Episodic Memory Retrieval Research Articles

Human hippocampal CA3 damage disrupts both recent and remote episodic memories.

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance.

Activation of cannabinoid receptor type 1 impairs spatial and temporal aspects of episodic-like memories in rats.

The endocannabinoid system modulates many brain functions, including episodic memories, which contain memories of time and places. Most studies have focused on the involvement of the endocannabinoid system in spatial memory; however, its role in temporal memory is not well understood. Few studies have tested whether the unilateral endocannabinoid system is sufficient to modulate memory retrieval. Here, we tested whether type 1 cannabinoid receptors in the right hippocampal cornu ammonis area 1 region are enough to modulate the retrieval of episodic memories, specifically their spatial and temporal components. Because rats have innate preferences for displaced or old familiar objects, we changed the locations of "old familiar" and "recent familiar" objects in an open field and measured the rats' exploration times to evaluate spatial and temporal memory. To address the influence of the type 1 cannabinoid receptors on the retrieval of episodic-like memories, two doses of arachidonylcyclopropylamide, a selective type 1 cannabinoid receptor agonist, were infused into the cornu ammonis area 1 of rats ten minutes before the discrimination trials. We observed that rats injected with a low dose of arachidonylcyclopropylamide spent less time investigating displaced objects, suggesting spatial memory impairment, whereas those receiving a high dose explored old familiar objects less frequently, suggesting temporal memory impairment. This indicates that unilateral activation of type 1 cannabinoid receptors in the cornu ammonis area 1 impairs the spatial and temporal aspects of episodic memories. This research mimics the influence of marijuana intoxication effects in humans, such as spatial and temporal disintegration.

Correlation Between Hippocampal Volume and Autobiographical Memory Depending on Retrieval Frequency in Healthy Individuals and Patients with Alzheimer's Disease.

The hippocampus plays an indispensable role in episodic memory, particularly during the consolidation process. However, its precise role in retrieval of episodic memory is still ambiguous. In this study, we investigated the correlation of hippocampal morphometry and the performance in an autobiographical memory task in 27 healthy controls and 24 patients suffering from Alzheimer's disease (AD). Most importantly, correlations were defined separately and comparatively for memory contents with different retrieval frequency in the past. In healthy subjects, memory performance for seldom retrieved autobiographical events was significantly associated with gray matter density in the bilateral hippocampus, whereas this correlation was not present for events with high retrieval frequency. This pattern of findings confirms that retrieval frequency plays a critical role in the consolidation of episodic autobiographical memories, thereby making them more independent of the hippocampal system. In AD patients, on the other hand, successful memory retrieval appeared to be related to hippocampal morphometry irrespective of the contents' retrieval frequency, comprising events with high retrieval frequency, too. The observed differences between patients and control subjects suggest that AD-related neurodegeneration not only impairs the function, but also decreases the functional specialization of the hippocampal memory system, which, thus, may be considered as marker for AD.

Cranial irradiation mediated spine loss is sex-specific and complement receptor-3 dependent in male mice

Cranial irradiation is the main therapeutic treatment for primary and metastatic malignancies in the brain. However, cranial radiation therapy produces long-term impairment in memory, information processing, and attention that contribute to a decline in quality of life. The hippocampal neural network is fundamental for proper storage and retrieval of episodic and spatial memories, suggesting that hippocampal signaling dysfunction could be responsible for the progressive memory deficits observed following irradiation. Previous rodent studies demonstrated that irradiation induces significant loss in dendritic spine number, alters spine morphology, and is associated with behavioral task deficits. Additionally, the literature suggests a common mechanism in which synaptic elimination via microglial-mediated phagocytosis is complement dependent and associated with cognitive impairment in aging as well as disease. We demonstrate sexual dimorphisms in irradiation-mediated alterations of microglia activation markers and dendritic spine density. Further, we find that the significant dendritic spine loss observed in male mice following irradiation is microglia complement receptor 3 (CR3)-dependent. By identifying sex-dependent cellular and molecular factors underlying irradiation-mediated spine loss, therapies can be developed to counteract irradiation-induced cognitive decline and improve patient quality of life.

