Short-term memory (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). In contrast, long-term memory (LTM) may hold an indefinite amount of information. The difference between the two memories, however, is not just in the 'time' variable but is above all functional. Nevertheless, the two systems are closely related. Practically, STM works as a kind of “scratchpad” for temporary recall of a limited number of data (in the verbal domain, roughly the George Miller’s ‘magical’ number 7 +/- 2 items) that come from the sensory register and are ready to be processed through attention and recognition.[1] On the other side, information collected in the LTM storage consist of memories for the performance of actions or skills (i.e., procedural memories, “knowing how”) and memories of facts, rules, concepts, and events (i.e., declarative memories, “knowing that”). Declarative memory includes semantic and episodic memory. The former concerns broad knowledge of facts, rules, concepts, and propositions ('general knowledge'), the latter is related to personal and experienced events and the contexts in which they occurred ('personal recollection').

Although STM is closely related to the concept of ‘working memory’ (WM), STM and WM represent two distinct entities. STM, indeed, is a set of storage systems whereas WM indicates the cognitive operations and executive functions associated with the organization and manipulation of stored information.[2] Nevertheless, one hears the terms STM and WM often used interchangeably.

Furthermore, one must distinguish STM from the ‘sensory memory’ (SM) such as the acoustical echoic and iconic visual memories which are shorter in duration (fraction of a second) than STM and reflect the original sensation, or perception, of the stimulus. In other words, SM is specific to the stimulus' modality of presentation. This ‘raw’ sensory information undergoes processing, and when it becomes STM gets expressed in a format different from that perceived initially.

The famous Atkinson and Shiffrin model (or multi-store model), proposed in the late 1960s, explains the functional correlations between STM, LTM, SM, and WM.[3] Later on, a considerable number of studies demonstrated the anatomical and functional distinction between memory processes as well as neural correlates and functioning of STM and LTM subsystems. In light of these findings, several memory models have been postulated.[4][5] While certain authors suggested the existence of a single memory system encompassing both short- and long-term storage,[6] after 50 years the Atkinson and Shiffrin model remains a valid approach for an explanation of the memory dynamics. In light of more recent research, however, the model has several problems mostly concerning the characteristics of STM, the relationship between STM and WM as well as the transition from STM to LTM. 

Short-term memory: meaning and system(s)

It is a storage system that includes several subsystems with limited capacity. Rather than being a limitation, this restriction is an evolutionary survival advantage, since it allows paying attention to limited but essential information, excluding confounding factors. It is the classic example of the prey that must focus on the hostile environment to recognize a possible attack by the predator. Given the functional peculiarities of the STM (collection of sensorial information), the subsystems are closely related to the modalities of sensory memory. As a consequence, there have been several sensorial-associated subsystems postulated, including the visuospatial, phonological (auditory-verbal), tactile, and olfactory domains. These subsystems involve different patterns and functional interconnections with the corresponding cortical and subcortical areas and centers. 

The concept of working memory

In 1974, Baddeley and Hitch developed an alternative model of STM which they termed as working memory.[7] Indeed, the WM model does not exclude the modal model but enriches its contents. On the other side, the short-term store can be used to characterize the functioning of the WM. WM refers more to the entire theoretical framework of the structures and processes used for the storage and temporary manipulation of information, of which STM is only a component. In other words, STM is a functional storage element, while WM is a set of processes that also involve storage phases. WM It is the memory that we constantly use, which is always "online" when we have to understand something or solve a problem or make an argument, the cognitive strategies for achieving short term goals. The proof of the importance of this sort of 'operating system' of memory shows by the evidence that WM deficits are associated with several developmental disorders of learning, including attention-deficit hyperactivity disorder (ADHD), dyslexia, and specific language impairment (SLI).[8]

Short-term and Long-term memory

These types of memory can be classically distinguished based on storage capacity and duration. The capacity of the STM, indeed, has limitations in the amount and duration of information it can maintain. In contrast, LTM features a seemingly unlimited capacity that can last years. The functional distinctions between systems of memory storing and the exact mechanisms for how memories transfer from ST to LTM remain a controversial issue. Do STM and LTM represent one or more systems with specific subsystems? Although the STM probably represents a sub-structure of the LTM, which is a sort of long-term activated storage, rather than looking for a 'physical' division, it seems appropriate to verify the mechanisms of transition from a memory that is only a passage to a lasting memory. Although the classic multi-modal model proposed that storage of ST memories occurs automatically without manipulation, the matter seems to be more involved. The phenomenon concerns quantitative (number of memories) and qualitative (quality of memory) features.

