: a matter of components.

Dissociation between the experience-dependent development of hippocampal theta sequences and single-trial phase precession.

Theta sequences are circuit-level activity patterns produced when groups of hippocampal place cells fire in sequences that reflect a compressed behavioral order of place fields within each theta cycle. The high temporal coordination between place cells exhibited in theta sequences is compatible with the induction of synaptic plasticity and has been proposed as one of the mechanisms underlying the encoding of episodic memory of recently acquired experience. Yet how theta sequences develop with experience has not been directly addressed. Here we simultaneously recorded large numbers of cells in the dorsal hippocampal CA1 area from rats exploring on a novel linear track. Although place cell firing activities accurately represented the animal's current location, distinct theta sequences were absent on the first lap but emerged immediately thereafter and remained stable once established. The absence of theta sequences on the first lap was not due to place field instability, decreased overall excitability of place cells, behavior variables, or the absence of individual neuronal phase precession. We observed strong single-lap phase precession in a significant percentage of place fields on the first lap and throughout the recording. Individual neuronal phase precession was stable from the first lap to subsequent laps but, across neurons, phase precession became more synchronized after experience, suggesting a novel mechanism for the generation of theta sequences. These results suggest that experience-independent temporal coding in individual neurons is combined with rapid plasticity of hippocampal neural networks during experience to acquire predictive representations of the immediate future.

Complementary roles of human hippocampal subfields in differentiation and integration of spatial context.

The unique circuitry of the hippocampus is thought to support the encoding and retrieval of context-rich episodic memories. Given the neuroanatomical differences between the hippocampal subfields, determining their functional roles during representation of contextual features in humans is an important yet unaddressed research goal. Prior studies suggest that, during the acquisition of information from the environment, the dentate gyrus (DG) and CA3 subfields rapidly differentiate competing contextual representations, whereas CA1, situated downstream from CA3/DG, is believed to process input from both CA3 and neocortical areas via the temporoammonic pathway. To further explore the functionality of these roles, we used high-resolution fMRI to investigate multivariate response patterns within CA3/DG and CA1 during the processing of spatial context. While undergoing functional imaging, participants viewed videos of virtual environments and were asked to discriminate between similar yet geometrically distinct cities. We manipulated a single contextual feature by systematically morphing the city configurations from one common geometric shape to another, resulting in four cities--two distinctively shaped cities and two intermediate "morphed" cities. Pattern similarity within CA3/DG scaled with geometric changes to the environment. In contrast, CA1 pattern similarity, as well as interregional pattern similarity between CA1 and parahippocampal cortex, increased for the regularly shaped configurations compared with the morphs. These results highlight different roles for subfields CA3/DG and CA1 in memory and advance our understanding of how subcomponents of the human hippocampal circuit represent contextual features of memories.

Spatiotemporal Neural Pattern Similarity Supports Episodic Memory

Formal computational models of human memory posit a central role of feature representations in episodic memory encoding and retrieval [1-4]. Correspondingly, fMRI studies have found that, in addition to activity level [5, 6], the neural activation pattern similarity across repetitions (i.e., self-similarity) was greater for subsequently remembered than forgotten items [7-9]. This self-similarity has been suggested to reflect pattern reinstatement due to study-phase retrieval [7, 10, 11]. However, the low temporal resolution of fMRI measures could determine neither the temporal precision of study-phase reinstatement nor the processing stage at which the reinstatement supported subsequent memory [12]. Meanwhile, although self-similarity has been shown to correlate with the activity level in the left lateral prefrontal cortex (LPFC) [10, 13], a causal link between left LPFC function and pattern similarity remains to be established. Combining transcranial direct current stimulation (tDCS) and EEG, we found that greater spatiotemporal pattern similarity (STPS) across repetitions of the same item (i.e., self-STPS) during encoding predicted better subsequent memory. The self-STPS located in the right frontal electrodes occurred approximately 500ms after stimulus onset, reflected item-specific encoding, and contributed to memory above and beyond the effects of ERP amplitude and global pattern similarity (i.e., similarity to all other items in memory space). Anodal stimulation over the left LPFC specifically enhanced memory performance and item-specific STPS in the right frontal electrodes. These results support a causal role of LPFC in enhancing STPS and memory and contribute to a mechanistic understanding of memory formation.

