Anterograde amnesia
Encyclopedia
Anterograde amnesia is a loss of the ability to create new memories
after the event that caused the 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. 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 involved are certain sites in the temporal cortex, especially in the hippocampus
and nearby subcortical regions.
is usually acquired in one of few ways: One type of cause is from agents like benzodiazepine
s, such as midazolam
, flunitrazepam
, lorazepam
, temazepam
, triazolam
, and nimetazepam
, which are known to have powerful amnesic effects. Another type of cause is a traumatic brain injury
in which there is usually damage to the hippocampus
or surrounding cortices. It can also be caused by shock or an emotional disorder. Illness, though much rarer, can also cause anterograde amnesia if it causes encephalitis, which is the inflammation of brain tissue. For example, herpes simplex virus type I, when left untreated for over ninety-six hours, may lead to permanent damage in hippocampal regions and lead to a permanent reduced or eliminated ability to encode new explicit memory (also known as declarative memory), which consists of two main subdivisions: episodic memory and semantic memory. If the damage due to encephalitis is over a certain threshold, encoding new episodic and/or semantic memory becomes impossible for the patient, leading to anterograde amnesia. Patients suffering from anterograde amnesia may have either 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 decades away from the ability to “map out” the wiring of a human brain in order 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 brain that are 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 seizure
s that originate in the MTL may have either side or both structures removed (there is one structure per hemisphere). In addition, patients with tumor
s 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 people who suffer from strokes have a chance of developing cognitive deficits that result in anterograde amnesia, since strokes can involve the temporal lobe and the temporal cortex, and the temporal cortex houses the hippocampus. As mentioned above, damage to the hippocampus and surrounding subcortical regions directly lead to anterograde amnesia.
, a phenomenon commonly known as a blackout. Studies show that rapid rises in blood alcohol concentration over a short period of time severely impairs or in some cases completely blocks 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 in blood alcohol concentration are caused by drinking large amounts of alcohol in short periods of time, especially on an empty stomach
, as the digestion
of 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 0.2% BAC, but can be reached as low as 0.14% BAC for inexperienced drinkers. The exact duration of these blackout periods is hard to determine, because most people fall asleep before they end. Upon reaching sobriety, usually after waking, long-term memory creation is completely restored.
Another common cause of anterograde amnesia related to consumption of alcohol is the effects of Korsakoff’s syndrome, a neurological disorder caused by the lack of thiamine (vitamin B1) in the brain. Chronic alcoholism causes this malnutrition, resulting in the syndrome, and among the symptoms of Korsakoff’s syndrome are apathy, confabulation (delusions that result in invented memories), and anterograde amnesia.
. Some patients with severe cases have a combined form of anterograde and retrograde amnesia, sometimes called global amnesia.
In the case that the amnesia is drug-induced, it may be short-lived and patients can recover from it. In the other case, which has been studied extensively since the early 1970s, patients often have damage that is permanent, although some recovery is possible, depending on the nature of the pathophysiology
. Usually, there remains some capacity for learning 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 that were presented to them after the injury occurred.
In most cases of anterograde amnesia, patients lose declarative memory
, or the recollection of facts, but they retain non-declarative memory, often called procedural memory
. For instance, they are able to remember and in some cases learn how to do things such as talking on the phone or riding a bicycle, 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 severely reduced in power. He, along with other patients with anterograde amnesia, were given the same maze to complete day after day. 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 that 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. In addition, patients have a diminished ability to remember the temporal context in which objects were presented. Certain authors claim that the deficit in temporal context memory is more significant than the deficit in semantic learning ability (described below).
, 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. In addition, neuroscientists are also in disagreement about the length of time involved in memory consolidation. Though most researchers including Hasselmo et al., have found that the consolidation process is spread out over several hours before transitioning from a fragile to a more permanent state, others, including Brown et al., posit 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.
, 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
. Non-declarative 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 that 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 point to the observation that the amount of tissue damaged does not necessarily correlate with the severity of the memory loss. Furthermore, the data does not explain the dichotomy that exists in the MTL memory system between episodic memory
and semantic memory
(described below).
An important finding in amnesic patients with MTL damage is the impairment of memory in all sensory modalities – sound, touch, smell, taste, sight. This reflects the fact that the MTL is a processor for all of the sensory modalities, and helps store these kind of thoughts into memory. In addition, subjects can often remember how to perform relatively simple tasks immediately (on the order of 10 seconds), but when the task becomes more difficult, even on the same time scale, subjects tend to forget. This demonstrates the difficulty of separating procedural memory
tasks from declarative memory; some elements of declarative memory may be used in learning procedural tasks.
