Amnesic Conditions Research Articles

Tat-Beclin-1 Ameliorates Memory by Improving Neuronal Cytoarchitecture and Mitigating Mitochondrial Dysfunction in Scopolamine-Induced Amnesic Male Mice.

Mitophagy, the targeted breakdown of damaged mitochondria, plays a vital role in maintaining cellular homeostasis. As impairment of mitophagy leads to neurodegeneration and memory decline, the current study explores the therapeutic potential of an autophagy inducer Tat-Beclin-1 during scopolamine-induced amnesia. Tat-Beclin-1 improved contextual and recognition memory and also mitochondrial ultrastructure by restoring mitochondrial length and area and reducing the number of fragmented mitochondria. Tat-Beclin-1 upregulated the expression of genes associated with mitophagy (PTEN-induced kinase 1, Parkin, Lamp2, and LC3), mitochondrial fusion (Mfn1, Mfn2, and optic atrophy1), and fission (dynamin-related protein 1 and Fis1) in amnesic mice. Subsequently, these results were supported by a decreased level of p-Drp1 (S616) and Drp 1 ratios and an increased level of Mfn2, LC3BI, and BII in Tat-Beclin-1-treated mice. Moreover, Tat-Beclin-1 maintained mitochondrial membrane potential and complex I/V activity in amnesic mice. Tat-Beclin-1 enhanced myelination and diminished the activity of acetylcholinesterase and caspase-3 activity. Sholl analysis revealed augmented dendritic branching and length, elevated dendritic spine density, and upregulated the expression of synaptophysin and PSD95 proteins, indicating neuronal plasticity enhancement by Tat-Beclin-1. Thus, these findings provide valuable insights into the therapeutic potential of Tat-Beclin-1, addressing mitochondrial dysfunction to mitigate cognitive impairment associated with amnesic conditions.

Aqueous Root Bark Extract of Daniellia oliveri (Hutch. & Dalz.) (Fabaceae) Protects Neurons against Diazepam‐Induced Amnesia in Mice

Daniellia oliveri (DO) is a traditional medicinal plant used for the treatment of diseases such as inflammation, schizophrenia, and epilepsy in Nigeria, Kenya, Congo, and Cameroon. This study was carried out to evaluate the potential neuroprotection effect of the aqueous root bark extract of Daniellia oliveri against diazepam-induced amnesia in mice. Thirty-six adult male mice were distributed into six groups: the three test groups received Daniellia oliveri root bark extract (100, 200, and 300 mg/kg), the normal control group received distilled water (10 ml/kg), a positive control group received piracetam (150 mg/kg), and the negative control received diazepam (2.5 mg/kg). Learning and memory were evaluated using the radial arm maze and the T-maze. Biomarkers of oxidative stress were also quantified in mice brains. Statistical analyses were performed using two-way ANOVA followed by Tukey's post hoc test. Daniellia oliveri root bark aqueous extract decreased the number of working memory errors and number of reference memory errors in amnesic mice evaluated in the radial arm maze. Also, an increase in glutathione activity and a decrease in malondialdehyde levels were noted in the hippocampi homogenate of the extract-treated mice as compared to the diazepam-demented but untreated group. Moreover, pretreatment with Daniellia oliveri aqueous root bark extract reversed the decrease in hippocampal cell density observed in the nontreated diazepam group. Taken together, these results suggest that the aqueous extract of DO leaves possesses antioxidant potential and might provide an opportunity for the management of neurological abnormalities in amnesic conditions.