Neural Systems Involved When Attending to a Speaker.

Remembering what a speaker said depends on attention. During conversational speech, the emphasis is on working memory, but listening to a lecture encourages episodic memory encoding. With simultaneous interference from background speech, the need for auditory vigilance increases. We recreated these context-dependent demands on auditory attention in 2 ways. The first was to require participants to attend to one speaker in either the absence or presence of a distracting background speaker. The second was to alter the task demand, requiring either an immediate or delayed recall of the content of the attended speech. Across 2 fMRI studies, common activated regions associated with segregating attended from unattended speech were the right anterior insula and adjacent frontal operculum (aI/FOp), the left planum temporale, and the precuneus. In contrast, activity in a ventral right frontoparietal system was dependent on both the task demand and the presence of a competing speaker. Additional multivariate analyses identified other domain-general frontoparietal systems, where activity increased during attentive listening but was modulated little by the need for speech stream segregation in the presence of 2 speakers. These results make predictions about impairments in attentive listening in different communicative contexts following focal or diffuse brain pathology.

Effects of enactment in episodic memory: a pilot virtual reality study with young and elderly adults.

None of the previous studies on aging have tested the influence of action with respect to the degree of interaction with the environment (active or passive navigation) and the source of itinerary choice (self or externally imposed), on episodic memory (EM) encoding. The aim of this pilot study was to explore the influence of these factors on feature binding (the association between what, where, and when) in EM and on the subjective sense of remembering. Navigation in a virtual city was performed by 64 young and 64 older adults in one of four modes of exploration: (1) passive condition where participants were immersed as passengers of a virtual car [no interaction, no itinerary control (IC)], (2) IC (the subject chose the itinerary, but did not drive the car), (3) low, or (4) high navigation control (the subject just moved the car on rails or drove the car with a steering-wheel and a gas pedal on a fixed itinerary, respectively). The task was to memorize as many events encountered in the virtual environment as possible along with their factual (what), spatial (where), and temporal (when) details, and then to perform immediate and delayed memory tests. An age-related decline was evidenced for immediate and delayed feature binding. Compared to passive and high navigation conditions, and regardless of age-groups, feature binding was enhanced by low navigation and IC conditions. The subjective sense of remembering was boosted by the IC in older adults. Memory performance following high navigation was specifically linked to variability in executive functions. The present findings suggest that the decision of the itinerary is beneficial to boost EM in aging, although it does not eliminate age-related deficits. Active navigation can also enhance EM when it is not too demanding for subjects’ cognitive resources.

Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making.

The role of encoding strategies in contextual memory deficits in patients with bipolar disorder

Contextual memory is important for the encoding and retrieval of episodic memory, which is often impaired in euthymic patients with bipolar disorder (BD). The objective was to investigate the effect of low and high cognitive support on encoding in an incidental contextual memory task in euthymic patients with BD. Twenty-three patients with a BD type I diagnosis (aged 23–63 years, 17 women and 6 men) and 29 healthy controls completed a recognition memory task for context (location of a recognised object). Participants were assigned to one of two incidental encoding conditions: (1) with a binding cue to encourage the association of the object to its location (judging the degree of appropriateness of an object in relation to its location) or (2) without a binding cue (judging daily use of objects). Patients showed a deficit in incidental contextual memory in the absence of a binding cue at encoding. Under incidental encoding with the binding cue, no differences were observed between the groups for contextual memory. Contextual memory deficits in BD patients were reduced by providing cognitive support at encoding. The role of this strategy should be investigated in larger samples to evaluate its use for cognitive remediation in BD patients.