MTL amnesic patients with localized damage to the hippocampus retain other perceptual abilities, such as the ability to intelligently function in society, to make conversation, to make one’s bed, etc. Additionally, anterograde amnesics without combined retrograde disorders (localized damage to the MTL system) have memories prior to the traumatic event. For this reason, the MTL is not the storage place of all memories; other regions in the brain also store memories. The key is that the MTL is responsible for the learning of new materials.
Another case described the onset of anterograde amnesia as a result of cell death in the fornix, another structure that carries information from the hippocampus to the structures of the limbic system
and the diencephalon
. The patient in this case did not show any disconnection syndrome, which is unexpected since the structures involved divide the brain hemispheres (both sides of her brain were able to communicate). Instead, she showed signs of amnesia. The final diagnosis was made by MRI. This particular amnesic syndrome is difficult to diagnose and often gets misdiagnosed by physicians as an acute psychiatric disorder.
describes the ability of the cortex to remap when necessary. Remapping can occur in cases like the one above, and, with time, the patient can recover and become more skilled at remembering. A case report describing a patient who had two lobectomies - in the first, doctors removed part of her right MTL first because of seizures originating from the region, and later her left because she developed a tumor — demonstrates this. This case is unique because it is the only one in which both sides of the MTL were removed at different times. The authors observed that the patient was able to recover some ability to learn when she had only one MTL, but observed the deterioration of function when both sides of the MTL were afflicted. The reorganization of brain function for epileptic patients has not been investigated much, but imaging results show that it is likely.
, known as H.M., in March 1953. H.M.'s chief complaint was the persistence of severe seizures after he had a bilateral lobectomy (both of his MTLs were removed). As a result, H.M. had bilateral damage to both the hippocampal formation and the perirhinal cortex
. H.M. had normal intelligence and perceptual ability and a decent vocabulary. However, he could not learn new words or remember things that had happened more than a few minutes earlier. However, he was able to learn some new skills. He was the first well-documented case of severe anterograde amnesia, and was still being studied until his death in 2008.
A similarly notable case was Clive Wearing
, an accomplished musicologist who contracted a cold virus that attacked his brain, causing Herpes simplex encephalitis. As a result, Wearing developed anterograde amnesia as well as retrograde amnesia, so he has little memory of what happened before the virus struck him in 1985 and cannot learn new declarative knowledge after the virus struck him as well. As a result of anterograde amnesia, Wearing repeatedly “wakes up” every day in thirty second intervals until his wife stops him because his episodic memory is non-functional (so he does not consciously recall having woken up thirty seconds prior). Despite this, however, Wearing maintained his ability to play the piano and conduct choirs. This is significant because it is a case study that demonstrates that declarative and procedural memory are separate. Therefore, despite that anterograde amnesia prevented Wearing from learning new bits of information that can be explained in words (declarative memory) and also prevented him from storing new memories of events or episodes (also part of declarative memory), he has little trouble in retaining his musical abilities (procedural memory) even though he has no conscious memory of having learned music.
Another remarkable case in the literature is E.P., a severely amnesic patient who was able to learn 3-word sentences. He performed better on consecutive tests over a 12-week period (24 study sessions). However, when asked how confident he was about the answers, it did not appear that his confidence increased. Bayley and Squire proposed that his learning was similar to the process required by procedural memory tasks; E.P. could not get the answers right when one word in the 3-word sentence was changed or the order of words was changed, and his ability to answer correctly, thus, became more of a "habit." Bayley and Squire claim that the learning may have happened in the neocortex, and that it happened without the conscious knowledge of E.P. They hypothesized that information may be acquired directly by the neocortex (which the hippocampus projects to) when there is repetition. This case illustrates the difficulty in separating procedural from declarative tasks; this adds another dimension to the complexity of anterograde amnesia.
One patient known by the codename Gene was involved in a motorcycle accident that damaged significant portions of his frontal and temporal lobes, including his left hippocampus. As a result, he cannot remember any specific episode in his life, such as a train derailment near his house. However, his semantic memory is intact; he remembers that he owns a car and two motorcycles, and he can even remember the names of his classmates in a school photograph.
In stark contrast, a woman whose temporal lobes were damaged in the front due to encephalitis lost her semantic memory; she lost her memory of many simple words, historical events, and other trivial information categorized under semantic memory. However, her episodic memory was left intact; she can recall episodes such as her wedding and her father’s death with great detail.