Older adults recruit dorsomedial prefrontal cortex to decrease negativity during retrieval of emotionally complex real-world events

Recent research from our lab has highlighted a prefrontally-mediated control mechanism that decreases the subjective richness of negative episodic events during older adults' episodic memory retrieval. The current study examined whether such a mechanism was also engaged during retrieval of real-world negative events. In a scanned autobiographical memory task, 56 participants (ages 18–83) were presented with images associated with the 2013 Boston Marathon Bombings. Images fell into three categories: primarily positive, primarily negative, and mixed-valence. Participants retrieved a personal memory associated with each image, elaborated on that memory in as much detail as possible, and rated memory positivity and memory negativity. Unlike in recent episodic memory studies, young and older adults did not differ in how prefrontal regions contributed to retrieval of autobiographical memories associated with primarily negative images. However, there was an age-related reversal in the role of dorsomedial prefrontal recruitment during retrieval of autobiographical memories associated with mixed-valence images: Activity was associated with increased negativity ratings in young adults and decreased negativity in older adults. These findings are the first evidence that older adults engage a prefrontally-mediated mechanism at the time of retrieval to reduce the negativity of memories for real-world emotional events, and further suggest that they may only do so in the case of emotional ambiguity. Such a mechanism could have important implications for understanding how older adults may respond to and evaluate negative events in their daily lives.

Directional coupling of slow and fast hippocampal gamma with neocortical alpha/beta oscillations in human episodic memory

Episodic memories hinge upon our ability to process a wide range of multisensory information and bind this information into a coherent, memorable representation. On a neural level, these 2 processes are thought to be supported by neocortical alpha/beta desynchronization and hippocampal theta/gamma synchronization, respectively. Intuitively, these 2 processes should couple to successfully create and retrieve episodic memories, yet this hypothesis has not been tested empirically. We address this by analyzing human intracranial electroencephalogram data recorded during 2 associative memory tasks. We find that neocortical alpha/beta (8 to 20 Hz) power decreases reliably precede and predict hippocampal "fast" gamma (60 to 80 Hz) power increases during episodic memory formation; during episodic memory retrieval, however, hippocampal "slow" gamma (40 to 50 Hz) power increases reliably precede and predict later neocortical alpha/beta power decreases. We speculate that this coupling reflects the flow of information from the neocortex to the hippocampus during memory formation, and hippocampal pattern completion inducing information reinstatement in the neocortex during memory retrieval.

Interdependence between dorsal and ventral hippocampus during spatial navigation.

IntroductionThe hippocampus is linked to the formation and retrieval of episodic memories and spatial navigation. In rats, it is an elongated structure divided into dorsal (septal) and ventral (temporal) regions paralleling the respective division in the posterior and anterior hippocampus in humans. The dorsal hippocampus has been suggested to be more important for spatial processing and the ventral to processing anxiety‐based behaviors. Far less is known regarding the degree to which these different regions interact during information processing. The anatomical connectivity suggests a flow of information between the dorsal and ventral regions; conversely, there are also commissural connections to the contralateral hippocampus. The current study examined the extent to which information from the dorsal hippocampus interacts with processing in the ipsilateral and contralateral ventral hippocampus following the acquisition of a spatial task.MethodsRats were well‐trained on a spatial reference version of the water maze, followed by muscimol inactivation of different hippocampal subregions in a within‐animal repeated design. Various combinations of bilateral, ipsilateral, and contralateral infusions were used.ResultsCombined dorsal and ventral inactivation produced a severe impairment in spatial performance. Inactivation of only the dorsal or ventral regions resulted in intermediate impairment with performance levels falling between controls and combined inactivation. Performance was impaired during contralateral inactivation and was almost equivalent to bilateral dorsal and ventral hippocampus inactivation, while ipsilateral inactivation resulted in little impairment.ConclusionsTaken together, results indicate that for spatial processing, the hippocampus functions as a single integrated structure along the longitudinal axis.

Increases in Theta Oscillatory Activity During Episodic Memory Retrieval Following Mindfulness Meditation Training.

Mindfulness meditation has been shown to improve episodic memory and increase theta oscillations which are known to play a role in episodic memory retrieval. The present study examined the effect of mindfulness meditation on episodic memory retrieval and theta oscillations. Using a longitudinal design, subjects in the mindfulness meditation experimental group who underwent 4 weeks of mindfulness meditation training and practice were compared to a waitlist control group. During the pre-training and post-training experimental sessions, subjects completed the Five Facet Mindfulness Questionnaire (FFMQ) and studied adjectives and either imagined a scene (Place Task) or judged its pleasantness (Pleasant Task). During the recognition test, subjects decided which task was performed with each word (“Old Place Task” or “Old Pleasant Task”) or “New.” FFMQ scores and source discrimination were greater post-training than pre-training in the mindfulness meditation experimental group. Electroencephalography (EEG) results revealed that for the mindfulness meditation experimental group theta power was greater post-training than pre-training in right frontal and left parietal channels and changes in FFMQ scores correlated with changes in theta oscillations in right frontal channels (n = 20). The present results suggest that mindfulness meditation increases source memory retrieval and theta oscillations in a fronto-parietal network.

