How does memory work? - Chapter 9

What is the associated anatomy between learning and memory?

Despite the vast stores of information contained in our brains, we continuously acquire new information. Learning is the process of acquiring new information, and the outcome of learning is memory. Memory is created when something is learned, and this learning may occur either by a single exposure or by the repetition of information, experiences, or actions. Researchers believe that humans and animals have several types of memory mediated by different systems: sensory memory, short-term memory (STM) or working memory and long-term memory (LTM). Researchers also make distinctions among the types of information stored. LTM is commonly divided into declarative memory, which consists of our conscious memory for both facts we have learned (semantic) and events we have experienced (episodic); and nondeclarative memory, which is nonconscious memory that cannot be verbally reported, often expressed through the performing of procedures (procedural memory). 

Researchers divide learning and memory into three major processing stages:

1. Encoding: is the processing of incoming information and experiences, which creates memory traces, traditionally thought to be alterations in the synaptic strength and number of neuronal connections. Encoding has two separate steps, (1) acquisition; sensory systems are constantly being bombarded by stimuli and most responses fade quickly and don't come near the STM. But all the stimuli are still available for processing, this is known as the sensory buffer. Not all memory traces appear to get past the second step, (2) consolidation; in which changes in the brain stabilize a memory over time, resulting in LTM. 

2. Storage: is the retention of memory traces. It is a result of acquisition and consolidation, and it represents the permanent record of the information. 

3. Retrieval: involves accessing stored memory traces, which may aid in decision making and change behavior. We have conscious access to some but not all the information stored in memory. 

The brain has the ability to learn, which means that at neuronal level changes occur in the synaptic connections between neurons. Learning can be accomplished in different kind of ways, an it appears that different parts of the brain are specialized for different types of learning. The hippocampus is the memory component in the brain and is a portion of the medial temporal lobe that is shaped like a seahorse. 

What is amnesia?

Memory deficit and loss, known collectively as amnesia, can result from brain damage caused by surgery, disease, and physical or psychological trauma. Typically, people with amnesia display deficits in specific types of memory or in aspects of memory processing. The loss of memory for events that occur after a lesion or other physiological trauma is called anterograde amnesia. It results from the inability to learn new things. A loss of memory for events and knowledge that occurred before the lesion or other physiological trauma is called retrograde amnesia. Retrograde amnesia can sometimes be temporally limited, extending back a few minutes or hours.

A lot of information about the organization of human memory was first derived from patients left accidentally amnesic after surgical treatments. The most interesting and famous of these patients was patient HM. His case holds a prominent position in the history of memory research for several reasons, one of them being that he had a memory deficit, but no other cognitive deficits. HM knew some of the autobiographical details of his life, and he retained all the other knowledge about his life and the world that he had learned up to two years immediately before his surgery. HM also changed scientist's understanding of the brain's memory processes. It had previously been thought that memory could not be separated from perceptual and intellectual functions, but these functions were completely intact by HM. 

What is dementia?

Memory loss can also be caused by diseases that result in dementia. Dementia is an umbrella term for the loss of cognitive functions in different domains beyond what is expected to be normal aging. The most common types of dementia are irreversible and are the result of neurodegenarative disease, vascular disease, or a combination of the two. The most common of these protein-associated neurodegenerative diseases is Alzheimer's disease, which contributes up to 60-70% of the dementia cases. AD is characterized by the extracellular deposition of aggregated beta-amyloid proteins, negatively affecting synapse formation and neuroplasticity, and also by intercellular accumulation of neurofibrillary tangles, which are aggregations of microtubules associated with hyper-phosphorylated tau protein. The medial temporal lobe are the first to be affected by AD, later it extends to lateral, temporal, parietal, and frontal neocortices. 

Vascular dementia is the second most common type of dementia, making up for 15% of the dementia cases. It is caused by decreased oxygenation of neural tissue and cell death, resulting from ischemic or hemorrhagic infarcts, rupture of small arterial vessels in the brain associated with diabetes, and rupture of cerebral arteries caused by the accumulation of beta-amyloid plaques in the walls of the vessels, which damages and weakens them. VD can have an impact on multiple brain areas, resulting in diverse symptoms, and can co-occur with AD. 