Vicari et al. describe that it remains unclear whether or not neural circuits involved in semantic and episodic memory overlap partially or completely, and this case seems to suggest that the two systems are independent. Both of the patient's hippocampal and diencephalic structures on the right and left sides were disconnected. When she came to Vicari et al.’s office, the patient C.L.’s chief complaint was forgetfulness involving both semantic and episodic memory. After administering a battery of neuropsychological tests, Vicari determined that C.L. performed well in tests of visual naming and sentence comprehension, visual-spatial ability, and “general semantic knowledge about the world.” They also noted an improved vocabulary and general knowledge base after 18 months. C.L.’s episodic memory, on the other hand, was far below expectations: She could not retain daily events, where she had gone on vacation, the names of places she had been, and other such information. However, this study and others like it are susceptible to subjectivity, since it is not always clear to distinguish between episodic and semantic memory. For this reason, the topic remains controversial and debated.
Poreh et al. describe a case study of patient A.D., whose damage to the fornix rendered the hippocampus useless but spared adjacent cortical areas — a fairly rare injury. When the patient was given a test with something he had some familiarity with, the patient was able to score well. In general, however, A.D. had severely impaired episodic memory but had some ability to learn semantic knowledge. Other studies show that animals with similar injuries can recognize objects with which they are familiar, but, when the objects are presented in a context that is unexpected, they do not score well on recognition tests.
), 50 First Dates
(humor), and the Star Trek: Enterprise
episode "Twilight" (plot device/tragic - a tragedy averted when the cure turns out to be retroactive). Dana Carvey
's character in the movie Clean Slate also had anterograde amnesia as a central plot point. The Tamil
action film Ghajini, based on the film Memento, and its Hindi remake
also uses anterograde amnesia as a central plot point, with the amnesiac protagonist played by Surya Sivakumar in the Tamil version
and by Aamir Khan
in the Hindi version
.
Another fictional character who suffers the illness is the Professor in the novel The Professor and the Housekeeper by Yoko Ogawa
. It is also suffered by Dory in the film Finding Nemo
, by Liz Lemon
's brother Mitch Lemon on 30 Rock
, and by Chihiro Shindo from Ef: A Fairy Tale of the Two. Gene Wolfe
's trilogy beginning with Soldier of the Mist
is written as the diary of a soldier in the Greco-Persian Wars
who suffers from the condition. The main character in Meg Gardiner
's novel The Memory Collector suffers brain damage brought on by contamination with a material containing carbon nanotubes.
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
after the event that caused the amnesia
Amnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause 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
Retrograde amnesia
Retrograde amnesia is a loss of access to events that occurred, or information that was learned, before an injury or the onset of a disease....
, where memories created prior to the event are lost. 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 involved are certain sites in the temporal cortex, especially in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
and nearby subcortical regions.
Causes
This disorderDisease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
is usually acquired in one of few ways: One type of cause is from agents like benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s, such as midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...
, flunitrazepam
Flunitrazepam
Flunitrazepam is marketed as a potent hypnotic, sedative, anticonvulsant, anxiolytic, amnestic, and skeletal muscle relaxant drug most commonly known as Rohypnol...
, lorazepam
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
, temazepam
Temazepam
Temazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is mostly prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep...
, triazolam
Triazolam
Triazolam is a benzodiazepine drug. It possesses pharmacological properties similar to that of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia...
, and nimetazepam
Nimetazepam
Nimetazepam is an intermediate-acting hypnotic drug which is a benzodiazepine derivative. It was first synthesized by a team at Hoffmann-La Roche in 1962. It possesses hypnotic, anxiolytic, sedative, and skeletal muscle relaxant properties. Nimetazepam is also an anticonvulsant. It is sold in 5 mg...
, which are known to have powerful amnesic effects. Another type of cause is a traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
in which there is usually damage to the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
or surrounding cortices. It can also be caused by shock or an emotional disorder. Illness, though much rarer, can also cause anterograde amnesia if it causes encephalitis, which is the inflammation of brain tissue. For example, herpes simplex virus type I, when left untreated for over ninety-six hours, may lead to permanent damage in hippocampal regions and lead to a permanent reduced or eliminated ability to encode new explicit memory (also known as declarative memory), which consists of two main subdivisions: episodic memory and semantic memory. If the damage due to encephalitis is over a certain threshold, encoding new episodic and/or semantic memory becomes impossible for the patient, leading to anterograde amnesia. Patients suffering from anterograde amnesia may have either 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 decades away from the ability to “map out” the wiring of a human brain in order 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 brain that are known to be involved in memory circuits removed, the most notable of which is known as the medial temporal lobe
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
(MTL) memory system, described below. Patients with seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s that originate in the MTL may have either side or both structures removed (there is one structure per hemisphere). In addition, patients with tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s 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 people who suffer from strokes have a chance of developing cognitive deficits that result in anterograde amnesia, since strokes can involve the temporal lobe and the temporal cortex, and the temporal cortex houses the hippocampus. As mentioned above, damage to the hippocampus and surrounding subcortical regions directly lead to anterograde amnesia.
