1.1 What is memory?
Memory is defined as the brain process of encoding, storing and retrieving information from the external and internal world. Memory is essential for animal survival and gives human beings the extraordinary ability to develop consciousness and ultimately the self.
Memory processes have been continuously refined and adapted throughout evolution of all the different species to eventually give rise to the today’s civilization. A quote of Elie Wiesel says:
“Without memory there is no culture. Without memory there would be no civilization, no society, no future”
If we ponder a moment on this sentence, we realize how important it is to study the cellular and circuit basis of memory to better understand human functioning.
1.1.1 Memory: a very old concept
The understanding of what memory is and how it works has a long history that can be traced back to ancient Greek philosophers (more than 2000 years ago). We can find written traces on the question of memory with Plato (in the Theaetetus, 191c, d) as well as in his pupil Aristotle’s treatise De memoria et reminiscentia (Smith and Ross, 1908). Plato believed that “memory serves as a bridge between the perceptual world and a rational world of idealized abstractions” (Radvansky, 2006) while Aristotle’s idea was that
“memories are mainly composed of associations among various stimuli or experiences”.
Another vision of Aristotle on memory, that came from Plato, can be found in his major treatise On the Soul in which he postulates that every human is born free of any knowledge and that memory consists of the accumulation of their life experiences; in other words when we born our brain is a “tabula rasa” or “blank state”. Even though their ideas about memory were not completely far from modern concepts of memory, there was no experimental or physical evidence of their statements. For this reason, their assertions remained undemonstrated for years. It is only around the 1800s, when a German philosopher and psychologist, Hermann Ebbinghaus (1850-1909), proposed that complex mental processes like memory could be studied by experimental research. He was one of
the precursors to first develop a scientific approach to study memory, experimental psychology. Ebbinghaus also participated to the establishment of the associationism movement (derived from empiricism: knowledge derives primarily from sensory experiences), which assumes that complex mental processes originate from more simple processes that associate between themselves. His major contribution to experimental study on memory are the discovery of the forgetting curve (the decline of retaining information through time), the spacing effect (learning is more performing if spaced in time) and it is considered to be one of the first that described the learning curve (learning increases in function of experience).
Despite the limitations of his work (i.e. he was the only subject for his studies) Ebbinghaus is considered today as fundamental and precursor of experimental research on memory.
1.2 Different forms of memories and their classification
In the early 1980s, it became generally accepted that memory exists under different forms.
This change became true thanks to human research, in parallel to animal experimentation, using a collection of learning tasks. Memory is a general term that covers a variety of multiple forms. Usually it encompasses the acquisition, retention and recall of information and knowledge, the use of skills, habits, experiences,…. but not only, memories are also depicted by their duration (short or long term period), and by the fact whether they are conscious (explicit) or unconscious (implicit).
A common way to investigate such puzzling organization is to assume that memory, in all its components and forms, is supported by multiple memory systems: well organized cognitive components, distributed across multiple neuronal networks (brain areas) that cooperate to perform distinct functions (Frankland et al., 2006; Kandel et al., 2014). In other words, distinct brain regions process and store different kinds of information. It is thus of major relevance to identify and study these memory systems in order to gain insight into memory functioning.
One of the first researchers to propose a distinction in memory was Wiliam James (1842-1910) who believed that memory deferred from habits (1980). From a psychology point of view, habits are defined as automatic-everyday behaviors that are continuously repeated without focusing our attention to their accomplishment. Habits are learned without intention and are mostly unconscious. Almost one decade later, McDoughall firstly proposed a differentiation between declarative (explicit) and procedural (implicit) memory, subsequently confirmed by experimental research (Figure 1). The former is the memory of people, things, places, events and facts that can be consciously recalled (or as the term
says: declared). The latter, procedural memory, is based on an action-motor system. It consists of memories of skills and more generally on how to do things that are acquired and recalled unconsciously.
