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Studies of the impact of brain injury on memory processes often focus on the quantity and episodic richness of those recollections. Here, we argue that the organization of one's recollections offers critical insights into the impact of brain injury on functional memory. It is well‐established in studies of word list memory that free recall of unrelated words exhibits a clear temporal organization. This temporal contiguity effect refers to the fact that the order in which word lists are recalled reflects the original presentation order. Little is known, however, about the organization of recall for semantically rich materials, nor how recall organization is impacted by hippocampal damage and memory impairment. The present research is the first study, to our knowledge, of temporal organization in semantically rich narratives in three groups: (1) Adults with bilateral hippocampal damage and severe declarative memory impairment, (2) adults with bilateral ventromedial prefrontal cortex (vmPFC) damage and no memory impairment, and (3) demographically matched non‐brain‐injured comparison participants. We find that although the narrative recall of adults with bilateral hippocampal damage reflected the temporal order in which those narratives were experienced above chance levels, their temporal contiguity effect was significantly attenuated relative to comparison groups. In contrast, individuals with vmPFC damage did not differ from non‐brain‐injured comparison participants in temporal contiguity. This pattern of group differences yields insights into the cognitive and neural systems that support the use of temporal organization in recall. These data provide evidence that the retrieval of temporal context in narrative recall is hippocampal‐dependent, whereas damage to the vmPFC does not impair the temporal organization of narrative recall. This evidence of limited but demonstrable organization of memory in participants with hippocampal damage and amnesia speaks to the power of narrative structures in supporting meaningfully organized recall despite memory impairment. [ABSTRACT FROM AUTHOR]

Decades of studies robustly support a critical role for the hippocampus in spatial memory across a wide range of species. Hippocampal damage produces clear and consistent deficits in allocentric spatial memory that requires navigating through space in rodents, non‐human primates, and humans. By contrast, damage to the hippocampus spares performance in most non‐navigational spatial memory tasks—which can typically be resolved using egocentric cues. We previously found that transient inactivation of the hippocampus impairs performance in the Hamilton Search Task (HST), a self‐ordered non‐navigational spatial search task. A key question, however, still needs to be addressed. Acute, reversible inactivation of the hippocampus may have resulted in an impairment in the HST because this approach does not allow for neuroplastic compensation, may prevent the development of an alternative learning strategy, and/or may produce network‐based effects that disrupt performance. We compared learning and performance on the HST in male rhesus macaques (six unoperated control animals and six animals that underwent excitotoxic lesions of the hippocampus). We found a significant impairment in animals with hippocampal lesions. While control animals improved in performance over the course of 45 days of training, performance in animals with hippocampal lesions remained at chance levels. The HST thus represents a sensitive assay for probing the integrity of the hippocampus in non‐human primates. These data provide evidence demonstrating that the hippocampus is critical for this type of non‐navigational spatial memory, and help to reconcile the many null findings previously reported. [ABSTRACT FROM AUTHOR]

The two most common paradigms for testing recognition memory in nonhuman primates provide conflicting evidence about its underlying neurobiology. The most widely used paradigm, preferential viewing, likely confounds memory with nonmnemonic processes like novelty processing, habituation, motivation, and others. Despite widespread use, preferential viewing correlates poorly with more traditional measures of explicit recognition. We propose that memory paradigms that require explicit choices should be preferred by researchers and weighted more heavily by readers. The two tests most widely used in nonhuman primates to assess the neurobiology of recognition memory produce conflicting results. Preferential viewing tests (e.g., visual paired comparison) produce robust impairments following hippocampal lesions, whereas matching tests (e.g., delayed nonmatching-to-sample) often show complete sparing. Here, we review the data, the proposed explanations for this discrepancy, and then critically evaluate those explanations. The most likely explanation is that preferential viewing tests are not a process-pure assessment of recognition memory, but also test elements of novelty-seeking, habituation, and motivation. These confounds likely explain the conflicting results. Thus, we propose that memory researchers should prefer explicit matching tests and readers interested in the neural substrates of recognition memory should give explicit matching tests greater interpretive weight. [ABSTRACT FROM AUTHOR]

Research on the role of the hippocampus in memory acquisition has generally focused on active learning. But to understand memory, it is at least as important to understand processes that happen offline, during both wake and sleep. In a study of patients with amnesia, we previously demonstrated that although a functional hippocampus is not necessary for the acquisition of procedural motor memory during training session, it is required for its offline consolidation during sleep. Here, we investigated whether an intact hippocampus is also required for the offline consolidation of procedural motor memory while awake. Patients with amnesia due to hippocampal damage (n = 4, all male) and demographically matched controls (n = 10, 8males) trained on the finger tapping motor sequence task. Learning was measured as gains in typing speed and was divided into online (during task execution) and offline (during interleaved 30 s breaks) components. Amnesic patients and controls showed comparable total learning, but differed in the pattern of performance improvement. Unlike younger adults, who gain speed across breaks, both groups gained speed only while typing. Only controls retained these gains over the breaks; amnesic patients slowed down and compensated for these losses during subsequent typing. In summary, unlike their peers, whose motor performance remained stable across brief breaks in typing, amnesic patients showed evidence of impaired access to motor procedural memory. We conclude that in addition to being necessary for the offline consolidation of motor memories during sleep, the hippocampus maintains access to motor memory across brief offline periods during wake. [ABSTRACT FROM AUTHOR]

A.V. is a young herpes simplex encephalitis (HSE) survivor who suffered extensive bilateral damage to the medial temporal lobe (MTL) leading to a severe and pervasive form of anterograde amnesia. Structural Magnetic Resonance Imaging (MRI) revealed lesions that encompass the hippocampus and amygdala in both hemispheres and that extend more laterally in the right temporal lobe. At the same time, detailed neuropsychological testing showed that the disparity between A.V.'s preserved intellectual functioning (Full Scale IQ: 115) and severe memory deficit (Delayed Memory Index: 42) is one of the largest on record. Despite this deficit, A.V. has regained a higher level of functioning and autonomy compared to previously documented amnesic cases with major bilateral MTL lesions. As a millennial, one advantage which A.V. has over prior amnesic cases is fluency with digital technology - particularly the smartphone. The analysis of his phone and specific app usage showed a pattern that is consistent with the strategy to offload cognitive tasks that would normally be supported by the MTL. A.V.'s behavior is significant in terms of rehabilitation and may have broader implications at the societal level and for public health given the ubiquity of smartphone technology and its potential to become integrated with neural mnemonic functions. [ABSTRACT FROM AUTHOR]

