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Objective: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia., Methods: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53)., Results: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05)., Conclusions: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation., Competing Interests: Dr. Bateman has received honoraria from the North Carolina Neurological Society and the South East Area Health Education Center and from Novo Nordisk for participation in educational activities. Dr. Berman has received honoraria from the International Parkinson and Movement Disorder Society. Dr. Fox serves as a consultant for Abbott, Boston Scientific, Magnus Medical, and Soterix Medical; and he owns intellectual property on using connectivity imaging to guide brain stimulation. The other authors report no financial relationships with commercial interests.

Background: Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory., Methods: Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated., Results: Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane., Conclusions: Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We investigated whether retrograde amnesia for the stress-induced impairment of extinction retrieval shares similar characteristics with original acquisition memories. The first experiment demonstrated that cycloheximide administered shortly after a single restraint stress session alleviated the impairment of extinction retrieval but not when administered following a longer delay (i.e., the amnesia for stress is time-dependent). A second experiment showed that the retrograde amnesia for stress could be alleviated by a second brief exposure to the stressor. These results demonstrating that amnesia for stress shares characteristics similar to original memories are explained using a retrieval-based memory integration model of retrograde amnesia., (© 2024 Briggs and McMullen; Published by Cold Spring Harbor Laboratory Press.)

Experiments demonstrating post-reactivation amnesia for learned fear in animals have generated a novel and influential hypothesis on the plasticity of memory, usually referred to as memory reconsolidation. The clinical potential of pharmacologically disrupting the process of memory reconsolidation has sparked a wave of interest into whether this phenomenon can also be demonstrated in humans, and ultimately harnessed for therapeutic purposes. In this essay we outline how the work of Karim Nader and colleagues has moved the field forward from a focus on extinction learning to the prospect of disrupting memory reconsolidation. We then review some promising findings on the necessary conditions, as well as potential boundary conditions, of pharmacologically disrupting the process of memory reconsolidation obtained in our laboratory. Even though laboratory experiments in animals and humans suggest that we may be at the brink of a breakthrough in fundamentally changing emotional memories, the necessary and sufficient conditions for targeting and disrupting memory reconsolidation in clinical practice are largely unknown. There is likely no universally effective reactivation procedure for triggering the reconsolidation of clinically significant emotional memories, and the impact of subtle boundary conditions observed in basic experiments compounds this issue. Notwithstanding these challenges, the discovery of changing emotional memory through disrupting the process of memory reconsolidation has unquestionably invigorated the field., Competing Interests: Competing Interests Merel Kindt is the co-founder of Kindt Clinics, an outpatient clinic for fears and phobias where people are treated with the memory reconsolidation intervention., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Dealing with memory loss is a major challenge for older people. Coping strategies for memory problems could enable cognitively impaired people to live independently for longer. We conducted a systematic review to summarize evidence on coping strategies for older people and people with cognitive impairment to stabilize everyday life functioning., Methods: We systematically searched the databases PubMed, PsychInfo, Scopus and WebofScience using a well-defined search string. Studies were included if they were published between January 1990 and February 2021 and written in English, German, Spanish, French, or Swedish language. Two blind researchers independently checked the studies for inclusion and exclusion criteria and evaluated the quality of the studies using Critical Appraisal Skills Programme-checklists. Evidence was summarized in a narrative synthesis., Results: A total of 16 relevant studies with adequate quality were identified. These studies reported on three categories of strategies: external, internal, and behavioral coping strategies. External strategies included reminder systems and integrated features in the environment and were used by people with and without cognitive impairments. Internal strategies such as visualization, verbalization, active remembering, and systematic thinking were reported less often by people with cognitive impairment than those without cognitive impairment. Behavioral strategies such as reducing expectations and acceptance of support was most frequently reported by people with cognitive impairment., Conclusions: The findings of our systematic review show a great number of coping strategies, which seem to depend on cognitive status. Appropriate training tools incorporating these strategies should be developed., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Confabulations generally refer to the emergence of memories of experiences and events that, in reality, never took place, and which are unintentionally produced. They are frequently observed in alcoholic Korsakoff's syndrome. The aim of the current study was to validate the Nijmegen-Venray Confabulation List (NVCL), an observation scale for quantifying both spontaneous and provoked confabulations. The NVCL was completed for 252 patients with alcoholic Korsakoff's syndrome. Exploratory and confirmatory factor analyses were conducted to test three- and four-factor models of the NVCL structure. A four-factor model (provoked confabulations, spontaneous confabulations, severity of spontaneous confabulations, and distorted sense of reality) fitted the data better than the initially proposed three-factor model (provoked confabulations, spontaneous confabulations, memory, and orientation). The new instrument is therefore referred to as the NVCL-R. We encourage clinicians to include the assessment of confabulations in the neuropsychological examination, and to do so with validated instruments such as the NVCL-R.

Background: Physical exercise is suggested to be effective for preventing cognitive decline in older adults, but the relative efficacy of different types of exercise have yet to be clarified., Objective: This single-blinded randomized controlled trial was designed to investigate the differential effects of aerobic exercise training (AT), resistance exercise training (RT), and combined exercise training (CT) on cognition in older adults with subjective memory complaints (SMC)., Methods: Community-dwelling older adults with SMC (n = 415; mean age = 72.3 years old) were randomly assigned to one of the four groups: AT, RT, CT, or control group. The study consisted of two phases: a 26-week intervention and a 26-week follow-up. The participants were evaluated at baseline, 26 weeks (postintervention), and 52 weeks (follow-up). The primary outcome of this study was memory function, which was assessed using the Logical Memory II subtest of the Wechsler Memory Scale-Revised (WMS-R) score. The secondary outcomes included global cognitive function, verbal fluency, working memory, processing speed, and executive functions., Results: Intention-to-treat analysis by a mixed-effect model repeated measure showed that the AT group had significantly improved performance on the WMS-R Logical Memory II test (2.74 [1.82-3.66] points) than the control group (1.36 [0.44-2.28] points) at the postintervention assessment (p = 0.037). The effect was more pronounced in those without amnesia than those with amnesia. No significant improvement was observed in the RT and CT groups., Conclusion: This study suggests that AT intervention can improve delayed memory in community-dwelling older adults, particularly in individuals without objective memory decline.