The experimental psychologist Endel Tulving (1927-) further divided declarative memory into episodic memory and semantic memory. Episodic memory is described as the autobiographical memory of personal events of our life that can be consciously (explicitly) recollected (e.g. recalling the day of your thesis defense). On the other side, semantic memory is the memory of facts or events that can explicitly be stored and recalled, in other words, the general knowledge that we acquire throughout life (e.g. recall the fact that Switzerland is a federal republic that consist of 26 Cantons and the city of Bern is the seat of the federal authorities).
Figure 1. Human Memory.
Different processes compose human memory. Memory can be categorized into explicit (conscious) and implicit (unconscious) memories. Implicit memory consists of procedural memory while explicit memory englobes declarative memory that can be further separated in episodic and semantic memories.
Memory can be classified into three different types: sensory memory, short-term memory (also known as working memory) and long-term memory (LTM). Sensory memory is the capacity to retain impressions of information coming from the sensory system after the original stimuli have ceased. It is indeed the shortest element of memory, and it is commonly defined as a buffer system for sensory information (typically few seconds).
Short-term memory is the ability to retain for a very short period of time (typically from 10-15 seconds to up to 30-60 seconds) a limited amount of information (generally around 5 to 7 items) that can be used immediately but cannot be manipulated. Finally, we have long-term memory, which is the capacity to store information over long periods of time (from minutes to years).
Human memory has four different stages: encoding, consolidation, storage, and recall (Figure 2). Encoding is the ability to transduce the perceived stimuli
Human Memory Implicit Memory Explicit
Memory Declarative
Memory Episodic
Memory
Semantic Memory
Procedural Memory
(item/context/event/person) of interest into a concept (or product) that can be stored in the brain (i.e. pattern of neuronal activity bearing the stimuli’ information). Consolidation is the process of stabilizing the encoded information. Storage is the process by which the brain can arrange the information that could be used later (recall). Recall or retrieval is the ability to take the information out of the repository and use it.
Figure 2. Memory stages.
Memory starts with the encoding of information from the external world. External information is firstly encoded: perceived stimuli are transduced into pattern of neuronal activity. The information is then consolidated. The brain can store the consolidated information by reorganizing it. The information can be recalled to be used again.
1.3 Associational learning as a model to study memory How researchers study memory?
The brain learns to form associations of daily life events that can be recalled. These associations are the building blocks to form brain representations of the external and internal world and have the potential to shape our behavior. From a psychology point of view, learning is the process that accommodates the formation of associations between the environment and behavior. To study memory, researchers use associative learning induced through different forms of conditioning. One of the most commonly used is classical conditioning in which a previously neutral stimulus is paired with another that produces a strong biological reaction.
Classical conditioning was firstly observed by the Russian physiologist Ivan Pavlov (1849-1936), also known as Pavlovian conditioning. In his experiment, Pavlov placed previously food-deprived dogs on a stand where they were restrained and gave them food (defined as the unconditioned stimulus, US). At the only presentation of food dogs started salivating (defined as the unconditioned response, UR). Pavlov then paired a tone (defined as the conditioned stimulus, CS) with the presentation of the food, creating a CS-US relationship. After repeated pairing of CS-US, dogs started salivating at the presentation of the tone alone (CS), creating what is called a conditioned response (CR). Pavlovian conditioning is known to be one of the most powerful learning paradigms to induce adaptive behavior that resist in time.
Watson and Rayner in 1920 tested for the first time this form of conditioning in humans
External inputs
ENCODING CONSOLIDATION STORAGE RECALL
with the famous study of “little Albert”, a 9-months old child (Watson and Rayner, 2000).
Albert learned to associate (fear) the presence of a white rat (CS) with a very disturbing loud noise (US) that made him cry of fear (UR). Albert was previously presented with a variety of stimuli such as rats, rabbit, monkeys and mask. The fear conditioning of Albert lasted for around 7 weeks with multiple trials per day. Finally, Albert started crying at the presentation of the CS alone (rat). With time, Albert started a process known as fear generalization, he basically feared also all the different animals that shared similar characteristics with the rat (white color, hairs, size,…). The idea behind Watson and Rayner experiment was to induce phobia (a fear that is out of proportion to the danger) by using classical conditioning. Their results provide evidence that conditional learning seems to be efficient in humans and that emotional conditioned responses persist in time.