Temporal discounting (TD) represents the mental devaluation of rewards that are available after a delay. Whether the hippocampus is critical for TD remains unclear, with marked discrepancies between animal and human studies: although animals with discrete hippocampal lesions display impaired TD, human participants with similar lesions show intact performance on classic intertemporal choice tasks. A candidate explanation for this discrepancy is that delays and rewards are experienced in the moment in animal studies but tend to be hypothetical in human studies. We tested this hypothesis by examining the performance of amnesic participants with hippocampal lesions (one female, six males) on a novel experiential intertemporal choice task that used interesting photographs occluded by thick lines as rewards (Patt et al., 2021). Using a logistic function to model indifference points data, we compared performance to that on a classic intertemporal choice task with hypothetical outcomes. Participants with hippocampal lesions displayed impaired patterns of choices in the experiential task but not in the hypothetical task. Specifically, hippocampal lesions were associated with decreased amplitude of the delay-reward tradeoff, with persistent choice of the delayed option despite delay increase. These results help explain previous discrepancies across animal and human studies, indicating that the hippocampus plays a critical role in temporal discounting when the outcomes of decisions are experienced in the moment, but not necessarily when they are hypothetical. [ABSTRACT FROM AUTHOR]

Point mutations in the β2 (N265S) and β3 (N265M) subunits of γ-amino butyric acid type A receptors (GABAARs) that render them insensitive to the general anesthetics etomidate and propofol have been used to link modulation of β2-GABAARs to sedation and β3-GABAARs to surgical immobility. These mutations also alter GABA sensitivity, and mice carrying the β3-N265M mutation have been reported to have impaired baseline memory. Here, we tested the effects of the β2-N265M and β3-N265M mutations on memory, movement, hotplate sensitivity, anxiety, etomidate-induced sedation, and intrinsic kinetics. We found that both β2-N265M and β3-N265M mice exhibited baseline deficits in the Context Preexposure Facilitation Effect learning paradigm. Exploratory activity was slightly greater in β2-N265M mice, but there were no changes in either genotype in anxiety or hotplate sensitivity. β2-N265M mice were highly resistant to etomidate-induced sedation, and heterozygous mice were partially resistant. In rapid solution exchange experiments, both mutations accelerated deactivation two- to three-fold compared to wild type receptors and prevented modulation by etomidate. This degree of change in the receptor deactivation rate is comparable to that produced by an amnestic dose of etomidate but in the opposite direction, indicating that intrinsic characteristics of GABAARs are optimally tuned under baseline conditions to support mnemonic function. [ABSTRACT FROM AUTHOR]

Objective The Rey Auditory Verbal Learning Test (RAVLT) is a widely used verbal memory measure that provides scores for different aspects of memory. It involves repeated auditory presentation and recall of a 15-item word list (List A) followed by presentation and recall of a distractor list (List B) and then un-cued immediate and delayed recalls (at 15 min and 1 week) of List A as well as recognition testing. Aims of this study are to provide Italian normative data for certain RAVLT Scores and Composite Indices to improve the diagnostic accuracy of the test in clinical settings and to provide further evidence on how RAVLT can differentiate different amnesia profiles due to focal lesions. Methods We enrolled 440 healthy participants and RAVLT Single Scores and Composite Indices have been analyzed by means of multiple regression to verify the influence of age, education, and gender. Results We computed the best linear models with RAVLT Single Scores and Composite Indices, as dependent variables, and the most suitable transformation of independent variables. By reversing the signs of the regression coefficients, the adjustment factors for each level of age and, if needed, education and gender have been computed and the adjusted scores have been standardized into Equivalent Scores. Conclusion Using these standardized measures, we differentiate three profiles of amnesia due to selective hippocampal sclerosis with severe encoding deficit, fornix lesions with source memory problems, and temporal lobe epilepsy with consolidation failure. [ABSTRACT FROM AUTHOR]

Whereas both human and animal lesion and human neuroimaging studies have implicated the hippocampus in memory for associations, some studies find preserved associative memory following hippocampal damage. Starting with a classic summed similarity model of item recognition, we can account for associative recognition without assuming a specific hippocampally-mediated associative process. We add one key assumption: that one item can influence activation of another item's features. Feature-strength patterns, evaluated for each probe item individually, are then diagnostic of whether an item was paired with one item versus another. We suggest that feature-level inference, without explicit storage of associations, may play a critical role in associative recognition tasks. [ABSTRACT FROM AUTHOR]

Introduction: Transient global amnesia (TGA) is defined as a sudden and transient episode of memory loss and accompanied by temporal disorientation. However, the mechanism by which time distortion occurs is not clearly elucidated yet.Methods: Between March 2019 and November 2020, we subjected 30 TGA patients to several time perception tasks and analyzed their magnetic resonance image (MRI) scans and compared the results with age- and sex-matched control group.Results: Among the 60 recruited subjects (64.5 ± 6.3 years), 70% were women. Fourteen patients had only anterograde amnesia. Furthermore, 46% of the patients with TGA (n = 14) had a history of Valsalva maneuver, and 70% of the patients (n = 21) had a pre-attack stress factor. The MRI scans of 14 patients (46.67%) showed hippocampal hyperintensity. With regard to the time production task, patients with TGA exhibited shorter times in all trials compared with their counterparts (5 s, 4.90 ± 1.16 vs. 5.53 ± 0.87; p value = 0.02: 15 s, 12.18 ± 4.55 vs. 14.42 ± 2.54; p value = 0.021). For the time comparison task, the number of correct answers given by patients with TGA was significantly lesser than that given by the control group (6.07 ± 1.23 vs. 6.90 ± 1.24; p value = 0.006).Conclusions: This is the first study to invesgating an altered time perception in patients with TGA. Although the exact neurophysiological mechanism remains unclear, our findings could aid in the elucidation of brain function across specific time frames. [ABSTRACT FROM AUTHOR]

An episode of temporary memory loss which is recovered within 24 hours is called transient global amnesia. The etiology and triggering factors are unclear but hippocampal lesions may contribute to this condition. Diffusion-weighted magnetic resonance imaging is used to detect these lesions. In this case report, two cases with transient global amnesia who had hippocampal lesions are presented. [ABSTRACT FROM AUTHOR]

Debate continues regarding the possible role of the hippocampus across short‐term and working memory tasks. The current study examined the possibility of a hippocampal contribution to precise, high‐resolution cognition and conjunctive memory. We administered visual working memory tasks featuring a continuous response component to a well‐established developmental amnesic patient with relatively selective bilateral hippocampal damage (Jon) and healthy controls. The patient was able to produce highly accurate response judgments regarding conjunctions of color and orientation or color and location, using simultaneous or sequential presentation of stimuli, with no evidence of any impairment in working memory binding, categorical accuracy, or continuous precision. These findings indicate that hippocampal damage does not necessarily lead to deficits in high‐resolution cognitive performance, even when the damage is severe and bilateral. [ABSTRACT FROM AUTHOR]

