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The Journal of Neuroscience : the... Dec 2022Associative binding is key to normal memory function and is transiently disrupted during periods of post-traumatic amnesia (PTA) following traumatic brain injury (TBI)....
Associative binding is key to normal memory function and is transiently disrupted during periods of post-traumatic amnesia (PTA) following traumatic brain injury (TBI). Electrophysiological abnormalities, including low-frequency activity, are common following TBI. Here, we investigate associative memory binding during PTA and test the hypothesis that misbinding is caused by pathological slowing of brain activity disrupting cortical communication. Thirty acute moderate to severe TBI patients (25 males; 5 females) and 26 healthy controls (20 males; 6 females) were tested with a precision working memory paradigm requiring the association of object and location information. Electrophysiological effects of TBI were assessed using resting-state EEG in a subsample of 17 patients and 21 controls. PTA patients showed abnormalities in working memory function and made significantly more misbinding errors than patients who were not in PTA and controls. The distribution of localization responses was abnormally biased by the locations of nontarget items for patients in PTA, suggesting a specific impairment of object and location binding. Slow-wave activity was increased following TBI. Increases in the δ-α ratio indicative of an increase in low-frequency power specifically correlated with binding impairment in working memory. Connectivity changes in TBI did not correlate with binding impairment. Working memory and electrophysiological abnormalities normalized at 6 month follow-up. These results show that patients in PTA show high rates of misbinding that are associated with a pathological shift toward lower-frequency oscillations. How do we remember what was where? The mechanism by which information (e.g., object and location) is integrated in working memory is a central question for cognitive neuroscience. Following significant head injury, many patients will experience a period of post-traumatic amnesia (PTA) during which this associative binding is disrupted. This may be because of electrophysiological changes in the brain. Using a precision working memory test and resting-state EEG, we show that PTA patients demonstrate impaired binding ability, and this is associated with a shift toward slower-frequency activity on EEG. Abnormal EEG connectivity was observed but was not specific to PTA or binding ability. These findings contribute to both our mechanistic understanding of working memory binding and PTA pathophysiology.
Topics: Male; Female; Humans; Amnesia; Memory, Short-Term; Amnesia, Retrograde; Brain Injuries, Traumatic; Psychotic Disorders
PubMed: 36316155
DOI: 10.1523/JNEUROSCI.0564-22.2022 -
Laeknabladid Nov 2022Transient Global Amnesia (TGA) is a benign syndrome characterized by sudden anterograde memory loss, that resolves spontaneously within 24 hours. TGA appears without...
BACKGROUND
Transient Global Amnesia (TGA) is a benign syndrome characterized by sudden anterograde memory loss, that resolves spontaneously within 24 hours. TGA appears without other focal neurological symptoms. The aim of this study was to study TGA in the greater Reykjavik-area.
METHODS
We retrospectively analysed the medical history of patients with a diagnosis of TGA (ICD-10 G45.4) at the University Hospital in Iceland in 2010-2021. Medical records were reviewed, and information about year and age at diagnosis, sex, symptoms, precipitating events, imaging results and risk factors were collected. Statistical processing was performed with Excel and Rstudio.
RESULTS
Overall, 348 attacks of TGA were identified with a mean frequency of 29 attacks/year, where 9.9% had an earlier history of TGA. The mean age was 64.1, with 50% of subjects between 58-70 years old. The sex distribution was equal (49.9% female). Possible precipitating events were found in 53.7% of cases, with physical activity being the most common one (24.4%), followed by sudden temperature change and emotional stress. In 96% of patients a computerized tomography was performed (no sign of acute changes were found), and magnetic resonance imaging (MRI) in 36.2% of cases. MRI showed restricted diffusion in the hippocampal area in 10.3% of cases.
DISCUSSION
TGA is not a rare but a benign syndrome. Our findings regarding age, sex distribution and precipitating events were in accordance with other studies. TGA is thought to result from a temporary hippocampal dysfunction supported by the clinical presentation and MRI findings. The cause of TGA is however still unknown.
Topics: Humans; Female; Middle Aged; Male; Amnesia, Transient Global; Retrospective Studies; Hippocampus; Magnetic Resonance Imaging; Risk Factors
PubMed: 36321932
DOI: 10.17992/lbl.2022.11.715 -
PloS One 2017Studies have suggested that benzodiazepines are amnestic drug par excellence, but when taken together, what level of evidence do they generate? Are other sedatives as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have suggested that benzodiazepines are amnestic drug par excellence, but when taken together, what level of evidence do they generate? Are other sedatives as amnestic as benzodiazepines? The aim of this study was to assess the level of scientific evidence for the amnestic effect of sedatives in pediatric patients who undergo health procedures.
