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• 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]

See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid-negative cases whose post-positon emission tomography diagnosis remained Alzheimer's disease. While the non-amnestic and non-specific amyloid-negative cases usually showed patterns of atrophy and hypometabolism suggestive of another degenerative disorder, the amnestic amyloid-negative cases had subtle atrophy and hypometabolism, restricted to the retrosplenial/posterior cingulate cortex. Patients with a negative amyloid positon emission tomography scan following an initial clinical diagnosis of Alzheimer's disease have heterogeneous clinical presentations and neuroimaging profiles; a majority showed a clinical progression that was consistent with a neurodegenerative condition. In contrast, in the subgroup of amnestic amyloid-negative cases, the clinical presentation and follow-up usually remained consistent with Alzheimer's disease. An alternative diagnosis was not made in about half of the amnestic amyloid-negative cases, highlighting the need for a clinical framework and terminology to define these patients, who may have underlying limbic-predominant, non-amyloid-related pathologies.

It is well established that the medial temporal lobe (MTL), including the hippocampus, is essential for long-term memory. In addition, recent studies suggest that the MTL may also support visual working memory (VWM), but the conditions under which the MTL plays a critical role are not yet clear. To address this issue, we used a color change detection paradigm to examine the effects of MTL damage on VWM by analyzing the receiver operating characteristics of patients with MTL damage and healthy age- and education-matched controls. Compared to controls, patients with MTL damage demonstrated significant reductions in VWM accuracy. Importantly, the patients were not impaired at making accurate high-confidence judgments that a change had occurred; however, they were impaired when making low-confidence responses indicating that they sensed whether or not there had been a visual change. Moreover, these impairments were observed under conditions that emphasized the retrieval of complex bindings or the retrieval of high-resolution bindings. That is, patients with MTL damage exhibited VWM impairments when they were required to remember either a larger number of low-resolution bindings (i.e., set size of 5 and obvious color changes) or a smaller number of high-resolution bindings (i.e., set size of 3 and subtle color changes). The results indicate that only some VWM processes are dependent on the MTL, and are consistent with the proposal that the MTL plays a critical role in forming complex, high-resolution bindings.

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]

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]

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]

We used whole-exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in-silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole-brain analysis and meta-analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next-generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets.

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.

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 cardinal feature of Post-traumatic stress-related disorder (PTSD) is a paradoxical memory alteration including both intrusive emotional hypermnesia and declarative/contextual amnesia. Most preclinical, but also numerous clinical, studies focus almost exclusively on the emotional hypermnesia aiming at suppressing this recurrent and highly debilitating symptom either by reducing fear and anxiety or with the ethically questionable idea of a rather radical erasure of traumatic memory. Of very mixed efficacy, often associated with a resurgence of symptoms after a while, these approaches focus on PTSD-related symptom while neglecting the potential cause of this symptom: traumatic amnesia. Two of our preclinical studies have recently demonstrated that treating contextual amnesia durably prevents, and even treats, PTSD-related hypermnesia. Specifically, promoting the contextual memory of the trauma, either by a cognitivo-behavioral, optogenetic or pharmacological approach enhancing a hippocampus-dependent memory processing of the trauma normalizes the fear memory by inducing a long-lasting suppression of the erratic traumatic hypermnesia. [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]

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]

BACKGROUND: Traumatic experience can result in life-long changes in the ability to cope with future stressors and emotionally salient events. These experiences, particularly during early development, are a significant risk factor for later life anxiety disorders such as posttraumatic stress disorder (PTSD). However, because traumatic experience typically results in strong episodic memories, it is not known whether such long-term memories are necessary for particular features of PTSD, such as enhanced fear and anxiety. Here, we used a fear conditioning procedure in juvenile rats before maturation of the neural systems supporting declarative memory to assess the necessity of early memory to the later life development of PTSD-related symptoms. METHODS: Nineteen-day old rats were exposed to unpredictable and inescapable footshocks, and fear memory for the shock context was assessed during adulthood. Thereafter, adult animals were either exposed to single-trial fear conditioning or elevated plus maze or sacrificed for basal diurnal corticosterone and quantification of neuronal glucocorticoid and neuropeptide Y receptors. RESULTS: Early trauma exposed rats displayed stereotypic footshock reactivity, yet by adulthood, hippocampus-dependent contextual fear-related memory was absent. However, adult rats showed sensitized fear learning, aberrant basal circadian fluctuations of corticosterone, increased amygdalar glucocorticoid receptors, decreased time spent in the open arm of an elevated plus maze, and an odor aversion associated with early-life footshocks. CONCLUSIONS: These results suggest that traumatic experience during developmental periods of hippocampal immaturity can promote lifelong changes in symptoms and neuropathology associated with human PTSD, even if there is no explicit memory of the early trauma.