Speakers design communication for their audience, providing more information in both speech and gesture when their listener is naïve to the topic. We test whether the hippocampal declarative memory system contributes to multimodal audience design. The hippocampus, while traditionally linked to episodic and relational memory, has also been linked to the ability to imagine the mental states of others and use language flexibly. We examined the speech and gesture use of four patients with hippocampal amnesia when describing how to complete everyday tasks (e.g., how to tie a shoe) to an imagined child listener and an adult listener. Although patients with amnesia did not increase their total number of words and instructional steps for the child listener, they did produce representational gestures at significantly higher rates for the imagined child compared to the adult listener. They also gestured at similar frequencies to neurotypical peers, suggesting that hand gesture can be a meaningful communicative resource, even in the case of severe declarative memory impairment. We discuss the contributions of multiple memory systems to multimodal audience design and the potential of gesture to act as a window into the social cognitive processes of individuals with neurologic disorders. [ABSTRACT FROM AUTHOR]

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with profound anterograde amnesia and a variable impairment of the past memory. Usually, the attacks are preceded by a precipitating event, last up to 24 h and are not associated with other neurological deficits. Diagnosis can be challenging because the identification of TGA requires the exclusion of some acute amnestic syndromes that occur in emergency situations and share structural or functional alterations of memory circuits. Magnetic Resonance Imaging (MRI) studies performed 24–96 h after symptom onset can help to confirm the diagnosis by identifying lesions in the CA1 field of the hippocampal cornu ammonis, but their practical utility in changing the management of patients is a matter of discussion. In this review, we aim to provide a practical approach to early recognition of this condition in daily practice, highlighting both the lights and the shadows of the diagnostic criteria. For this purpose, we summarize current knowledge about the clinical presentation, diagnostic pathways, differential diagnosis, and the expected long-term outcome of TGA. [ABSTRACT FROM AUTHOR]

Background and aims: Transient global amnesia (TGA) is a clinical syndrome characterized by sudden anterograde amnesia not accompanied by other neurological symptoms. There is no consensus on the underlying pathophysiological mechanism. However, diffusion-weighted imaging (DWI) of the magnetic resonance imaging (MRI) has demonstrated hippocampal lesions in as many as 50% of cases. This paper describes a series of patients with TGA and hippocampal lesions. Methods: This study assessed vascular risk factors in patients older than age 18 admitted to the Hospital Universitario San Ignacio, Bogota, Colombia, from May 2017 to June 2020 with a diagnosis of TGA and evidence of hippocampal ischemic lesion on 3 Tesla brain MRI. Results: The authors identified 36 patients, 72.2% female, with mean age 62 years. Cardiovascular risk factors, most frequently high blood pressure, carotid disease, and dyslipidemia, were present in 75% of these patients. Hippocampal lesions were unilateral in 80% of cases, with median size 2.5 mm, most frequently located at the hippocampal body. Approximately 14% of patients also presented acute ischemic lesions in locations other than the hippocampus. Conclusions: TGA is a clinical entity previously considered to have undetermined etiology. The present study used brain MRI to identify a group of patients with hippocampal ischemic lesions, finding associated vascular risk factors in a high proportion of them. [ABSTRACT FROM AUTHOR]

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a temporary memory disorder with a profound anterograde amnesia and a variable impairment of the past memory. Since the first description, dating back over 60 years, several cases have beenreported in the literature. Nevertheless, TGA remains one of the most mysterious diseases in clinical neurology. The debate regarding the etiology of this disease has focused mainly on three different mechanisms: vascular (due to venous flow changes or focal arterial ischemia), epileptic, and migraine related. However, to date there is no scientific proof of any of these mechanisms. Furthermore, the demonstration by diffusion-weighted MRI of lesions in the CA1 field of the hippocampus cornu ammonis led us to hypothesize that the selective vulnerability of CA1 neurons to metabolic stress could play a role in the pathophysiology of TGA. In this review, we summarize current knowledge on the anatomy, vascularization and function of the hippocampus. Furthermore, we discuss the emerging theories on the etiology and the pathophysiological cascade leading to an impairment of hippocampal function during the attacks. [ABSTRACT FROM AUTHOR]

Theta is one of the most prominent extracellular synchronous oscillations in the mammalian brain. Hippocampal theta relies on an intact medial septum (MS) and has been consistently recorded during the training phase of some learning paradigms, suggesting that it may be implicated in hippocampus-dependent long-term memory processing. Object recognition memory (ORM) allows animals to identify familiar items and is essential for remembering facts and events. In rodents, long-term ORM formation requires a functional hippocampus but the involvement of the MS in this process remains controversial. We found that training adult male Wistar rats in a long-term ORM-inducing learning task involving exposure to two different, but behaviorally equivalent novel stimuli objects increased hippocampal theta power, and that suppressing theta via optogenetic MS inactivation caused amnesia. Importantly, the amnesia was specific to the object the animals were exploring when the MS was inactivated. Taken together, our results indicate that the MS is necessary for long-term ORM formation and suggest that hippocampal theta activity is causally linked to this process. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a–1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested. [ABSTRACT FROM AUTHOR]

Background and Purpose: Transient global amnesia (TGA) is a rare neurological disorder causing a transient disturbance of episodic long‐term memory. Its etiology remains yet to be identified; the only consistently reported findings in patients with TGA are small hyperintense lesions in the hippocampus on diffusion‐weighted magnetic resonance imaging (DWI). The aim of this study was to define whether these lesions are subfield specific, as suggested previously. Methods: High‐resolution multiplanar reformation T1 and DWI of the hippocampus were acquired in 25 patients after TGA with a total of 43 hippocampal lesions. Hippocampal subfields were determined using the FreeSurfer software and the location of the DWI lesions was transformed to the T1 images after data co‐registration. Additionally, hippocampal subfield volumes in each patient were calculated and compared with that of 20 healthy controls. Results: Hippocampal lesions were most frequently detected in the cornu ammonis area 1 (CA1) subfield (30.2%), the hippocampal tail (28.0%), and the subiculum (21.0%); however, lesions were also found in other subfields. There was no significant difference between patients and controls concerning the volumes of the hippocampal subfields. Conclusions: Contrasting previous assumptions, we found DWI hyperintense lesions not to be restricted to the CA1 subfield. The visualization of focal hippocampal lesions on diffusion imaging located to several different hippocampal subfields suggests a potential pathophysiology of TGA independent of microstructural hippocampal anatomy and subfield‐specific vulnerability. [ABSTRACT FROM AUTHOR]

Hippocampal atrophy is a widely used biomarker for Alzheimer's disease (AD), but the cost, time, and contraindications associated with magnetic resonance imaging (MRI) limit its use. Recent work has shown that a low-cost upper extremity motor task has potential in identifying AD risk. Fifty-four older adults (15 cognitively unimpaired, 24 amnestic mild cognitive impairment, and 15 AD) completed six motor task trials and a structural MRI. Several measures of motor task performance significantly predicted bilateral hippocampal volume, controlling for age, sex, education, and memory. Thus, this motor task may be an affordable, non-invasive screen for AD risk and progression. [ABSTRACT FROM AUTHOR]

