Introduction

Memory is the capability of the brain to encode, store, and retrieve information or data when they are needed. Without memory, it is impossible to perform daily activities or form relationships or learn and progress in our life. That is, memory represents our identity.

According to the multistore model of memory (also known as the modal model), proposed by Atkinson and Shiffrin in 1968, memory consists of three stores: a sensory register, short-term memory (STM), and long-term memory (LTM). STM is the capacity to store and manipulate information for a short time,[1] while the LTM relates to storing the information for an extended period. STM, also referred to as short-term storage or primary or active memory, indicates different systems of memory involved in the retention of pieces of information (memory chunks) for a relatively short time (usually up to 30 seconds). On the contrary, LTM may hold an indefinite amount of information for an indefinite time.

Based on cognitive psychology studies, since the late sixties of the last century, researchers proposed to divide LTM into two major two subsets of LTM, explicit memory and implicit memory.[2] The explicit memory is also termed as declarative memory as it can be expressed voluntarily, through language and other communication manners. In 1972, the Estonian scientist Endel Tulving suggested the distinction between two types of explicit memory, episodic and semantic memory and illustrated the principles of these memory systems in a book entitled 'Organization of memory' (New York, Academic Press, 1972). Although over the years Tulving modified the construct of semantic and episodic memory, this nosographic approach for memory taxonomy remains a key concept in contemporary cognitive neuroscience. The semantic memory represents the conscious and intentional memory of concepts and meanings, whereas the episodic memory is the conscious recollection of an episode, of the sequence of events that characterized it, and of its space-time location. In other words, the explicit memory concerns itself with the ability to consciously remember the general concepts, ideas, and events that occurred through the person's life. Within explicit memory, episodic memory has an autobiographical reference referring to personally experienced events (context-sensitivity), whereas semantic is detached from the autobiographical reference and cannot be defined in terms of its context-sensitivity. Of note, both episodic and semantic memory can be accessed unintentionally and a strict distinction between the two explicit memory systems cannot be made. Probably, the two forms of memory are highly interactive and share functional properties and neural bases.

On the other hand, implicit memory does not require conscious intervention to be retrieved. That is, its recovery is not in the form of memories, but through actions or automatisms, "knowing how." It represents, in turn, our abilities (e.g., swimming, cycling, driving the car) and is therefore referred to as procedural memory.

By summarizing LTM can be divided into two subsets:

• Explicit (or declarative) memory
  • Episodic memory
  • Semantic memory
• Implicit (or procedural) memory

Although the modal model represents an excellent basis for understanding the modalities of memory, it seems to operate an excessive simplification of matter and has been criticized for being a passive and linear model. Based on a wide range of studies conducted on the subject, several alternative memory models have been proposed. Most likely, a model that can explain memory functioning in detail has yet to be proposed. Therefore, it is reasonable to believe that the various models and theories should be integrated. In this context, the Working Model of Memory proposed by Baddeley and Hitch, in 1974, offers an explanation of how STM works.[3] STM, indeed, is more than just one simple unitary store and comprises different components such as the central executive, and the visuospatial components. In this complex scenario, working memory (WM) represents the capacity to temporarily store and manipulate data in the service of ongoing tasks through a multicomponent system. That is, WK represents an information processing system to allow the storage of information into the LTM sets by way of STM.[1]

Development

Overall, explicit memory continues to develop throughout the years, including rapid changes during the first two years of life, until the person reaches 60, which then the explicit memory begins to diminish progressively.The difference in explicit memory between the different age groups, adults, childhood, and infants is due to several reasons. The first reason, the medial temporal lobe is formed and matured before birth, except for the hippocampus, more specifically except for the dentate gyrus, which continues to develop until 11 months of age. The second reason is the rapid myelination, which happens during the first year of life. The final reason is that the connections between the medial temporal lobe and the cortex areas such as the prefrontal cortex are well established between the age of 10 to 18 years.[4][5][6]

Mechanism

Pieces of evidence on the functioning of memory (centers, networks, mechanisms) have been obtained from the study of clinical cases in which anatomical alterations due to trauma or surgery have led to deficits of varying degrees of memory. The most famous clinical case was the American Henry Gustav Molaison, better known as the patient H.M., the most studied person in the history of neuroscience and protagonist as a 'living experiment' of at least a hundred scientific publications. HM's amnesia was a consequence of an intervention, performed to treat drug-resistant epilepsy, which consisted of a bilateral lobotomy of the medial temporal cortex extended several centimeters towards the inside of the brain and including part of the amygdala, the entorhinal cortex and a good part of the hippocampus. After the intervention, the patient showed signs of a very serious form of amnesia. His memory, in fact, was intact as regards the events preceding the surgery but was no longer able to form new LTMs. Many other cognitive faculties, however, remained intact. The procedural memory was also not impaired as H.M. was able to learn how to perform new tasks, even if he could not verbalize what he had learned. The unfortunate case of H.M., who preserved the severe memory deficit for life, allowed for the first time to highlight that non-declarative memory is based on neuronal circuits other than those of the medial temporal lobe and above all does not require conscious memory processes.[7]

