In neurology, anterograde amnesia is the inability to create new memories after an event that caused amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories created prior to the event are lost while new memories can still be created. Both can occur together in the same patient. To a large degree, anterograde amnesia remains a mysterious ailment because the precise mechanism of storing memories is not yet well understood, although it is known that the regions of the brain involved are certain sites in the temporal cortex, especially in the hippocampus and nearby subcortical regions.
Signs and symptoms People with anterograde amnesic syndromes may present widely varying degrees of forgetfulness. Some with severe cases have a combined form of anterograde and retrograde amnesia, sometimes called global amnesia.
In the case of drug-induced amnesia, it may be short-lived and patients can recover from it. In another case, which has been studied extensively since the early 1970s, patients often have permanent damage, although some recovery is possible, depending on the nature of the pathophysiology. Usually, some capacity for learning remains, although it may be very elementary. In cases of pure anterograde amnesia, patients have recollections of events prior to the injury, but cannot recall day-to-day information or new facts presented to them after the injury occurred.
In most cases of anterograde amnesia, patients lose explicit memory, or the recollection of facts, while retaining procedural memory. For instance, one may preserve the skill required to complete some tasks, e.g., using a telephone or riding a bike, but they may not remember what they had eaten earlier that day for lunch. One extensively studied anterograde amnesiac patient, codenamed H.M., demonstrated that despite his amnesia preventing him from learning new declarative information, procedural memory consolidation was still possible, albeit at a severely reduced pace. He, along with other patients with anterograde amnesia, were given the same maze to complete day after day.Downes JJ, Mayes AR, MacDonald C, Hunkin NM. "Temporal order memory in patients with Korsakoff's syndrome and medial temporal amnesia" Neuropsychologia 2002; 40(7):853–61.
Despite having no memory of having completed the maze the day before, unconscious practice of completing the same maze over and over reduced the amount of time needed to complete it in subsequent trials. From these results, Corkin et al. concluded despite having no declarative memory (i.e. no conscious memory of completing the maze exists), the patients still had a working procedural memory (learning done unconsciously through practice). This supports the notion that declarative and procedural memory are consolidated in different areas of the brain. Patients have a diminished ability to remember the temporal context in which objects were presented. Certain authors claim the deficit in temporal context memory is more significant than the deficit in the semantic learning ability (described below).
Causes This disorder is usually acquired in one of four ways. One cause is the use of benzodiazepine drugs such as midazolam, flunitrazepam, lorazepam, temazepam, nitrazepam, triazolam, clonazepam, alprazolam, diazepam, and nimetazepam. All of these are known to have powerful amnesic effects. This has also been recorded in non-benzodiazepine sedatives or "z-drugs" which act on the same set of receptors, such as zolpidem (also known as Ambien), eszopiclone (also known as Lunesta), and zopiclone (also known by brand names Imovane and Zimovane). A second cause is a traumatic brain injury in which damage is usually done to the hippocampus or surrounding cortices. It may also be caused by PTSD, a shocking event, or an emotional disorder.
Illness, though much rarer, can also cause anterograde amnesia if it causes encephalitis, which is the inflammation of brain tissue. There are several types of encephalitis: one such is herpes simplex encephalitis (HSV), which, if left untreated, can lead to neurological deterioration. How HSV gains access to the brain is unknown. The virus shows a distinct predilection for certain parts of the brain. Initially, it is present in the limbic cortices. It may then spread to the adjacent frontal and temporal lobes. Damage to specific areas can result in reduced or eliminated ability to encode new explicit memories, giving rise to anterograde amnesia.Ishihara K, Kawamura M, Kaga E, Katoh T, Shiota J. "Amnesia following herpes simplex encephalitis". Brain and Nerve (Tokyo) Volume: 52 Issue: 11 pp. 979–83 Published: November, 2000.
Patients with anterograde amnesia may have episodic, semantic, or both types of explicit memory impaired for events after the trauma that caused the amnesia. This suggests that memory consolidation for different types of memory takes place in different regions of the brain. Despite this, current knowledge on human memory is still insufficient to "map out" the wiring of a human brain to discover which parts of which lobe are responsible for the various episodic and semantic knowledge within a person's memory.
Amnesia is seen in patients who, for the reason of preventing another more serious disorder, have parts of their brains known to be involved in memory circuits removed, the most notable of which is known as the medial temporal lobe (MTL) memory system, described below. Patients with seizures originating in the MTL may have either side or both structures removed (there is one structure per hemisphere). Patients with tumors who undergo surgery will often sustain damage to these structures, as is described in a case below. Damage to any part of this system, including the hippocampus and surrounding cortices, results in amnesic syndromes. This is why after a stroke people have a chance of developing cognitive deficits that result in anterograde amnesia, since strokes can involve the temporal lobe in the temporal cortex, and the temporal cortex houses the hippocampus.