Δ9-tetrahydrocannabinol modulates the proteasome system in the brain

Cannabis is the most consumed illicit drug worldwide. Its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), affects multiple brain functions, including cognitive performance, by modulating cannabinoid type-1 (CB1) receptors. These receptors are strongly enriched in presynaptic terminals, where they modulate neurotransmitter release. We analyzed, through a proteomic screening of hippocampal synaptosomal fractions, those proteins and pathways modulated 3 h after a single administration of an amnesic dose of THC (10 mg/kg, i.p.). Using an isobaric labeling approach, we identified 2040 proteins, 1911 of them previously reported in synaptic proteomes, confirming the synaptic content enrichment of the samples. Initial analysis revealed a significant alteration of 122 proteins, where 42 increased and 80 decreased their expression. Gene set enrichment analysis indicated an over-representation of mitochondrial associated functions and cellular metabolic processes. A second analysis focusing on extreme changes revealed 28 proteins with altered expression after THC treatment, 15 of them up-regulated and 13 down-regulated. Using a network topology-based scoring algorithm we identified those proteins in the mouse proteome with the greatest association to the 28 modulated proteins. This analysis pinpointed a significant alteration of the proteasome function, since top scoring proteins were related to the proteasome system (PS), a protein complex involved in ATP-dependent protein degradation. In this regard, we observed that THC decreases 20S proteasome chymotrypsin-like protease activity in the hippocampus. Our data describe for the first time the modulation of the PS in the hippocampus following THC administration under amnesic conditions that may contribute to an aberrant plasticity at synapses.

Classic and recent advances in understanding amnesia.

Neurological amnesia has been and remains the focus of intense study, motivated by the drive to understand typical and atypical memory function and the underlying brain basis that is involved. There is now a consensus that amnesia associated with hippocampal (and, in many cases, broader medial temporal lobe) damage results in deficits in episodic memory, delayed recall, and recollective experience. However, debate continues regarding the patterns of preservation and impairment across a range of abilities, including semantic memory and learning, delayed recognition, working memory, and imagination. This brief review highlights some of the influential and recent advances in these debates and what they may tell us about the amnesic condition and hippocampal function.

Chapter 36 - Functional (dissociative) retrograde amnesia

Retrograde amnesia is described as condition which can occur after direct brain damage, but which occurs more frequently as a result of a psychiatric illness. In order to understand the amnesic condition, content-based divisions of memory are defined. The measurement of retrograde memory is discussed and the dichotomy between "organic" and "psychogenic" retrograde amnesia is questioned. Briefly, brain damage-related etiologies of retrograde amnesia are mentioned. The major portion of the review is devoted to dissociative amnesia (also named psychogenic or functional amnesia) and to the discussion of an overlap between psychogenic and "brain organic" forms of amnesia. The "inability of access hypothesis" is proposed to account for most of both the organic and psychogenic (dissociative) patients with primarily retrograde amnesia. Questions such as why recovery from retrograde amnesia can occur in retrograde (dissociative) amnesia, and why long-term new learning of episodic-autobiographic episodes is possible, are addressed. It is concluded that research on retrograde amnesia research is still in its infancy, as the neural correlates of memory storage are still unknown. It is argued that the recollection of episodic-autobiographic episodes most likely involves frontotemporal regions of the right hemisphere, a region which appears to be hypometabolic in patients with dissociative amnesia.

Editorial: Further Understanding of Serotonin 7 Receptors' Neuro-psycho-pharmacology.

Editorial: Further Understanding of Serotonin 7 Receptors' Neuro-psycho-pharmacology.