Less common are the frontotemporal lobar dementias, a heterogenous group of neurodegenerative diseases characterized by accumularions of different proteins in the frontal and temporal lobes but not the parietal and occipital lobes, resulting in language and behavioral changes that may overlap with AD.

What are the mechanisms of memory?

What are the short-term forms of memory?

Short-term memories persist for milliseconds, seconds, or minutes. They include transient retention of sensory information in sensory structures, short-term stores for information about yourself and the world, and memory used in the service of other cognitive functions. 

• Sensory memory: When your mother suddenly walks into the room, beginning an argument and you are watching an important part of the football game, the auditory verbal information she just presented to you seems to persist as a sort of echo in your head, even when you are not really paying attention to it. We refer to this type of memory as sensory memory. 

• Short-term memory: Has a longer time course - seconds to minutes - and a more limited capacity. The Modal Model proposes that information is first stored in sensory memory. From there, items selected by attentional processes can move into ST storage. Once in the STM, if the item is rehearsed, it can be moved into LTM. The modal model suggests that, at each stage, information can be lost due to decay (information degrades and is lost over time), and interference (new information displaces old information), or because of a combination of the two. 

Studies of patients with brain damage enable us to test the hierarchically structured model model of memory. A typical test to evaluate STM is the digit span test, which involves reading and remembering a list of digits and, after a delay for a few seconds, repeating the numbers. Remarkably, however, in a LTM test of associative learning, in which words are paired, a patient KF retained the ability to form certain types of new LTM that could last much longer than a few seconds. This displayed an interesting dissociation between the STM (which had been damaged) and the LTM. If this interpretation of the finding is true, than STM might not be required in order to form LTM. 

• Working memory: The concept of working memory was developed to extend the concept of STM and to elaborate the kinds of mental processes that are involved when information is retained over a period of seconds to minutes. Working memory represents a limited-capacity store for retaining information over the short term and for performing mental operations on the contents of this store.

Psychologists Baddeley and Hitch argued that the idea of a unitary short-term memory was insufficient to explain the maintenance and processing of information over short periods. They proposed a three-part working memory systems consisting of a central executive mechanism that presides over and coordinates the interactions between two subordinate STM stores and LTM stores. The phonological loop is a hypothesized mechanism for acoustically coding information in working memory. The visuospatial sketch pad is a short-term memory store that parallels the phonological loop and permits information storage in either purely visual or visuospatial codes. 

Deficits in STM abilities, such as remembering items on a digit span test, can be correlated with damage to subcomponents of the working memory system. 

What are the long-term forms of memory?

Information retained for a significant time is referred to as long-term memory. Theorists have tended to split the LTM into two major divisions, taking into account the observable fact that people with amnesia may retain one type of LTM and not another. 

• Declarative memory: is defined as memory for events and for facts, both personal and general, to which we have conscious access and which we can verbally report. This form of memory is sometimes referred to as explicit memory. Episodic memory comprised memories of events that the person has experienced that include what happened, where it happened, when, and with whom. Episodic memory differs from personal knowledge. You have personal knowledge about the day you were born, but you do not remember the experience. Semantic memory is objective knowledge that is factual in nature but does not include the context in which it was learned. Semantic memory reflects knowing facts and concepts such as how to tell time. 

• Nondeclarative memory: is so named because it is not expressed verbally. It is also known as implicit memory because it is knowledge that we are not conscious of. Several types of memory fall under this category. Nondeclarative memory is revealed when previous experiences facilitate performance on a task that does not require intentional recollection of experiences. 

  • Procedural memory: is one form of nondeclarative memory, which is required for tasks that include learning motor skills - such as riding a bike or swimming - and cognitive skills, such as reading. One test of procedural memory is the serial reaction-time task. The idea is that healthy participants respond faster to the complex repeating sequence than they do to a totally random sequence. 

  • Priming: is another form of nondeclarative memory. Priming refers to a change in response to a stimulus, or in the ability to identify a stimulus, following prior exposure to that stimulus. 

What holds the medial temporal lobe memory system?

The formation of new declarative memories depends on the medial temporal lobe. This region includes the; amygdala, the hippocampus, and the surrounding parahippocampal, entorhinal, and peririhinal cortical areas. They are all involved in the long-term memory. 