• Meal-related memory inhibits eating in humans. • Amnesia is associated with overeating and impaired interoception in humans. • Research in rodents and humans implicates the hippocampus in these effects. • Obesity disrupts memory and hippocampal functioning in rodents and humans. • These effects of obesity may create a vicious cycle that perpetuates obesity. This paper reviews evidence demonstrating a bidirectional relationship between memory and eating in humans and rodents. In humans, amnesia is associated with impaired processing of hunger and satiety cues, disrupted memory of recent meals, and overconsumption. In healthy participants, meal-related memory limits subsequent ingestive behavior and obesity is associated with impaired memory and disturbances in the hippocampus. Evidence from rodents suggests that dorsal hippocampal neural activity contributes to the ability of meal-related memory to control future intake, that endocrine and neuropeptide systems act in the ventral hippocampus to provide cues regarding energy status and regulate learned aspects of eating, and that consumption of hypercaloric diets and obesity disrupt these processes. Collectively, this evidence indicates that diet-induced obesity may be caused and/or maintained, at least in part, by a vicious cycle wherein excess intake disrupts hippocampal functioning, which further increases intake. This perspective may advance our understanding of how the brain controls eating, the neural mechanisms that contribute to eating-related disorders, and identify how to treat diet-induced obesity. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is a heterogeneous entity that can be categorized into related but different subtypes. In this study, we analyzed the gray matter structural changes of amnestic MCI (aMCI) and non-amnestic MCI (naMCI), and how it resulted in diverse cognitive impairment.Methods: Altogether 77 individuals were recruited, including 28 cognitively normal controls (NC), 25 naMCI subjects, and 24 aMCI subjects. All participants underwent a 3.0 T magnetic resonance (MR) scan and a detailed neuropsychological examination. Cortical thickness and subcortical nuclei volume were extracted by Freesurfer software and compared among groups. The areas with significant differences were further analyzed by general linear regression to identify the risk factors of each cognitive impairment subtypes.Results: Significant differences were observed in bilateral hippocampi, amygdala, thalamus, accumbens, left transverse temporal gyrus and left precuneus among groups. AMCI and naMCI were significantly different in the right hippocampus, bilateral amygdala, left precuneus, and left transverse temporal gyrus. Linear regression analysis revealed that the atrophy of left precuneus was a risk factor of memory, executive function (EF) and visuospatial impairment (p < 0.001). The atrophy of left amygdala, right accumbens and left thalamus were risk factors of memory, EF and language impairment respectively (p < 0.05).Conclusions: These findings confirmed that different gray matter structural changes could lead to specific neuropsychological features in MCI subtypes. Thorough understanding of MCI subtypes and the underlying pathology would be beneficial for precise diagnosis and intervention. [ABSTRACT FROM AUTHOR]

When considering future outcomes, humans tend to discount gains more than losses. This phenomenon, referred to as the temporal discounting sign effect, is thought to result from the greater anticipated emotional impact of waiting for a negative outcome (dread) compared to waiting for a positive outcome (mixture of savoring and impatience). The impact of such anticipatory emotions has been proposed to rely on episodic future thinking. We evaluated this proposal by examining the presence and magnitude of a sign effect in the intertemporal decisions of individuals with hippocampal amnesia, who are severely impaired in their ability to engage in episodic mental simulation, and by comparing their patterns of choices to those of healthy controls. We also measured loss aversion, the tendency to assign greater value to losses compared to equivalent gains, to verify that any reduction in the sign effect in the hippocampal lesion group could not be explained by a group difference in loss aversion. Results showed that participants with hippocampal amnesia exhibited a sign effect, with less discounting of monetary losses compared to gains, that was similar in magnitude to that of controls. Loss aversion, albeit greater in the hippocampal compared to the control group, did not account for the sign effect. These results indicate that the sign effect does not depend on the integrity of hippocampally mediated episodic processes. They suggest instead that the impact of anticipatory emotions can be factored into decisions via semantic future thinking, drawing on non-contextual knowledge about oneself. [ABSTRACT FROM AUTHOR]

Language use has long been understood to be tailored to the intended addressee, a process termed audience design. Audience design is reflected in multiple aspects of language use, including adjustments based on the addressee's knowledge about the topic at hand. In group settings, audience design depends on representations of multiple individuals, each of whom may have different knowledge about the conversational topic. A central question, then, concerns how these representations are encoded and retrieved in multiparty conversation where successful conversation requires keeping track of who knows what. In the present research, we probe the biological memory systems that are involved in this process of multiparty audience design. We present the results of two experiments that compare language use in persons with bilateral hippocampal damage and severe declarative memory impairment (amnesia), and demographically matched neurotypical comparison participants. Participants played a game in which they discussed abstract images with one partner in conversation, and then discussed the images again with the same partner or with a new partner in a three-party conversation. Neurotypical participants' language use reflected newly formed representations of which partner was familiar with which images. Participants with amnesia showed evidence of partner-specific audience design in multiparty conversation but it was attenuated, especially when success required rapid alternations between representations of common ground. The findings suggest partial independence of the formation and use of partner-specific representations from the hippocampal-dependent declarative memory system and highlight the unique contributions of the declarative memory system to flexible and dynamic language use. • Individuals with amnesia produce partner-specific language in multiparty settings. • Dynamic and flexible partner-specific language use with limited success in amnesia. • Using partner-specific knowledge is partially independent from declarative memory. [ABSTRACT FROM AUTHOR]

Little is known about the role of declarative memory in the ongoing perception of one's personality. Seven individuals who developed a rare and severe type of anterograde amnesia following damage to their medial temporal lobes were identified from our neurological patient registry. We examined the stability of their personality ratings on the Big Five Inventory over five retest periods and assessed the accuracy of their ratings via analyses of self–caregiver agreement. The patients portrayed a stable sense of self over the course of 1 year. However, their self-ratings differed from those provided by the caregivers. Intriguingly, these discrepancies diminished when caregivers retrospectively rated the patients' personalities prior to their brain injury, suggesting that patients' perceptions of themselves were stuck in the past. We interpret our findings to indicate that the ability to form new declarative memories is not required for maintaining a stable sense of self but may be important for updating one's sense of self over time. [ABSTRACT FROM AUTHOR]

Patients with Alzheimer's disease (AD) suffer from various types of memory distortions. We showed that confabulations are plausible memories, mainly reflecting the recall of repeated personal events mistakenly considered by confabulating patients as specific and unique events. The aim of this study is to see whether the notion that over-learned information interferes in episodic memory recall, as it does in confabulation, can be extended to another type of memory distortion, namely false recognition (i.e., a claim to recognize something that was not encountered previously). If this is the case, it should be expected that in an episodic recognition memory task AD patients produce more false recognition for well known non-studied, non to-be-remembered material than for unknown non-studied, non to-be-remembered material. In order to verify this prediction, AD patients and normal controls (NC) were administered two experiments. In Experiment 1, we presented pictures, of which half were supposed to be well known and the other half unknown monuments. For each picture, participants were asked to say whether or not the monument was known or not to them. Immediately following this semantic encoding task, participants were administered an episodic recognition memory task in which, in the same way as in the previous phase, among the non-studied items, half were supposed to be well known and the other half unknown. In Experiment 2 the same procedure was used employing well known and unknown symbols. It was predicted that AD patients make more false recognitions for non-studied well-known items than for non-studied unknown items. The results show that this is actually the case, suggesting that confusion between "uniqueness," i.e., specific unique events, and "multiplicity," i.e., repeated events, is also involved in false recognition. [ABSTRACT FROM AUTHOR]