We sought to confirm and extend the findings of studies that reported that acetylcholinesterase inhibitor drugs protect against electroconvulsive therapy (ECT)-induced cognitive impairment. We randomized 30 patients with depression (n=24) or schizophrenia (n=6) to receive either donepezil (10 mg/day; n=15) or placebo (n=15) during a fixed course of 6 thrice-weekly, modified, bifrontotemporal sine wave ECT, and for 30 days subsequently. We assessed memory using the Postgraduate Institute Memory Scale (PGI-MS) at baseline, and again at days 2, 7, and 30 after the ECT course. At baseline, memory functioning was comparable in the 2 groups. At 2 days post-ECT, memory functioning was impaired on almost all 10 subtests and on the total scale. At 30 days post-ECT, memory functioning improved to (numerically) above baseline levels on almost all subtests and on the total scale, with the bulk of the improvement evident by day 7, itself. There was no significant difference between groups in the primary outcome, improvement in PGI-MS scores between Days 2 and 30 post-ECT. On almost all subtests, also, there was no significant difference between groups. In summary, we found that donepezil (10 mg/day) did not improve memory outcomes after ECT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective : To understand the experience of people who seek help for subjective cognitive concern and memory loss, including people not referred for further assessment. To understand the patients' perspective of the medical process of receiving a cognitive assessment. This work is situated within the context of policy priorities for dementia diagnosis. Methods : Participants with and without dementia were recruited through NHS trusts and community organisations in four regional areas in England. Data were collected using longitudinal qualitative interviews. Transcript data were thematically analysed. Results : Sample of 41 people (mean 75 years, 25 dementia diagnoses). Interpretative thematic analyses focused on the presence or absence of trust in relational experiences. There were three transition points where trust could be specifically developed or undermined: (1) deciding to seek help; (2) healthcare practitioners' response to help-seeking; (3) process and outcome of assessment. Triggers for help-seeking for subjective cognitive concern were being prompted by family and knowing a relative with dementia. When participants perceived healthcare practitioners' behaviour as dismissive, they had less trust in the outcome of the healthcare encounter. Misunderstandings and absence of trust in assessment processes led to participants stating they did not fully agree with the outcomes of the assessment. Conclusions : Healthcare practitioners have an important role in supporting people with subjective cognitive concern ensuring patients have trust in assessment outcomes. Where the validity of the assessment process is seen as ambiguous, people can be left dealing with uncertainty, rather than being clear about ways they can manage their condition, situation or status.

Kent Cochrane (K.C.) has been investigated by researchers for nearly three decades after intracranial trauma from a motorcycle accident at age 30 resulted in a striking profile of amnesia. K.C. suffered severe anterograde amnesia in both verbal and non-verbal domains which was accompanied by selective retrograde amnesia for personal events experienced prior to the time of his injury (episodic memory), with relative preservation of memory for personal and world facts (semantic memory), and of implicit memory. This pattern of spared and impaired memory extended to spatial memory for large-scale environments and beyond memory to future imagining and decision-making. Post-mortem brain findings at age 62 included moderate diffuse atrophy, left orbitofrontal contusion, left posterior cerebral artery infarct, and left anterior frontal watershed infarct. Notably, there was severe neuronal loss and gliosis of the hippocampi bilaterally. The left hippocampus was severely affected anteriorly and posteriorly, but CA2, CA4, and the dentate gyrus (DG) were focally spared. There was associated degeneration of the left fornix. The right hippocampus showed near complete destruction anteriorly, with relative preservation posteriorly, mainly of CA4 and DG. Bilateral parahippocampal gyri and left anterior thalamus also showed neuron loss and gliosis. There was no evidence of co-existing neurodegenerative phenomena on beta-amyloid, phosphorylated tau, or TDP-43 immunostaining. The extent of damage to medial temporal lobe structures is in keeping with K.C.'s profound anterograde and retrograde amnesia, with the exception of the unexpected finding of preserved CA2/CA4 and DG. K.C.'s case demonstrates that relatively clean functional dissociations are still possible following widespread brain damage, with structurally compromised brain regions unlikely to be critical to cognitive functions found to be intact. In this way, the findings presented here add to K.C.'s significant contributions to our understanding of clinical-anatomical relationships in memory., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim of the Study: Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF). In this study, we aimed to demonstrate the effect of surgery on the ALF phenomena thus contributing to potential explanation of the causal mechanism., Materials and Methods: We evaluated 51 patients with TLE related to hippocampal sclerosis who had amygdalohippocampectomy and had remained seizure-free after surgery. A control group consisted of 24 healthy individuals. All were given a verbal learning test assessing recall after 30 min, 1 week and 6 weeks., Results: In our study, the Left-TLE (L-TLE) group showed a statistically significant reduction in the performance at all assessment intervals from 30 min to 1 week compared to the Right-TLE and control groups regarding verbal learning memory test (VLMT) as well as for logical memory. The forgetting rates in the VLMT from 30 min to 1 week were not statistically significantly different between all 3 groups. The logical memory test results equally showed no statistically significant difference in the forgetting rates for the 3 groups between 30 min and 1 week., Conclusions and Clinical Implications: These results may support ongoing debates assuming the initial low performance in the memory of L-TLE patients to be directly related with left hippocampal-temporal tissue loss irrespective of epileptic activity. The discovery of the ALF phenomenon explains that standard memory tests are unable to detect memory loss in some patients who are experiencing a significant level of problems with forgetfulness in their daily lives., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The objective of this work is to devise and validate a sensitive and specific test for confabulatory impairment. We conceived a screening test for confabulation, the Confabulation Screen (CS), a brief test using 10 questions of episodic memory (EM), where confabulators most frequently confabulate. It was postulated that the CS would predict confabulations not only in EM, but also in the other subordinate structures of personal temporality, namely the present and the future. Thirty confabulating amnesic patients of various aetiologies and 97 normal controls entered the study. Participants were administered the CS and the Confabulation Battery (Dalla Barba, G., & Decaix, C. (2009). "Do you remeber what you did on March 13 1985?" A case study of confabulatory hypermnesia. Cortex, 45 (5), 566-574). Confabulations in the CS positively and significantly correlated with confabulations in personal temporality domains of the CB, namely EM, orientation in time and place and episodic plans. Conversely, as expected, they did not correlate with confabulations in impersonal temporality domains of the CB. Consistent with results of previous studies, the most frequently observed type of confabulation in the CS was Habits Confabulation. The CS had high construct validity and good discriminative validity in terms of sensitivity and specificity. Cut-off scores for clinical and research purposes are proposed. The CS provides efficient and valid screening for confabulatory impairment.