METHODS
The literature was searched to identify randomized controlled trials that evaluated anterograde and retrograde amnesia in 1-19-year-olds who received sedative drugs during health procedures. Electronic databases, including PubMed, Scopus and Cochrane Library besides clinical trial registries and grey literature were searched. Two independent reviewers performed data extraction and risk of bias assessment using the Cochrane Collaboration's Tool. The meta-analyses were performed by calculating relative risk (RR) to 95% confidence intervals (CI). The quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS
Fifty-four studies were included (4,168 participants). A higher occurrence of anterograde amnesia was observed when benzodiazepines, the most well-studied sedatives (n = 47), were used than when placebo was used (n = 12) (RR = 3.10; 95% CI: 2.30-4.19, P<0.001; I2 = 14%), with a moderate level of evidence. Higher doses of alpha2-adrenergic agonists (clonidine/dexmedetomidine) produced more anterograde amnesia than lower doses (n = 2) (RR = 1.83; 95% CI: 1.03-3.25; P = 0.038; I2 = 0%), with a low level of evidence; benzodiazepines' amnestic effects were not dose-dependent (n = 3) (RR = 1.54; 95% CI: 0.96-2.49; P = 0.07; I2 = 12%) but the evidence was low. A qualitative analysis showed that retrograde amnesia did not occur in 8 out of 10 studies.
CONCLUSIONS
In children, moderate evidence support that benzodiazepines induce anterograde amnesia, whereas the evidence for other sedatives is weak and based on isolated and small studies. Further clinical trials focused on the amnesia associated with non-benzodiazepine sedatives are therefore needed.
TRIAL REGISTRATION
PROSPERO CRD42015017559.
Topics: Adolescent; Amnesia, Anterograde; Amnesia, Retrograde; Benzodiazepines; Child; Child, Preschool; Clonidine; Dexmedetomidine; Female; Humans; Hypnotics and Sedatives; Infant; Male; Randomized Controlled Trials as Topic; Young Adult
PubMed: 28686702
DOI: 10.1371/journal.pone.0180248 -
Neuropsychologia Jun 2023The hippocampus plays a critical role in episodic memory and imagination. One theoretical model posits that the hippocampus is important for scene construction, namely,...
The hippocampus plays a critical role in episodic memory and imagination. One theoretical model posits that the hippocampus is important for scene construction, namely, the ability to conjure and maintain a scene-based representation in one's mind. To test one idea put forth by this view, we examined whether amnesia is associated with more severe impairment in memory when the to-be-remembered content places high demands on scene construction. To do so, we examined free recall performance for abstract (i.e., low scene imagery) and concrete, high scene-imagery single words in seven amnesic patients with hippocampal lesions and concomitant scene-construction deficits, and compared their performance to demographically matched healthy controls. As expected, amnesic patients were severely impaired in their free recall performance; however, their impairment did not differ as a function of word type. That is, their impairment was equally severe for words that evoke high versus low scene imagery. These findings suggest that the role of the hippocampus in verbal memory extends to content that does not place high demands on scene construction. Theoretical implications of these findings are discussed.
Topics: Humans; Mental Recall; Amnesia; Hippocampus; Imagination; Memory, Episodic
PubMed: 36931459
DOI: 10.1016/j.neuropsychologia.2023.108543 -
Perspectives on Psychological Science :... Nov 2019Can purely psychological trauma lead to a complete blockage of autobiographical memories? This long-standing question about the existence of repressed memories has been... (Review)
Review
Can purely psychological trauma lead to a complete blockage of autobiographical memories? This long-standing question about the existence of repressed memories has been at the heart of one of the most heated debates in modern psychology. These so-called memory wars originated in the 1990s, and many scholars have assumed that they are over. We demonstrate that this assumption is incorrect and that the controversial issue of repressed memories is alive and well and may even be on the rise. We review converging research and data from legal cases indicating that the topic of repressed memories remains active in clinical, legal, and academic settings. We show that the belief in repressed memories occurs on a nontrivial scale (58%) and appears to have increased among clinical psychologists since the 1990s. We also demonstrate that the scientifically controversial concept of dissociative amnesia, which we argue is a substitute term for memory repression, has gained in popularity. Finally, we review work on the adverse side effects of certain psychotherapeutic techniques, some of which may be linked to the recovery of repressed memories. The memory wars have not vanished. They have continued to endure and contribute to potentially damaging consequences in clinical, legal, and academic contexts.
Topics: Amnesia; Humans; Psychological Trauma; Psychotherapy; Repression, Psychology
PubMed: 31584864
DOI: 10.1177/1745691619862306 -
Hippocampus Feb 2016Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and...
Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255-257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A->B, B->C, C->D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A->C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre-experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre-experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to-be-learned relations were arbitrary. However, accuracy improved for older adults when they could use pre-experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and anterior temporal regions may have resulted in an inability to use prior knowledge to flexibly express indirect relational knowledge.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Amnesia; Female; Follow-Up Studies; Hippocampus; Humans; Learning; Male; Middle Aged; Photic Stimulation; Young Adult
PubMed: 26234960
DOI: 10.1002/hipo.22501 -
International Journal of Molecular... Aug 2023The role of histamine H3 receptors (H3Rs) in memory and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer's...
