Hippocampus In Retrieval Research Articles

Anterior Cingulate Cortex Signals the Need to Control Intrusive Thoughts during Motivated Forgetting.

How do people limit awareness of unwanted memories? When such memories intrude, a control process engages the right DLPFC (rDLPFC) to inhibit hippocampal activity and stop retrieval. It remains unknown how the need for control is detected, and whether control operates proactively to prevent unwelcome memories from being retrieved, or responds reactively, to counteract intrusions. We hypothesized that dorsal ACC (dACC) detects the emergence of an unwanted trace in awareness and transmits the need for inhibitory control to rDLPFC. During a memory suppression task, we measured in humans (both sexes) trial-by-trial variations in the theta power and N2 amplitude of dACC, two EEG markers that are thought to reflect the need for control. With simultaneous EEG-fMRI recordings, we tracked interactions among dACC, rDLPFC, and hippocampus during suppression. We found a clear role of dACC in detecting the need for memory control and upregulating prefrontal inhibition. Importantly, we identified distinct early (300–450 ms) and late (500–700 ms) dACC contributions, suggesting both proactive control before recollection and reactive control in response to intrusions. Stronger early activity was associated with reduced hippocampal activity and diminished BOLD signal in dACC and rDLPFC, suggesting that preempting retrieval reduced overall control demands. In the later window, dACC activity was larger, and effective connectivity analyses revealed robust communication from dACC to rDLPFC and from rDLPFC to hippocampus, which are tied to successful forgetting. Together, our findings support a model in which dACC detects the emergence of unwanted content, triggering top-down inhibitory control, and in which rDLPFC countermands intruding thoughts that penetrate awareness.SIGNIFICANCE STATEMENT Preventing unwanted memories from coming to mind is an adaptive ability of humans. This ability relies on inhibitory control processes in the prefrontal cortex to modulate hippocampal retrieval processes. How and when reminders to unwelcome memories come to trigger prefrontal control mechanisms remains unknown. Here we acquired neuroimaging data with both high spatial and temporal resolution as participants suppressed specific memories. We found that the anterior cingulate cortex detects the need for memory control, responding both proactively to early warning signals about unwelcome content and reactively to intrusive thoughts themselves. When unwanted traces emerge in awareness, anterior cingulate communicates with prefrontal cortex and triggers top-down inhibitory control over the hippocampus through specific neural oscillatory networks.

Hippocampal GABA enables inhibitory control over unwanted thoughts

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled.

Effects of internal and external vividness on hippocampal connectivity during memory retrieval

Successful memory for an image can be supported by retrieval of one’s personal reaction to the image (i.e., internal vividness), as well as retrieval of the specific details of the image itself (i.e., external vividness). Prior research suggests that memory vividness relies on regions within the medial temporal lobe, particularly the hippocampus, but it is unclear whether internal and external vividness are supported by the hippocampus in a similar way. To address this open question, the current study examined hippocampal connectivity associated with enhanced internal and external vividness ratings during retrieval. Participants encoded complex visual images paired with verbal titles. During a scanned retrieval session, they were presented with the titles and asked whether each had been seen with an image during encoding. Following retrieval of each image, participants were asked to rate internal and external vividness. Increased hippocampal activity was associated with higher vividness ratings for both scales, supporting prior evidence implicating the hippocampus in retrieval of memory detail. However, different patterns of hippocampal connectivity related to enhanced external and internal vividness. Further, hippocampal connectivity with medial prefrontal regions was associated with increased ratings of internal vividness, but with decreased ratings of external vividness. These findings suggest that the hippocampus may contribute to increased internal and external vividness via distinct mechanisms and that external and internal vividness of memories should be considered as separable measures.

Accessing Real-Life Episodic Information from Minutes versus Hours Earlier Modulates Hippocampal and High-Order Cortical Dynamics.

It is well known that formation of new episodic memories depends on hippocampus, but in real-life settings (e.g., conversation), hippocampal amnesics can utilize information from several minutes earlier. What neural systems outside hippocampus might support this minutes-long retention? In this study, subjects viewed an audiovisual movie continuously for 25 min; another group viewed the movie in 2 parts separated by a 1-day delay. Understanding Part 2 depended on retrieving information from Part 1, and thus hippocampus was required in the day-delay condition. But is hippocampus equally recruited to access the same information from minutes earlier? We show that accessing memories from a few minutes prior elicited less interaction between hippocampus and default mode network (DMN) cortical regions than accessing day-old memories of identical events, suggesting that recent information was available with less reliance on hippocampal retrieval. Moreover, the 2 groups evinced reliable but distinct DMN activity timecourses, reflecting differences in information carried in these regions when Part 1 was recent versus distant. The timecourses converged after 4 min, suggesting a time frame over which the continuous-viewing group may have relied less on hippocampal retrieval. We propose that cortical default mode regions can intrinsically retain real-life episodic information for several minutes.