Several studies pertaining to déjà vu have consistently made a connection with the perirhinal region, a region located below the hippocampus. This idea is strengthened by the fact that déjà vu is an erroneous sense of familiarity and that familiarity appears to largely depend on the perirhinal region in healthy subjects. In this context, the role of the hippocampus is particularly unclear as it is unknown whether or not it plays a role in the genesis of déjà vu. We report on the case of OHVR, an epileptic patient who suffers from severe episodic amnesia related to massive isolated bilateral damage to the hippocampus. In contrast, the perirhinal region is intact structurally and functionally. This patient reports frequent déjà vu but also another experiential phenomenon with a prominent feeling of prescience, which shows some of the characteristics of déjà vécu. She clearly distinguishes both. She also developed a form of synaesthesia by attributing affective valence to numbers. This study shows that déjà vu can occur in cases of amnesia with massively damaged hippocampi and confirms that the perirhinal region is a core region for déjà vu, using a different approach from previous reports. It also provides clues about a potential influence of hippocampal alterations in déjà vécu. [ABSTRACT FROM AUTHOR]

Déjà vu is characterised by feelings of familiarity and concurrent awareness that this familiarity is wrong. Previous neuropsychological research has linked déjà vu during seizures in individuals with unilateral temporal-lobe epilepsy (uTLE) to rhinal-cortex abnormalities, and to recognition-memory deficits that selectively affect familiarity assessment. Here, we examined whether bilateral TLE patients with déjà vu (bTLE) show a similar pattern of performance. Using two experimental tasks, we found that bTLE patients exhibit deficits not only for familiarity but also for recollection. Relative to uTLE, this broader impairment also involved hippocampal abnormalities. Our findings confirm rhinal-cortex contributions to the generation of false familiarity in déjà vu that parallel its contributions to familiarity on recognition-memory tasks. While they do not rule out a role for recollection in identifying this familiarity as wrong, the deficits observed in bTLE patients weigh against the notion that any such role is necessary for déjà vu to occur. [ABSTRACT FROM AUTHOR]

Just as hippocampal lesions are principally responsible for “temporal lobe” amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, “diencephalic” amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology. [ABSTRACT FROM AUTHOR]

Theoretical accounts of moral decision making imply distinct ways in which episodic memory processes may contribute to judgments about moral dilemmas that entail high conflict between a harmful action and a greater good resulting from such action. Yet, studies examining the status of moral judgment in amnesic patients with medial temporal lobe (MTL) lesions have yielded inconsistent results. To examine whether and how episodic processes contribute to high conflict moral decisions, amnesic patients with MTL damage and control participants were asked to judge the moral acceptability of a harmful action across two conditions that differed in the framing of the moral question. We predicted that personal (but not abstract) framing would engage episodic processes involved in mental simulation, yielding a selective impairment in MTL patients in the personal framing condition. This prediction was not confirmed as neither patients nor controls were influenced by the framing of the moral question. With the exception of a patient whose lesion extended into the amygdala bilaterally, patients were less willing than controls to endorse the utilitarian option, rejecting the harmful action despite its beneficial outcome. They also rated actions as emotionally more intense than did controls. These findings suggest that episodic processes involved in mental simulation are necessary to prospectively evaluate action‐outcome contingencies. [ABSTRACT FROM AUTHOR]

A prevailing view in cognitive neuroscience suggests that different forms of learning are mediated by dissociable memory systems, with a mesolimbic (i.e., midbrain and basal ganglia) system supporting incremental trial‐and‐error reinforcement learning and a hippocampal‐based system supporting episodic memory. Yet, growing evidence suggests that the hippocampus may also be important for trial‐and‐error learning, particularly value or reward‐based learning. In the present report, we use a lesion‐based neuropsychological approach to clarify hippocampal contributions to such learning. Six amnesic patients with medial temporal lobe damage and a group of healthy controls were administered a simple value‐based learning task involving probabilistic trial‐and‐error acquisition of stimulus–response‐outcome (reward or none) contingencies modeled after Li et al. (Proceedings of the National Academy of Sciences, 2011, 108(1), 55–60). As predicted, patients were significantly impaired on the task, demonstrating reduced learning of the contingencies. Our results provide further supportive evidence that the hippocampus' role in cognition extends beyond episodic memory tasks and call for further refinement of theoretical models of hippocampal functioning. [ABSTRACT FROM AUTHOR]

Numerous evidences suggest the existence of relationships between the impairment of episodic memory, acute stress exposure and variations in self-awareness (SA). Here, we examined 27 patients presenting transient global amnesia (TGA), a clinical condition which combines episodic amnesia and high anxiety, thanks to state and trait questionnaires of SA. We observed variation of SA depending on the stage of TGA (acute, recovery and follow-up). We also found preexisting differences in patient's awareness of their own image when the precipitating event was physical, encouraging us to give more consideration to the social determinants of stress in physiological cascade of TGA. [ABSTRACT FROM AUTHOR]

• The mammillothalamic pathway plays a key role in temporal and contextual memory. • The mammillothalamic pathway mediates hippocampo-cortical functions. • The mammillothalamic pathway plays an important role in oscillatory co- ordination. The medial diencephalon, in particular the mammillary bodies and anterior thalamic nuclei, has long been linked to memory and amnesia. The mammillary bodies provide a dense input into the anterior thalamic nuclei, via the mammillothalamic tract. In both animal models, and in patients, lesions of the mammillary bodies, mammillothalamic tract and anterior thalamic nuclei all produce severe impairments in temporal and contextual memory, yet it is uncertain why these regions are critical. Mounting evidence from electrophysiological and neural imaging studies suggests that mammillothalamic projections exercise considerable distal influence over thalamo-cortical and hippocampo-cortical interactions. Here, we outline how damage to the mammillary body-anterior thalamic axis, in both patients and animal models, disrupts behavioural performance on tasks that relate to contextual ("where") and temporal ("when") processing. Focusing on the medial mammillary nuclei as a possible 'theta-generator' (through their interconnections with the ventral tegmental nucleus of Gudden) we discuss how the mammillary body-anterior thalamic pathway may contribute to the mechanisms via which the hippocampus and neocortex encode representations of experience. [ABSTRACT FROM AUTHOR]