The case of HM shows that the anterior portions of the hippocampus, the perirhinal and entorhinal cortices, were completely removed. Another case of RB shows the story of a patient who lost his memory due to a ischemic episode during heart bypass surgery. He could no longer form long-term memories. He also had a mild temporal retrograde amnesia that went back to about one-two years before surgery. The findings of his specific hippocampal damage in patient RB supports the idea that the hippocampus is crucial for the formation of long-term memories. 

Further evidence that the hippocampus is involved in the long-term memory acquisition comes from patients with transient global amnesia (TGA). This syndrome has a number of causes, but it is triggered most commonly by physical exertion in men over 50 and by emotional stress in women over 50. The vertebrobasilar artery system, which supplies blood to the medial temporal lobe and the diencephalon, has been implicated as a critical site. High-resolution imaging data now suggest that the lesions caused by an ischemic episode are located in the CA1 subfield of the hippocampus and that these neurons are selectively vulnerable to metabolic stress. 

Patients with TGA have similar symptoms as those of people with permanent damage to the medial temporal lobe, such as HM. But we do not know whether TGA patients have normal implicit learning of memory, in part because their impairment does not last long enough for researchers to adequately index things like procedural learning. But, the answer to this question would improve our understanding of human memory and of a form of amnesia that any of us could experience later in life. 

Further evidence of hippocampal involvement in long-term memory formation comes form patients with Alzheimer's disease (AD), in whom the hippocampus deteriorates more rapidly than in people undergoing the normal aging process. But, some patients with anterior temporal lobe damage and the consequent dense retrograde amnesia, however, can still form new long-term episodic memories. This condition is known as isolated retrograde amnesia. 

Is there evidence from animals with medial temporal lobe lesions?

To test whether the amygdala plays an essential part in memory formation, surgical lesions were created in the medial temporal lobe and amygdala of monkeys. The brain-lesioned monkeys were tested with a population behavioral task, known as the delayed non-match-to-sample task: a monkey is placed in a box with a rectractable door in the front. While the door is closed so that the monkey cannot see out, a food reward opened, and the monkey is allowed to pick up the object again, and the same object plus a new object are put in position. The new object now covers the food reward, and after a delay that can be varied, the door is reopened and the monkey must pick up the new object to get the food reward. With training, the monkey can pick new, or nonmatching objects. It was found that the monkey's memory was impaired only if the hippocampus ánd amygdala were lesioned. This finding led to the (incorrect) idea that the amygdala is a key structure in memory. 

Researchers indicated that lesions of the hippocampus and amygdala produced even more severe memory deficits, but only when the cortex surrounding these regions was also lesioned. When lesions of the hippocampus and amygdala were made, but the surrounding cortex was spared, the presence or absence of the amygdala lesion did not affect the monkey's memory. 

Another key question that animal researchers have addressed involves the kind of memory and learning that is impaired with lesions to the hippocampus. When electrodes were implanted in the rat hippocampus, certain cells, place cells, fired only when the rat was situated in a particular location and facing a particular direction. They provide evidence that the hippocampus has cells that encode contextual information. 

Damage to the temporal lobe outside of the hippocampus can produce the loss of semantic memory, even while the ability to acquire new episodic memories remains intact. 

Can you distinguish human memory systems with imaging?

Aggleton and Brown proposed the idea that encoding processes that merely identify an item as being familiar (recognition) and encoding processes that correctly identify an item as having been seen before (recollection) depend on different regions of the medial temporal lobe. A study revealed that the hippocampus is activated when information is correctly recollected. The findings of studies strongly suggest that the hippocampus is involved in both encoding and retrieval of episodic memories, but not of memories based on familiarity. Such data raised the question of which brain regions are involved in episodic versus nonepisodic memory encoding and retrieval. Results of studies demonstrate a double association in the medial temporal lobe for encoding different forms of memory: one medial temporal lobe mechanism involving the perirhinal cortex that supports familiarity-based recognition memory, and a second system involving the hippocampus and posterior parahippocampal cortex that supports recognition based on the recollection of sources (episodic) information. 