Adaptive top-down suppression of hippocampal activity and the purging of intrusive memories from consciousness.

When reminded of unwanted memories, people often attempt to suppress these experiences from awareness. Prior work indicates that control processes mediated by the dorsolateral prefrontal cortex (DLPFC) modulate hippocampal activity during such retrieval suppression. It remains unknown whether this modulation plays a role in purging an intrusive memory from consciousness. Here, we combined fMRI and effective connectivity analyses with phenomenological reports to scrutinize a role for adaptive top-down suppression of hippocampal retrieval processes in terminating mnemonic awareness of intrusive memories. Participants either suppressed or recalled memories of pictures depicting faces or places. After each trial, they reported their success at regulating awareness of the memory. DLPFC activation was greatest when unwanted memories intruded into consciousness and needed to be purged, and this increased engagement predicted superior control of intrusive memories over time. However, hippocampal activity was decreased during the suppression of place memories only. Importantly, the inhibitory influence of the DLPFC on the hippocampus was linked to the ensuing reduction in intrusions of the suppressed memories. Individuals who exhibited negative top-down coupling during early suppression attempts experienced fewer involuntary memory intrusions later on. Over repeated suppressions, the DLPFC-hippocampus connectivity grew less negative with the degree that they no longer had to purge unwanted memories from awareness. These findings support a role of DLPFC in countermanding the unfolding recollection of an unwanted memory via the suppression of hippocampal processing, a mechanism that may contribute to adaptation in the aftermath of traumatic experiences.

Medial temporal and neocortical contributions to remote memory for semantic narratives: Evidence from amnesia

Studies of remote memory for semantic facts and concepts suggest that hippocampal lesions lead to a temporally graded impairment that extends no more than ten years prior to the onset of amnesia. Such findings have led to the notion that once consolidated, semantic memories are represented neocortically and are no longer dependent on the hippocampus. Here, we examined the fate of well-established semantic narratives following medial temporal lobe (MTL) lesions. Seven amnesic patients, five with lesions restricted to the MTL and two with lesions extending into lateral temporal cortex (MTL+), were asked to recount fairy tales and bible stories that they rated as familiar. Narratives were scored for number and type of details, number of main thematic elements, and order in which the main thematic elements were recounted. In comparison to controls, patients with MTL lesions produced fewer details, but the number and order of main thematic elements generated was intact. By contrast, patients with MTL+ lesions showed a pervasive impairment, affecting not only the generation of details, but also the generation and ordering of main steps. These findings challenge the notion that, once consolidated, semantic memories are no longer dependent on the hippocampus for retrieval. Possible hippocampal contributions to the retrieval of detailed semantic narratives are discussed.

Competitive Trace Theory: A Role for the Hippocampus in Contextual Interference during Retrieval

Much controversy exists regarding the role of the hippocampus in retrieval. The two dominant and competing accounts have been the Standard Model of Systems Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make opposing predictions as to the necessity of the hippocampus for retrieval of remote memories. Under SMSC, memories eventually become independent of the hippocampus as they become more reliant on cortical connectivity, and thus the hippocampus is not required for retrieval of remote memories, only recent ones. MTT on the other hand claims that the hippocampus is always required no matter the age of the memory. We argue that this dissociation may be too simplistic, and a continuum model may be better suited to address the role of the hippocampus in retrieval of remote memories. Such a model is presented here with the main function of the hippocampus during retrieval being “recontextualization,” or the reconstruction of memory using overlapping traces. As memories get older, they are decontextualized due to competition among partially overlapping traces and become more semantic and reliant on neocortical storage. In this framework dubbed the Competitive Trace Theory (CTT), consolidation events that lead to the strengthening of memories enhance conceptual knowledge (semantic memory) at the expense of contextual details (episodic memory). As a result, remote memories are more likely to have a stronger semantic representation. At the same time, remote memories are also more likely to include illusory details. The CTT is a novel candidate model that may provide some resolution to the memory consolidation debate.

HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory.