The acute phase of influenza infection is rarely associated with significant cognitive dysfunction. We describe a case of a 24 year-old man who developed global amnesia in the acute phase of influenza A infection. His deficits resolved over the course of several weeks. Transient abnormalities of diffusion and T2-weighted imaging were seen in the bilateral hippocampi. We review cerebral complications of influenza and discuss the possible role of previously proposed mechanisms in our patient's case.

Background: Morphine is wildly used as a painkiller in clinics, but causes several side effects such as hyperalgesia, depression and more notably amnesia. Here, we assumed that insulin-like Growth Factor-1 (IGF-1) as a peptide with widespread distribution of receptors in brain regions, especially hippocampus, might be capable to alleviate morphine-induced amnesia. Methods: Thirty one male Wistar rats were divided into four groups including: morphine+saline, saline+saline, Morphine+IGF-1 and Saline+IGF-1 groups. The animals were cannulated in hippocampus using stereotaxic apparatus. IGF-1 (5 μg/ 1μL /rat) was intrahippocampally injected 30 minutes prior to morphine (10 mg/kg/i.p) injection, and then rats were trained in step-through passive avoidance task. First Latency time (FLT) to enter and total time spent (TTS) in dark were measured 1.5 and 24 hours later. Control group received the same volume of saline. Results: The results showed that injection of 10 mg/kg morphine, compared with saline, significantly decreased FLT (p =0.001), but increased TTS (p =0.001) 24 hours after the training. Whereas, administration of IGF-1 compared with morphine, significantly increased FLT (p =0.001), but decreased TTS (p =0.001) assessed 24 hours after the training, Conclusions: These findings indicate that administration of morphine disturbs passive avoidance learning and memory and injection of IGF-1, 30 minutes before morphine injection, prevents amnesia.

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.

The brain's cholinergic system occupies a central role in normal cognition and age-related cognitive decline, including Alzheimer's disease (AD). This study sought to investigate the role of antioxidant defense and cholinergic systems on rutin-induced antiamnesia in mice. Rutin (1, 5, or 50 mg/kg, p.o.) or vehicle (10 ml/kg, p.o.) was administered for three consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg, i.p) was given, 5 min post-scopolamine injection, open field, Y-maze, or Morris water maze (MWM) (five days consecutive training sessions) tasks was carried out. The mice were sacrificed on day 7 to assays for biomarkers of oxidative stress and cholinergic system. Scopolamine significantly reduced spontaneous alternation behavior in Y-maze and prolonged escape latency in MWM tasks when compared to vehicle-treated control indicative of working memory and spatial learning deficits. However, the pretreatment of mice with rutin (1, 5, or 50 mg/kg) prevented scopolamine-induced working memory and spatial learning impairments without affecting spontaneous locomotor activity. Scopolamine-induced nitrosative/oxidative stress and increased acetylcholinesterase activity in the prefrontal cortex and hippocampus were significantly attenuated by the pretreatment of mice with rutin. rutin restored cognitive function in scopolamine-induced amnesia through enhancement of antioxidant defense and cholinergic systems. [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]

Transient global amnesia (TGA) is a benign memory disorder with etiologies that have been debated for a long time. The prevalence of stressful events before a TGA attack makes it hard to overlook these precipitating factors, given that stress has the potential to organically effect the brain. Cortical spreading depression (CSD) was proposed as a possible cause decades ago. Being a regional phenomenon, CSD seems to affect every aspect of the micro-mechanism in maintaining the homeostasis of the central nervous system (CNS). Corresponding evidence regarding hemodynamic and morphological changes from TGA and CSD have been accumulated separately, but the resemblance between the two has not been systematically explored so far, which is surprising especially considering that CSD had been confirmed to cause secondary damage in the human brain. Thus, by deeply delving into the anatomic and electrophysiological properties of the CNS, the CSD-TGA model may render insights into the basic pathophysiology behind the façade of the enigmatic clinical presentation. [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]

Deep inside the temporal lobe of the brain, the hippocampus has a central role in our ability to remember, imagine and dream.

