Patients with hippocampal amnesia cannot imagine new experiences.
Ontology highlight
ABSTRACT:
SUBMITTER: Hassabis D
PROVIDER: S-EPMC1773058 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed ?1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.
| S-EPMC3970513 | biostudies-literature
Project description:The necessity of the hippocampus for acquiring new semantic concepts is a topic of considerable debate. However, it is generally accepted that any role the hippocampus plays in semantic memory is time limited and that previously acquired information becomes independent of the hippocampus over time. This view, along with intact naming and word-definition matching performance in amnesia, has led to the notion that remote semantic memory is intact in patients with hippocampal amnesia. Motivated by perspectives of word learning as a protracted process where additional features and senses of a word are added over time, and by recent discoveries about the time course of hippocampal contributions to on-line relational processing, reconsolidation, and the flexible integration of information, we revisit the notion that remote semantic memory is intact in amnesia. Using measures of semantic richness and vocabulary depth from psycholinguistics and first and second language-learning studies, we examined how much information is associated with previously acquired, highly familiar words in a group of patients with bilateral hippocampal damage and amnesia. Relative to healthy demographically matched comparison participants and a group of brain-damaged comparison participants, the patients with hippocampal amnesia performed significantly worse on both productive and receptive measures of vocabulary depth and semantic richness. These findings suggest that remote semantic memory is impoverished in patients with hippocampal amnesia and that the hippocampus may play a role in the maintenance and updating of semantic memory beyond its initial acquisition.
| S-EPMC4679630 | biostudies-literature
Project description:Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n = 38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic and entorhinal cortical volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Network abnormalities may explain the variability across studies of amnesia and speak to debates in memory neuroscience.
| S-EPMC6639076 | biostudies-literature
Project description:Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8-9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by approximately 20-30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.
| S-EPMC240744 | biostudies-literature
Project description:Episodic memories formed during the first postnatal period are rapidly forgotten, a phenomenon known as 'infantile amnesia'. In spite of this memory loss, early experiences influence adult behavior, raising the question of which mechanisms underlie infantile memories and amnesia. Here we show that in rats an experience learned during the infantile amnesia period is stored as a latent memory trace for a long time; indeed, a later reminder reinstates a robust, context-specific and long-lasting memory. The formation and storage of this latent memory requires the hippocampus, follows a sharp temporal boundary and occurs through mechanisms typical of developmental critical periods, including the expression switch of the NMDA receptor subunits from 2B to 2A, which is dependent on brain-derived neurotrophic factor (BDNF) and metabotropic glutamate receptor 5 (mGluR5). Activating BDNF or mGluR5 after training rescues the infantile amnesia. Thus, early episodic memories are not lost but remain stored long term. These data suggest that the hippocampus undergoes a developmental critical period to become functionally competent.
| S-EPMC5003643 | biostudies-literature
Project description:A growing body of work suggests the hippocampus contributes to a variety of cognitive domains beyond its traditional role in memory. We propose that the hippocampus, in its capacity for relational binding, representational flexibility, and online maintenance and integration of multimodal relational representations, is a key contributor to language processing. Here we test the hypothesis that the online interpretation of pronouns is hippocampus-dependent. We combined eye tracking with neuropsychological methods, where participants (4 patients with bilateral hippocampal damage and severe declarative memory impairment, 4 patients with ventromedial prefrontal cortex [vmPFC] damage, and healthy comparison participants) viewed a scene while listening to short dialogues introducing 2 characters; for example, Melissa is playing violin for Debbie/Danny as the sun is shining overhead. She is wearing a blue/purple dress. Consistent with previous work, analysis of eye gaze showed that younger and older healthy comparison participants and the vmPFC patients rapidly identified the intended referent of the pronoun when gender uniquely identified the referent, and when it did not, they showed a preference to interpret the pronoun as referring to the first-mentioned character. By contrast, hippocampal patients, while exhibiting a similar gender effect, exhibited significant disruptions in their ability to use information about which character had been mentioned first to interpret the pronoun. This finding suggests that the hippocampus plays a role in maintaining and integrating information even over a very short discourse history. These observed disruptions in referential processing demonstrate how promiscuously the hallmark processing features of the hippocampus are used in service of a variety of cognitive domains including language.