Alcohol intoxication
Anterograde amnesia can also be caused by alcohol intoxicationShort-term effects of alcohol
Short-term effects of alcohol on the human body can take many forms. The drug alcohol, to be specific ethanol, is a central nervous system depressant with a range of side-effects. The amount and circumstances of consumption play a large part in determining the extent of intoxication; for example,...
, a phenomenon commonly known as a blackout. Studies show that rapid rises in blood alcohol concentration over a short period of time severely impairs or in some cases completely blocks the brain's
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
ability to transfer short-term memories
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
created during the period of intoxication to long-term memory for storage and later retrieval. Such rapid rises in blood alcohol concentration are caused by drinking large amounts of alcohol in short periods of time, especially on an empty stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
, as the digestion
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
of 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
Binge drinking
Binge drinking or heavy episodic drinking is the modern epithet for drinking alcoholic beverages with the primary intention of becoming intoxicated by heavy consumption of alcohol over a short period of time. It is a kind of purposeful drinking style that is popular in several countries worldwide,...
), 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 0.2% BAC, but can be reached as low as 0.14% BAC for inexperienced drinkers. The exact duration of these blackout periods is hard to determine, because most people fall asleep before they end. Upon reaching sobriety, usually after waking, long-term memory creation is completely restored.
Another common cause of anterograde amnesia related to consumption of alcohol is the effects of Korsakoff’s syndrome, a neurological disorder caused by the lack of thiamine (vitamin B1) in the brain. Chronic alcoholism causes this malnutrition, resulting in the syndrome, and among the symptoms of Korsakoff’s syndrome are apathy, confabulation (delusions that result in invented memories), and anterograde amnesia.
Symptoms
Patients who suffer from anterograde amnesic syndromes may present with widely varying degrees of forgetfulnessForgetting
Forgetting refers to apparent loss of information already encoded and stored in an individual's long term memory. It is a spontaneous or gradual process in which old memories are unable to be recalled from memory storage. It is subject to delicately balanced optimization that ensures that...
. Some patients with severe cases have a combined form of anterograde and retrograde amnesia, sometimes called global amnesia.
In the case that the amnesia is drug-induced, it may be short-lived and patients can recover from it. In the other case, which has been studied extensively since the early 1970s, patients often have damage that is permanent, although some recovery is possible, depending on the nature of the pathophysiology
Pathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
. Usually, there remains some capacity for learning 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 that were presented to them after the injury occurred.
In most cases of anterograde amnesia, patients lose declarative memory
Declarative memory
Declarative memory is one of two types of long term human memory. It refers to memories which can be consciously recalled such as facts and knowledge. Its counterpart is known as non-declarative or Procedural memory, which refers to unconscious memories such as skills...
, or the recollection of facts, but they retain non-declarative memory, often called procedural memory
Procedural memory
Procedural memory is memory for how to do things. Procedural memory guides the processes we perform and most frequently resides below the level of conscious awareness. When needed, procedural memories are automatically retrieved and utilized for the execution of the integrated procedures involved...
. For instance, they are able to remember and in some cases learn how to do things such as talking on the phone or riding a bicycle, 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 severely reduced in power. He, along with other patients with anterograde amnesia, were given the same maze to complete day after day. 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 that 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. In addition, patients have a diminished ability to remember the temporal context in which objects were presented. Certain authors claim that the deficit in temporal context memory is more significant than the deficit in semantic learning ability (described below).
Pathophysiology
The pathophysiology of anterograde amnesic syndromes varies with the extent of damage and the regions of the brains that were damaged. The most well-described regions indicated in this disorder are the medial temporal lobe (MTL), basal forebrainBasal forebrain
The basal forebrain is a collection of structures located ventrally to the striatum. It is considered to be the major cholinergic output of the central nervous system . It includes a group of structures that lie near the bottom of the front of the brain, including the nucleus basalis, diagonal band...