When you think back on the first concert you even saw, you probably recall where an when you saw it. An early theory proposed that the fundamental role of the hippocampus is to build and maintain spatial maps. The main support of this theory was the discovery of the place cells identified in the hippocampus. How the brain solves the problem of bundling all this information - question known as the binding problem - is central to understanding episodic memory. The binding-of-items-and-contexts model proposes that the perirhinal cortex represents information about specific items, the parahippocampal cortex represents information about the context in which these items were encountered, and the processing in the hippocampus binds the representation of items with their context. As a result, the hippocampus is able to relate the various types of information about something that the individual encounters. This form of memory is referred to as relational memory. 

In sum, the evidence from a number of studies indicates that the medial temporal lobe supports different forms of memory and that these different forms of memory are supported by different subdivisions of this brain region. Relational memory is memory for relations among the constituent elements of an experience - time, place, person etc. The relationsal memory theory proposes that the hippocampus supports memory for all manner of relations.  

When our memory fails, we usually forget events that happened in the past. Sometimes, however, something more surprising occurs, we remember events that have never happened to us before. You can investigate falls memories using a technique. In this technique, participants are presented with a list of words that are all highly associated with a word that is not presented. When participants are asked subsequently to recall or recognize the words in the list, they show a strong tendency to falsely remember the associated word that was not presented. This memory illusion is so powerful that participants often report having a vivid memory of seeing the nonpresented critical item in the study list. The vividness of such memories make it difficult to separate the cognitive and neural basis of true and false memories. 

True memories are associated with a greater activity in the medial temporal lobe and sensory areas, which are activated when a true item is first presented. False memories do not activate sensory areas; instead, regions associated with top-down cognitive control are more active for false memories. 

What is memory consolidation?

Consolidation is the process that stabilizes a memory over time after it is first acquired. Consolidation processes occur at the cellular level, as well as at the system level. 

The medial temporal lobes are essential for the early consolidation and initial storage of information for episodic and semantic memories. The mechanisms of the slower consolidation process, however, remain more controversial. There are two main theories:

• Standard consolidation theory: it considers the neocortex to be crucial for the storage of fully consolidated long-term memories, whereas the hippocampus plays only a temporary role. The representations of an events that are distributed throughout the cortex come together in the medial temporal lobe, where the hippocampus binds them. Consolidation occurs after repeated reactivation of the memory creates direct connection within the cortex itself between the various representations so that it no longer requires the hippocampus as the middle man to bind them. 

• Multiple trace theory: it suggests that the long-term stores for semantic information rely solely on the neocortex, while episodic memory, consolidated or not, continues to rely on the hippocampus for retrieval. A new memory trace is set down in the hippocampus every time an episodic memory is retrieved: the more times a memory is retrieved, the more traces are set down. This theory suggests that episodic memories degrade over time and are slowly converted into semantic memory. 

Evidence also shows that sleep plays an important role in memory consolidation after learning. The idea is that hippocampal neurons replay patterns of firing that were experienced during learning. Research also shows that stress can have a great impact on episodic memory consolidation when high levels of cortisol influence the hippocampal function. 

What is the cellular basis of learning and memory?

Researchers have long believed that the synapse, with its dynamic connections, was a structure involved in the mechanisms of memory. Most models of the cellular bases of memory hold that memory is the result of changes in the strength of synaptic interactions among neurons in neural networks. Hebb proposed that synaptic connections between coactivated cells change in a manner dependent on their activity. This theory, Hebb's law, is commonly summarized as 'Cells that fire together, wire together'. Hebb proposed that the strengthening of synaptic connections results when a weak input and a strong input act on a cell at the same time. This learning theory is called Hebbian learning. 

There are three major excitatory neural pathways of the hippocampus that extend from the CA1 cells: 

1. The perforant pathway is the way between the entorhinal cortex and subiculum. 

2. The granule cells have distinctive-looking unmyelinated axons, known as the mossy fibers, which connect the dentate gyrus to the dendritic spines of the hippocampal CA3 pyramidal cells. 

3. The CA3 cells are connected to the CA1 by axon collaterals, known as the Schaffer collaterals.

Stimulation leads to greater synaptic strength in the perforant pathway so that, when the axons were stimulated again later, larger postsynaptic responses resulted in the granule cells of the dentate gyrus. This phenomenon is called the long-term potentiation (LTP) and its discovery confirmed the Hebb's law. The NDMA receptors are seen to be key in forming LTP, but they are not in maintaining it.