To understand the neural basis of episodic memory it is necessary to appreciate the significance of the fornix. This pathway creates a direct link between those temporal lobe and medial diencephalic sites responsible for anterograde amnesia. A collaboration with Andrew Mayes made it possible to recruit and scan 38 patients with colloid cysts in the third ventricle, a condition associated with variable fornix damage. Complete fornix loss was seen in three patients, who suffered chronic long-term memory problems. Volumetric analyses involving all 38 patients then revealed a highly consistent relationship between mammillary body volume and the recall of episodic memory. That relationship was not seen for working memory or tests of recognition memory. Three different methods all supported a dissociation between recollective-based recognition (impaired) and familiarity-based recognition (spared). This dissociation helped to show how the mammillary body-anterior thalamic nuclei axis, as well as the hippocampus, is vital for episodic memory yet is not required for familiarity-based recognition. These findings set the scene for a reformulation of temporal lobe and diencephalic amnesia. In this revised model, these two regions converge on overlapping cortical areas, including retrosplenial cortex. The united actions of the hippocampal formation and the anterior thalamic nuclei on these cortical areas enable episodic memory encoding and consolidation, impacting on subsequent recall. [Display omitted] • Dissociation of recall from recognition in closely matched patient groups. • Mammillary body atrophy predicts levels of episodic memory recall. • Deconstruction of Papez circuit. • Diencephalic and temporal lobe sites create vital supports in unified memory system. • Spotlight on convergent inputs to medial cortical areas for consolidation. [ABSTRACT FROM AUTHOR]

The underlying pathophysiology of Transient global amnesia (TGA) remains elusive. Reports of perfusion abnormalities in TGA were inconsistent, but semi-automated analysis of perfusion CT (CTP) may improve reliability and precision of perfusion deficit detection. Per institutional protocol, all TGA patients undergo multiphasic contrast-CT with arch to vertex CT angiography, intracranial CT venography, MRI, and EEG upon admission. During the study period consecutive patients diagnosed with TGA underwent CTP during the early acute amnestic phase. We retrospectively reviewed the clinical and radiological findings. Five patients (3 female. median age 71, range 47–74) fulfilled entry criteria. Automated CTP analysis revealed the absence of an ischemic core (defined by CBF < 30%) or conventionally defined clinically relevant hypoperfusion area (defined by Time-to-maximum (Tmax) >6 s) in any of the patients. However, four of the five patients demonstrated territories of benign oligemia defined as Tmax>4 s in areas supplied by the Posterior Cerebral Artery. Three of these four patients had clear involvement of the bilateral medial temporal lobes. None of the patients had epileptic activity on their EEG. Both CTA and MRI were normal apart for small foci of restricted diffusion in the hippocampus of four patients. Deficits in perfusion were found in the hippocampi of 60% of patients in the acute phase of TGA using automated image analysis software. This method may provide a quick and simple method to detect these abnormalities. These perfusion abnormalities could help solidify the diagnosis at an early stage and may advance our understanding of this elusive syndrome. • The underlying pathophysiology of Transient global amnesia (TGA) remains unclear. • We aim to delineate perfusion deficits in TGA patients using CT perfusion (CTP). • Automated CTP was performed in five patients during the early amnestic period (<3H). • Hypoperfusion (4/5 patients) was limited to posterior cerebral artery territories. • CTP detected medial temporal hypoperfusion in 3/5 TGA patients. [ABSTRACT FROM AUTHOR]

Background and purpose: The detection rate of diffusion‐weighted (DWI) hyperintense lesions varies widely in patients with transient global amnesia (TGA). The aim was to examine the association of hyperintense lesions on DWI magnetic resonance imaging (MRI) with patient characteristics, precipitating factors, clinical presentation and MRI settings in patients with TGA. Methods: In this multicenter retrospective observational study, using the standardized diagnosis entry system of electronic health records of four tertiary medical centers in the Kansai district of Japan, TGA patients (n = 261) who underwent brain MRI within 28 days of onset were examined. When the onset time was unavailable, the discovery time was used. Results: Diffusion‐weighted hyperintense lesions were observed in 79 patients (30%). There were no significant differences in age, sex, vascular risk factors, precipitating factors or clinical presentation between patients with and without DWI lesions. The detection rate increased linearly 24 h after onset and then reached a plateau of 60%–80% by 84 h. After 84 h, the detection rate decreased rapidly. In a multivariate logistic regression model, MRI examination 24–84 h after onset (odds ratio 7.00, 95% confidence interval 3.50–13.99) and a thin‐slice (≤3 mm) DWI sequence (odds ratio 7.59, 95% confidence interval 3.05–18.88) were independent predictors of DWI lesions. Conclusions: This study suggests that DWI hyperintense lesions in TGA are not associated with patient characteristics and clinical presentation. Brain MRI examination 24–84 h after onset and thin‐slice DWI sequences enhance the detection of DWI lesions in TGA patients. [ABSTRACT FROM AUTHOR]

The hippocampus is essential for normal memory but does not act in isolation. The anterior thalamic nuclei may represent one vital partner. Using DREADDs, the behavioral consequences of transiently disrupting anterior thalamic function were examined, followed by inactivation of the dorsal subiculum. Next, the anterograde transport of an adeno-associated virus expressing DREADDs was paired with localized intracerebral infusions of a ligand to target specific input pathways. In this way, the direct projections from the anterior thalamic nuclei to the dorsal hippocampal formation were inhibited, followed by separate inhibition of the dorsal subiculum projections to the anterior thalamic nuclei. To assay spatial working memory, all animals performed a reinforced T-maze alternation task, then a more challenging version that nullifies intramaze cues. Across all four experiments, deficits emerged on the spatial alternation task that precluded the use of intramaze cues. Inhibiting dorsal subiculum projections to the anterior thalamic nuclei produced the severest spatial working memory deficit. This deficit revealed the key contribution of dorsal subiculum projections to the anteromedial and anteroventral thalamic nuclei for the processing of allocentric information, projections not associated with head-direction information. The overall pattern of results provides consistent causal evidence of the two-way functional significance of direct hippocampal-anterior thalamic interactions for spatial processing. At the same time, these findings are consistent with hypotheses that these same, reciprocal interactions underlie the common core symptoms of temporal lobe and diencephalic anterograde amnesia. [ABSTRACT FROM AUTHOR]

Reports on social cognition in patients with developmental amnesia resulting from bilateral hippocampal lesions are rare, although the link between social cognition and temporal lobe structures is well established. We present the case of a 23-year-old male epilepsy patient, BM, with developmental amnesia due to perinatal cerebral hypoxia. The patient was examined with neuroimaging and neuropsychological methods and compared to IQ-matched patients with epilepsy to control for effects of epilepsy. In addition, we used a test battery that evaluates emotion recognition and theory of mind to study his social cognition abilities. Structural high-resolution magnetic resonance imaging showed bilateral hippocampal atrophy. The comparison to controls showed that, in addition to the well-documented memory disorders in developmental amnesia, BM showed remarkable deficits in 9 out of 17 social cognitive tasks assessing emotion recognition and theory of mind. In contrast, BM's performance on tasks of executive functions was largely preserved. The relevance of deficits in social cognition for patients with developmental amnesia is discussed. [ABSTRACT FROM AUTHOR]