A growing body of research indicates that the medial temporal lobe (MTL) is essential not only for long-term episodic memory but also for visual working memory (VWM). In particular, recent work has shown that the MTL is especially important for VWM when complex, high-resolution binding is required. However, all of these studies tested VWM for multiple items which invites the possibility that working memory capacity was exceeded and patient impairments instead reflected deficits in long-term memory. Thus, the precise conditions under which the MTL is critical for VWM and the type of working memory processes that are affected by MTL damage are not yet clear. To address these issues, we examined the effects of MTL damage on VWM for a single item (i.e., a square that contained color, location, and orientation information) using confidence-based receiver operating characteristic methods to assess VWM discriminability and to separate perceiving- and sensing-based memory judgments. This approach was motivated by dual-process theories of cognition that posit distinct subprocesses underlie performance across perception, working memory, and long-term memory. The results indicated that MTL patients were significantly impaired in VWM for a single item. Interestingly, the patients were not impaired at making accurate high-confidence judgments that a change had occurred (i.e., perceiving), rather they were impaired at making low-confidence judgments that they sensed whether or not there had been a change in the absence of identifying the exact change. These results demonstrate that the MTL is critical in supporting working memory even for a single item, and that it contributes selectively to sensing-based discriminations., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Administration of 5-HT receptor antagonist to snails trained in conditioned food aversion prior to reminding of the conditioning stimulus caused amnesia. At the early period of amnesia (day 3), injections of protein synthesis inhibitor cycloheximide without reminder or reminder alone were ineffective. At the same time, injections of the inhibitor combined with reminder led to memory recovery; this effect in most animals persisted for at least 10 days. In the rest snails, aversive responses to presentations of the conditioning stimulus persisted for 2 days. Cycloheximide injection and reminder in 10 days after induction of amnesia did not affect its development or caused a transient memory recovery (2 days). We hypothesized that amnesia is an active process unfolding in time. One of mechanism of this process is reminder-induced and protein synthesis-depended reactivation of amnesia. Inhibitor of protein synthesis disturbed this reactivation and led to recovery of the initial memory of conditioned food aversion.

Current theory has divided memory into multiple systems, resulting in a fractionated account of human behaviour. By an alternative perspective, memory is a single system. However, debate over the details of different single-system theories has overshadowed the converging agreement among them, slowing the reunification of memory. Evidence in favour of dividing memory often takes the form of dissociations observed in amnesia, where amnesic patients are impaired on some memory tasks but not others. The dissociations are taken as evidence for separate explicit and implicit memory systems. We argue against this perspective. We simulate two key dissociations between classification and recognition in a computational model of memory, A Theory of Nonanalytic Association. We assume that amnesia reflects a quantitative difference in the quality of encoding. We also present empirical evidence that replicates the dissociations in healthy participants, simulating amnesic behaviour by reducing study time. In both analyses, we successfully reproduce the dissociations. We integrate our computational and empirical successes with the success of alternative models and manipulations and argue that our demonstrations, taken in concert with similar demonstrations with similar models, provide converging evidence for a more general set of single-system analyses that support the conclusion that a wide variety of memory phenomena can be explained by a unified and coherent set of principles.