Enhanced spontaneous retrieval of cues from emotional events: An ERP study

Recent evidence points to enhanced episodic memory retrieval not only for emotional items but also for neutral information encoded in emotional contexts. However, prior research only tested instructed explicit recognition, and hence here we investigated whether memory retrieval is also heightened for cues from emotional contexts when retrieval is not explicitly probed. During the first session of a two-session experiment, neutral objects were presented on different background scenes varying in emotional and neutral contents. One week later, objects were presented again (with no background) intermixed with novel objects. In both sessions, participants were instructed to attentively watch the stimuli (free viewing procedure), and during the second session, ERPs were also collected to measure the ERP Old/New effect, an electrophysiological correlate of episodic memory retrieval. Analyses were performed using cluster-based permutation tests in order to identify reliable spatio-temporal ERP differences. Based on this approach, old relative to new objects, were associated with larger ERP positivity in an early (364–744 ms) and late time window (760–1148 ms) over distinct central electrode clusters. Interestingly, significant late ERP Old/New differences were only observed for objects previously encoded with emotional, but not neutral scenes (504 to 1144 ms). Because these ERP differences were observed in a non-instructed retrieval context, our results indicate that long-term, spontaneous retrieval for neutral objects, is particularly heightened if encoded within emotionally salient contextual information. These findings may assist in understanding mechanisms underlying spontaneous retrieval of emotional associates and the utility of ERPs to study maladaptive involuntary memories in trauma- and stress-related disorders.

Dementia Risk Elevates Brain Activity During Memory Retrieval: A Functional MRI Analysis of Middle Aged and Older Adults.

Longitudinal research suggests that genetic, lifestyle, and environmental factors enhance one's risk for developing Alzheimer's disease and related dementias (ADRD). However, it is not known how an accumulation of such factors impact brain functioning. One barrier to this research is that increased risk for ADRD affects the cerebrovascular system and, therefore, alters the link between neural activity and the fMRI BOLD signal. To better interpret fMRI findings, several steps were taken to adjust fMRI activity thereby reducing such cerebrovascular effects. We hypothesized that as the number of ADRD risk factors increase, brain regions within the medial temporal lobes and the default mode network would exhibit altered brain activity during an episodic memory retrieval task. Middle-aged and older adults (aged 50-74) free of dementia were recruited with varying levels of risk and underwent a neuropsychological battery and fMRI. In the memory task, participants viewed a pair of pictures. In an alternative-forced-choice test, participants viewed a picture cue and had to determine which of four pictures was paired with the cue. Increased dementia risk was positively associated with brain activity in regions of interest within the default mode network, the hippocampus, and the entorhinal cortex during memory retrieval. Whole-brain analyses revealed additional positive associations in prefrontal and occipito-temporal cortices. Risk factors most contributing to these elevated levels of brain activity included hypertension, diabetes, obesity, and cholesterol. We also ruled out confounds due to in-scanner performance and premorbid ability. Cumulative risk might represent early signs of burnout in brain regions underlying episodic memory.

Sharp-wave ripples in the hippocampus

Neuroscience What are the brain mechanisms responsible for episodic memory retrieval? Norman et al. investigated epilepsy patients who had electrodes implanted in the hippocampus and a variety of cortical areas. Using a visual learning paradigm, they examined the temporal relationship between the incidence of hippocampal sharp-wave ripples and recall. Effective encoding of visual information was associated with higher incidence of ripples. Successful recall was preceded by an increased probability of ripples, which were also associated with transient reemergence of activation patterns in higher visual cortical areas. Hippocampal ripples may thus boost recollections during episodic memory retrieval. Science , this issue p. [eaax1030][1] [1]: /lookup/doi/10.1126/science.aax1030

Hippocampal sharp-wave ripples linked to visual episodic recollection in humans.

Hippocampal sharp-wave ripples (SWRs) constitute one of the most synchronized activation events in the brain and play a critical role in offline memory consolidation. Yet their cognitive content and function during awake, conscious behavior remains unclear. We directly examined this question using intracranial recordings in human patients engaged in episodic free recall of previously viewed photographs. Our results reveal a content-selective increase in hippocampal ripple rate emerging 1 to 2 seconds prior to recall events. During recollection, high-order visual areas showed pronounced SWR-coupled reemergence of activation patterns associated with recalled content. Finally, the SWR rate during encoding predicted subsequent free-recall performance. These results point to a role for hippocampal SWRs in triggering spontaneous recollections and orchestrating the reinstatement of cortical representations during free episodic memory retrieval.

