Memories remain dynamic after consolidation, and when reactivated, they can be rendered vulnerable to various pharmacological agents that disrupt the later expression of memory (i.e., amnesia). Such drug-induced post-reactivation amnesia has traditionally been studied in AAA experimental designs, where a memory is initially created for a stimulus A (be it a singular cue or a context) and later reactivated and tested through exposure to the exact same stimulus. Using a contextual fear conditioning procedure in rats and midazolam as amnestic agent, we recently demonstrated that drug-induced amnesia can also be obtained when memories are reactivated through exposure to a generalization stimulus (GS, context B) and later tested for that same generalization stimulus (ABB design). However, this amnestic intervention leaves fear expression intact when at test animals are instead presented with the original training stimulus (ABA design) or a novel generalization stimulus (ABC design). The underlying mechanisms of post-reactivation memory malleability and of MDZ-induced amnesia for a generalization context remain largely unknown. Here, we evaluated whether, like typical CS-mediated (or AAA) post-reactivation amnesia, GS-mediated (ABB) post-reactivation amnesia displays key features of a destabilization-based phenomenon. We first show that ABB post-reactivation amnesia is critically dependent on prediction error at the time of memory reactivation and provide evidence for its temporally graded nature. In line with the known role of GluN2B-NMDA receptor activation in memory destabilization, we further demonstrate that pre-reactivation administration of ifenprodil, a selective antagonist of GluN2B-NMDA receptors, prevents MDZ-induced ABB amnesia. In sum, our data reveal that ABB MDZ-induced post-reactivation amnesia exhibits the hallmark features of a destabilization-dependent phenomenon. Implication of our findings for a reconsolidation-based account of post-reactivation amnesia are discussed.

Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following hypoxic-ischaemic events. Here, we report a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11-35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, the diencephalic structures also appear to play a role in the patients' memory deficit.

Transient global amnesia (TGA) was first described by Bender in 1956 and is characterized by sudden, temporary, and anterograde memory loss. This study aimed to explore the possible mechanisms of and lesions responsible for TGA.

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.

While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level.

This study evaluated alterations in cortical morphology in patients with transient global amnesia (TGA).

Omega-3 polyunsaturated fatty acids (PUFA) are critical for optimal brain health and are involved in psychiatric and neurological ailments. Here, we report the effects of higher endogenous omega-3 PUFA on memory impairment in the hippocampus by studying mice with transgenic expression of the fat-1 gene that converts omega-6 to omega-3 PUFA. We performed Y-maze and passive avoidance tests to evaluate the memory function of fat-1 mice treated with scopolamine. Fat-1 mice showed induced alternation in the Y-maze test and increased latency in the passive avoidance test. The effects of scopolamine on hippocampal neurogenesis were confirmed by increases in the number of Ki-67- and DCX-positive cells in the fat-1 mice. Western blotting revealed increased brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein levels, and lower scopolamine-induced apoptosis based on the cleaved-caspase 3 protein level in fat-1 mice. These findings suggest that higher endogenous omega-3 PUFA prevented granular cell loss, increased BDNF signaling, and decreased apoptosis signaling in scopolamine-treated fat-1 mice. These processes may underlie granular cell survival and suggest potential therapeutic targets for memory impairment.

The goal of the present study was to investigate spatial memory in a group of patients with amnesia due to Korsakoff's syndrome (KS). We used a virtual spatial memory task that allowed us to separate the use of egocentric and allocentric spatial reference frames to determine object locations. Research investigating the ability of patients with Korsakoff's amnesia to use different reference frames is scarce and it remains unclear whether these patients are impaired in using ego- and allocentric reference frames to the same extent. Twenty Korsakoff patients and 24 matched controls watched an animation of a bird flying in one of three trees standing in a virtual environment. After the bird disappeared, the camera turned around, by which the trees were briefly out of sight and then turned back to the center of the environment. Participants were asked in which tree the bird was hiding. In half of the trials, a landmark was shown. Half of the trials required an immediate response whereas in the other half a delay of 10 s was present. Patients performed significantly worse than controls. For all participants trials with a landmark were easier than without a landmark and trials without a delay were easier than with a delay. While controls were above chance on all trials patients were at chance in allocentric trials without a landmark present and with a memory delay. Patients showed no difference in the ego- and the allocentric condition. Together the findings suggest that despite the amnesia, spatial memory and especially the use of ego- and allocentric reference frames in Korsakoff patients are spared.

The purpose of the present study was to investigate whether amnesic patients show a bivalency effect. The bivalency effect refers to the performance slowing that occurs when switching tasks and bivalent stimuli appear occasionally among univalent stimuli. According to the episodic context binding account, bivalent stimuli create a conflict-loaded context that is re-activated on subsequent trials and thus it is assumed that it depends on memory binding processes. Given the profound memory deficit in amnesia, we hypothesized that the bivalency effect would be largely reduced in amnesic patients. We tested sixteen severely amnesic patients and a control group with a paradigm requiring predictable alternations between three simple cognitive tasks, with bivalent stimuli occasionally occurring on one of these tasks. The results showed the typical bivalency effect for the control group, that is, a generalized slowing for each task. In contrast, for amnesic patients, only a short-lived slowing was present on the task that followed immediately after a bivalent stimulus, indicating that the binding between tasks and context was impaired in amnesic patients.