The role of the hippocampus in mnemonic integration and retrieval: complementary evidence from lesion and inactivation studies

Two forms of account have been proposed for how animals form integrated memories for patterns of stimulation: the elemental account holds that the elements that make up the pattern become directly linked to one another, whereas the configural account holds that these elements become bound together through their capacity to activate a separate, shared configural memory. The hippocampus and perirhinal cortex have been linked to both elemental and configural processes. Here, we assessed the role of the rat hippocampus and perirhinal cortex in these distinct ways of processing patterns of sensory stimulation involving auditory, visual context and temporal information. Using selective lesions and inactivation techniques we identified a specific role for the hippocampus in the retrieval of configural memories but not of those that could be encoded elementally; we also identified a role for the rat perirhinal cortex in visual contextual learning. These results, using a novel combination of behavioural assays, provide clear support for the view that patterns of stimulation can be encoded either elementally or configurally, and that disruption of hippocampal function leaves rats reliant on elemental processes.

Dorsal hippocampal involvement in different forms of memory retrieval

Event Abstract Back to Event Dorsal hippocampal involvement in different forms of memory retrieval Mihaela Iordanova1*, Mark Good1, Dean Burnett1 and Robert Honey1 1 Cardiff University, School of Psychology, United Kingdom Two studies examined the role of the dorsal hippocampus in retrieval of configural memories involving which auditory stimulus (tone or clicker) was presented where (spotted or checked context) and when (morning or afternoon). We developed a novel procedure in which rats were required to learn that in the morning the tone occurred in the spotted context and the clicker in the checked context, and in the afternoon the tone occurred in the checked context and the clicker in the spotted context. Configural knowledge was revealed by pairing the tone with shock in a third context at midday, and showing that the configurations paired with the tone (morning and spotted context; afternoon and checked context) provoked the most fear at test. In Experiment 1, inactivation of the dorsal hippocampus with muscimol (a gamma-Aminobutyric acid agonist) microinfusions at test abolished retrieval of configural memories involving which stimulus was presented where and when. In Experiment 2, identical hippocampal inactivation at test, however, did not affect retrieval of which auditory stimulus was presented where (spotted or checked context) or which stimulus was presented when (morning or afternoon). Our results provide important evidence that the hippocampus is critical for the retrieval of configural memories involving what-where-when, but not other memories involving the same constituents i.e. what-where or what-when). These results are particularly consistent with the view that the hippocampus is necessary for the retrieval of configural memories with episodic content. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Iordanova M, Good M, Burnett D and Honey R (2009). Dorsal hippocampal involvement in different forms of memory retrieval. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.178 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Jun 2009; Published Online: 10 Jun 2009. * Correspondence: Mihaela Iordanova, Cardiff University, School of Psychology, Cardiff, United Kingdom, iordanovamd@cardiff.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mihaela Iordanova Mark Good Dean Burnett Robert Honey Google Mihaela Iordanova Mark Good Dean Burnett Robert Honey Google Scholar Mihaela Iordanova Mark Good Dean Burnett Robert Honey PubMed Mihaela Iordanova Mark Good Dean Burnett Robert Honey Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Learning and memory: recent findings.

Recent findings from neuroimaging, event-related potential and lesion investigations reflect a rapidly emerging view that the memory system is widely distributed throughout the cortex. It is clear that the pattern of cortical involvement during encoding and retrieval of memories is critically dependent on the nature and complexity of task demands. This has implications, both for existing models of memory function, and in the methodology of future investigations and the issues they address. No consensus has yet been reached on a number of issues, perhaps most notably the role of the hippocampus in retrieval, but advances in measurement techniques should enable some of these matters to be resolved. Further work must address the complex dynamics of the memory system, the extent to which the same regions underlie different functions, and how different regions interact and reflect common functions.

Hippocampal histamine receptors: possible role on the mechanisms of memory in the rat, II.

In this paper it was studied the role of histamine and histamine receptors in the hippocampus of rats on an active avoidance response induced by an ultrasonic tone. The animals had to learn to walk through a swinging door into a safe compartment only after the conditioning ultrasonic tone was on in order to avoid an electric shock to their feet. Trained animals were implanted in the ventral hippocampus with microinjection cannulae and injected twice with 1 microliter of saline solution containing pyrilamine (PYR, H1-HA antagonist), ranitidine (RAN, H2-HA antagonist) or histamine. The histamine antagonists were applied in a dose of 65.5 nmol each while histamine was administered in a dose of 45 nmol. The two variables measured were the time in sec the rats take to present the conditioned avoidance response and the accumulated percentage of conditioned avoidance response (CAR). Results showed that histamine administration significantly increased the latency time to escape and decreased the % CAR. These effects were not blocked by the administration of RAN. However, administration of PYR completely counteracted the HA effects. Present findings confirm our previous findings about the inhibitory effect of histamine on the hippocampal retrieval mechanisms and give further support to the hypothesis that HA acts on the memory processes in the hippocampal formation, by activation of H1-histamine receptors.