Perhaps memory has been the cognitive faculty that has been most extensively studied by all neuroscience professionals. In a century that has been characterized by an increase in life expectancy, much of the effort has been focused on studying the normal and pathological decline of memory in the elderly population.

However, today I will talk, in broad terms, about the development of memory in early ages . Specifically, the development of memory in the fetus (that is, from the 9th week of pregnancy until it is conceived, approximately week 38) and in the newborn.

Memory in childhood

We’ll probably all agree that babies are super smart and that they already learn in their mother’s womb. More than one mom could tell us more than one story about it, I’m sure. But is there really such a thing as declarative memory? And if there is, why don’t most of us remember anything about our childhood before the age of three?

Furthermore, I inform you that if you have any memory from before the age of 2-3 years it is probably a false memory . This phenomenon is called childhood amnesia. And now we could ask ourselves, if infantile amnesia exists does it mean that neither the fetus, nor the newborn, nor the child until the age of 3 have a memory? Obviously not. In general, it is assumed that memory occurs in different ways and that each of these presentations involves different brain regions and circuits. Learning involves many memory mechanisms and some of them are not related to the hippocampus (the fundamental structure for the consolidation of new memories).

I will talk about three fundamental learning mechanisms : classical conditioning, operant conditioning and explicit memory or declarative . I will briefly introduce each one of these concepts and show what the main human research on the neurodevelopment of these functions, essential for the normal learning of the child, postulates.

Classic conditioning

Classical conditioning is a type of associative learning. It was described in the 19th century by Ivan Pavlov – the widely spoken experiment of the little bell and the salivating dogs. Basically, in classical conditioning a “neutral stimulus” (without any adaptive value for the organism) is associated with an “unconditioned stimulus”. That is, a stimulus that innately produces a response (similarly, but not equally, to a reflex). Thus the “neutral stimulus” becomes a “conditioned stimulus” since it will produce the same response as the “unconditioned stimulus”.

So, do babies associate? A small experiment was carried out in which they were given a small puff of air, or “buf”, in the eye (unconditioned stimulus), which led to a blinking response due to the air – as a reflex. In later tests the “buf” was performed at the same time as the administration of a specific auditory tone (“neutral stimulus”). After some tests the simple production of the tone resulted in the blink response – it had become a “conditioned stimulus”. Tone and “buf” had therefore become associated.

And the fetus, is it able to associate? It has been seen that babies can respond to stimuli that have been presented to them before their birth. For this purpose, the heart rate of a melody presented during pregnancy has been measured through the mother’s abdomen. Once the baby was born, the heart response was compared by presenting new melodies (control melodies) from the previously learned melody. The heart rate was found to change selectively to the melody presented during pregnancy. Therefore, the fetus is able to associate stimuli.

From a neuroanatomical point of view it is not surprising that babies and fetuses generate associations. In these types of associative learning, in which fear or other emotional responses do not intervene, one of the main brain structures in charge is the cerebellum.

Neurogenesis – the birth of new neurons – of the cerebellum cortex is completed by 18-20 weeks of gestation. In addition, at birth the Purkinje cells -main cells in the cerebellum- show a similar morphology to those of the adult. During the first months after birth there are changes at the biochemical level and in the neuronal connectivity that lead to the cerebellum being fully operational.

Still, there will be slight variations. In the first months the most conditionable stimuli are the taste and smell ones, while in later stages the conditionability to other stimuli increases . When emotional aspects are involved in classical conditioning, associative learning involves other structures, whose neurodevelopment is more complex, since more factors must be taken into account. Therefore, I will not talk about it today because it would divert the main topic of the text.

Operating Conditioning

operant conditioning or instrumental is another type of associative learning. Its discoverer was Edward Thorndike, who investigated the memory of rodents through mazes . Basically, it is a type of learning that consists of the fact that if behaviours are followed by pleasant consequences, they will be repeated more, and the unpleasant ones will tend to disappear.

This type of memory is difficult to study in the human fetus, so most current studies have been done on babies under one year old. One experimental method that has been used is to present a toy to an infant, such as a train that will move if the child pulls a lever. Obviously babies associate the pulling of the lever with the movement of the train, but in this case we will find significant differences according to age . In the case of 2-month-old children, if once they have associated the movement of the lever with that of the train we remove the stimulus, then instrumental learning will last approximately 1-2 days. This basically means that if after about four days we present the stimulus to them, the learning will have been forgotten. However, the development of the brain at an early age progresses at a frenetic pace, and instead, 18-month-old subjects can sustain instrumental learning for up to 13 weeks. Thus, we can summarize it by saying that the mnesic gradient of operant conditioning improves with age.

What structures does operative conditioning involve? The main neural substrates are those that form the neostriatum -Caudado, Putament and Núcleo Accumbens-. For those who do not know this structure, they are basically nuclei of subcortical grey substance -that is, below the cortex and above the brain stem-. These nuclei regulate the pyramidal motor circuits, responsible for voluntary movement. They also intervene in affective and cognitive functions and there is an important relationship with the limbic system. By the time we are born the striatum is fully formed and its biochemical pattern matures at 12 months.