The hippocampus is linked with both sleep and memory, but there is debate about whether a salient aspect of sleep – dreaming – requires its input. To address this question, we investigated if human patients with focal bilateral hippocampal damage and amnesia engaged in dreaming. We employed a provoked awakening protocol where participants were woken up at various points throughout the night, including during non-rapid eye movement and rapid eye movement sleep, to report their thoughts in that moment. Despite being roused a similar number of times, dream frequency was reduced in the patients compared to control participants, and the few dreams they reported were less episodic-like in nature and lacked content. These results suggest that hippocampal integrity may be necessary for typical dreaming to occur, and aligns dreaming with other hippocampal-dependent processes such as episodic memory that are central to supporting our mental life.

Word learning requires learners to bind together arbitrarily-related phonological, visual, and conceptual information. Prior work suggests that this binding can be robustly achieved via incidental cross-situational statistical exposure to words and referents. When cross-situational statistical learning (CSSL) is tested in the laboratory, there is no information on any given trial to identify the referent of a novel word. However, by tracking which objects co-occur with each word across trials, learners may acquire mappings through statistical association. While CSSL behavior is well-characterized, its brain correlates are not. The arbitrary nature of CSSL mappings suggests hippocampal involvement, but the incremental, statistical nature of the learning raises the possibility of neocortical or procedural learning systems. Prior studies have shown that neurological patients with hippocampal pathology have word-learning impairments, but this has not been tested in a statistical learning paradigm. Here, we used a neuropsychological approach to test whether patients with bilateral hippocampal pathology (N = 3) could learn new words in a CSSL paradigm. In the task, patients and healthy comparison participants completed a CSSL word-learning task in which they acquired eight word/object mappings. During each trial of the CSSL task, participants saw two objects on a computer display, heard one novel word, and selected the most likely referent. Across trials, words were 100% likely to co-occur with their referent, but only 14.3% likely with non-referents. Two of three amnesic patients learned the associations between objects and word forms, although performance was impaired relative to healthy comparison participants. Our findings show that the hippocampus is not strictly necessary for CSSL for words, although it may facilitate such learning. This is consistent with a hybrid account of CSSL supported by implicit and explicit memory systems, and may have translational applications for remediation of (word-) learning deficits in neurological populations with hippocampal pathology.

A recent neuropsychological study found that amnesic patients with hippocampal damage (HP) and severe declarative memory impairment produce markedly fewer responses than healthy comparison (CO) participants in a semantic feature generation task (Klooster and Duff, 2015), consistent with the idea that hippocampal damage is associated with semantic cognitive deficits. Participants were presented with a target word and asked to produce as many features of that word as possible (e.g., for target word “book,” “read words on a page”). Here, we use the response sequences collected by Klooster and Duff (2015) to develop a vector space model of semantic search. We use this model to characterize the dynamics of semantic feature generation and consider the role of the hippocampus in this search process. Both HP and CO groups tended to initiate the search process with features close in semantic space to the target word, with a gradual decline in similarity to the target word over the first several responses. Adjacent features in the response sequence showed stronger similarity to each other than to non-adjacent features, suggesting that the search process follows a local trajectory in semantic space. Overall, HP patients generated features that were closer in semantic space to the representation of the target word, as compared to the features generated by the CO group, which ranged more widely in semantic space. These results are consistent with a model in which a compound retrieval cue (containing a representation of the target word and a representation of the previous response) is used to probe semantic memory. The model suggests that the HP group's search process is restricted from ranging as far in semantic space from the target word, relative to the CO group. These results place strong constraints on the structure of models of semantic memory search, and on the role of hippocampus in probing semantic memory.

Glufosinate ammonium (GA) intoxication causes several neurologic complications. We report a rare but typical case of GA intoxication associated with anterograde amnesia and bilateral hippocampal involvement. A 53-year-old woman with GA intoxication presented to the emergency department. Initial general and neurologic examinations were unremarkable but, from the day after admission, she exhibited anterograde amnesia. On brain magnetic resonance imaging, the signal intensity in the hippocampus was symmetrically and bilaterally increased. She was discharged with no medical problems, but the anterograde amnesia remained. Eleven days after the onset of amnesia, she returned to the neurology outpatient department with persisting anterograde amnesia but improving symptoms.