The gamma band effect for episodic memory encoding is absent in epileptogenic hippocampi

ObjectiveThe analysis of hippocampal local field potentials in humans during the encoding of episodic memories has revealed that a robust increase in gamma band oscillatory power predicts successful item encoding, termed the gamma band subsequent memory effect (SME). No previous investigation has looked for differences in this pattern between epileptogenic and non-epileptogenic sources; we sought to examine the gamma band effect in seizure patients to address this question. MethodsWe recorded hippocampal activity in nine patients who underwent stereoelectroencephalography for seizure localization and also performed the Free Recall task, a standard test of episodic memory. We compared gamma band oscillatory activity between 15 electrodes localized to epileptogenic hippocampi and 24 electrodes in non-epileptogenic hippocampi. ResultsThe epileptogenic hippocampi exhibited a significant decrease in gamma band power during successful item encoding, whereas the non-epileptogenic group exhibited the expected positive gamma band effect (t(37)=4.69, p<0.0001). ConclusionsThe typical gamma band effect is reversed for epileptogenic hippocampi. SignificanceThis is the first study to demonstrate a difference for epileptogenic hippocampi for an important oscillatory pattern that normally predicts successful item encoding. Patients with epilepsy suffer selective impairment of episodic memory ability, so our findings are especially relevant for clinicians and memory researchers alike.

Human single-unit recordings reveal a link between place-cells and episodic memory.

Human single-unit recordings reveal a link between place-cells and episodic memory.

Remembering the Past

Our ability to remember past events requires efficient encoding and successful “re-collection” of event features, such as the time, place, people, thoughts, and feelings associated with a past experience. Neuroimaging studies have demonstrated that episodic memory depends on specific brain mechanisms within the prefrontal cortex, medial temporal lobe, and ventral posterior parietal cortex that interact with the cortical sites that store event features. In this article, I present an analysis of the neural correlates of episodic memory, along with a theoretical framework, Cortical Binding of Relational Activity (CoBRA), that integrates the dynamic links between efficient encoding and successful retrieval of episodic memory.

Early remodeling of the neocortex upon episodic memory encoding.

Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, whereas reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural, and functional remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal-hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states.

Endogenous serotonin facilitates hippocampal long-term potentiation at CA3/CA1 synapses.

Encoding of episodic memory requires long-term potentiation (LTP) of neurotransmission at excitatory synapses of the hippocampal circuitry. Previous data obtained with the application of exogenous 5-hydroxytryptamine (5-HT) in hippocampal slices indicate that 5-HT blocks LTP, which contrasts with the facilitatory effect of selective serotonin reuptake inhibitors (SSRIs) on learning and memory observed in vivo. Here, we investigated the effects of endogenous 5-HT, released from terminals by the monoamine releaser 3,4-methylenedioxymethamphetamine (MDMA), on LTP of field EPSPs induced by theta-burst stimulation and recorded at CA3/CA1 synapses of rat hippocampal slices. LTP was greater in the presence of MDMA (10 µM; 45.76 ± 15.75%; n = 28) than in controls (31.26 ± 11.03; n = 21; p < 0.01). This facilitatory effect on LTP persisted when the entry of MDMA in noradrenergic terminals was prevented by the selective noradrenaline reuptake inhibitor nisoxetine (44.90 ± 14.07%; n = 27 vs. 34.49 ± 12.94%; n = 20 in controls; p < 0.05). In both conditions, the facilitation of LTP was abolished by the SSRI citalopram that prevented the entry of MDMA in 5-HT terminals and the subsequent 5-HT release. These data show that, unlike exogenous 5-HT application, release of endogenous 5-HT does not impair cellular mechanisms responsible for induction of LTP, indicating that 5-HT is not detrimental to learning and memory. Moreover, facilitation of LTP by endogenous 5-HT may underlie the in vivo positive effects of augmented 5-HT tone on cognitive performance.

Contributions of Feature Binding During Encoding and Functional Connectivity of the Medial Temporal Lobe Structures to Episodic Memory Deficits Across the Prodromal and First-Episode Phases of Schizophrenia.