Regarding quantitative data, although the number of Miller of 7 +/- 2 items identifies the number of elements included among individual slots, the grouping of memory bits into larger chunks (chunking) could allow storing a lot more information of bigger size and continuing to keep the magic number. The qualitative issue, or memory modulation within processing, is a fascinating phenomenon. It seems that the elements of STM undergo processing, which provides a sort of editing that involves the fragmentation of each element (chunking) and its re-elaboration and re-elaboration. This phase of memory processing is called encoding and can condition subsequent processing, including storage, and retrieval. The encoding process encompasses automatic (without conscious awareness) and effortful processing (through attention, practice, and thought) and allows us to retrieve information to be used to make decisions, answer questions, and so on. There are three pathways followed during the encoding step: the visual (information represented as a picture), acoustic (information represented as a sound), and semantic encoding (the meaning of the information). The processes interconnect with each other, so that information is broken down into different components. During recovery, the pathway that has produced the coding facilitates the recovery of the other components through a singular chain reaction. A particular perfume, for instance, makes us recall a specific episode or image. Of note, the encoding process affects the recovery, but the recovery itself undergoes a series of potential changes that can alter the initial content.

In neurofunctional terms, the difference between STM and LTM is the occurrence, in the LTM, of a series of events that must fix the engram(s) definitively. This effect occurs through the establishment of neural networks and expresses as neurofunctional phenomena including the long term potentiation (LTP) which is an increase in the strength of the neural transmission deriving from the strengthening of synaptic connections. This process requires gene expression and the synthesis of new proteins and is related to long-lasting structural alterations in the synapses (synaptic consolidation) of the brain areas involved such as the hippocampus is the case of declarative memories.

The role of the hippocampal network

Of note, the hippocampal neurogenesis regulates the maintenance of LTP.[9] However, the hippocampal network, including the parahippocampal gyrus, hippocampus, and neocortical areas is not the place where memories are stored, but it has a crucial role in forming new memories and in their subsequent reactivation. It seems that the hippocampus has a limited capacity and acquires information quickly and automatically without keeping it for long. Over time, the originally available information becomes permanent in other brain structures (in the cortex), independently from the activity of the hippocampus itself. The crucial mechanism of this transfer is the reactivation ("replay") of the configurations of neural activity. In other words, the hippocampus and the medial temporal structures connected to it are crucial for holding an event as a whole as it distributes in an organized way memory traces. It is an operating system that through different software can store, organize, process, and recover hardware files. This hippocampal-guided reactivation (retrieval) leads to the creation of direct connections between the cortical traces and then to the formation of an integrated representation in the neocortex including the visual association cortex for visual memory, the temporal cortex for auditory memory, and the left lateral temporal cortex for knowledge of word meaning. Moreover, the hippocampus has other specific tasks, for example, in the spatial memory organization.

Other brain areas are involved in memory processes; for example, the learning of motor skills has links to the activation of the cerebellar regions and brainstem nuclei. Furthermore, learning of perceptive activities (improvements in the processing of perceptive stimuli essential in everyday life activities such as understand spoken and written language)  involves, basal ganglia and sensory and associative cortices whereas learning cognitive skills (related to problem-solving) involve the medial temporal lobes initially.

Different clinical conditions including, strokes, brain aneurysms, traumatic brain injuries, primitive or metastatic neoplasms, and infectious diseases (e.g., encephalitis) may impair various components of STM. However, the damage to the STM is seldom selective. For example, aneurysm rupture can lead to STM loss, as well as LTM loss. Apart from diseases which induce STM alterations through direct neural damage, a wide range of medical conditions such as systemic infections, thyroid diseases, surgery (e.g., neuroinflammation-mediated postoperative delirium and postoperative cognitive dysfunction,[10] or psychiatric diseases (e.g., depression) or psychological (e.g., psychological trauma) can also impact STM. In this regard, pieces of evidence demonstrated that violence exposure during childhood impairs cognitive processes, including memory (psychogenic amnesia).[11] Cancer treatments, including radiation and chemotherapy, can induce STM damage through a complex neuroinflammation mechanism.[12]

Neurodegenerative conditions are paramount causes of memory impairment. For instance, one of the first signs of dementia is STM loss. In particular, memory loss (without interference in daily life or independent function) is the main feature of mild cognitive impairment (MCI) which represents the stage between the expected cognitive decline of normal aging and the more severe decline observed in Alzheimer disease (AD). Moreover, alterations in different memory domains have been shown in Parkinson disease (PD),[13] in those affected by Huntington disease (HD),[14] and in primary progressive aphasia (PPA).[15]

Other conditions that can impair memory tasks are alcohol and drug abuse (e.g., marijuana), heavy cigarette smoking, sleep deprivation, severe stress, and vitamin B12 deficiency. Prolonged high alcohol intake can lead to Korsakoff syndrome, which is a complex amnestic disorder with neuropsychological sequelae caused by vitamin B1 (thiamine) deficiency. In addition to alcohol, other causes can lead to vitamin B1 deficiency (non-alcoholic Korsakoff syndrome) with related memory disorders, including dietary deficiencies, prolonged vomiting, and eating disorders. Again, Korsakoff-like amnestic syndromes have also presented after brain lesions involving anteromedian thalamus and hippocampus.[16]