Introduction: Aim of this study is to identify and describe the MRI findings in patients with Transient Global Amnesia (TGA), specifically on Diffusion Weighted Imaging (DWI) sequence. Methods: MRI findings in 12 patients with clinical diagnosis of TGA were retrospectively analysed. MRI brain was performed with a 3T scanner on 11 patients and 1.5T scanner on 1 patient. DWI were acquired at B value of 1000 s/mm2 in 4 patients, 2000 s/mm2 in 2 patients and both 1000 and 2000 s/mm2 in 6 patients. Results: There were 7 female and 5 male patients. The mean age was 65.67 years (range 61-74 years). The median time interval between the onset of symptom and MRI scan was 47.5 hours, range 25-114 hours. 11 of the 12 patients showed punctate foci of restricted diffusion in hippocampus (mean size 3.7 mm (range 2-6.5 mm). 10 patients showed foci in left hippocampus. Nine patients showed a single focus, 1 patient showed three foci and 1 patient showed four foci. In 6 patients who had DWI MRI at both B values, scans at B value of 1000 s/mm2 revealed abnormality in 4 patients, while higher B value imaging improved sensitivity in one patient and one patient had a negative scan at both B values. Conclusion: We have highlighted the MRI finding of typical punctate foci of bright signal in hippocampus seen on DWI in patients diagnosed with TGA. Detection on a routine stroke MRI protocol can avoid need for dedicated TGA protocols or repeat scan, improving the workflow.

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]

Word learning requires learners to bind together arbitrarily-related phonological, visual, and conceptual information. Prior work suggests that this binding can be robustly achieved via incidental cross-situational statistical exposure to words and referents. When cross-situational statistical learning (CSSL) is tested in the laboratory, there is no information on any given trial to identify the referent of a novel word. However, by tracking which objects co-occur with each word across trials, learners may acquire mappings through statistical association. While CSSL behavior is well-characterized, its brain correlates are not. The arbitrary nature of CSSL mappings suggests hippocampal involvement, but the incremental, statistical nature of the learning raises the possibility of neocortical or procedural learning systems. Prior studies have shown that neurological patients with hippocampal pathology have word-learning impairments, but this has not been tested in a statistical learning paradigm. Here, we used a neuropsychological approach to test whether patients with bilateral hippocampal pathology (N = 3) could learn new words in a CSSL paradigm. In the task, patients and healthy comparison participants completed a CSSL word-learning task in which they acquired eight word/object mappings. During each trial of the CSSL task, participants saw two objects on a computer display, heard one novel word, and selected the most likely referent. Across trials, words were 100% likely to co-occur with their referent, but only 14.3% likely with non-referents. Two of three amnesic patients learned the associations between objects and word forms, although performance was impaired relative to healthy comparison participants. Our findings show that the hippocampus is not strictly necessary for CSSL for words, although it may facilitate such learning. This is consistent with a hybrid account of CSSL supported by implicit and explicit memory systems, and may have translational applications for remediation of (word-) learning deficits in neurological populations with hippocampal pathology. [ABSTRACT FROM AUTHOR]

Background: Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of larger anterograde and milder retrograde amnesia that lasts up to 24 h. Objectives: We aimed to investigate the long-term risk of dementia up to 8 years in subjects with TGA. Method: We conducted a control cohort study using the Taiwan National Health Insurance Research database from 2005 to 2012 with an 8-year follow-up period. From all potential participants >18 years of age without dementia history, we identified TGA subjects and non-TGA controls with age, gender and comorbidities matched in a 1:3 ratio. The yearly incidence of dementia was compared in TGA and non-TGA cohorts. The cumulative hazard ratio (HR) of dementia was estimated. The risk factors of dementia after TGA were investigated. Results: A total of 181 TGA subjects and 543 non-TGA controls were included in the study. There were 14 dementia cases in the 181 TGA cohorts during the follow-up period with yearly incidence rates of 20.14 per 1,000 person. The adjusted HR for dementia in TGA cohorts was 2.23 (95% CI 1.12–4.44, p = 0.023) compared with non-TGA cohorts after adjusting for age, gender and comorbidities. Age and diabetes were significantly associated with dementia in TGA. Conclusions: TGA increased the long-term risk of dementia. Age and diabetes were notable factors associated with dementia after TGA. [ABSTRACT FROM AUTHOR]

Is There a Role of Epigenetically Inherited Neurogenesis on Infantile Amnesia? Even though higher rates of memory retention in young ages appear to be an adaptive advantage, hippocampal neurogenesis and infantile amnesia are widespread among mammals and are probably adaptive I per se i . Some encouraging advances are identifying that microRNAs correct processing could be related to neurogenesis regulation (Choi et al., [8]), however, a possible link between heritable microRNAs and neurogenesis is not known yet and should be a further research question together with other heritable epigenetic traits. Prenatal stress inhibits hippocampal neurogenesis but spares olfactory bulb neurogenesis. [Extracted from the article]