Patients with and at risk for psychosis may have difficulty using associative strategies to facilitate episodic memory encoding and recall. In parallel studies, patients with first-episode schizophrenia (n = 27) and high psychosis risk (n = 28) compared with control participants (n = 22 and n = 20, respectively) underwent functional MRI during a remember-know memory task. Psychophysiological interaction analyses, using medial temporal lobe (MTL) structures as regions of interest, were conducted to measure functional connectivity patterns supporting successful episodic memory. During encoding, patients with first-episode schizophrenia demonstrated reduced functional coupling between MTL regions and regions involved in stimulus representations, stimulus selection, and cognitive control. Relative to control participants and patients with high psychosis risk who did not convert to psychosis, patients with high psychosis risk who later converted to psychosis also demonstrated reduced connectivity between MTL regions and auditory-verbal and visual-association regions. These results suggest that episodic memory deficits in schizophrenia are related to inefficient recruitment of cortical connections involved in associative memory formation; such deficits precede the onset of psychosis among those individuals at high clinical risk.

Respiration phase‐locks to fast stimulus presentations: Implications for the interpretation of posterior midline “deactivations”

The posterior midline region (PMR)-considered a core of the default mode network-is deactivated during successful performance in different cognitive tasks. The extent of PMR-deactivations is correlated with task-demands and associated with successful performance in various cognitive domains. In the domain of episodic memory, functional MRI (fMRI) studies found that PMR-deactivations reliably predict learning (successful encoding). Yet it is unclear what explains this relation. One intriguing possibility is that PMR-deactivations are partially mediated by respiratory artifacts. There is evidence that the fMRI signal in PMR is particularly prone to respiratory artifacts, because of its large surrounding blood vessels. As respiratory fluctuations have been shown to track changes in attention, it is critical for the general interpretation of fMRI results to clarify the relation between respiratory fluctuations, cognitive performance, and fMRI signal. Here, we investigated this issue by measuring respiration during word encoding, together with a breath-holding condition during fMRI-scanning. Stimulus-locked respiratory analyses showed that respiratory fluctuations predicted successful encoding via a respiratory phase-locking mechanism. At the same time, the fMRI analyses showed that PMR-deactivations associated with learning were reduced during breath-holding and correlated with individual differences in the respiratory phase-locking effect during normal breathing. A left frontal region--used as a control region--did not show these effects. These findings indicate that respiration is a critical factor in explaining the link between PMR-deactivation and successful cognitive performance. Further research is necessary to demonstrate whether our findings are restricted to episodic memory encoding, or also extend to other cognitive domains.

Altered neural function during episodic memory encoding and retrieval in major depression

Memory impairments are common in major depression. Neural processing during non-emotional episodic memory in depressed patients has only sparsely been investigated, since the majority of studies have focused on emotional stimuli. The aim of this study was to explore neural correlates of episodic memory in depressive patients and to assess brain regions related to subsequent memory performance. Forty-six participants (23 depressed patients) performed a non-emotional episodic memory encoding and retrieval task while brain activation was measured with functional magnetic resonance imaging. Patients with depression showed decreased activation in the right prefrontal cortex and right cingulate cortex during memory encoding, but increased activation in the right inferior frontal gyrus (IFG) during recognition memory. While a strong association between hippocampal and parahippocampal activation during memory encoding with subsequent memory performance became evident in healthy controls, this relationship was absent in patients with depression. Taken together, these findings demonstrate that memory related brain regions are affected in their appropriate functioning during memory encoding in depressed patients. Therefore, patients with depression may rely to a greater degree on other brain regions such as the IFG during episodic memory retrieval.