| S-EPMC3974972 | biostudies-literature
Project description:The human hippocampus is widely believed to be necessary for the rapid acquisition of new declarative relational memories. However, processes supporting on-line inferential word use ("fast mapping") may also exercise a dissociable learning mechanism and permit rapid word learning without the hippocampus (Sharon et al. (2011) Proc Natl Acad Sci USA 108:1146-1151). We investigated fast mapping in severely amnesic patients with hippocampal damage (N = 4), mildly amnesic patients (N = 6), and healthy comparison participants (N = 10) using on-line measures (eye movements) that reflected ongoing processing. All participants studied unique word-picture associations in two encoding conditions. In the explicit-encoding condition, uncommon items were paired with their names (e.g., "This is a numbat."). In the fast mapping study condition, participants heard an instruction using a novel word (e.g., "Click on the numbat.") while two items were presented (an uncommon target such as a numbat, and a common distracter such as a dog). All groups performed fast mapping well at study, and on-line eye movement measures did not reveal group differences. However, while comparison participants showed robust word learning irrespective of encoding condition, severely amnesic patients showed no evidence of learning after fast mapping or explicit encoding on any behavioral or eye-movement measure. Mildly amnesic patients showed some learning, but performance was unaffected by encoding condition. The findings are consistent with the following propositions: the hippocampus is not essential for on-line fast mapping of novel words; but is necessary for the rapid learning of arbitrary relational information irrespective of encoding conditions.
| S-EPMC4301585 | biostudies-literature
Project description:Recent evidence suggests that the human hippocampus-known primarily for its involvement in episodic memory-plays a role in a host of motivationally relevant behaviors, including some forms of value-based decision-making. However, less is known about the role of the hippocampus in value-based learning. Such learning is typically associated with a striatal system, yet a small number of studies, both in human and nonhuman species, suggest hippocampal engagement. It is not clear, however, whether this engagement is necessary for such learning. In the present study, we used both functional MRI (fMRI) and lesion-based neuropsychological methods to clarify hippocampal contributions to value-based learning. In Experiment 1, healthy participants were scanned while learning value-based contingencies (whether players in a "game" win money) in the context of a probabilistic learning task. Here, we observed recruitment of the hippocampus, in addition to the expected ventral striatal (nucleus accumbens) activation that typically accompanies such learning. In Experiment 2, we administered this task to amnesic patients with medial temporal lobe damage and to healthy controls. Amnesic patients, including those with damage circumscribed to the hippocampus, failed to acquire value-based contingencies, thus confirming that hippocampal engagement is necessary for task performance. Control experiments established that this impairment was not due to perceptual demands or memory load. Future research is needed to clarify the mechanisms by which the hippocampus contributes to value-based learning, but these findings point to a broader role for the hippocampus in goal-directed behaviors than previously appreciated.
| S-EPMC6715285 | biostudies-literature
Project description:The hippocampus plays an essential role in the formation and retrieval of episodic memories in humans and contextual memories in animals. However, amnesia is not always observed when this structure is compromised. To determine why this is the case, we compared the effects of several different circuit manipulations on memory retrieval and hippocampal activity. Mice were first trained on context fear conditioning and then optogenetic and chemogenetic tools were used to alter activity during memory retrieval. We found that retrieval was only impaired when manipulations caused widespread changes (increases or decreases) in hippocampal activity. Widespread increases occurred when pyramidal cells were excited and widespread decreases were found when GABAergic neurons were stimulated. Direct hyperpolarization of excitatory neurons only moderately reduced activity and did not produce amnesia. Surprisingly, widespread decreases in hippocampal activity did not prevent retrieval if they occurred gradually prior to testing. This suggests that intact brain regions can express contextual memories if they are given adequate time to compensate for the loss of the hippocampus.
| S-EPMC8562570 | biostudies-literature
Project description:BackgroundLittle is known about the neural correlates of dissociative amnesia, a transdiagnostic symptom mostly present in the dissociative disorders and core characteristic of dissociative identity disorder (DID). Given the vital role of the hippocampus in memory, a prime candidate for investigation is whether total and/or subfield hippocampal volume can serve as biological markers of dissociative amnesia.MethodsA total of 75 women, 32 with DID and 43 matched healthy controls (HC), underwent structural magnetic resonance imaging (MRI). Using Freesurfer (version 6.0), volumes were extracted for bilateral global hippocampus, cornu ammonis (CA) 1-4, the granule cell molecular layer of the dentate gyrus (GC-ML-DG), fimbria, hippocampal-amygdaloid transition area (HATA), parasubiculum, presubiculum and subiculum. Analyses of covariance showed volumetric differences between DID and HC. Partial correlations exhibited relationships between the three factors of the dissociative experience scale scores (dissociative amnesia, absorption, depersonalisation/derealisation) and traumatisation measures with hippocampal global and subfield volumes.ResultsHippocampal volumes were found to be smaller in DID as compared with HC in bilateral global hippocampus and bilateral CA1, right CA4, right GC-ML-DG, and left presubiculum. Dissociative amnesia was the only dissociative symptom that correlated uniquely and significantly with reduced bilateral hippocampal CA1 subfield volumes. Regarding traumatisation, only emotional neglect correlated negatively with bilateral global hippocampus, bilateral CA1, CA4 and GC-ML-DG, and right CA3.ConclusionWe propose decreased CA1 volume as a biomarker for dissociative amnesia. We also propose that traumatisation, specifically emotional neglect, is interlinked with dissociative amnesia in having a detrimental effect on hippocampal volume.
| S-EPMC9975991 | biostudies-literature