A recent neuropsychological study found that amnesic patients with hippocampal damage (HP) and severe declarative memory impairment produce markedly fewer responses than healthy comparison (CO) participants in a semantic feature generation task (Klooster and Duff, 2015), consistent with the idea that hippocampal damage is associated with semantic cognitive deficits. Participants were presented with a target word and asked to produce as many features of that word as possible (e.g., for target word "book," "read words on a page"). Here, we use the response sequences collected by Klooster and Duff (2015) to develop a vector space model of semantic search. We use this model to characterize the dynamics of semantic feature generation and consider the role of the hippocampus in this search process. Both HP and CO groups tended to initiate the search process with features close in semantic space to the target word, with a gradual decline in similarity to the target word over the first several responses. Adjacent features in the response sequence showed stronger similarity to each other than to non-adjacent features, suggesting that the search process follows a local trajectory in semantic space. Overall, HP patients generated features that were closer in semantic space to the representation of the target word, as compared to the features generated by the CO group, which ranged more widely in semantic space. These results are consistent with a model in which a compound retrieval cue (containing a representation of the target word and a representation of the previous response) is used to probe semantic memory. The model suggests that the HP group's search process is restricted from ranging as far in semantic space from the target word, relative to the CO group. These results place strong constraints on the structure of models of semantic memory search, and on the role of hippocampus in probing semantic memory. [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]

Semantic dementia (SD) is a clinical variant of frontotemporal lobar degeneration (FTLD) characterized by progressive deterioration of semantic memory with relative sparing of other cognitive functions. It is associated with mainly left anterior temporal atrophy, and is also referred to as "left-temporal lobe variant" of FTLD. Recently, patients with mainly right-sided atrophy, or "right-temporal lobe variant"(RTLV), have been described. While some authors have reported that the initial and most significant deficit in these right-sided cases is a difficulty in recognizing famous people, others have observed that major behavioral abnormalities are the presenting symptoms. Here we report a detailed neuropsychological, language, behavioral and neuroimaging assessment of JT, a case of right temporal lobe variant of FTLD. JT showed early and prominent behavioral changes accompanied by a severe impairment in recognizing foods by their look, flavor or name. Later she also developed a difficulty in recognizing familiar people and objects. Standardized caregiver questionnaires of JT's pre- and post-morbid personality and interpersonal functioning showed that she went from being a flexible, dominant, extraverted, person to showing rigid, submissive and introverted behaviors. Her levels of neuroticism significantly increased, while her scores on agreeableness and cognitive and emotional empathy dropped. Voxel-based morphometry (VBM) showed most significant atrophy in the right amygdala/anterior hippocampal complex and collateral sulcus, extending to the right insula. We discuss the atypical cognitive and behavioral features of this case of RTLV of FTLD and stress the importance of behavioral changes and atypical semantic deficits for early diagnosis.

A brain region known as the hippocampus is required when people assess different options before making a value-based choice.

Choosing between two items involves deliberation and comparison of the features of each item and its value. Such decisions take more time when choosing between options of similar value, possibly because these decisions require more evidence, but the mechanisms involved are not clear. We propose that the hippocampus supports deliberation about value, given its well-known role in prospection and relational cognition. We assessed the role of the hippocampus in deliberation in two experiments. First, using fMRI in healthy participants, we found that BOLD activity in the hippocampus increased as a function of deliberation time. Second, we found that patients with hippocampal damage exhibited more stochastic choices and longer reaction times than controls, possibly due to their failure to construct value-based or internal evidence during deliberation. Both sets of results were stronger in value-based decisions compared to perceptual decisions.

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.

Objective: In subjects with mild cognitive impairment (MCI), interference during memory consolidation may further degrade subsequent recall of newly learned information. We investigated whether spatial and object memory are differentially susceptible to interference.Method: Thirty-nine healthy young subjects, 39 healthy older subjects, and 12 subjects suffering from MCI encoded objects and their spatial position on a 4-by-5 grid. Encoding was followed by either: (i) a pause; (ii) an interference task immediately following encoding; or (iii) an interference task following encoding after a 6-min delay. Type of interference (no, early, delayed) was applied in different sessions and order was counterbalanced. Twelve minutes after encoding, subjects saw objects previously presented or new ones. Subjects indicated whether they recognized the object, and if so, the objects’ position during encoding.Results: Interference during consolidation provoked a negative effect on spatial memory in young more than older controls. In MCI, object but not spatial memory was affected by interference. Furthermore, a shift from fine- to coarse-grained spatial representation was observed in MCI. No differential effect of early vs. late interference (EI vs. LI) in either of the groups was detected.Conclusions: Data show that consolidation in healthy aging and MCI differs from consolidation in young controls. Data suggest differential processes underlying object and spatial memory and that these are differentially affected by aging and MCI.

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]

Objective: Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment.Method: A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined.Results: Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531).Conclusion: VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy. [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]