Attribute amnesia describes the failure to unexpectedly report the attribute of an attended stimulus, likely reflecting a lack of working memory consolidation. Previous studies have shown that unique meaningful objects are immune to attribute amnesia. However, these studies used highly dissimilar foils to test memory, raising the possibility that good performance at the surprise test was based on an imprecise (gist-like) form of long-term memory. In Experiment 1, we explored whether a more sensitive memory test would reveal attribute amnesia in meaningful objects. We used a four-alternative-forced-choice test with foils having mis-matched exemplar (e.g., apple pie/pumpkin pie) and/or state (e.g., cut/full) information. Errors indicated intact exemplar, but not state information. Thus, meaningful objects are vulnerable to attribute amnesia under the right conditions. In Experiments 2A-2D, we manipulated the familiarity signals of test items by introducing a critical object as a pre-surprise target. In the surprise trial, this critical item matched one of the foil choices. Participants selected the critical object more often than other items. By demonstrating that familiarity influences responses in this paradigm, we suggest that meaningful objects are not immune to attribute amnesia but instead side-step the effects of attribute amnesia.

Memory and perception have long been considered separate cognitive processes, and amnesia resulting from medial temporal lobe (MTL) damage is thought to reflect damage to a dedicated memory system. Recent work has questioned these views, suggesting that amnesia can result from impoverished perceptual representations in the MTL, causing an increased susceptibility to interference. Using a perceptual matching task for which fMRI implicated a specific MTL structure, the perirhinal cortex, we show that amnesics with MTL damage including the perirhinal cortex, but not those with damage limited to the hippocampus, were vulnerable to object-based perceptual interference. Importantly, when we controlled such interference, their performance recovered to normal levels. These findings challenge prevailing conceptions of amnesia, suggesting that effects of damage to specific MTL regions are better understood not in terms of damage to a dedicated declarative memory system, but in terms of impoverished representations of the stimuli those regions maintain.

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.

Human memory is thought to depend on a circuit of connected brain regions, but this hypothesis has not been directly tested. We derive a human memory circuit using 53 case reports of strokes causing amnesia and a map of the human connectome (n = 1000). This circuit is reproducible across discovery (n = 27) and replication (n = 26) cohorts and specific to lesions causing amnesia. Its hub is at the junction of the presubiculum and retrosplenial cortex. Connectivity with this single location defines a human brain circuit that incorporates > 95% of lesions causing amnesia. Lesion intersection with this circuit predicts memory scores in two independent datasets (N1 = 97, N2 = 176). This network aligns with neuroimaging correlates of episodic memory, abnormalities in Alzheimer's disease, and brain stimulation sites reported to enhance memory in humans.

While absence attacks and complex partial seizures have been well documented in patients with epilepsy, the delineation of pure episodes of memory loss without additional clinical manifestations remains poorly characterised. The recently described condition of transient epileptic amnesia (TEA) is critically examined, and four new cases are described, in each of which there were episodes of pure memory loss which subsequently proved to be epileptic in origin. The anatomical and pathophysiological basis of TEA is presumed to be similar to transient global amnesia (TGA), that is, it is likely to be primarily hippocampal in origin, but with more variable involvement of limbic and adjacent temporal lobe neocortical structures.

To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings.

Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia.

Episodic memories formed during infancy are rapidly forgotten, a phenomenon associated with infantile amnesia, the inability of adults to recall early-life memories. In both rats and mice, infantile memories, although not expressed, are actually stored long term in a latent form. These latent memories can be reinstated later in life by certain behavioral reminders or by artificial reactivations of neuronal ensembles activated at training. Whether the recovery of infantile memories is limited by developmental age, maternal presence, or contingency of stimuli presentation remains to be determined. Here, we show that the return of inhibitory avoidance memory in rats following a behavioral reactivation consisting of an exposure to the context (conditioned stimuli [CS]) and footshock (unconditioned stimuli [US]) given in a temporally unpaired fashion, is evident immediately after US and is limited by the developmental age at which the reactivations are presented; however, it is not influenced by maternal presence or the time interval between training and reactivation. We conclude that one limiting factor for infantile memory reinstatement is developmental age, suggesting that a brain maturation process is necessary to allow the recovery of a "lost" infantile memory.

This study aimed to determine the ability of deep learning using convolutional neural networks (CNNs) to diagnose transient global amnesia (TGA) based on electroencephalography (EEG) data, and to differentiate between patients with recurrent TGA events and those with a single TGA event.

In the present study, we investigated the effects of Acori graminei rhizoma (AGR) on learning and memory for the Morris water maze task and on the central cholinergic system of the rats with excitotoxic medial septum (MS) lesion. On the water maze test, the rats were trained to find a platform that was in a fixed position during 6 days and then they received a 60 s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesioning of the MS impaired the performance on the maze test and it caused degeneration of choline acetyltransferase and acetylcholine esterase in the hippocampus, which are markers of the central cholinergic system. Daily administrations of AGR (100 mg kg(-1), i.p.) for 21 consecutive days produced reversals of the ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus that was induced by ibotenic acid. These results demonstrated that AGR ameliorated learning and memory deficits through their effects on the central nervous system, and neuroprotection was partly evaluated through the effect of AGR on the cholinergic system. Our studies suggest that AGR can possibly be used as treatment for Alzheimer's disease.

Older adults often have increasing memory problems (amnesia), and approximately 50 million people worldwide have dementia. This syndrome gradually affects a patient over a period of 10-20 years. Intelligent virtual agents may support people with amnesia.