Semantic memory

A semantic control network is a system of connection between different areas in the brain that works eventually to store, retrieve, or assign meaning to the words, events, ETC.[8]A recent model proposes the establishment of semantic processing after a broad range of neuroimaging and pathological data had been collected through the years and determined what brain regions included in this network. Semantic processing starts with what is called model-specific representations, which means analyzing and processing individual information in its distinct area. For instance, the sound and the visual appearance of the keyboard express in different areas, if you hear the music of the piano, the sound will transmit, and undergo interpretation in the auditory regions, for example, the primary auditory cortex. As for the appearance of the keyboard, it will be represented in the visual areas, such as the primary visual cortex. After this step, these different inputs will be conveyed to the higher convergence zones, which are the inferior parietal lobe and the lateral and ventral temporal lobe. The received inputs in the previous areas will be stored and organized concurrently or individually depending on the similarities and dissimilarities of the information. In the example of the keyboard, the two inputs will be attached and saved together. These zones, able the brain to effectively manipulate any stored concepts to create new ideas or thoughts and classify them in certain groups. Another vital area in semantic processing is the prefrontal cortex, which helps to regulate and select the semantic memory content, which means it ables the brain to recall and remember only the relevant facts or ideas related to that concept.[9]

Episodic memory

Episodic memory is the ability to consciously recall or experience a specific event that occurred through the person's life, and it's different from the semantic memories in that you can remember the exact time and place in which the event occurred, or you gained that information.[8]In general, episodic memory occurs through extensive connections between the neocortex and the parahippocampal regions and the hippocampus (HPC), and the HPC is considered the most critical structure in forming episodic memory.Not all areas that support the generation of episodic memory are activated at the same time, nor in all tasks. Instead, these regions form what is called process-specific alliances, a temporary association between certain areas that are controlled by a moment to a moment demand.[10]There are many areas in the neocortex involved in episodic memory formation, such as the prefrontal cortex, the amygdala, the anterior temporal cortex. Based on the content of the signal, the neocortex connection with the hippocampus splits into two divisions, the first division is the posterior neocortex, with the posterior hippocampal, which is concerned with spatiotemporal memory content. The second division is the anterior neocortex with the anterior hippocampus, and it's concerned with the emotional, semantic, and schemas part of the memory.Inputs that are obtained by the neocortex have separate pathways, depending on the content of the signal. Information that carries spatial content is transferred to the parahippocampal cortex. On the other hand, non-spatial inputs are conveyed to the perirhinal cortex. Following the previous steps, the spatial and the non-spatial information travel to the medial and lateral entorhinal cortex, respectively. Finally, the spatial and the non-spatial information are sent to the anterior HPC and posterior HPC, respectively. While the HPC receives this information separately, they begin to converge inside the HPC.[11][12]

Clinical Significance

Various pathological processes can compromise the functioning of explicit memory in its components.

Alzheimer Disease (AD)

Dementia is an acquired progressive cognitive impairment that affects the daily activity, and the single major cause of dementia is Alzheimer's disease (AD) accounting for 50 to 75 % of all cases of dementia. The majority of AD appears in a sporadic pattern and seems to result from a complex interplay between environmental and genetic factors. The two cardinal features that characterize AD are the presence of amyloid plaques and neurofibrillary tangles. The amyloid plaques are abnormally folded AB proteins that accumulate extracellularly; on the other hand, and the neurofibrillary tangles are paired helical filaments that contain hyperphosphorylated tau.Most patients with AD complain of gradual progressive impairment in explicit memory, and they may also experience behavioral change, disability, hallucinations, and even seizures. The expected death of AD patients is 8.5 years after the first presentation.[13] There is no current treatment regimen for AD, and the available treatment is directed only to the symptoms and improving the quality of life as the disease progress. Financial and home support are mandatory for these patients as they become more dependent and immobile as the disease progress. Acetylcholine esterase inhibitors are the mainstay treatment for symptomatic patients; moreover, memantine is an alternative treatment for moderate to severe patients.[14]

Transient Global Amnesia (TGA)

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of temporary anterograde amnesia lasting no more than 24 hours without any other neurological deficits. TGA affects middle-aged and older adults, occurring in 3.4 to 10.4 per 100000 people. The cause and mechanism of TGA are still unclear, but some research suggests jugular vein valve incompetence as a potential mechanism.

TGA is a clinical diagnosis, relying only on a detailed history and physical examination. Patients with TGA are often brought by someone who witnessed the event because TGA patients are not aware of their problem. On physical examination, TGA patients have normal sensory, motor, and cognitive abilities except for the ability to store new information. Other diagnostic tests like EEG and imaging are not routinely performed unless an alternative diagnosis has been suspected, like epilepsy or transient ischemic attack (TIA).

There is no particular treatment for TGA, as this syndrome is self-limited and temporary. Overall, recurrent TGA is relatively uncommon, although it can happen over the years. Patients with TGA have no increase in long term risk for cerebrovascular events.[15]