, and fornix. Beyond the details described below, the precise process of how we remember — on a micro scale — remains a mystery. Neuropsychologists
Neuropsychology
Neuropsychology studies the structure and function of the brain related to specific psychological processes and behaviors. The term neuropsychology has been applied to lesion studies in humans and animals. It has also been applied to efforts to record electrical activity from individual cells in...
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. In addition, neuroscientists are also in disagreement about the length of time involved in memory consolidation. Though most researchers including Hasselmo et al., have found that the consolidation process is spread out over several hours before transitioning from a fragile to a more permanent state, others, including Brown et al., posit 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 gyrusDentate gyrus
The dentate gyrus is part of the hippocampal formation. It is thought to contribute to new memories as well as other functional roles. It is notable as being one of a select few brain structures currently known to have high rates of neurogenesis in adult rats, .The dentate gyrus cells receive...
, subicular complex), perirhinal
Perirhinal cortex
Perirhinal cortex is a cortical region in the medial temporal lobe that is made up of Brodmann areas 35 and 36. In rats, it is located along and dorsal to the rhinal sulcus. It receives highly-processed sensory information from all sensory regions, and is generally accepted to be an important...
, entorhinal
Entorhinal cortex
The entorhinal cortex is located in the medial temporal lobe and functions as a hub in a widespread network for memory and navigation. The EC is the main interface between the hippocampus and neocortex...
, and parahippocampal cortices. It is known to be important for the storage and processing of declarative memory
Declarative memory
Declarative memory is one of two types of long term human memory. It refers to memories which can be consciously recalled such as facts and knowledge. Its counterpart is known as non-declarative or Procedural memory, which refers to unconscious memories such as skills...
, which allows for factual recall. It is also known to communicate with the neocortex
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
in the establishment and maintenance of long-term memories, although its known functions are independent of long-term memory
Long-term memory
Long-term memory is memory in which associations among items are stored, as part of the theory of a dual-store memory model. According to the theory, long term memory differs structurally and functionally from working memory or short-term memory, which ostensibly stores items for only around 20–30...
. Non-declarative 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 that 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 point to the observation that the amount of tissue damaged does not necessarily correlate with the severity of the memory loss. Furthermore, the data does not explain the dichotomy that exists in the MTL memory system between episodic memory
Episodic memory
Episodic memory is the memory of autobiographical events that can be explicitly stated. Semantic and episodic memory together make up the category of declarative memory, which is one of the two major divisions in memory...
and semantic memory
Semantic memory
Semantic memory refers to the memory of meanings, understandings, and other concept-based knowledge unrelated to specific experiences. The conscious recollection of factual information and general knowledge about the world is generally thought to be independent of context and personal relevance...
(described below).
An important finding in amnesic patients with MTL damage is the impairment of memory in all sensory modalities – sound, touch, smell, taste, sight. This reflects the fact that the MTL is a processor for all of the sensory modalities, and helps store these kind of thoughts into memory. In addition, subjects can often remember how to perform relatively simple tasks immediately (on the order of 10 seconds), but when the task becomes more difficult, even on the same time scale, subjects tend to forget. This demonstrates the difficulty of separating procedural memory
Procedural memory
Procedural memory is memory for how to do things. Procedural memory guides the processes we perform and most frequently resides below the level of conscious awareness. When needed, procedural memories are automatically retrieved and utilized for the execution of the integrated procedures involved...
tasks from declarative memory; some elements of declarative memory may be used in learning procedural tasks.
MTL amnesic patients with localized damage to the hippocampus retain other perceptual abilities, such as the ability to intelligently function in society, to make conversation, to make one’s bed, etc. Additionally, anterograde amnesics without combined retrograde disorders (localized damage to the MTL system) have memories prior to the traumatic event. For this reason, the MTL is not the storage place of all memories; other regions in the brain also store memories. The key is that the MTL is responsible for the learning of new materials.
Other memory systems
A limited number of cases have been described in which patients with damage to other parts of the brain acquired anterograde amnesia. Easton and Parker observed that damage to either the hippocampus or the surrounding cortices does not seem to result in severe amnesia in primate models. They suggested that damage to the hippocampus and surrounding structures alone does not explain the amnesia that they saw in patients, or the fact that increasing damage does not correlate with the degree of impairment. Furthermore, the data do not explain the dichotomy that exists in the MTL memory system between episodic and semantic memory (described below). To demonstrate their hypothesis, they used a primate model with damage to the basal forebrain. They proposed that the disruption of neurons that project from the basal forebrain to the MTL are responsible for some of the impairment in anterograde amnesia. Easton and Parker also report that MRI scans of patients with severe anterograde amnesia show damage beyond to cortical areas around the hippocampus and amygdala (a region of brain involved in emotions) and to surrounding white matter (white matter in the brain consists of axons, long projections of neuronal cell bodies).Another case described the onset of anterograde amnesia as a result of cell death in the fornix, another structure that carries information from the hippocampus to the structures of the limbic system
Limbic system
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...