The involvement of protein synthesis in the mechanisms of conditioned food aversion memory impairment and recovery in grape snails was studied. It was found that protein synthesis inhibitor (cycloheximide) injections before a reminder by the conditioned stimulus (CS) caused amnesia development. Three days after amnesia induction, injections of cycloheximide or another protein synthesis inhibitor, anisomycin, combined with a reminder by four CSs resulted in memory retrieval, which was saved for 24 h. Cycloheximide injections and the administration of one CS as a reminder to an amnestic animals caused the memory expression only in response to this CS, while it was absent the next day. The isolated administration of a reminder or inhibitor injections without a reminder was not effective. It is suggested that amnesia is an active process and that one of its mechanisms may be a protein-dependent amnesia reactivation caused by a reminder. The administration of protein synthesis inhibitors led to impairment of amnesia reactivation and to recovery of the state formed before amnesia induction and thus to the recovery of conditioned food aversion memory., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Whether accelerated long-term forgetting (ALF) and classic organic amnesia, particularly hippocampal-amnesia, differ qualitatively or merely quantitatively is disputed. Qualitative difference accounts postulate that ALF patients show normal recall memory for at least minutes, during which hippocampal-amnesics already show accelerated forgetting and impaired recall but, thereafter, ALF patients show accelerated forgetting and impaired delayed recall. These delayed impairments may be more severe than those shown by hippocampal-amnesics. In contrast, quantitative difference accounts postulate that ALF patients merely have mild hippocampal-amnesia, so their later forgetting rates and recall levels are sub-normal but always better than those of hippocampal-amnesics with worse initial recall levels (i.e., there is no cross-over in forgetting rates at longer delays). Many ALF studies in people with epilepsy have demonstrated evidence of a single dissociation-with accelerated delayed forgetting relative to healthy controls. Even when initial recall seems genuinely normal, uncompromised by patients needing more learning trials or showing below-average performance on more demanding recall tests, without further evidence, a quantitative interpretation remains possible. Resolution of the dispute requires evidence of a double dissociation between ALF patients and hippocampal-amnesics with more impaired initial recall in a comparison also involving matched controls. The only two studies that have made this comparison found that there was a cross-over interaction between initial and delayed recall in the ALF and amnesic patients, inconsistent with quantitative difference accounts. The functional and pathological conditions underlying this cross-over effect need to be systematically explored, controlling for potential methodological confounds, in temporal lobe epilepsy and transient epileptic amnesia as well as non-epileptic conditions. Future research must also explore under what conditions, if any, milder hippocampal-amnesics show relatively normal delayed forgetting of recall, and for how long, if at all, ALF patients show completely normal recall. Relatedly, the functional and pathological heterogeneity of ALF needs systematic exploration., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Visual statistical learning (VSL) refers to the learning of environmental regularities. Classically considered an implicit process, one patient with isolated hippocampal damage is severely impaired at VSL tasks, suggesting involvement of explicit memory. Here, we asked whether memory impairment (MI) alone, absent of clear hippocampal pathology, predicted deficits across different VSL tasks. A classic VSL task revealed no learning in MI participants (Exp. 1), while imposing attentional demands (Exp. 2: flicker detection, Exp. 3: gender/location categorization) during familiarization revealed modest residual VSL. MI with nonspecific neural correlates predicted impaired VSL overall, but attentional processes may be harnessed for rehabilitation.

When individuals select the recently studied (and familiar) item in a multiple-choice memory test, they direct a greater proportion of viewing time toward the to-be-selected item when their choice is correct than when their choice is incorrect. Thus, for both correct and incorrect choices, individuals indicate that the chosen item is old, but viewing time nevertheless distinguishes between old and new items. What kind of memory supports this preferential viewing effect? We recorded eye movements while participants made three-alternative, forced-choice recognition memory judgments for scenes. In experiment 1 ( n = 30), the magnitude of the preferential viewing effect was strongly correlated with measures of conscious, declarative memory: recognition accuracy as well as the difference in confidence ratings and in response times for correct and incorrect choices. In four analyses that minimized the contribution of declarative memory in order to detect a possible contribution from other processes, the preferential viewing effect was absent. In experiment 2, five memory-impaired patients with medial temporal lobe lesions exhibited a diminished preferential viewing effect. These patients also exhibited poor recognition accuracy and reduced differences in confidence ratings and response times for correct and incorrect choices. We propose that the preferential viewing effect is a phenomenon of conscious, declarative memory and is dependent on the medial temporal lobe. The findings support the link between medial temporal lobe function and declarative memory. When the effects of experience depend on the medial temporal lobe, the effects reflect conscious memory., Competing Interests: The authors declare no conflict of interest.

Technology allowing genetically targeted cells to be modulated by light has revolutionized neuroscience in the past decade, and given rise to the field of optogenetic stimulation. For this, non-native, light activated proteins (e.g., channelrhodopsin) are expressed in a specific cell phenotype (e.g., glutamatergic neurons) in a subset of central nervous system nuclei, and short pulses of light of a narrow wavelength (e.g., blue, 473 nm) are used to modulate cell activity. Cell activity can be increased or decreased depending on which light activated protein is used. We review how the greater precision provided by optogenetics has transformed the study of neural circuits, in terms of cognition and behavior, with a focus on learning and memory. We also explain how optogenetic modulation is facilitating a better understanding of the mechanistic underpinnings of some neurological and psychiatric conditions. Based on this research, we suggest that optogenetics may provide tools to improve memory in neurological conditions, particularly diencephalic amnesia and Alzheimer's disease., (© 2018 Wiley Periodicals, Inc.)

Alzheimer's disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis, and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity, and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated proinflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12 month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored. Initially, S100A9 fibrils were morphologically verified by atomic force microscopy and Thioflavin T assay. They were then administered intranasally alone or with Glu-Abs for 14 days followed by a 5 day MWM protocol before hippocampal and prefrontal cortical neurochemical analysis. S100A9 aggregates evoked spatial amnesia which correlated with disrupted glutamate and dopaminergic neurochemistry. Hippocampal glutamate release, elevation of DOPAC and HVA, as well as DOPAC/DA and HVA/DA ratios were subsequently reduced by Glu-Abs which simultaneously prevented the spatial memory deficit. The present outcomes emphasized the pathogenic nature of S100A9 fibrillar aggregates in causing spatial memory amnesia associated with enhanced hippocampal glutamate release and DA-ergic disruption in the aging brain. This finding might be exploited during dementia management through a neuroprotective strategy.