Anterograde amnesia can be the first clinical sign that Alzheimer's disease is developing within the brain. Although later the complications can be much more widespread and strongly impair cognitive processes, at the initial stage of Alzheimer's the changes observed can be restricted to anterograde amnesia and a mild deficit in retaining newly learnt sequences. This is explained by the fact that the disease is initiated within the medial temporal lobe and first affects the entorhinal cortex that directly sends and receives information from the hippocampal formation.
Alcohol intoxication
Anterograde amnesia can also be caused by alcohol intoxication, a phenomenon commonly known as a blackout. Studies show rapid rises in blood alcohol concentration over a short period of time severely impair or in some cases completely block the brain's ability to transfer short-term memories created during the period of intoxication to long-term memory for storage and later retrieval. Such rapid rises are caused by drinking large amounts of alcohol in short periods of time, especially on an empty stomach, as the dilution of alcohol by food slows the absorption of alcohol. Alcohol-related anterograde amnesia is directly related to the rate of consumption of alcohol, and is often associated with binge drinking, and not just the total amount of alcohol consumed in a drinking episode.
Test subjects have been found not to experience amnesia when drinking slowly, despite being heavily intoxicated by the end of the experiment. When alcohol is consumed at a rapid rate, the point at which most healthy people's long-term memory creation starts to fail usually occurs at approximately 0.20% BAC, but can be reached as low as 0.14% BAC for infrequent drinkers. The exact duration of these blackout periods is hard to determine, because most people fall asleep before they black out. Upon reaching sobriety, usually after waking, long-term memory creation is completely restored.
Severe alcohol use disorder is associated with thiamine (vitamin B1) deficiency in the brain, which can cause Korsakoff syndrome and is often preceded by Wernicke encephalopathy.
The memory impairment that is pathognomonic to Korsakoff's syndrome predominantly affects the declarative memory, leaving non-declarative memory that is often procedural in nature relatively intact.Hayes, S., Fortier, C., Levine, A., Milberg, W., McGlinchey, R. "Implicit Memory in Korsakoff's Syndrome: A Review of Procedural Learning and Priming Studies". Neuropsychol Rev (2012) 22:132–53. The disproportionate severity in anterograde episodic memory processes in contrast to other cognitive processes is what differentiates Korsakoff syndrome from other conditions such as alcohol-related dementia. Evidence for the preservation of certain memory processes in the presence of severe anterograde episodic memory serve as an experimental paradigm to investigate the components of human memory.
Pathophysiology The pathophysiology of anterograde amnesic syndromes varies with the extent of damage and the regions of the brain that were damaged. The most well-described regions indicated in this disorder are the medial temporal lobe (MTL), basal forebrain, and fornix. Beyond the details described below, the precise process of how we remember – on a micro scale – remains a mystery. Neuropsychologists and scientists are still not in total agreement over whether forgetting is due to faulty encoding, accelerated forgetting, or faulty retrieval, although a great deal of data seem to point to the encoding hypothesis.
Neuroscientists are in disagreement about the length of time involved in memory consolidation. Though most researchers, including Hasselmo et al., have found the consolidation process is spread out over several hours before transitioning from a fragile to a more permanent state, others, including Brown et al., posits that memory consolidation can take months or even years in a drawn-out process of consolidation and reinforcement. Further research into the length of time of memory consolidation will shed more light on why anterograde amnesia sometimes affects some memories gained after the event(s) that caused the amnesia, but does not affect other such memories.
Medial temporal lobe
The MTL memory system includes the hippocampal formation (CA fields, dentate gyrus, subicular complex), perirhinal, entorhinal, and parahippocampal cortices. It is known to be important for the storage and processing of declarative memory, which allows for factual recall. It is also known to communicate with the neocortex in the establishment and maintenance of long-term memories, although its known functions are independent of long-term memory. Nondeclarative memory, on the other hand, which allows for the performance of different skills and habits, is not part of the MTL memory system. Most data point to a "division of labor" among the parts of this system, although this is still being debated and is described in detail below.
In animal models, researchers have shown monkeys with damage to both the hippocampus and its adjacent cortical regions were more severely impaired in terms of anterograde amnesia than monkeys with damage localized to hippocampal structures. However, conflicting data in another primate study points to the observation that the amount of tissue damaged does not necessarily correlate with the severity of the memory loss.Easton A, Parker A. "A cholinergic explanation of dense amnesia". Cortex. 2003 Sep–Dec; 39(4–5):813–26. The data does not explain the dichotomy that exists in the MTL memory system between episodic memory and semantic memory (described below).