Many decisions require flexible reasoning that depends on inference, generalization, and deliberation. Here, we review emerging findings indicating that the hippocampus, known for its role in long-term memory, contributes to these flexible aspects of value-based decision-making. This work offers new insights into the role of memory in decision-making and suggests that memory may shape decisions even in situations that do not appear, at first glance, to depend on memory at all. Uncovering the pervasive role of memory in decision-making challenges the way we define what memory is and what it does, suggesting that memory's primary purpose may be to guide future behavior and that storing a record of the past is just one way to do so. Memory plays a pervasive role in flexible decision-making that depends on inference, generalization, and deliberation. This function of memory in decision-making is supported by the hippocampus, suggesting that the role of the hippocampus may be to create a record of the past in the service of future behavior. This view reconciles findings from the fields of memory and decision-making. It offers new insight into why some memories are prioritized over others, why memory loss sometimes leads to impaired decision-making, and why decisions are shaped by regret and counterfactual thinking. [ABSTRACT FROM AUTHOR]

Memories for events that happen early in life are fragile—they are forgotten more quickly than expected based on typical adult rates of forgetting. Although numerous factors contribute to this phenomenon, data show that one major source of change is the protracted development of neural structures related to memory. Recent empirical studies in early childhood reveal that the development of specific subdivisions of the hippocampus (i.e., the dentate gyrus) is related directly to variations in memory. Yet, the hippocampus is only one region within a larger network supporting memory. Data from young children have also shown that activation of cortical regions during memory tasks and the functional connectivity between the hippocampus and cortex relate to memory during this period. Taken together, these results suggest that protracted neural development of the hippocampus, cortex, and connections between these regions contribute to the fragility of memories early in life and may ultimately contribute to childhood amnesia. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to study whether ultra‐high field 7 T magnetic resonance imaging (MRI) can demonstrate chronic focal defects in the hippocampus corresponding to the former acute diffusion‐weighted imaging (DWI) lesions and to assess chronic T2‐hyperintense hippocampal lesion load in transient global amnesia (TGA) patients. Methods: Follow‐up of 7 T MRI of the hippocampus was performed in 13 patients with documented hippocampal DWI lesions (detected via 3 T MRI) after acute TGA. The location of the DWI lesions was transformed to 7 T T2 images after data co‐registration. Additionally, the T2‐hyperintense lesion load was estimated in each patient and compared with that of 13 healthy controls. Results: Magnetic resonance imaging (7 T) was performed after a median of 4 months. No structural abnormality at the site of the previous TGA lesion was observed in any case. None of the controls showed DWI lesions. There was no significant difference between patients and controls concerning the number (P = 0.67) or volume (P = 0.45) of T2‐hyperintense hippocampal lesions. Conclusions: Diffusion‐weighted imaging lesions in patients with TGA do not provoke any visible sequelae and do not result in hippocampal cavities. The occurrence of incidental hippocampal T2 lesions after TGA is not more frequent than in controls. [ABSTRACT FROM AUTHOR]

Alzheimer disease is a neurodegenerative problem that progressively results in the impairment of cognitive functions in the brain. This research aimed to define neural influences of the chronic administration of the mixture Figs (Ficus carica) and Olive oil (Olea europaea) as medicinal plants to delay cholinergic abnormality and oxidative stress in amnesia induced by Scopolamine as a model of Alzheimer's disease in the hippocampus region of male Albino Rats. The rats were divided into five equal main groups (ten rats for each group): the first main group was labeled negative control receiving normal saline, rats in the second group received a dose of mixture dried Figs (F. carica) and Olive oil (4ml/kg) orally for four weeks (experientially period), the third group produced memory deficits by scopolamine (2 mg/kg, i.p at daily), the fourth group was treated using a mixture of Figs and Olive oil at daily oral dose of (4 ml/kg) followed by the intraperitoneal dose of scopolamine (2 mg/kg) for four weeks, finally, the fifth group was given an oral dose daily of (1 mg/kg) Rivastigmine and Scopolamine (2 mg/kg at daily). At the end of the experimental period (four weeks); the changes of behavioral activities and the acetylcholinesterase (AchE) levels in the homogenate hippocampus of the rats' brains were investigated. This research was to assess the efficacy of Ficus carica and Olive oil mixture on cognitive functions. The findings showed that the combination of dried Figs and Olive oil produced a considerable decrease in AchE levels in the hippocampus. The outcomes suggested that the daily administration of the mixture F. carica and Olive oil resulted in the enhancement of behavioral activities and reduction in the levels of AchE due to the antioxidant properties and protective benefits of the mixture. [ABSTRACT FROM AUTHOR]

Explanations of memory-guided navigation in rodents typically suggest that cue- and place-based navigations are independent aspects of behavior and neurobiology. The results of many experiments show that hippocampal damage causes both anterograde and retrograde amnesia (AA; RA) for place memory, but only RA for cue memory. In the present experiments, we used a concurrent cue-place water task (CWT) to study the effects of hippocampal damage before or after training on cue- and place-guided navigation, and how cue and place memory interact in damaged and control rats. We found that damaging the hippocampus before training caused a delay in the expression of cue-place navigation strategies relative to intact control animals; surprisingly, place navigation strategies emerged following pre-training hippocampal damage. With additional training, both control and damaged rats used local cues to navigate in the CWT. Damaged animals also show minor impairments in latency to navigate to the correct cue following a cue contingency reversal. By contrast to these anterograde effects, damage made after training causes RA for cue choice accuracy and latency to navigate to the correct cue. In addition, the extent of hippocampal damage predicted impairments in choice accuracy when lesions were made after training. These data extend previous work on the role of the hippocampus in cue and place memory-guided navigation, and show that the hippocampus plays an important role in both aspects of memory and navigation when present during the learning experience. • The CWT examines cue and place-based navigation in parallel and their interactions. • Pre-training versus post-training hippocampal damage differently affects the CWT. • Pre-training damage delays but does not prevent cue- or place-based strategies. • Post-training hippocampal damage impairs cue choice accuracy related to lesion size. [ABSTRACT FROM AUTHOR]