Dopamine Enhances Item Novelty Detection via Hippocampal and Associative Recall via Left Lateral Prefrontal Cortex Mechanisms.

The involvement of fronto-striatal circuits in item and associative memory retrieval as well as in the stabilization of memories by retrieval practice suggests that both retrieval and re-encoding of stored memories might rely on dopaminergic mechanisms in humans. We tested these hypotheses in a placebo-controlled pharmacological fMRI study using 2 mg of the D2 antagonist haloperidol administered acutely before a cued associative recall task of previously encoded picture-word pairs in 53 healthy humans of both sexes. The cued associative recall was moreover repeated 3 d later outside the scanner without pharmacological intervention. Dopaminergic modulation significantly improved associative recall performance and recognition accuracy of verbal items. Moreover, we observed a significant dopamine effect on re-encoding in terms of increased specificity of associative memories from the first to the second cued associative recall. Better association memory under haloperidol was linked with higher activity in the left lateral prefrontal cortex and right parietal cortex, suggesting that dopamine facilitates associative retrieval through increased recruitment of frontoparietal monitoring processes. In contrast, improved recognition of verbal items under haloperidol was reflected by enhanced novelty detection in the hippocampus and increased activity in saliency networks. Together, these results show distinct but concomitant positive effects of dopamine on associative recall and item recognition and suggest that the specificity of associative recall through re-encoding mechanisms is likewise augmented by dopamine.SIGNIFICANCE STATEMENT Although the neurotransmitter dopamine has been linked with learning and memory for a long time, dopaminergic effects on item recognition in humans were demonstrated only recently. The involvement of fronto-striatal monitoring processes in association retrieval suggests that associative memory might be particularly affected by dopamine. Moreover, fronto-striatal dopaminergic signals have been hypothesized to determine the updating and re-encoding of previously retrieved memories. We here demonstrate clear facilitative effects of dopamine on associative recall and item recognition mediated by prefrontal and hippocampal mechanisms respectively. Additionally, effects on re-encoding were reflected by increased specificity of associative memories. These results augment our understanding of dopaminergic processes in episodic memory retrieval and offer new perspectives on memory impairments in dopamine-related disorders and their treatment.

ACCUMULATION OF DEMENTIA RISK FACTORS ALTERS BRAIN REGIONS OF EPISODIC MEMORY: AN FMRI ANALYSIS

Longitudinal research suggests that genetic, lifestyle, and environmental factors enhance one's risk for developing Alzheimer's disease and related dementias (ADRD). However, it is not known how an accumulation of multiple risk factors alters brain function. One barrier to this research is that increased risk for ADRD affects the cerebrovascular system, thus decoupling neural activity from the fMRI blood oxygen level dependent (BOLD) signal. Previous studies that have found an association between risks for ADRD and brain activity suffer challenges in interpretation because the BOLD signal was not calibrated, likely leading to an overestimation of such associations. We hypothesized that as the number of ADRD risk factors increase, brain regions within the medial temporal lobes and the default mode network (DMN) would exhibit altered brain activity during an episodic memory retrieval task. To reduce the influence of non-neural influences on the BOLD signal, several steps were taken to calibrate fMRI BOLD activity. Participants ranged in age from 50 to 70 years. Participants were recruited with varying levels of risk for dementia and from this initial screening a dementia risk score was calculated. They also underwent a neuropsychological battery to screen out possible dementia. Using fMRI, brain activity was assessed while participants completed a memory task by viewing a pair of pictures, followed by an alternative-forced-choice test, where participants viewed a picture cue and had to determine which of four pictures was paired with the cue. After correcting the fMRI BOLD signal, whole-brain analyses revealed that increased dementia risk was negatively associated with brain activity in the hippocampus—a task positive region—and was positively associated with the lateral parietal cortex—a task negative region. We found evidence that adults with an accumulation of risk factors for dementia exhibit decreased modulation of brain activity in critical regions underlying episodic memory. These findings call into question previous studies that did not calibrate the BOLD signal and found compensatory hyperactivity in these regions. Instead, cumulative risk likely represents early dysfunction of the default mode and brain regions underlying episodic memory.