Memory, Time and Autonoetic Consciousness

Memory and time have multifaceted links. Along the time axis, memory is divided into short- and long-term memory. Another popular time-dependent distinction is between new and old memories and anterograde and retrograde memory impairments, respectively. Time-embedment characterizes the processing of mnemonic information, which encompasses the stages of registration, encoding, consolidation, and storage. Along the content axis, memory is partitioned into five long-term memory systems (procedural, priming, perceptual, semantic, and episodic), which are regarded to build up on each other from both a phylogenetic and ontogenetic perspective. These memory systems are accompanied by different niveaus of self and levels of consciousness. Among these long-term memory systems, the episodic memory system holds a special connection with time, which we aim to detail. In 2005, Tulving defined the episodic memory system as the conjunction of subjective time, autonoetic consciousness, and the experiencing self. Drawing on this last definition of the episodic memory, which lays an emphasis on the linkage to the self, Markowitsch has subsequently promoted the use of the construct “episodic-autobiographical” memory system. The episodic-autobiographical memory system features mental time travelling, an essential property that enables one individual to flexibly travel in subjective time in his/her past and, in addition, to flexibly project him/herself in the future. This property provides a “glue” for the self, supporting a coherent view of one's own person. According to Tulving and Markowitsch, it is unlikely that non-human animals possess the capacity for mental time travelling and the ability to “look into future” (“proscopy”). Furthermore, Tulving and Markowitsch had proposed that the ability for mental time travelling is dependent on age and intellect. Subsequent studies have confirmed that mental time travelling is one of the last features of the episodic- autobiographical memory system that achieves full functionality in humans and is the first one to be afflicted by old age, amnesia or neurodegenerative dementias (e.g., Alzheimer's dementia). At the brain level, the emergence of the capacity for mental time travelling is accompanied by ample structural and functional reorganization of elements of the brain networks supporting episodic-autobiographical memory, autonoetic consciousness, and self-referential processing.In human beings, damage to certain brain regions may alter the sense and consciousness of time in quite different ways. Herein, we have the goal to review changes in time perception and consciousness of time, which accompany different forms of amnesia. Patients with anterograde amnesia manifest an inability to consciously acquire new information for long-term storage and as a consequence are often “stuck in time”. ‘Chronotaraxis’ may accompany certain forms of preponderantly anterograde amnesia, as we aim to exemplify by drawing upon own cases, which were investigated medically, neuropsychologically, and with neuroimaging methods. Patients with retrograde amnesia manifest an inability to consciously retrieve already stored old mnemonic information, usually from the episodic-autobiographical memory domain. They lack the capacity to “ecphorize” old memories. Interestingly, the memory impairments are very similar in the patients with focal traumatic brain injuries and in those with psychogenic forms of amnesia: The patients are unable to engage in mental time traveling into their past. In addition, they show an impaired ability to imagine future personal events, being as a consequence trapped in a “noetic existence”. In psychogenic amnesia with pronounced retrograde memory impairments, we found (via functional neuroimaging) evidence of defective synchronization during retrieval between processing of affectively loaded personal events (that is presumed to preponderantly engage the right hemisphere) and fact-based processing (that is considered to preferentially recruit the left hemisphere). These data are relevant in the light of studies pointing to a right hemisphere bias for higher forms of consciousness. We conjecture that this synchronization abnormality not only leads to a memory blockade, but also to shrinkage of mental time traveling and loss of autonoetic consciousness in psychogenic or functional amnesic conditions.

EPA-1815 – Biographical memory, autonoetic consciousness and the self

Introduction Episodic-autobiographical memory (EAM) is the highest ontogenetic human achievement and is defined as the conjunction of subjective time, autonoetic consciousness and the experiencing self. The EAM system is more susceptible to insults than other memory systems and is predominantly affected in amnesic disorders. Dissociative amnesia is triggered by psychological stress and usually presents with retrograde memory impairment in the EAM domain. Objectives This work's objectives are establishing greater recognition of the changes in the area of personality dimensions, self and autonoetic consciousness, accompanying dissociative amnesia. Aims We review data from own patients with dissociative amnesia or fugue Methods Patients were investigated medically, neuropsychologically and neuroradiologically. Results We found impairments of self and self-referential processing in patients with dissociative amnesia, such as profound loss of personal identity, decreased ability for self-reflection and self projection and anomalous self-face processing. We also identified changes in personality dimensions involving affectivity, perception, cognition (e.g. social cognition) and behavior. Conclusions The observed changes in self and autonoetic consciousness may represent a consequence of amnesia. Studies indicate a right hemispheric bias for higher forms of self awareness. In retrograde dissociative amnesia, we found a hypometabolism in right fronto-temporal areas, suggesting a defective synchronization during retrieval between processing of affectively-loaded personal events and fact-based processing. This synchronization abnormality in our opinion not only leads to a memory blockade, but also to a shrinkage of self and loss of autonoetic consciousness in dissociative amnesic conditions.