and the diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
. The patient in this case did not show any disconnection syndrome, which is unexpected since the structures involved divide the brain hemispheres (both sides of her brain were able to communicate). Instead, she showed signs of amnesia. The final diagnosis was made by MRI. This particular amnesic syndrome is difficult to diagnose and often gets misdiagnosed by physicians as an acute psychiatric disorder.
Reorganization of memory
When there is damage to just one side of the MTL, there is opportunity for normal functioning or near-normal function for memories. NeuroplasticityNeuroplasticity
Neuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
describes the ability of the cortex to remap when necessary. Remapping can occur in cases like the one above, and, with time, the patient can recover and become more skilled at remembering. A case report describing a patient who had two lobectomies - in the first, doctors removed part of her right MTL first because of seizures originating from the region, and later her left because she developed a tumor — demonstrates this. This case is unique because it is the only one in which both sides of the MTL were removed at different times. The authors observed that the patient was able to recover some ability to learn when she had only one MTL, but observed the deterioration of function when both sides of the MTL were afflicted. The reorganization of brain function for epileptic patients has not been investigated much, but imaging results show that it is likely.
Famous cases
The most famous case that has been reported is that of patient Henry MolaisonHM (patient)
Henry Gustav Molaison , famously known as HM or H.M., was an American memory disorder patient who was widely studied from late 1957 until his death...
, known as H.M., in March 1953. H.M.'s chief complaint was the persistence of severe seizures after he had a bilateral lobectomy (both of his MTLs were removed). As a result, H.M. had bilateral damage to both the hippocampal formation and the perirhinal cortex
Perirhinal cortex
Perirhinal cortex is a cortical region in the medial temporal lobe that is made up of Brodmann areas 35 and 36. In rats, it is located along and dorsal to the rhinal sulcus. It receives highly-processed sensory information from all sensory regions, and is generally accepted to be an important...
. H.M. had normal intelligence and perceptual ability and a decent vocabulary. However, he could not learn new words or remember things that had happened more than a few minutes earlier. However, he was able to learn some new skills. He was the first well-documented case of severe anterograde amnesia, and was still being studied until his death in 2008.
A similarly notable case was Clive Wearing
Clive Wearing
Clive Wearing is a British musicologist, conductor, and keyboardist suffering from an acute and long-lasting case of anterograde and retrograde amnesia, meaning that he lacks the ability to form new memories.-Musical career:...
, an accomplished musicologist who contracted a cold virus that attacked his brain, causing Herpes simplex encephalitis. As a result, Wearing developed anterograde amnesia as well as retrograde amnesia, so he has little memory of what happened before the virus struck him in 1985 and cannot learn new declarative knowledge after the virus struck him as well. As a result of anterograde amnesia, Wearing repeatedly “wakes up” every day in thirty second intervals until his wife stops him because his episodic memory is non-functional (so he does not consciously recall having woken up thirty seconds prior). Despite this, however, Wearing maintained his ability to play the piano and conduct choirs. This is significant because it is a case study that demonstrates that declarative and procedural memory are separate. Therefore, despite that anterograde amnesia prevented Wearing from learning new bits of information that can be explained in words (declarative memory) and also prevented him from storing new memories of events or episodes (also part of declarative memory), he has little trouble in retaining his musical abilities (procedural memory) even though he has no conscious memory of having learned music.
Another remarkable case in the literature is E.P., a severely amnesic patient who was able to learn 3-word sentences. He performed better on consecutive tests over a 12-week period (24 study sessions). However, when asked how confident he was about the answers, it did not appear that his confidence increased. Bayley and Squire proposed that his learning was similar to the process required by procedural memory tasks; E.P. could not get the answers right when one word in the 3-word sentence was changed or the order of words was changed, and his ability to answer correctly, thus, became more of a "habit." Bayley and Squire claim that the learning may have happened in the neocortex, and that it happened without the conscious knowledge of E.P. They hypothesized that information may be acquired directly by the neocortex (which the hippocampus projects to) when there is repetition. This case illustrates the difficulty in separating procedural from declarative tasks; this adds another dimension to the complexity of anterograde amnesia.