Imagination as a dialogue

Neuroscience The hippocampus constructs scene imagery to facilitate recollected or imagined mental representations. However, input from the ventromedial prefrontal cortex (vmPFC) is also needed for scene construction. How do these regions interact when we imagine a scene? Barry et al. addressed this question using magnetoencephalography. Participants imagined novel scenes or single objects after being given a cue. The direction of information flow during scene imagination mirrored that observed during episodic memory retrieval, in which vmPFC drives hippocampal activity. These results indicate that the vmPFC selects the elements for a scene, whereas the hippocampus is necessary to construct the scene imagery. The vmPFC strongly modulates the construction of spatially coherent, contextually appropriate scene imagery. Episodic memory and imagination thus use similar regional dialogue in the brain. J. Neurosci. 39 , 4375 (2019).

Coordinated representational reinstatement in the human hippocampus and lateral temporal cortex during episodic memory retrieval

Theoretical models of episodic memory have proposed that retrieval depends on interactions between the hippocampus and neocortex, where hippocampal reinstatement of item-context associations drives neocortical reinstatement of item information. Here, we simultaneously recorded intracranial EEG from hippocampus and lateral temporal cortex (LTC) of epilepsy patients who performed a virtual reality spatial navigation task. We extracted stimulus-specific representations of both item and item-context associations from the time-frequency patterns of activity in hippocampus and LTC. Our results revealed a double dissociation of representational reinstatement across time and space: an early reinstatement of item-context associations in hippocampus preceded a later reinstatement of item information in LTC. Importantly, reinstatement levels in hippocampus and LTC were correlated across trials, and the quality of LTC reinstatement was predicted by the magnitude of phase synchronization between hippocampus and LTC. These findings confirm that episodic memory retrieval in humans relies on coordinated representational interactions within a hippocampal-neocortical network.

Anodal Transcranial Direct Current Stimulation to the Left Rostrolateral Prefrontal Cortex Selectively Improves Source Memory Retrieval.

Functional neuroimaging studies have consistently implicated the left rostrolateral prefrontal cortex (RLPFC) as playing a crucial role in the cognitive operations supporting episodic memory and analogical reasoning. However, the degree to which the left RLPFC causally contributes to these processes remains underspecified. We aimed to assess whether targeted anodal stimulation-thought to boost cortical excitability-of the left RLPFC with transcranial direct current stimulation (tDCS) would lead to augmentation of episodic memory retrieval and analogical reasoning task performance in comparison to cathodal stimulation or sham stimulation. Seventy-two healthy adult participants were evenly divided into three experimental groups. All participants performed a memory encoding task on Day 1, and then on Day 2, they performed continuously alternating tasks of episodic memory retrieval, analogical reasoning, and visuospatial perception across two consecutive 30-min experimental sessions. All groups received sham stimulation for the first experimental session, but the groups differed in the stimulation delivered to the left RLPFC during the second session (either sham, 1.5 mA anodal tDCS, or 1.5 mA cathodal tDCS). The experimental group that received anodal tDCS to the left RLPFC during the second session demonstrated significantly improved episodic memory source retrieval performance, relative to both their first session performance and relative to performance changes observed in the other two experimental groups. Performance on the analogical reasoning and visuospatial perception tasks did not exhibit reliable changes as a result of tDCS. As such, our results demonstrate that anodal tDCS to the left RLPFC leads to a selective and robust improvement in episodic source memory retrieval.

NEUROPSYCHOLOGICAL PERFORMANCE DIFFERENCES BETWEEN TWO GROUPS OF PROBABLE-AD PATIENTS FROM DIFFERENT AREAS OF BRAZILNEUROPSYCHOLOGICAL PERFORMANCE DIFFERENCES BETWEEN TWO GROUPS OF PROBABLE-AD PATIENTS FROM DIFFERENT AREAS OF BRAZIL