Day‐to‐day life involves the perception of events that resemble one another. For the sufficient encoding and retrieval of similar information, the hippocampus provides two essential computational processes. Pattern separation refers to the differentiation of overlapping memory representations, whereas pattern completion reactivates memories based on noisy or degraded input. Evidence from human and rodent studies suggest that pattern separation specifically relies on neuronal ensemble activity in hippocampal subnetworks in the dentate gyrus and CA3. Although a role for CA1 in pattern separation has been shown in animal models, its contribution in the human hippocampus remains elusive. In order to elucidate the contribution of CA1 neurons to pattern separation, we examined 14 patients with an acute transient global amnesia (TGA), a rare self‐limiting dysfunction of the hippocampal system showing specific lesions to CA1. Patients' pattern separation performance was tested during the acute amnestic phase and follow‐up using an established mnemonic similarity test. Patients in the acute phase showed a profound deficit in pattern separation (p < .05) as well as recognition memory (p < .001) that recovered during follow‐up. Specifically, patients tested in a later stage of the amnesia were less impaired in pattern separation than in recognition memory. Considering the time dependency of lesion‐associated hippocampal deficits in early and late acute stages of the TGA, we showed that the pattern separation function recovered significantly earlier than recognition memory. Our results provide causal evidence that hippocampal CA1 neurons are critical to pattern separation performance in humans. [ABSTRACT FROM AUTHOR]

We thank all the commentators for their thoughts on our review of Fast Mapping (FM) in adults, where we questioned the evidence that FM is a distinct learning mechanism, and urged caution over the excitement generated by the original report of FM in adults with amnesia using the fast mapping paradigm (FMP). While some commentators remain convinced that there is good evidence to support a FM process in adults, most reported a skepticism similar to ours. Here we respond to the main comments, and clarify some of the terms of debate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To emphasize the most appropriate magnetic resonance imaging (MRI) diffusion protocol for the detection of lesions that cause transient global amnesia, in order to perform an accurate examination, as well as to determine the ideal time point after the onset of symptoms to perform the examination. Materials and Methods: We evaluated five patients with a diagnosis of transient global amnesia treated between 2012 and 2015. We analyzed demographic characteristics, clinical data, symptom onset, diffusion techniques, and radiological findings. Examination techniques included a standard diffusion sequence (b value = 1000 s/mm2; slice thickness = 5 mm) and a optimized diffusion sequence (b value = 2000 s/mm2; slice thickness = 3 mm). Results: Brain MRI was performed at 24 h or 36 h after symptom onset, except in one patient, in whom it was performed at 12 h after (at which point no changes were seen) and repeated at 36 h after symptom onset (at which point it showed alterations in the right hippocampus). The standard and optimized diffusion sequences were both able to demonstrate focal changes in the hippocampi in all of the patients but one, in whom the changes were demonstrated only in the optimized sequence. Conclusion: MRI can confirm a clinical hypothesis of transient global amnesia. Knowledge of the optimal diffusion parameters and the ideal timing of diffusion-weighted imaging (> 24 h after symptom onset) are essential to improving diagnostic efficiency. [ABSTRACT FROM AUTHOR]

A 65-year-old man with no underlying medical history visited the neurology department due to transient amnesia lasting for about 8 h. During the amnesia episode, he was alert but showed repetitive questioning. The episode fulfilled the diagnostic criteria for transient global amnesia (TGA). On workups for excluding alternative diagnoses, the brain magnetic resonance imaging revealed a 3 × 6 cm-sized hemorrhagic pituitary tumor extending to the left medial temporal lobe and anterior hippocampus. The electroencephalogram revealed intermittent slowing in the left temporal region with normal backgrounds. The tumor was surgically removed and pathologically proven to be a nonfunctioning adenoma. At 6 months postoperatively, no complication or new amnestic episode occurred. Thus, our case had a typical TGA as the first manifestation of a pituitary tumor. There were no features of epileptic amnesia. Transiently altered flow status from a mass effect in the memory-eloquent area might be the possible pathogenic mechanism underlying the TGA though there still remains a probability of chance concurrence of TGA and tumor. [ABSTRACT FROM AUTHOR]

Background: Hypnotics and general anaesthetics impair memory by altering hippocampal synaptic plasticity. We recently reported on a neurosteroid analogue with potent hypnotic activity [(3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile; 3β-OH], which does not cause developmental neurotoxicity in rat pups. Here, we investigated the effects of 3β-OH on neuronal excitability in the subiculum, the major output structure of the hippocampal formation, and synaptic plasticity at two key hippocampal synapses in juvenile rats.Methods: Biophysical properties of isolated T-type calcium currents (T-currents) in the rat subiculum were investigated using acute slice preparations. Subicular T-type calcium channel (T-channel) subtype mRNA expression was compared using qRT-PCR. Using electrophysiological recordings, we examined the effects of 3β-OH and an endogenous neuroactive steroid, allopregnanolone (Allo), on T-currents and burst firing properties of subicular neurones, and on the long-term potentiation (LTP) in CA3-CA1 and CA1-subiculum pathways.Results: Biophysical and molecular studies confirmed that CaV3.1 channels represent the dominant T-channel isoform in the subiculum of juvenile rats. 3β-OH and Allo inhibited rebound burst firing by decreasing the amplitude of T-currents in a voltage-dependent manner with similar potency, with 30-80% inhibition. Both neurosteroids suppressed LTP at the CA1-subiculum, but not at the CA3-CA1 Schaffer collateral synapse.Conclusions: Neurosteroid effects on T-channels modulate hippocampal output and provide possible molecular mechanisms for the amnestic action of the novel hypnotic 3β-OH. Effects on T-channels in the subiculum provide a novel target for amnestic effects of hypnotics. [ABSTRACT FROM AUTHOR]

Highlights • Serotonergic 5-HT 6 receptor tone on memory and/or amnesia. • Dose-response curves of 5-HT 6 receptor experimental molecules. • Different intrinsic activity. • Hippocampal serotonergic tone under amnesic states. Abstract To our knowledge the intrahippocampal serotonergic 5-HT 6 receptor tone on memory and amnesia models remains unexplored. Hence, in the present work we tested intrahippocampal administration of serotonin or 5-hydroxytryptamine (5-HT) 6 receptor experimental molecules with differential intrinsic activity. Methods: In the present study, Automatized Autoshaping memory task was used, useful measuring memory, neural markers, and pharmacological effects. We are hypothesizing that experimental molecules with differential intrinsic activity might reveal serotonergic tone. Particularly, intrahippocampal administration of 5-HT 6 receptor compounds with differential intrinsic activity (i.e., agonistic and antagonistic) might evidencing a serotonergic tone via this receptor. Bilateral intrahippocampal dose-response curves show that administration of EMD386088 (10 and 100 μg) had no effect or (50 μg) decreased conditioned responses (CR) in short- and long-term memory (STM and LTM, respectively); while SB-399885 (10 or 100 μg) significantly decreased CR in STM and LTM (24 and 48-h) or (50 μg) had no effect; thus suggesting that there is a 5-HT 6 receptor tone regulating both STM and LTM. Moreover, intrahippocampal inactive doses of EMD386088 (5 μg) plus SB-399885 (0.5 μg) did not affect STM and LTM; however, partially or completely prevented the scopolamine or dizocilpine-induced amnesia. Thus confirming that both drugs exerted their effects through 5-HT 6 receptor and that there is a hippocampal serotonergic tone under amnesic states, similar to that striatal. [ABSTRACT FROM AUTHOR]