EPA-1384 – The missing link between dissociative amnesia and dementia

Introduction Despite suggestions that chronic stress is involved in the pathogeny of dementias, no systematic studies investigated the possibility of a link between dissociative amnesia and neurodegenerative dementias. Methods We analyzed data from over a dozen patients with functional dissociative amnesia, whom we investigated with neuropsychological methods, structural and functional neuroimaging. We followed prospectively approximately half of these patients for more than a decade. Results We evidenced in a substantial sample of patients with dissociative amnesia with preponderant retrograde memory impairments a hypometabolism during resting state in the right temporo-frontal region, with a decrease in the infero-lateral prefrontal cortex. Additional preliminary data from DTI suggested a decreased integrity of long distance fiber tracts important for conscious mnemonic processing. We found a chronic course of the memory impairments in a substantial number of patients with dissociative amnesic conditions. In some chronic cases of dissociative amnesia we noted a fairly stable course, while in other cases we observed a progressive global cognitive deterioration. Discussion These findings point to a non-homogenous course of dissociative amnesia. Conclusion The search for a link between dissociative amnesic conditions and dementia should take into consideration multiple variables, such as the age at the onset of trauma, gender, the recurrence, type and severity of trauma, the presence of psychiatric and medical co-morbidity, pre-morbid personality characteristics (e.g. neuroticism), genetic polymorphisms, educational and occupational attainment, cognitive reserve and the progression of metabolic and microstructural brain changes.

Anterograde episodic memory in Korsakoff syndrome.

A profound anterograde memory deficit for information, regardless of the nature of the material, is the hallmark of Korsakoff syndrome, an amnesic condition resulting from severe thiamine (vitamin B1) deficiency. Since the late nineteenth century when the Russian physician, S. S. Korsakoff, initially described this syndrome associated with "polyneuropathy," the observed global amnesia has been a primary focus of neuroscience and neuropsychology. In this review we highlight the historical studies that examined anterograde episodic memory processes in KS, present a timeline and evidence supporting the myriad theories proffered to account for this memory dysfunction, and summarize what is known about the neuroanatomical correlates and neural systems presumed affected in KS. Rigorous study of KS amnesia and associated memory disorders of other etiologies provide evidence for distinct mnemonic component processes and neural networks imperative for normal declarative and nondeclarative memory abilities and for mnemonic processes spared in KS, from whence emerged the appreciation that memory is not a unitary function. Debate continues regarding the qualitative and quantitative differences between KS and other amnesias and what brain regions and neural pathways are necessary and sufficient to produce KS amnesia.

Nicotine evoked improvement in learning and memory is mediated through NPY Y1 receptors in rat model of Alzheimer's disease

We investigated the role of endogenous neuropeptide Y (NPY) system in nicotine-mediated improvement of learning and memory in rat model of Alzheimer's disease (AD). Intracerebroventricular (icv) colchicine treatment induced AD-like condition in rats and showed increased escape latency (decreased learning), and amnesic condition in probe test in Morris water maze. In these rats, nicotine (0.5mg/kg, intraperitoneal), NPY (100ng/rat, icv) or NPY Y1 receptor agonist [Leu31, Pro34]-NPY (0.04ng/rat, icv) decreased escape latency by 54.76%, 55.81% and 44.18%, respectively, on day 4 of the acquisition. On the other hand, selective NPY Y1 receptor antagonist, BIBP3226 (icv) produced opposite effect (44.18%). In the probe test conducted at 24h time point, nicotine, NPY or [Leu31, Pro34]-NPY increased the time spent by 72.72%, 44.11% and 26.47%, respectively; while BIBP3226 caused reduction (8.82%). It seems that while NPY or [Leu31, Pro34]-NPY potentiated, BIBP3226 attenuated the learning and memory enhancing effects of nicotine. Brains of colchicine treated rats showed significant reduction in NPY-immunoreactivity in the nucleus accumbens shell (cells 62.23% and fibers 50%), bed nucleus of stria terminalis (fibers 71.58%), central nucleus of amygdala (cells 74.33%), arcuate nucleus (cells 70.97% and fibers 69.65%) and dentate gyrus (cells 58.54%). However, in these rats nicotine treatment for 4 days restored NPY-immunoreactivity to the control level. We suggest that NPY, perhaps acting via NPY Y1 receptors, might interact with the endogenous cholinergic system and play a role in improving the learning and memory processes in the rats with AD-like condition.