Ongoing theta oscillations predict encoding of subjective memory type

Recent human electro-encephalography (EEG) studies show that ongoing brain states support successful encoding of human memory, including recognition. However it is not known whether ongoing cortical activity qualitatively determines different memory types at encoding. In this study, using a remember/know procedure, we measured the EEG oscillations that emerge before and during the encoding of abstract visual stimuli in episodic and non-episodic memory, focusing on the theta (2–8Hz) and alpha (9–12Hz) oscillation range. We found that enhanced prestimulus theta oscillations precede episodic memory encoding, compared to non-episodic encoding. The prestimulus difference appeared at frontal and temporal sites. Furthermore, the theta enhancement reappeared after stimulus onset. Enhanced upper alpha oscillations suggested increased working memory processing in the case of episodic memory. Finally, the pre- and post-stimulus theta and alpha amplitudes showed different correlation patterns for episodic and non-episodic encoding. Our results are the first to suggest that encoding of episodic memory depends on preparatory processing in the form of frontal and temporal theta oscillations.

The new risk variant CACNA1C and brain circuits in schizophrenia

In recent genome-wide association studies of severe psychiatric disorders, several risk genes have been detected, but their neurobiological function is widely unknown. A polymorphism in the gene encoding the alpha-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) has been associated with schizophrenia and bipolar disorder and may have impact on structure and function of the amygdala. Wolf et al. [1] investigated the influence of the SNP rs1006737 in CACNA1C on gray matter volumes of the amygdala in patients with schizophrenia, bipolar disorder and obsessive compulsive disorder (OCD). The risk genotype had significant effect on the relative amygdala volume in patients with schizophrenia, while this group and bipolar patients had a smaller left amygdala compared to controls. This supports the hypothesis of disturbed calcium metabolism as a neurobiological background of affective symptoms in schizophrenia. However, CACNA1C is also known to be involved in learning and memory. In a functional MRI study of two independent samples of healthy probands, Krug et al. [2] investigated the impact of rs1006737 on episodic memory encoding and retrieval in the right hippocampus. In both samples, they replicated that in the retrieval condition, carriers of the minor allele (A) had lower activations than G/G allele carriers, thus strengthening the hypothesis that this risk genotype is associated with dysfunction of hippocampus-related memory processes. Schizophrenia has been linked to disturbances in neuronal circuits such as the cortico–striato–thalamo–cortical loop. As a consequence, disinhibition of the thalamus plays a prominent role in the overflow of information to the prefrontal cortex and possibly is involved in the generation of positive symptoms. In a resting-state functional MRI study, Klingner et al. [3] found higher thalamocortical functional connectivity in chronic schizophrenia patients compared to healthy controls. Specifically, the connectivity to the right ventrolateral prefrontal and bilateral motor and sensory cortical areas was affected. Structural analysis revealed involvement of medial and anterior thalamic nuclei in correlation with the prefrontal and superior temporal cortex, contributing to alterations of the network in schizophrenia. However, treatment with antipsychotics may have an influence on macroconnectivity and myelination of fiber tracts. In a cell culture study of oligodendrocytes with or without the presence of the cuprizone, a white matter damaging agent, Xu et al. [4] reported that clozapine and quetiapine, but not haloperidol or olanzapine counteracted effects of cuprizone. These findings are relevant for the growing knowledge about the influence of antipsychotics on pathophysiological aspects such as myelination-related dysconnectivity in schizophrenia. In a clinical assessment of 56.861 schizophrenia patients, Grohmann et al. [5] compared the typical neuroleptic flupentixol to haloperidol and second-generation antipsychotics with respect to drug utilization and adverse drug reactions (ADR). Flupentixol ranked lowest among all ADR. Extrapyramidal symptoms were most frequently detected in flupentixol and risperidone and least in the olanzapine-/quetiapine-treated group. Altogether, the results justify the treatment approach with flupentixol in a subgroup of schizophrenia patients. Disturbances in semantic processing are proposed to be involved in the pathophysiology of formal thought disorder in schizophrenia. In a functional MRI study, Sass et al. [6] A. Schmitt (&) P. Falkai Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nusbaumstr. 7, 80336 Munich, Germany e-mail: andrea.schmitt@med.uni-muenchen.de