Among other causes of memory impairment, a common side effect of electroconvulsive therapy (ECT) is STM alteration during treatment. A special issue concerns medications-induced memory loss. The list of drugs implicated includes benzodiazepines (BDZs), antiepileptic drugs,[17] opioids,[18] tricyclic antidepressants.[19] Concerning statin use and memory loss, there is weak evidence (observational data, including case reports).[20] Most of these drugs (e.g., benzodiazepines) act by impairing memory processing and, in turn, can present an obstacle to the consolidation of information.[21]

Epidemiological data are related to the different conditions which induce memory impairment. For instance, concerning neurodegenerative diseases, about 15 to 20 % of people aged 65 or older have mild cognitive impairment; of this, approximately one-third develop AD within 5 years’ follow-up.[22] Furthermore, the existing cases of AD (prevalence) are of 5.8 million Americans (2018), and estimates are that the annual number of new cases (incidence) of all dementias will double by 2050.[23] Again, PD affects approximately 1% of the population above 60 years, whereas the incidence of Huntington disease is of 0.38 per 100000 per year.[24][25] For non-neurodegenerative conditions, it is difficult to make an epidemiological estimate as the decline of memory is not always in the clinical picture. 

The amnestic syndrome

Amnestic syndrome is an impairment in the ability to form new memories. Regardless of etiology, it seems that memories of recent events (STM) are most vulnerable, whereas older memories (LTM) are more 'resilient' and protected from damage. This concept is not new, as, towards the end of the nineteenth century, the French psychologist Theodule-Armand Ribot (1839-1916) demonstrated that amnesia affects memories in reverse order of their development.[26] This idea is why a substantial distinction is necessary between anterograde amnesia and retrograde amnesia. The former concerns the new memories and the latter what is well established by neural networks, which is why some conditions (e.g., drugs such as BDZs) can lead to a deficit, especially within the STM. In turn, amnestic disorders primarily affect anterograde memories. 

Neural correlates for STM domains and damages.

Research proved that lesions to the prefrontal cortex in primates caused STM alterations. Based on the brain area affected by the damage, research has demonstrated specific modifications in the different domains of STM. The assumption is that these different components are the expression of different neuronal correlates. In this regard, neuroimaging studies reported significant information. For instance, inferior parietal lobule, frontal premotor regions, and insula in the dominant hemisphere are the major neural correlates of the phonological STM subtype.[27] In particular, depending on the type of function, the cerebral areas appointed to the phonological aspects of the verbal STM are the inferior parietal cortex left for the phonological warehouse and the Broca area for articulatory revision. Again neuroimaging investigations proved that the neural correlates of spatial STM memory involve the occipital extrastriate, posterior parietal, dorsolateral premotor, and prefrontal cortices.[28] Yet, fRMI studies highlighted the importance of the area dorsal frontal (ocular fields, Brodmann area 8) for retaining oculomotor information, and the intraparietal sulcus responsible for retaining the space positions.

On the other side, the medial temporal lobes play a fundamental role in the coding and consolidation of the type of memories that are accessible to consciousness, but these regions do not permanently preserve memories and are not necessary for encoding or consolidating other types of memory. The demonstration comes from the emblematic case of patient H.M. who, suffering from severe posttraumatic epilepsy, was operated on median resection of the temporal lobe bilaterally.[29] A serious picture of amnesia emerged in which the older memories (e.,g. childhood) had remained almost intact, but the subject showed difficulty in recovering memories acquired in the 3 years before the operation, especially for personal events (retrograde amnesia). Above all, he demonstrated a severe incapacity to store new information (anterograde amnesia) although the STM was not impaired. In other cases, however, patients showed deficits in WM despite LTM preserved. For example, although the patient K.M. had difficulty in immediately recalling lists of 4 words, he was also faster and better than normal subjects to learn long lists of words.[30] In this latter case, the damage had localized in the left temporoparietal regions (perisylvian area).

Relationship between STM and LTM: clinical evidence.

Because STM and LTM are distinct memories with distinct mechanisms, a selective deterioration of STM may not impair the tasks of LTM. However, it is also true that difficulties in STM performances can trigger a pathogenetic chain that involves other types of memory. Probably, the interconnections between STM and LTM require more explanation.[31] Several clinical pieces of evidence prove a mechanistic relationship between the two systems. For instance, deficits in verbal STM are commonly recognized in children with reading difficulties and are associated with learning disorders featuring impairment in reading. Similarly, in its early stages (i.e., mild cognitive impairment), Alzheimer disease typically affects STM but not LTM, which becomes progressively altered as the disease progresses.