P-372 - Amnesia of psychogenic etiology

Amnesia is usually attributed to distinct brain damage and represents an inability to acquire new memories for long-term storage (anterograde amnesia). Retrograde amnesia - the inability to recall previously stored information - is rarer and often etiologically -linked to psychological factors. We currently witness an increased interest in the neurobiology of dissociative and disproportionate amnesias. The latter typically arise after (mild) traumatic brain injury, but cannot be explained by the locus or extent of brain damage. This work's objectives are establishing recognition of clinical, neuropsychological and neurobiological characteristics of amnesias of psychological etiology and distinguishing true from feigned amnesias. We aim to emphasize that amnesic conditions that are etiologically linked to psychological factors are more frequent than usually assumed and discuss implications for diagnosis and management. In addition to own research data, a comprehensive review of case reports and series of amnesias related to psychological factors was performed. As DSM-IV-TR implies, most amnesias of psychological etiology are retrograde. Anterograde amnesia however might also occur. Modern neuroimaging has evidenced metabolic, structural and hodological brain changes in affected patients and even indicated that metabolic changes might be reversed following successful treatment and memory recovery. Amnesias of psychological etiology is more common than previously assumed. They might co-occur with mild head injury and even more serious brain pathology. Their prompt diagnosis and treatment - which are imperative for minimizing chronic disability - might be aided by insights from combined use of functional and structural brain imaging.

Gedächtnis und Brain Imaging

Presented are current views about memory and memory disturbances. Subsequently, cases of patients are given in whom environmentally-induced stress and trauma situations provoked enduring amnesic conditions in the autobiographic area. It is shown that for many of the patients activity changes can be demonstrated on the brain level, which are evoked by stress and trauma events. Consequently, after the field of neurologically caused, also psychiatrically caused disturbances become available for functional brain imaging.

P300 as an Index of Recognition in a Standard and Difficult Match-to-Sample Test: A Model of Amnesia in Normal Adults

Earlier research has supported the use of a P300 (P3)-based procedure to detect simulated amnesia. In the present experiment, an attempt was made to model the behavior and event-related potentials (ERPs) that amnestic patients might demonstrate with relatively easy recognition memory tests, by increasing the difficulty of a match-to-sample recognition memory test taken by 18 memory-unimpaired undergraduates. None of the participants in the modeled amnesic condition were classified as having intact recognition memory as the result of P3-based intra-individual tests (specificity = 100%). The results support the utility of a P3 procedure for the detection of malingering by demonstrating the procedure to be a valid measure of impaired recognition with this model of amnesia.

Practical Ways of Improving Memory Storage and Retrieval Problems in Patients with Head Injuries

Memory disorders resulting from head injuries can be very distressing to both patients and carers. Understanding memory processes can be helpful in selecting the best memory strategies for particular patients. These strategies are discussed together with definitions of amnesic conditions and memory aids. The important message from using such memory strategies is that patients learning how to improve their poor memory have a far greater chance of improvement in the long term than those who simply rehearse items to be memorised.

Memory Loss During Pregnancy

Objective To investigate possible impairment of memory during pregnancy. Design The performance of pregnant women in a variety of tests of memory was compared to that of controls. Setting The Bristol Maternity Hospital. Subjects Forty-eight volunteer pregnant women attending for routine antenatal checks were compared to 19 nonpregnant controls. Main outcome measures Subjectively perceived rating of memory impairment, objective measures of recall, recognition and priming memory. Results Pregnant and control groups were given a series of tests of memory at the end of which they were asked to rate their own memory at present compared to some weeks ago (when they were not pregnant). Of the pregnant women 39 out of 48 (81%) rated their current memory as being impaired; only three out of 19 (16%) of the control subjects did so. Objective tests revealed that the pregnant group was significantly impaired in the recall of lists of words, particularly when learning was incidental rather than explicit. The pregnant group was also significantly impaired in two measures of priming memory. No significant deficit was found in recognition. The deficits were found for both primigravid and multigravid women, and were present in all trimesters of pregnancy. Conclusions The majority of women believe their memory to be impaired during pregnancy. Objectively, during pregnancy there is significant impairment of memory as tested by recall or by priming, but not by recognition. The pattern of memory loss differs from that of other amnesic conditions. Information imparted to pregnant patients may not be retained as well as might be expected.