During normal aging there are some cognitive and behavioral changes similar to those observed in a transitional state or mild cognitive impairment (MCI) and early onset dementia, making it challenging for health care professionals to reach an accurate and reliable diagnosis. Objective: The current study examined the performance of two different groups of patients diagnosed with probable Alzheimer’s disease (AD) on a neuropsychological test battery. Methods: Twenty-two AD patients from Brasília-DF (AD1) and thirty-four AD patients from Palmas-TO, northern Brazil (AD2), were selected and a short neuropsychological battery administered. To verify the reliability of these previous diagnoses of AD, both groups of patients were compared with a group of healthy controls. Results: AD patients showed cognitive deficit but scores were lower for the AD2 group compared with the AD1 group considering the cut-off point. Notably, patients from the AD1 group were older (p=0.004) and had less formal education (p<0.001) than those from the AD2 group. Comparing different cognitive domains between AD groups, post hoc analysis showed that the AD1 group was characterized by deficits in episodic memory retrieval (p<0.001), semantic memory (p<0.001) and verbal fluency (p<0.001). In contrast, the AD2 group showed lower scores in attention (p=0.007), executive functioning (p<0.001) and working memory (p<0.001). Conclusion: This pattern suggests that the Palma group of patients had a neuropsychological profile that was inconsistent with AD. Although the results of this study have important clinical implications, the effects of age, education, and gender on cognitive performance should be explored further.

Overlapping frontoparietal networks in response to oculomotion and traumatic autobiographical memory retrieval: implications for eye movement desensitization and reprocessing

ABSTRACT Background: Oculomotor movements have been shown to aid in the retrieval of episodic memories, serving as sensory cues that engage frontoparietal brain regions to reconstruct visuospatial details of a memory. Frontoparietal brain regions not only are involved in oculomotion, but also mediate, in part, the retrieval of autobiographical episodic memories and assist in emotion regulation. Objective: We sought to investigate how oculomotion influences retrieval of traumatic memories by examining patterns of frontoparietal brain activation during autobiographical memory retrieval in post-traumatic stress disorder (PTSD) and in healthy controls. Method: Thirty-nine participants (controls, n = 19; PTSD, n = 20) recollected both neutral and traumatic/stressful autobiographical memories while cued simultaneously by horizontal and vertical oculomotor stimuli. The frontal (FEF) and supplementary (SEF) eye fields were used as seed regions for psychophysiological interaction analyses in SPM12. Results: As compared to controls, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, PTSD showed: i) increased SEF and FEF connectivity with the right dorsolateral prefrontal cortex, ii) increased SEF connectivity with the right dorsomedial prefrontal cortex, and iii) increased SEF connectivity with the right anterior insula. By contrast, as compared to PTSD, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, controls showed: i) increased FEF connectivity with the right posterior insula and ii) increased SEF connectivity with the precuneus. Conclusions: These findings provide a neurobiological account for how oculomotion may influence the frontoparietal cortical representation of traumatic memories. Implications for eye movement desensitization and reprocessing are discussed.

The Neural Dynamics of Novel Scene Imagery.

Retrieval of long-term episodic memories is characterized by synchronized neural activity between hippocampus and ventromedial prefrontal cortex (vmPFC), with additional evidence that vmPFC activity leads that of the hippocampus. It has been proposed that the mental generation of scene imagery is a crucial component of episodic memory processing. If this is the case, then a comparable interaction between the two brain regions should exist during the construction of novel scene imagery. To address this question, we leveraged the high temporal resolution of MEG to investigate the construction of novel mental imagery. We tasked male and female humans with imagining scenes and single isolated objects in response to one-word cues. We performed source-level power, coherence, and causality analyses to characterize the underlying interregional interactions. Both scene and object imagination resulted in theta power changes in the anterior hippocampus. However, higher theta coherence was observed between the hippocampus and vmPFC in the scene compared with the object condition. This interregional theta coherence also predicted whether imagined scenes were subsequently remembered. Dynamic causal modeling of this interaction revealed that vmPFC drove activity in hippocampus during novel scene construction. Additionally, theta power changes in the vmPFC preceded those observed in the hippocampus. These results constitute the first evidence in humans that episodic memory retrieval and scene imagination rely on similar vmPFC–hippocampus neural dynamics. Furthermore, they provide support for theories emphasizing similarities between both cognitive processes and perspectives that propose the vmPFC guides the construction of context-relevant representations in the hippocampus.SIGNIFICANCE STATEMENT Episodic memory retrieval is characterized by a dialog between hippocampus and ventromedial prefrontal cortex (vmPFC). It has been proposed that the mental generation of scene imagery is a crucial component of episodic memory processing. An ensuing prediction would be of a comparable interaction between the two brain regions during the construction of novel scene imagery. Here, we leveraged the high temporal resolution of MEG and combined it with a scene imagination task. We found that a hippocampal–vmPFC dialog existed and that it took the form of vmPFC driving the hippocampus. We conclude that episodic memory and scene imagination share fundamental neural dynamics and the process of constructing vivid, spatially coherent, contextually appropriate scene imagery is strongly modulated by vmPFC.