Objective: Brahmi vati (BV) is an Ayurvedic polyherbal formulation used since ancient times and has been prescribed in seizures associated with schizophrenia and related memory loss by Ayurvedic practitioners in India. The aim of the study was to investigate these claims by evaluation of anticonvulsant, antischizophreniac, and memory-enhancing activities. Antioxidant condition of brain was determined by malondialdehyde (MDA) and reduced glutathione (GSH) levels estimations. Acetylcholinesterase (AChE) was quantitatively estimated in the brain tissue., Methods: Brahmi vati was prepared in-house by strictly following the traditional Ayurvedic formula. Bacoside A rich fraction (BA) of Bacopa monnieri was prepared by extraction and fractionation. It was than standardized by High Performance Liquid Chromatography (HPLC) and given in the dose of 32.5mg/kg body weight to the different groups of animals for 7days. On the seventh day, activities were performed adopting standard procedures., Key Findings: Brahmi vati showed significant anticonvulsant, memory-enhancing and antischizophrenia activities, when compared with the control groups and BA. It cause significantly higher brain glutathione levels. Acetylcholinesterase activity was found to be significantly low in BV-treated group., Conclusion: The finding of the present study suggests that BV may be used to treat seizures associated with schizophrenia and related memory loss., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Positive allosteric modulators of AMPA receptors (AMPA-PAMs) are described to facilitate cognitive processes in different memory-based models. Among them, S 47445 is a novel potent and selective AMPA-PAM. In order to assess its efficacy after repeated administration, S 47445 effect was evaluated in two aging-induced memory dysfunction tasks in old mice, one short-term working memory model evaluated in a radial maze task and one assessing contextual memory performance. S 47445 was shown to improve cognition in both models sensitive to aging. In fact, administration of S 47445 at 0.3 mg/kg (s.c.) reversed the age-induced deficits of the working memory model whatever the retention interval. Moreover, in the contextual task, S 47445 also reversed the age-induced deficit at all tested doses (from 0.03 to 0.3 mg/kg, p.o.). Since donepezil, an acetylcholinesterase inhibitor, induces only moderate symptomatic effects on memory in Alzheimer's disease patients, an alternative strategy for treatment of cognitive symptoms could be to act simultaneously on both glutamatergic AMPA receptors and cholinergic pathways by combining pharmacological treatments. The present study further examined such effects by assessing combinations of S 47445 and donepezil given orally during 9 days in aged C57/Bl6J mice using contextual memory task (CSD) and the working memory model of serial alternation task (AT). Interestingly, a significant synergistic memory-enhancing effect was observed with the combination of donepezil at 0.1 mg/kg with S 47445 at 0.1 mg/kg p.o. in the CSD or with S 47445 at 0.1 and 0.3 mg/kg in AT in comparison to compounds given alone and without any pharmacokinetic interaction.

Memory complaints and deficits are common in patients with epilepsy, especially temporal lobe epilepsy (TLE), where memory-related brain structures are directly involved in the epileptic process. In recent years, substantial progress has been made in delineating memory impairment in TLE, challenging the traditional neuropsychological approach of the disorder. In particular, several lines of evidence have suggested that, beyond the apparent deficit demonstrable by standardized neuropsychological evaluations, TLE may also negatively interact with long-term memory, producing considerable loss of information of the patient's autobiographical history and an inability to maintain newly acquired information over a period of time. These observations have led to the development of innovative assessment techniques, and prompted a new domain of investigation focused on the relationships between interictal epileptiform activities and the integrity of anatomo-functional systems. The present paper reviews the available evidence for long-term memory deficits in TLE with respect to remote and very long-term memory, and discusses their putative pathophysiological mechanisms and the developing potential strategies to improve memory functioning., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Humanin (HN) is an endogenous 24-residue peptide. A highly potent HN derivative, S14G-HN, which has a substitution of serine 14 to glycine, reduced amyloid burden and suppressed cognitive impairment in a mouse model of Alzheimer's disease. S14G-HN also suppressed amnesia induced by a muscarinic receptor antagonist in rodents. To understand the effects of HN on brain function, we tested the effect of S14G-HN on diazepam (DZP)-induced memory impairment and anxiety in mice using the object recognition test and zero-maze test, respectively. Intraperitoneal injection of S14G-HN reversed the DZP-induced memory deficit, whereas no significant change was observed in behavioral markers of anxiety. S14G-HN had no effect on locomotor activity in either test, indicating that S14G-HN did not affect physical functioning or motivation. These results suggest that HN preferentially influences cognitive function but not emotional function in the central nervous system., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Intrusions on verbal memory tests have been used as an index for clinical confabulation. Severe memory impairments in combination with executive dysfunction have been suggested to be the underlying mechanism of confabulation, but to date, this relation is unclear. The aim of this study was (a) to examine the relation between (different types of) intrusions and confabulations in a large sample of confabulating patients with Korsakoff's syndrome (KS) and (b) to investigate whether different measures of executive functioning and memory performance are related to provoked and spontaneous confabulation., Method: The Dutch version of the California Verbal Learning Test (CVLT) and various executive function and memory tests were administered to a group of 51 confabulating patients with KS. Professional caregivers rated the severity of provoked and spontaneous confabulation behavior of the patients using the Nijmegen-Venray Confabulation List-20 (NVCL-20)., Results: The total number of intrusions on the CVLT was not related to either provoked or spontaneous confabulation scores. None of the CVLT intrusion scores correlated significantly with any of the confabulation scores, but we did find small-to-medium, positive correlations between unrelated intrusions and both provoked confabulations and spontaneous confabulation. Provoked confabulation behavior was associated with executive dysfunction and poorer memory performances. Spontaneous confabulation was not related to performance on measures of executive function and memory., Conclusions: The total number of intrusions on verbal memory tests and clinical confabulations appear to be different phenomena. Only unrelated intrusions produced on the CVLT might possibly be related to confabulations. The production of provoked, but not spontaneous, confabulation is associated with executive dysfunction and memory deficits.