Therefore, we could infer the possibility that there was a primitive instrumental conditioning in the fetus ; although the circumstances and context make it difficult to think of effective experimental designs to evaluate this function.

Declarative memory

And now comes the fundamental issue. Do newborns have declarative memory? First we should define the concept of declarative memory and differentiate it from its sister: the implicit memory or procedural memory .

Declarative memory is to what is popularly known as memory, that is, the fixation in our memories of facts and information that are acquired through learning and experience , and to which we have conscious access. Implicit memory, on the other hand, is that which fixes patterns and motor procedures that are revealed by their execution and not so much by their conscious memory -and if you don’t believe me, try explaining all the muscles you use to ride a bike and the specific movements you perform.

We will find two fundamental problems in the study of declarative memory in newborns: first, the baby does not speak and therefore we will not be able to use verbal tests for evaluation. Secondly, and as a consequence of the previous point, it will be difficult to discriminate the tasks in which the baby makes use of its implicit or explicit memory.

The conclusions on the ontogeny of memory that I will speak about in a few moments will be from the paradigm of “preference for novelty”. This experimental method is simple and consists of two experimental phases: firstly, a “familiarisation phase” in which the child is shown a series of stimuli – generally images of different types – over a fixed period of time, and a second “test phase” in which he is presented with two stimuli: a new one and one that he had previously seen in the familiarisation phase.

Generally the visual preference for novelty is observed by the baby, by means of different measuring instruments . Therefore, the idea is that if the newborn baby looks at the new stimulus longer, it will mean that it recognizes the other. Would the recognition of new images therefore be an adequate paradigm for the construct of declarative memory? It has been seen that patients with damage to the medial temporal lobe (MTP) do not show a preference for novelty if the period between the familiarization phase and the test is greater than 2 minutes. In studies of lesions in primates it has also been seen that the TML and especially the hippocampus are necessary structures for recognition and therefore for preference to novelty. However, other authors have reported that behavioural measures of novelty preference are more sensitive to damage to the hippocampus than other recognition tasks. These results would call into question the construct validity of the novelty preference paradigm. However, it is generally considered to be a pre-existing type of memory and a good, though not the only, study paradigm.

Characteristics of the declarative memory

So, I will talk about three basic characteristics of declarative memory from this experimental model :

Coding

By coding – not consolidation – we refer to the baby’s ability to integrate information and fix it . In general, studies show that 6-month-old children already show a preference for novelty and we therefore conclude that they recognise it. Even so, we found significant differences in coding times with respect to 12-month-old children, for example, these latter needing shorter exposure times in the familiarisation phase in order to code and fix the stimuli. Specifically, a 6-month-old child needs three times as much time to show recognition ability as a 12-month-old. However, the differences in relation to age are attenuated from the age of 12 months onwards and children from 1 to 4 years have been found to show equivalent behaviour with similar familiarisation periods. In general, these results point to the fact that while the beginnings of declarative memory appear in the first year of life, we will find an effect of age on coding ability that will occur especially in the first year of life. These changes can be related to different neurodevelopmental processes, which I will discuss later.

Retention

By retention we mean the time or “delay” in which the newborn can keep information , in order to later recognize it. Applied to our paradigm, this would be the time we allow to pass between the familiarization phase and the test phase. Since coding times are equivalent, babies older than a few months may show higher percentages of retention. In an experiment comparing the performance of this function in 6- and 9-month-old children, it was observed that only 9-month-old children could retain information if a “delay” was applied between the two phases of the experiment. In contrast. The 6-month-old children showed a preference for novelty only if the test phase was performed immediately after the familiarization phase. Broadly speaking, the effects of age on retention were seen to occur until early childhood.

Recovery or evocation

By evocation we refer to the ability to rescue a memory from long-term memory and make it operational for a purpose . It is the main capacity we use when we bring our experiences or memories to the present. It is also the most difficult capacity to evaluate in babies because of the lack of language. In a study that used the paradigm we have talked about, the authors solved the problem of language in a quite original way. They made different groups of newborns: 6, 12, 18 and 24 months. In the familiarization phase they presented them with objects on a background with a specific color. When the four groups were tested immediately afterwards, they all showed similar preferences for novelty as long as the background color in the test phase was the same as in the familiarization phase. When this was not the case, and a different background colour was applied in the test, only the 18 and 24 month old babies showed a preference for novelty. This shows that the memory of the babies is extremely specific. Small changes in the central stimulus or in the context can lead to impaired resilience.

Neurodevelopment of the hippocampus

To understand the neurodevelopment of the hippocampus and relate it to the behavioral events we have discussed, we must understand a number of processes in relation to neuronal maturation that are common to all areas of the brain.

