Concept: Memory disorders
Transient amnesic syndromes are striking clinical phenomena that are commonly encountered by physicians in acute medical settings. Diagnosis of such syndromes can be challenging, and their causes have been debated for over 50 years. Critical clinical distinctions, such as between transient global amnesia (TGA) and transient epileptic amnesia (TEA), as well as important clues to the underlying pathophysiology, have recently been revealed. TGA is characterized by the sudden onset of a profound anterograde and retrograde amnesia that lasts for up to 24 h, with neuroimaging after an acute TGA event showing transient perturbation of specific hippocampal circuits that are involved in memory processing. Some cases of transient amnesia are attributable to focal seizure activity and are termed TEA, which has a clinical presentation similar to that of TGA, but can be distinguished from the latter by the brevity and frequency of amnesic attacks. Moreover, TEA carries a risk of persistent memory impairment that can be mistaken for dementia. Here, we summarize clinically relevant aspects of transient amnesic syndromes, giving practical recommendations for diagnosis and patient management. We describe results from imaging and epidemiological studies that have shed light on the functional anatomy and pathophysiological mechanisms underlying these conditions.
After traumatic brain injury (TBI) and emergence from coma, the majority of people experience posttraumatic amnesia (PTA), characterized by confusion, disorientation, retrograde and anterograde amnesia, poor attention, and sometimes agitation and delusions. An international team of researchers and clinicians developed recommendations for assessment and management of PTA.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 2 years ago
Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory engrams). Memory engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of engrams “silent engrams” and the cells bearing them “silent engram cells.” The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes. Here, we show that the full-fledged optogenetic recall persists at least 8 d after learning under protein synthesis inhibition-induced amnesia. This long-term retention of memory information correlates with equally persistent retention of functional engram cell-to-engram cell connectivity. Furthermore, inactivation of the connectivity of engram cell ensembles with its downstream counterparts, but not upstream ones, prevents optogenetic memory recall. Consistent with the previously reported lack of retention of augmented synaptic strength and reduced spine density in silent engram cells, optogenetic memory recall under amnesia is stimulation strength-dependent, with low-power stimulation eliciting only partial recall. Finally, the silent engram cells can be converted to active engram cells by overexpression of α-p-21-activated kinase 1, which increases spine density in engram cells. These results indicate that memory information is retained in a form of silent engram under protein synthesis inhibition-induced retrograde amnesia and support the hypothesis that memory is stored as the specific connectivity between engram cells.
We describe a mathematical model of learning and memory and apply it to the dynamics of forgetting and amnesia. The model is based on the hypothesis that the neural systems involved in memory at different time scales share two fundamental properties: (1) representations in a store decline in strength (2) while trying to induce new representations in higher-level more permanent stores. This paper addresses several types of experimental and clinical phenomena: (i) the temporal gradient of retrograde amnesia (Ribot’s Law), (ii) forgetting curves with and without anterograde amnesia, and (iii) learning and forgetting curves with impaired cortical plasticity. Results are in the form of closed-form expressions that are applied to studies with mice, rats, and monkeys. In order to analyze human data in a quantitative manner, we also derive a relative measure of retrograde amnesia that removes the effects of non-equal item difficulty for different time periods commonly found with clinical retrograde amnesia tests. Using these analytical tools, we review studies of temporal gradients in the memory of patients with Korsakoff’s Disease, Alzheimer’s Dementia, Huntington’s Disease, and other disorders.
Whole-body cryotherapy (WBC), which consists of a short exposure to very cold and dry air in special ‘cryo-chambers’, is believed to reduce inflammation and musculoskeletal pain as well as improve athletes' recovery. This is the case of a 63-year-old male, who presented with transient global amnesia (TGA) after undertaking a WBC session. TGA is a clinical syndrome characterised by a sudden onset of anterograde amnesia, sometimes coupled with a retrograde component, lasting up to 24 hours without other neurological deficits. Even though the patient completely recovered, as expected, in 24 hours, this case highlights that WBC is potentially not as risk free as thought to be initially. To conclude, before WBC can be medically recommended, well-conducted studies investigating the possible adverse events are required.