The Potent and Selective Histamine H3 Receptor Antagonist E169 Counteracts Cognitive Deficits and Mitigates Disturbances in the PI3K/AKT/GSK-3β Signaling Pathway in MK801-Induced Amnesia in Mice.
The role of histamine H3 receptors (H3Rs) in memory and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer's disease (AD), is well-accepted. Therefore, the procognitive effects of acute systemic administration of H3R antagonist E169 (2.5-10 mg/kg, i.p.) on MK801-induced amnesia in C57BL/6J mice using the novel object recognition test (NORT) were evaluated. E169 (5 mg) provided a significant memory-improving effect on MK801-induced short- and long-term memory impairments in NORT. The E169 (5 mg)-provided effects were comparable to those observed with the reference phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and were abrogated with the H3R agonist ()-α-methylhistamine (RAMH). Additionally, our results demonstrate that E169 ameliorated MK801-induced memory deficits by antagonism of H3Rs and by modulation of the level of disturbance in the expression of PI3K, Akt, and GSK-3β proteins, signifying that E169 mitigated the Akt-mTOR signaling pathway in the hippocampus of tested mice. Moreover, the results observed revealed that E169 (2.5-10 mg/kg, i.p.) did not alter anxiety levels and locomotor activity of animals in open field tests, demonstrating that performances improved following acute systemic administration with E169 in NORT are unrelated to changes in emotional response or in spontaneous locomotor activity. In summary, these obtained results suggest the potential of H3R antagonists such as E169, with good in silico physicochemical properties and stable retained key interactions in docking studies at H3R, in simultaneously modulating disturbed brain neurotransmitters and the imbalanced Akt-mTOR signaling pathway related to neurodegenerative disorders, e.g., AD.
Topics: Animals; Mice; Mice, Inbred C57BL; Glycogen Synthase Kinase 3 beta; Phosphatidylinositol 3-Kinases; Dizocilpine Maleate; Histamine H3 Antagonists; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinase; TOR Serine-Threonine Kinases; Amnesia; Alzheimer Disease; Signal Transduction; Cognition
PubMed: 37628900
DOI: 10.3390/ijms241612719 -
Brain Topography Mar 2023Pure amnestic seizures are defined as self-limited episodes with isolated, anterograde memory loss and have been attributed to bilateral dysfunction of mesial temporal...
Pure amnestic seizures are defined as self-limited episodes with isolated, anterograde memory loss and have been attributed to bilateral dysfunction of mesial temporal structures. This type of seizure can occur in patients with different forms of temporal lobe epilepsy and has been more recently associated with a late-onset epileptic syndrome, called transient epileptic amnesia (TEA). The mechanisms of such prolonged manifestations are not well known and notably its ictal or post-ictal origin remains poorly understood. We report a case of prolonged anterograde amnesia (lasting several hours) following a brief seizure induced by stimulation of the left entorhinal cortex, recorded during stereo-EEG (SEEG). This episode was associated with prolonged changes in the intracerebral EEG signal complexity (entropy) within bilateral mesial temporal structures, particularly the entorhinal cortices, with a progressive normalization paralleling the clinical recovery. Our case shows that long-lasting (hours) memory impairment may follow brief seizure that led to prolonged electrophysiological signals alterations in bilateral mesial temporal structures.
Topics: Humans; Epilepsy; Seizures; Epilepsy, Temporal Lobe; Amnesia; Electroencephalography
PubMed: 36624220
DOI: 10.1007/s10548-022-00930-z -
Biological Psychiatry Jan 2017Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are...
BACKGROUND
Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia.
METHODS
We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice.
RESULTS
We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e.g., two-way active avoidance and fear conditioning. Retrograde amnesia of learned associative memories is elicited by inducible neuron-specific ablation of Nptn gene expression in adult mice, which shows that neuroplastins are indispensable for the availability of previously acquired associative memories. Using single-photon emission computed tomography imaging in awake mice, we identified brain structures activated during memory recall. Constitutive neuroplastin deficiency or Nptn gene ablation in adult mice causes substantial electrophysiologic deficits such as reduced long-term potentiation. In addition, neuroplastin-deficient mice reveal profound physiologic and behavioral deficits, some of which are related to depression and schizophrenia, which illustrate neuroplastin's essential functions.
CONCLUSIONS
Neuroplastins are essential for learning and memory. Retrograde amnesia after an associative learning task can be induced by ablation of the neuroplastin gene. The inducible neuroplastin-deficient mouse model provides a new and unique means to analyze the molecular and cellular mechanisms underlying retrograde amnesia and memory.
Topics: Amnesia, Retrograde; Animals; Association Learning; Avoidance Learning; Behavior, Animal; Excitatory Postsynaptic Potentials; Fear; Hippocampus; Membrane Glycoproteins; Memory; Mice; Mice, Inbred C57BL; Mice, Knockout
PubMed: 27215477
DOI: 10.1016/j.biopsych.2016.03.2107 -
Medicina 2022
Topics: Amnesia, Transient Global; Diagnosis, Differential; Humans; Magnetic Resonance Imaging
PubMed: 36220048
DOI: No ID Found