1.4 Finding the locus of memory in the brain
This led to the idea that changes within the brain may occur and that learned information could be stored somewhere in the brain.
1.4.1 19th century, the advent of experimental research
With the advent of experimental research in the 19th century, questions on memory begun to find some answers. Pioneer neuropsychologist Karl Lashley (1890-1958), inspired by Richard Semon’s book “The Mneme” in 1921, believed that memory was physically located in a specific brain area (see chapter 6.2). To test this idea, he performed lesions in the brain of rats and monkeys and tested their memory performance after surgical interventions. Because of his limited methodology and the restricted knowledge on memory itself (i.e. he did not differentiate short-term from long-term memory and do not considered the possibility that memories, according to their nature could be stored in different areas) he was unable to locate memory to a specific brain area. He concluded with the theory of “mass action” that basically states: “the amount of lost memory was proportional to the amount of cortex removed (lesioned)”. He consequently theorized that any specific functional area of the cortex could be replaced by another one. He called this equipotentiality.
1.4.2 First evidence of the physical location of memory in the brain
Parallel to Lashley’ lesional studies using animal models, other researchers reported different observational studies in humans related to memory functions.
One of the very probably first evidence that memory was located in the medial temporal
lobe (MTL) of the cerebral cortex came with the invention, in the 1930s, of the Montreal procedure developed by the American-Canadian neurosurgeon Wilder Graves Penfield (1891-1976). Developed for the surgical treatment of patients with epileptic seizures, brief electrical stimulations were applied to different brain areas on conscious patients. The responses were observed and epileptic areas were identified for subsequent resection.
Penfield reported that stimulations of MTL lead to the recall of vivid memories in some patients (Milner, 1977). These findings have been replicated by modern surgeons (Bartolomei et al., 2004).
Maybe the most famous evidence of the possible location of memory in the brain emerged with the studies of Scoville and Milner (1957) on patients whose MTL were resected because of psychoses and intractable seizures. Although in their original report, Scoville and Milner reported at least ten different patients with differently severe memory defects and with different bilateral MTL resections, particular attention has been paid to patient Henry Molaison (H.M.). H.M. developed epileptic seizures one year after he fell off a bicycle when he was 9 years old. At the age of 16 H.M. seizures became untreatable with drugs and at the age of 27 he underwent bilateral medial temporal lobectomy including the removal of both hippocampi. The consequences of this intervention were immediately clear, H.M. developed anterograde amnesia, the inability to form new episodic memories. He also presented graded retrograde amnesia, the inability to recall memories closed in time to the surgery. Surprisingly, H.M. could recall old memories, for example he could remember his childhood or his university years. His working memory was intact as well as his ability to form long-term procedural memories like learning new motor skills despite him not being conscious of learning them.
Around the same period and in the following years some other examples of human memory impairment cases appeared and were studied experimentally. One of these studies was reported by Stuart Zola-Morgan in 1986 and concerned R.B. patient who after an ischemic episode developed memory impairment (Zola-Morgan et al., 1986). As it reported in the study, in his last 5 years before death, R.B. formal memory tests demonstrated considerable anterograde amnesia but not retrograde amnesia or any sign of other cognitive deficits. Post-mortem histological investigation revealed bilateral lesion of specific subregions called CA1 fields (see next chapter). This case has been one of the first where lesions were determined by extensive and detailed neuropsychological and neuropathological examination and were limited to the hippocampus.
Altogether, these studies give us an extraordinary insight on the brain mechanisms of memory. Damage to the MTL is sufficient to cause episodic memory impairment and the
severity of memory impairment strongly depends on the locus and the extent of the damage. These human studies indicate a central role of the MTL in human episodic memory.