Episodic versus semantic memory
As described above, patients with anterograde amnesia have a wide range of forgetfulness. Declarative memory can be further subdivided into episodic and semantic memory. Episodic memory is described as the recollection of autobiographical information with a temporal and/or spatial context, whereas semantic memory involves recall of factual information with no such association (language, history, geography, etc.) In a case study of a girl who developed anterograde amnesia during childhood, it was determined that the patient C.L. retained semantic memory while suffering an extreme impairment of episodic memory.One patient known by the codename Gene was involved in a motorcycle accident that damaged significant portions of his frontal and temporal lobes, including his left hippocampus. As a result, he cannot remember any specific episode in his life, such as a train derailment near his house. However, his semantic memory is intact; he remembers that he owns a car and two motorcycles, and he can even remember the names of his classmates in a school photograph.
In stark contrast, a woman whose temporal lobes were damaged in the front due to encephalitis lost her semantic memory; she lost her memory of many simple words, historical events, and other trivial information categorized under semantic memory. However, her episodic memory was left intact; she can recall episodes such as her wedding and her father’s death with great detail.
Vicari et al. describe that it remains unclear whether or not neural circuits involved in semantic and episodic memory overlap partially or completely, and this case seems to suggest that the two systems are independent. Both of the patient's hippocampal and diencephalic structures on the right and left sides were disconnected. When she came to Vicari et al.’s office, the patient C.L.’s chief complaint was forgetfulness involving both semantic and episodic memory. After administering a battery of neuropsychological tests, Vicari determined that C.L. performed well in tests of visual naming and sentence comprehension, visual-spatial ability, and “general semantic knowledge about the world.” They also noted an improved vocabulary and general knowledge base after 18 months. C.L.’s episodic memory, on the other hand, was far below expectations: She could not retain daily events, where she had gone on vacation, the names of places she had been, and other such information. However, this study and others like it are susceptible to subjectivity, since it is not always clear to distinguish between episodic and semantic memory. For this reason, the topic remains controversial and debated.
Familiarity and the fractionation of memory
It is clear that the right hippocampus is necessary for familiarity in spatial tasks, whereas the left hippocampus is necessary for familiarity-based recollection in verbal tasks. Some researchers claim that the hippocampus is important for the retrieval of memories, whereas adjacent cortical regions can support familiarity-based memories. These are memory decisions that are made based on matching already-existing memories (before the onset of pathology) to the current situation. According to Gilboa et al., patients with localized hippocampal damage can score well on a test if it is based on familiarity.Poreh et al. describe a case study of patient A.D., whose damage to the fornix rendered the hippocampus useless but spared adjacent cortical areas — a fairly rare injury. When the patient was given a test with something he had some familiarity with, the patient was able to score well. In general, however, A.D. had severely impaired episodic memory but had some ability to learn semantic knowledge. Other studies show that animals with similar injuries can recognize objects with which they are familiar, but, when the objects are presented in a context that is unexpected, they do not score well on recognition tests.
Islands of memory
Patients with anterograde amnesia have trouble recalling new information and new autobiographical events, but the data are less consistent in regards to the latter. Medveds and Hirst recorded the presence of islands of memory — detailed accounts — that were described by such patients. The island memories were a combination of semantic and episodic memories. The researchers recorded patients giving long narratives with a fair amount of detail that resembled memories that the patients had prior to the trauma. The appearance of islands of memory could have something to do with the functioning of adjacent cortical areas and the neocortex. In addition, the researchers suspect that the amygdala played a role in the narratives.Anterograde amnesia in popular culture
In both film and literature, anterograde amnesia is used for its (often puzzling) dramaturgical possibilities, and both its humorous and tragical implications, often as a plot device; more often than not, the story relies on the condition. Examples for all four are the films Memento (dramaturgyDramaturgy
Dramaturgy is the art of dramatic composition and the representation of the main elements of drama on the stage. Dramaturgy is a distinct practice separate from play writing and directing, although a single individual may perform any combination of the three. Some dramatists combine writing and...
), 50 First Dates
50 First Dates
50 First Dates is a 2004 American romantic comedy film directed by Peter Segal and written by George Wing. The film stars Adam Sandler as a woman-chasing veterinarian and Drew Barrymore as an amnesiac, along with Rob Schneider, Sean Astin, Lusia Strus, Blake Clark, and Dan Aykroyd.Most of the film...