Confabulation, the production of statements and actions that are unintentionally incongruous to the subject's history, background, present and future situation, is a rather infrequent disorder, observed in several conditions affecting the nervous system. Little is known about the quantitative and qualitative evolution of confabulation in time. In this study we evaluated longitudinally the evolution of this disorder in a group of severe confabulators, using the Confabulation Battery (CB), a sensitive tool to detect confabulations in various memory domains. It was found that confabulations were stable over time and not temporally limited. It was also found that "Habits Confabulations" (HCs), i.e., habits and repeated personal events mistaken as specific, unique past and future personal episodes, or well-known public events when semantic knowledge is concerned, was the more frequently observed type of confabulation. Confabulations were also more prominent in the domain of Temporal Consciousness (TC), i.e., a specific form of consciousness that allows individuals to remember their personal past, to be oriented in their present world and to predict their personal future, than in Knowing Consciousness (KC), i.e., a specific form of consciousness allowing individuals to be aware of past, present and future impersonal knowledge and information. Confabulations showed also persistence, i.e., confabulations at the same questions over time, and consistency, i.e., same type of confabulation at the same question over time. These findings are discussed within the framework of the Memory, Consciousness and Temporality Theory., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Anoxia can result in selective hippocampal damage with associated impairments in declarative memory. Whilst memory impairments and brain structures are thought to be stable, there are little data regarding the effects of ageing or change over time in patients with amnesia from anoxic brain injury., Methods: To assess change over time, we compared structural magnetic resonance imaging (MRI) with data obtained over ten years previously in two well-characterized patients with amnesia (JRW and RS) who experienced an anoxic brain injury. Six healthy, age-matched control participants were recruited to compare brain volumes with the patients at Time 2. Wechsler adult intelligence scale-revised and Wechsler memory scale-revised scores were compared to scores on the same tests administered 13 and 19 years prior., Results: Patients with amnesia had significantly smaller hippocampal volumes than controls, but comparable medial temporal lobe and ventricular volumes. Memory, intellectual function and brain volumes were stable over time., Conclusion: Patients with an amnesia due to anoxia have memory impairments and smaller hippocampal volumes compared to controls; however, memory, intelligence and structural volumes remain stable over time. At ages 50 and 57, they do not appear to have early age-associated cognitive decline that is sometimes observed in patients with traumatic brain injury.

The Medio-Dorsal Nuclei (MDN) including the thalamic magnocellular and parvocellular thalamic regions has been implicated in verbal memory function. In a 77 year old lady, with a prior history of a clinically silent infarct of the left MDN, we observed the acute onset of spontaneous confabulations when an isolated new infarct occurred in the right MDN. The patient and five age-matched healthy subjects underwent Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI). The thalamic lesions were localized by overlapping Morel Thalamic Atlas with structural MRI data. DTI was used to assess: i) white matter alterations (Fractional Anisotropy, FA) within fibers connecting the ischemic areas to cortex; ii) the micro-structural damage (Mean Diffusivity) within the thalamic sub-regions defined by their structural connectivity to the Anterior Cingulate Cortex (ACC) and to the temporal lobes. These target regions were chosen because their damage is considered associated with the appearance of confabulations. Thalamic lesions were localized within the parvocellular regions of the right and left MDNs. The structural connectivity study showed that the fiber tracts, connecting the bilaterally damaged thalamic regions with the frontal cortex, corresponded to the anterior thalamic radiations (ATR). FA within these tracts was significantly lower in the patient as compared to controls. Mean diffusivity within the MDNs projecting to Broadman area (BA) 24, BA25 and BA32 of ACC was significantly higher in the patient than in control group. Mean diffusivity values within the MDN projecting to temporal lobes in contrast were not different between patient and controls. Our findings suggest the involvement of bilateral MDNs projections to ACC in the genesis of confabulations and help provide clarity to the longstanding debate on the origin of confabulations.

Our day-to-day experiences are often similar to one another, occurring in the same place at the same time of day, with common people and objects, and with a shared purpose. Humans have an episodic memory to represent unique, personal events that are rich in detail [1]. For this to occur, at least two basic neural mechanisms are required: one to orthogonalize or "separate" overlapping input patterns at encoding and another to reinstate or "complete" memories from partial cues at retrieval [2-6]. To what extent do these purported "pattern separation" and "pattern completion" mechanisms rely on distinct subfields of the hippocampus [6]? Computational models [4-6] and lesion and genetic studies in rodents [7-12] largely point to the dentate gyrus as responsible for pattern separation and the CA3 and CA1 subfields for pattern completion (but see [13-16]). In high-resolution fMRI studies of humans, behavioral discrimination and completion tasks designed to approximate pattern separation and pattern completion, respectively, elicit the predicted pattern of activity in the dentate gyrus and CA3/CA1 [17-21]. Likewise, impaired behavioral discrimination has been demonstrated in individuals with hippocampal lesions [22, 23], but the lesions most likely encompass other subfields. Examination of these processes in individuals with selective lesions to hippocampal subfields is needed to infer causation [19]. Here, we report the rare case of BL, a 54-year-old man with bilateral ischemic lesions to the hippocampus [24] primarily affecting the dentate gyrus. Studying BL provides the unique opportunity to directly evaluate theories of hippocampal function that assign the dentate gyrus a specific role in discriminating old from new memories., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Recollection is used to refer to the active process of setting up retrieval cues, evaluating the outcome, and systematically working toward a representation of a past experience that we find acceptable. In this study we report on three patients showing different patterns of confabulation affecting recollection and consciousness differentially. All patients confabulated in the episodic past domain. However, whereas in one patient confabulation affected only recollection of events concerning his personal past, present and future, in another patient confabulation also affected recollection of impersonal knowledge. The third patient showed an intermediate pattern of confabulation, which affected selectively the retrieval of past information, both personal and impersonal. We suggest that our results are in favor of a fractionation of processes involved in recollection underling different disorders of consciousness., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Confabulation is often observed in amnesic patients after brain damage. However, evidence regarding the relationship between confabulation and other neuropsychological functions is scarce. In addition, previous studies have proposed two possibilities of the relationship between confabulation and false memory, in which patients with confabulation are likely to retrieve false memories, or confabulations are relatively independent of false memories. The present study investigated how confabulation is related to various cognitive functions, including orientation, attention, frontal lobe function, memory, and mental status, and to false memories, as assessed by the Deese-Roediger-Mcdermott (DRM) paradigm. Patients with organic amnesia participated, and confabulations were evaluated using the Confabulation Battery. Amnestic patients were classified into two groups: confabulating (CP) and nonconfabulating patients (NCP). The CP group was significantly impaired in time orientation, attention, and verbal memory, compared to the NCP group and age-matched healthy controls (HC). Results of the DRM paradigm revealed no significant difference in false memory retrieval induced by critical lures across CP, NCP, and HC groups. Confabulating responses in organic amnesia could be in part induced by disturbance of time consciousness and attention control in severe impairment of verbal memories, and confabulation and false memory could be modulated by different cognitive systems.