First of all, we have the bias to think that “neurogenesis”, or the birth of new neurons, is all that brain development is about. That’s a huge mistake. Maturation also involves “cell migration”, by which neurons reach their final proper position. When they have reached their position, the neurons send their axons to the target regions that they will innervate, and these axons will subsequently be myelinated. When the cell is operational, the processes of “dendritic arborization” of the cell body and the axon will begin. In this way, we will obtain a large number of synapses – “synaptogenesis” – which will largely be eliminated during childhood according to our experiences. In this way, the brain ensures that it leaves only those synapses that participate in operational circuits. In more adult stages, “Apoptosis” will also play a very important role, eliminating those neurons that, similarly to synapses, do not have a relevant role in the neuronal circuits. Therefore, maturing in our brain is not about adding, but rather about subtracting. The brain is a spectacular organ and always seeks efficiency. Maturation is similar to the task Michelangelo performed to sculpt his David from a block of marble. The only difference is that we are sculpted by our experiences, parents, loved ones, etc., to give rise to our phenotype.

With this speech I wanted to say something very simple that we will now quickly understand. If we observe the hypocampal neuroanatomy we will be surprised to know that most of the structures that are related to it (entorhinal cortex, subicle, horn of Ammonis…) can already be differentiated at week 10 of gestation, and at week 14-15 they are already cellularly differentiated. Cellular migration is also very rapid and in the first trimester already resembles that of an adult. So why, if the hippocampus is already formed and operational three months after the child is born, do we observe such a difference in our experiments between children of 6 and 12 months, for example? For the same reason I have already stressed in other entries: the hippocampus is not everything and neither is neurogenesis. The dentate gyrus – a neighbouring structure of the hippocampus – requires a significantly longer developmental period than the hippocampus, and the authors claim that its granular cell layers mature at 11 months of birth and adopt a similar adult morphology at one year of age. On the other hand, in the hippocampus we find different groups of GABAergic cells -small inhibitory interneurons- that have been seen to play an essential role in the combined processes of memory and attention.

GABAergic cells are among those that take longer to mature in our nervous system and it has even been seen that GABA plays opposite roles depending on the age we observe. These cells mature between 2 and 8 years of age. Thus, a large part of the mnesic gradient that we observe in the capacity of coding, retention and recovery will be due to the maturation of the connections between the hippocampus and the dentate gyrus and, in addition, to the formation of the inhibitory circuits.

It doesn’t end here…

As we have seen, declarative memory depends on the medial temporal lobe (MTL) and the maturation of the gyrus dentate explains much of the differences we observe in babies from 1 month to 2 years. But is that all? There is one question we have not yet answered. Why does infant amnesia occur? Or why don’t we remember anything about it before the age of 3? Once again the question is answered if we leave the hippocampus alone for a while.

The maturation of the connections between the LTM and the prefrontal cortex regions has been associated with a large number of mnestic strategies in the adult child. Declarative memory is continuously developed during childhood and improves through strategies in coding, retention and recovery skills. Neuroimaging studies have shown that while the ability to remember a story is related to LTM in children 7 to 8 years old; in children 10 to 18 years old it is related to both LTM and prefrontal cortex. Therefore, one of the main hypotheses explaining childhood amnesia is the poor functional connections between the prefrontal cortex and the hippocampus and the LTM. Even so there is no definitive conclusion to this question and other molecular hypotheses in this respect are also interesting . But these are points that we will deal with on another occasion.

Conclusions

When we are born, the brain accounts for 10% of our body weight – when we are adults it is 2% – and spends 20% of the body’s oxygen and 25% of its glucose – this is about the same as an adult. In exchange for this, we are dependent beings who need the care of a parent. No baby can survive on its own. We are an easy target in any natural environment. The reason for this “neuro-dispensation” is that the fetus and baby possess a considerable amount of learning mechanisms – some of which have not been cited here, such as the ability to “priming”. There is something that all grandmothers say and it is true: babies and children are sponges. But they are because our evolution has demanded it. And this is not just in humans, but in other mammals.

Therefore, declarative or explicit memory exists in babies, but in an immature form . To mature satisfactorily, it requires the experience and education of the social environment in which we are involved as gregarious mammals. But why study all this?

In a society that has put its clinical focus on cancer and Alzheimer’s, more minority diseases are forgotten, such as infantile paralysis, autism, various learning disorders, ADHD – which does exist, gentlemen, it does – epilepsies in children and a long etcetera (I am sorry if I leave even more minorities unnamed); which affect our children. They cause delays in their school development. They also cause them to be delayed and socially rejected. And we are not talking about people who have completed their life cycle. We are talking about children whose insertion into society may be at stake.

Understanding normal neurodevelopment is essential for understanding pathological development . And understanding the biological substratum of a pathology is indispensable for the search for pharmacological targets, effective non-pharmacological therapies and the search for early diagnostic and preventive methods. And to do this we must not only investigate memory, but all the cognitive faculties that are affected in the above-mentioned pathologies: language, normal psychomotor development, attention, executive functions, etc. Understanding this is indispensable.

Text corrected and edited by Frederic Muniente Peix

Bibliographic references:

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Libros:

  • Shaffer RS, Kipp K (2007). Psicología del Desarrollo. Infancia y adolescencia (7ªed). México: Thomson editores S.A.