(humor), and the Star Trek: Enterprise
Star Trek: Enterprise
Star Trek: Enterprise is a science fiction television series. It follows the adventures of humanity's first warp 5 starship, the Enterprise, ten years before the United Federation of Planets shown in previous Star Trek series was formed.Enterprise premiered on September 26, 2001...
episode "Twilight" (plot device/tragic - a tragedy averted when the cure turns out to be retroactive). Dana Carvey
Dana Carvey
Dana Thomas Carvey is an American actor and stand-up comedian, best known for his work as a cast member on Saturday Night Live and for playing the role of Garth in the Wayne's World movies.-Early life:...
's character in the movie Clean Slate also had anterograde amnesia as a central plot point. The Tamil
Tamil cinema
Tamil cinema is the film industry based in Chennai, Tamil Nadu, India, dedicated to the production of films in the Tamil language. It is based in Chennai's Kodambakkam district, where several South Indian film production companies are headquartered...
action film Ghajini, based on the film Memento, and its Hindi remake
Ghajini (2008 film)
Ghajini is a 2008 Indian Hindi action film written and directed by A. R. Murugadoss and produced by Tagore Madhu and Madhu Mantena. It is a remake of Murugadoss's own 2005 Tamil film Ghajini starring Surya Sivakumar in the lead role. The film stars Aamir Khan, Asin Thottumkal and Jiah Khan in lead...
also uses anterograde amnesia as a central plot point, with the amnesiac protagonist played by Surya Sivakumar in the Tamil version
Tamil cinema
Tamil cinema is the film industry based in Chennai, Tamil Nadu, India, dedicated to the production of films in the Tamil language. It is based in Chennai's Kodambakkam district, where several South Indian film production companies are headquartered...
and by Aamir Khan
Aamir Khan
Aamir Hussain Khan is an Indian film actor, director and producer who has established himself as one of the leading actors of Hindi cinema....
in the Hindi version
Bollywood
Bollywood is the informal term popularly used for the Hindi-language film industry based in Mumbai , Maharashtra, India. The term is often incorrectly used to refer to the whole of Indian cinema; it is only a part of the total Indian film industry, which includes other production centers producing...
.
Another fictional character who suffers the illness is the Professor in the novel The Professor and the Housekeeper by Yoko Ogawa
Yoko Ogawa
is a Japanese writer.-Biography:Ogawa was born in Okayama, Okayama Prefecture, graduated from Waseda University, and lives in Ashiya, Hyōgo, with her husband and son. Since 1988, she has published more than twenty works of fiction and nonfiction. Her novel The Professor's Beloved Equation has been...
. It is also suffered by Dory in the film Finding Nemo
Finding Nemo
Finding Nemo is a 2003 American comi-drama animated film written by Andrew Stanton, directed by Andrew Stanton and Lee Unkrich and produced by Pixar. It tells the story of the overly protective clownfish Marlin who, along with a regal tang called Dory , searches for his abducted son Nemo...
, by Liz Lemon
Liz Lemon
Elizabeth Miervaldis "Liz" Lemon is the main character of the American television series 30 Rock. She is portrayed by Tina Fey, who is also the creator of the series and its showrunner.-Personal history:...
's brother Mitch Lemon on 30 Rock
30 Rock
30 Rock is an American television comedy series created by Tina Fey that airs on NBC. The series is loosely based on Fey's experiences as head writer for Saturday Night Live...
, and by Chihiro Shindo from Ef: A Fairy Tale of the Two. Gene Wolfe
Gene Wolfe
Gene Wolfe is an American science fiction and fantasy writer. He is noted for his dense, allusive prose as well as the strong influence of his Catholic faith, to which he converted after marrying into the religion. He is a prolific short story writer and a novelist, and has won many awards in the...
's trilogy beginning with Soldier of the Mist
Soldier of the Mist
Soldier of the Mist is a 1986 fantasy novel by Gene Wolfe published by Tor Books; it won the 1987 Locus Award for Best Fantasy Novel, and was nominated for the Nebula Award for Best Novel and the World Fantasy Award....
is written as the diary of a soldier in the Greco-Persian Wars
Greco-Persian Wars
The Greco-Persian Wars were a series of conflicts between the Achaemenid Empire of Persia and city-states of the Hellenic world that started in 499 BC and lasted until 449 BC. The collision between the fractious political world of the Greeks and the enormous empire of the Persians began when Cyrus...
who suffers from the condition. The main character in Meg Gardiner
Meg Gardiner
Meg Gardiner is an Edgar Award-winning American crime writer, who currently lives in the United Kingdom. Her best-known books are the Evan Delaney novels...
's novel The Memory Collector suffers brain damage brought on by contamination with a material containing carbon nanotubes.