Alzheimer’s disease (AD) is characterized by retrograde memory deficits primarily caused by dysfunction of the hippocampal complex. Unresolved questions exist concerning the time course of hippocampal involvement in conscious recollection of declarative knowledge, as reports of temporal gradients of retrograde amnesia have been inconclusive. The aim of this study was to examine whether the extent and severity of retrograde amnesia is mediated by retrieval frequency or, in contrast, whether it depends on the age of the memory according to the assumptions of the main current theories of memory formation. We compared recall of past public events in patients with AD and healthy control (HC) individuals using the Historic Events Test (HET). The HET assesses knowledge about famous public events of the past 60 years divided into four time segments and consists of subjective memory rating, dating accuracy, and contextual memory tasks. Although memory for public events was impaired in AD patients, there was a strong effect of retrieval frequency across all time segments and both groups. As AD and HC groups derived similar benefits from greater retrieval frequency, cortical structures other than the hippocampal complex may mediate memory retrieval. These findings suggest that more frequently retrieved events and facts become more independent of the hippocampal complex and thus better protected against early damage of AD. This could explain why cognitive activity may delay the onset of memory decline in persons who develop AD.
Bilateral thalamic infarction involving the artery of Percheron (AOP) can cause diagnostic difficulties due to the varying clinical presentations. AOP infarcts presented with isolated memory impairment are not common and the factors affecting the persistence of memory disorders are still unknown. A 41-year-old male patient was hospitalized with acute unconsciousness. MRI disclosed bilateral paramedian thalamic infarction The patient had isolated memory deficit and his anterograde amnesia continued without any change in the past decade. More cases might answer the questions concerning the intra- and extra-thalamic structures responsible for the amnesic syndrome and the factors affecting the persistence of the symptoms.
Post-traumatic amnesia (PTA) after traumatic brain injury (TBI) comprises anterograde amnesia (AA), disorientation and retrograde amnesia (RA). However, RA is often neither assessed nor emphasized. A recent study demonstrated that, whilst AA and disorientation were both present in non-TBI in-patients uniformly taking opioids, RA was absent. This suggests potentially significant utility with RA-assessment alone, since opioids are commonly prescribed post-TBI.
Efficacy and harms of pharmacological interventions for neurobehavioral symptoms in post traumatic amnesia after traumatic brain injury: a systematic review and meta-analysis protocol
- JBI database of systematic reviews and implementation reports
- Published over 2 years ago
The objective of this systematic review is to synthesize the best available evidence on the effectiveness and harms of pharmacotherapy as compared to all types of comparators for the management of neurobehavioral symptoms in post-traumatic amnesia in adults aged 16 years and over who have sustained a traumatic brain injury. This review forms part of a larger project which aims to gather the evidence for the pharmacological treatment of neurobehavioral symptoms post traumatic brain injury as a prelude to the development of a clinical guideline.
Autobiographical amnesia is found in patients with focal or diffuse brain damage (“organic amnesia”), but also without overt brain damage (at least when measured with conventional brain imaging methods). This last condition is usually named dissociative amnesia at present, and was originally described as hysteria. Classically and traditionally, dissociative amnesia is seen as a disorder that causes retrograde amnesia in the autobiographical domain in the aftermath of incidents of major psychological stress or trauma. In the present study one of the probably largest published collections of patients (28) with psychogenically caused autobiographical amnesia, who were assessed with comprehensive neuropsychological tests, will be described and documented in order to identify variables which are central for the occurrence of dissociative amnesia. The presented cases demonstrate that autobiographical amnesia without direct brain damage can have very mixed clinical presentations, causes and consequences. The described cases of psychogenic amnesia are clustered according to a number of manifestations and features, which include a reduced effort to perform cognitively at a normal level, a forensic background, anterograde (instead of retrograde) autobiographical amnesia, the fugue condition, concurrent somatic diseases, and their appearance in childhood and youth. It is concluded that autobiographical amnesia of a psychogenic origin may occur within a variety of symptom pictures. For all patients, it probably serves a protective function by offering them a mechanism to exit a life situation which appears to them unmanageable or adverse.