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes., Significance Statement: In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function., (Copyright © 2015 Guderian et al.)

In 1953, neurosurgeon William Beecher Scoville performed a bilateral mesial temporal lobe resection on patient Henry Molaison, who suffered from epilepsy. The operation was novel as a treatment for epilepsy and had an unexpected consequence: a severe compromise of Molaison's anterograde memory. In a landmark 1957 publication, Scoville and Milner concluded that mesial temporal lobe structures, particularly the hippocampi, were integral to the formation of new, recent memories. Over the next 5 decades, more than 100 researchers studied Molaison's memory, behavior, and learning skills, making him one of the most famous patients in the history of cognitive neuroscience. Following his death in 2008, his brain was scanned in situ and ex vivo and then sectioned into 2401 sections. Histological evaluation of Molaison's brain further elucidated which mesial temporal lobe structures were preserved or resected in his operation, shedding new light on the neuroanatomic underpinnings of short-term memory. Scoville regretted Molaison's surgical outcome and spoke vigorously about the dangers of bilateral mesial temporal lobe surgery. This report is the first historical account of Molaison's case in the neurosurgical literature, serving as a reminder of Molaison's contributions and of the perils of bilateral mesial temporal lobe surgery., (Published by Elsevier Inc.)

For over a century, clinicians have consistently described the paradoxical co-existence in posttraumatic stress disorder (PTSD) of sensory intrusive hypermnesia and declarative amnesia for the same traumatic event. Although this amnesia is considered as a critical etiological factor of the development and/or persistence of PTSD, most current animal models in basic neuroscience have focused exclusively on the hypermnesia, i.e., the persistence of a strong fear memory, neglecting the qualitative alteration of fear memory. The latest is characterized by an underrepresentation of the trauma in the context-based declarative memory system in favor of its overrepresentation in a cue-based sensory/emotional memory system. Combining psychological and neurobiological data as well as theoretical hypotheses, this review supports the idea that contextual amnesia is at the core of PTSD and its persistence and that altered hippocampal-amygdalar interaction may contribute to such pathologic memory. In a first attempt to unveil the neurobiological alterations underlying PTSD-related hypermnesia/amnesia, we describe a recent animal model mimicking in mice some critical aspects of such abnormal fear memory. Finally, this line of argument emphasizes the pressing need for a systematic comparison between normal/adaptive versus abnormal/maladaptive fear memory to identify biomarkers of PTSD while distinguishing them from general stress-related, potentially adaptive, neurobiological alterations., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The amnesic potential of scopolamine is well manifested through synaptic plasticity gene expression changes and behavioral paradigms of memory impairment. However, the underlying mechanism remains obscure and consequently ideal therapeutic target is lacking. In this context, chromatin-modifying enzymes, which regulate memory gene expression changes, deserve major attention. Therefore, we analyzed the expression of chromatin-modifying enzymes and recovery potential of enzyme modulators in scopolamine-induced amnesia. Scopolamine administration drastically up-regulated DNA methyltransferases (DNMT1) and HDAC2 expression while CREB-binding protein (CBP), DNMT3a and DNMT3b remained unaffected. HDAC inhibitor sodium butyrate and DNMT inhibitor Aza-2'deoxycytidine recovered scopolamine-impaired hippocampal-dependent memory consolidation with concomitant increase in the expression of synaptic plasticity genes Brain-derived neurotrophic factor (BDNF) and Arc and level of histone H3K9 and H3K14 acetylation and decrease in DNA methylation level. Sodium butyrate showed more pronounced effect than Aza-2'deoxycytidine and their co-administration did not exhibit synergistic effect on gene expression. Taken together, we showed for the first time that scopolamine-induced up-regulation of chromatin-modifying enzymes, HDAC2 and DNMT1, leads to gene expression changes and consequent decline in memory consolidation. Our findings on the action of scopolamine as an epigenetic modulator can pave a path for ideal therapeutic targets. We propose the following putative pathway for scopolamine-mediated memory impairment; scopolamine up-regulates hippocampal DNMT1 and HDAC2 expression, induces methylation and deacetylation of BDNF and Arc promoter, represses gene expression and eventually impairs memory consolidation. On the other hand, Aza-2 and NaB inhibit DNMT1 and HDAC2 respectively, up-regulate BDNF and Arc expression and recover memory consolidation. We elucidate the action of scopolamine as an epigenetic modulator and hope that DNMT1 and HDAC2 would be ideal therapeutic targets for memory disorders., (© 2015 International Society for Neurochemistry.)

In an earlier paper we described a structured, theory-driven training programme which was administered to 10 individuals with moderate-to-severe memory impairment. All individuals received an errorless-fading-of-cues protocol in the use of personal digital assistants (PDAs) or smartphones (Svoboda, Richards, Leach, & Mertens, 2012) and demonstrated generalisation of acquired skills to day-to-day memory challenges. Maintenance of intervention gains over the long-term is another indicator of successful generalisation. Here we present the maintenance of device use in the same group of individuals 12 to 19 months after programme completion. A within-subject, ABABB multi-case experimental design was used to evaluate the impact of PDA or smartphone use on day-to-day memory functioning at baseline, immediately post-intervention, at return to baseline, and at short-term and long-term follow-up. Results presented here focus predominantly on long-term follow-up. All 10 individuals showed maintenance of gains in day-to-day functioning as quantified across several ecologically valid questionnaire and task-based measures. This was corroborated by family members with whom six of the participants resided. This study further demonstrates the programme's clinical effectiveness in enabling individuals with moderate-to-severe memory impairment to function more independently and with greater confidence up to 19 months following programme completion.