Memory loss during pregnancy

To investigate possible impairment of memory during pregnancy. The performance of pregnant women in a variety of tests of memory was compared to that of controls. The Bristol Maternity Hospital. Forty-eight volunteer pregnant women attending for routine antenatal checks were compared to 19 nonpregnant controls. Subjectively perceived rating of memory impairment, objective measures of recall, recognition and priming memory. Pregnant and control groups were given a series of tests of memory at the end of which they were asked to rate their own memory at present compared to some weeks ago (when they were not pregnant). Of the pregnant women 39 out of 48 (81%) rated their current memory as being impaired; only three out of 19 (16%) of the control subjects did so. Objective tests revealed that the pregnant group was significantly impaired in the recall of lists of words, particularly when learning was incidental rather than explicit. The pregnant group was also significantly impaired in two measures of priming memory. No significant deficit was found in recognition. The deficits were found for both primigravid and multigravid women, and were present in all trimesters of pregnancy. The majority of women believe their memory to be impaired during pregnancy. Objectively, during pregnancy there is significant impairment of memory as tested by recall or by priming, but not by recognition. The pattern of memory loss differs from that of other amnesic conditions. Information imparted to pregnant patients may not be retained as well as might be expected.

Performance in free recall following rupture and repair of intracranial aneurysm

There have been many reports of global memory disorder following rupture and repair of intracranial aneurysms. These reports suggest a more anterior basis for the amnesic syndrome than the various sites in the diencephalon and the temporal lobe that have so far been implicated. Patients from a consecutive series of 76 cases of aneurysmal subarachnoid hemorrhage demonstrated a moderate deficit in free recall, but aneurysms at different sites within the cerebrovascular system did not produce significantly different degrees of impairment. The results are consistent with the idea that aneurysmal subarachnoid hemorrhage gives rise to diffuse cerebral damage, and do not necessitate any revision of conventionally accepted accounts of the neuropathology of amnesic conditions.

Hypothermia: Amnesic agent, punisher, and conditions sufficient to attenuate amnesia

In three experiments, the effects of prior experience with hypothermia as a manipulation to attenuate amnesia were examined. In Experiment 1, prior experience with one hypothermia treatment did not appear to influence the amnesic effects of hypothermia. In Experiment 2, hypothermia treatment was made contingent upon stepping into a darkened chamber of a passive avoidance apparatus daily for 8 days. By Day 8, latencies indicated that subjects could remember the previous hypothermia treatments. The values of hypothermia found to produce learning in Experiment 2 were then used to evaluate several retrieval hypotheses concerning the prevention of amnesia in Experiment 3. Rats which received eight daily hypothermia treatments, as well as rats restrained without immersion, showed little evidence of amnesia following a train-hypothermia treatment. Results were interpreted as supporting the view that amnesia may be produced because important contextual cues necessary for memory retrieval are usually absent during testing.

Memory Function After Closed Head Injury: A Review of the Quantitative Research

Studies which provide quantitative analyses of memory function following closed head injury were reviewed. Specific issues covered include criteria for assessing post-traumatic amnesia (PTA), PTA duration, relation of PTA duration to later memory impairment, memory functions within PTA, and comparisons between PTA and other amnesic conditions. Issues associated with the assessment of retrograde amnesia were also reviewed. With regard to memory function after PTA has terminated, we described and discussed normative data, the time course of recovery, and issues related to the nature of the later memory impairment. Directions for future work which seem particularly useful from a practical and theoretical viewpoint were also considered.