Some patients with organic amnesia show confabulation, the production of statements and actions unintentionally incongruous to the subject's history, present and future situation. It has been shown that confabulators tend to report as unique and specific personal memories, events or actions that belong to their habits and routines (Habits Confabulations). We consider that habits and routines can be characterized by multiplicity, as opposed to uniqueness. This paper examines this phenomenon whereby confabulators mistake multiplicity, i.e., repeated events, for uniqueness, i.e., events that occurred in a unique and specific temporo-spatial context. In order to measure the ability to discriminate unique from repeated events we used four runs of a recognition memory task, in which some items were seen only once at study, whereas others were seen four times. Confabulators, but not non-confabulating amnesiacs (NCA), considered repeated items as unique, thus mistaking multiplicity for uniqueness. This phenomenon has been observed clinically but our study is the first to demonstrate it experimentally. We suggest that a crucial mechanism involved in the production of confabulations is thus the confusion between unique and repeated events., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Although anterograde amnesia can occur after damage in various brain sites, hippocampal dysfunction is usually seen as the ultimate cause of the failure to learn new episodic information. This assumption is supported by anatomical evidence showing direct hippocampal connections with all other sites implicated in causing anterograde amnesia. Likewise, behavioural and clinical evidence would seem to strengthen the established notion of an episodic memory system emanating from the hippocampus. There is, however, growing evidence that key, interconnected sites may also regulate the hippocampus, reflecting a more balanced, integrated network that enables learning. Recent behavioural evidence strongly suggests that medial diencephalic structures have some mnemonic functions independent of the hippocampus, which can then act upon the hippocampus. Anatomical findings now reveal that nucleus reuniens and the retrosplenial cortex provide parallel, disynaptic routes for prefrontal control of hippocampal activity. There is also growing clinical evidence that retrosplenial cortex dysfunctions contribute to both anterograde amnesia and the earliest stages of Alzheimer's disease, revealing the potential significance of this area for clinical studies. This array of findings underlines the importance of redressing the balance and the value of looking beyond the hippocampus when seeking to explain failures in learning new episodic information.

Declarative memory for rapidly learned, novel associations is thought to depend on structures in the medial temporal lobe (MTL), whereas associations learned more gradually can sometimes be supported by nondeclarative memory and by structures outside the MTL. A recent study suggested that even rapidly learned associations can be supported by structures outside the MTL when an incidental encoding procedure termed "fast mapping" (FM) is used. We tested six memory-impaired patients with bilateral damage to hippocampus and one patient with large bilateral lesions of the MTL. Participants saw photographs and names of animals, plants, and foods that were previously unfamiliar (e.g., mangosteen). Instead of asking participants to study name-object pairings for a later memory test (as with traditional memory instructions), participants answered questions that allowed them to infer which object corresponded to a particular name. In a second condition, participants learned name-object associations of unfamiliar items by using standard, explicit encoding instructions (e.g., remember the mangosteen). In FM and explicit encoding conditions, patients were impaired (and performed no better than a group that was given the same tests but had not previously studied the material). The same results were obtained in a second experiment that used the same procedures with modifications to allow for more robust learning and more reliable measures of performance. Thus, our results with the FM procedure and memory-impaired patients yielded the same deficits in learning and memory that have been obtained by using other more traditional paradigms.

The ability to imagine the future (prospection) relies on many of the same brain regions that support memory for the past. To date, scientific research has primarily focused on the neural substrates of episodic forms of prospection (mental simulation of spatiotemporally specific future events); however, little is known about the neural substrates of semantic prospection (mental simulation of future nonpersonal facts). Of particular interest is the role of the medial temporal lobes (MTLs), and specifically the hippocampus. Although the hippocampus has been proposed to play a key role in episodic prospection, recent evidence suggests that it may not play a similar role in semantic prospection. To examine this possibility, amnesic patients with MTL lesions were asked to imagine future issues occurring in the public domain. The results showed that patients could list general semantic facts about the future, but when probed to elaborate, patients produced impoverished descriptions that lacked semantic detail. This impairment occurred despite intact performance on standard neuropsychological tests of semantic processing and did not simply reflect deficits in narrative construction. The performance of a patient with damage limited to the hippocampus was similar to that of the remaining patients with MTL lesions and amnesic patients' impaired elaboration of the semantic future correlated with their impaired elaboration of the semantic past. Together, these results provide novel evidence from MTL amnesia that memory and prospection are linked in the semantic domain and reveal that the MTLs play a critical role in the construction of detailed, multi-element semantic simulations., (Copyright © 2012 Wiley Periodicals, Inc.)

We studied 11 patients with transient global amnesia (TGA) and ten patients with functional retrograde amnesia (FRA). Patients with TGA had a uniform clinical picture: a severe, relatively isolated amnesic syndrome that started suddenly, persisted for 4-12 h, and then gradually improved to essentially normal over the next 12-24 h. During the episode, the patients had severe anterograde amnesia for verbal and non-verbal material and retrograde amnesia that typically covered at least two decades. Thirty hours to 42 days after the episode, the patients had recovered completely and performed normally on tests of anterograde and retrograde amnesia. By contrast, patients with FRA had a sudden onset of memory problems that were characterized by severe retrograde amnesia without associated anterograde amnesia and with a clinical presentation that otherwise varied considerably. The episodes persisted from several weeks to more than two years, and some of the patients had not recovered at the time of our last contact with them. The uniform clinical picture of TGA and the variable clinical picture of FRA presumably reflect their respective neurologic ('organic') and psychogenic ('non-organic') aetiologies.