The Brain Might Not Be a Blank Slate at Birth After All

Tabula rasa – a prevailing concept

In 1689, the English philosopher and physician John Locke published “An Essay Concerning Human Understanding” in which he stated that the newborn mind is a “tabula rasa” – a blank slate.

Locke was an early empiricist. Empiricism is a philosophical concept that suggests direct sensory experiences are the raw materials for building knowledge. Empiricist thinkers posit that the newborn mind cannot formulate ideas until it experiences life through the senses, and that humans cannot acquire knowledge beyond the direct experience – even in adulthood.

If I ask you to imagine a new color, song or fragrance – what do you conjure up in your mind? Locke and peers would testify that anything you formulate during this task is merely a combination of the sensory experiences you have already encountered; colors that you have seen, melodies you have heard before or a scent you have already sniffed.

Though empiricism has been challenged by opposing schools of thought, such as rationalism, the blank slate theory regarding the newborn brain has prevailed and is somewhat mirrored in traditional neurobiology.

The brain’s generative grammar – a new theory

Neurobiologists study the biological mechanisms of the nervous system. Over recent decades, technological advancements have enabled this study at the cellular level, granting researchers deeper insight into how nerve cells (neurons) generate, carry and transmit electrical and chemical signals, and how their complex circuitry can change and adapt (neuroplasticity). We now know that these molecular processes underpin our ability to learn and to form memories.

A longstanding belief in neurobiology is that the developing brain creates these connections from scratch, ultimately building on an accumulation of sensory information and experience over time.

Dr. George Dragoi, associate professor of psychiatry and neuroscience at Yale University, has a different opinion.

Dragoi has been studying the hippocampus, a key brain structure in learning and memory, for three decades. Drawing from his own research and that of others in neurobiology, he recently published an article in Nature Reviews Neuroscience outlining an alternative theory regarding the developing brain.

Dragoi suggested that a pre-existing dynamic exists – a “cellular template” of sorts – that shapes how our brains represent and learn about the world. It is activated sequentially, which, he explained, is why we generally cannot recall memories from early life when neuronal activity is not yet organized sequentially; at that time, we were just living in the present moment as it happened. But over time, the cellular templates lead to the activation of a more complex template that allows us to form memories that relate to places and time.

This template is essential for internally generated representations, which are crucial for the cognitive processes underlying learning and memory, prospection and inference, according to Dragoi.

Technology Networks interviewed Dragoi to learn more about the research that has shaped his perspective, how it refutes the blank slate theory and what it might mean for our understanding of brain development.

We also interviewed Dr. Antonio Fernandez-Ruiz, assistant professor in the department of neurobiology and behavior at Cornell University, to hear his thoughts on the theory.

Molly Campbell (MC): Your research has found that, in the hippocampus (of rodents), there are clusters of cells and eventually sequences that are predictably activated by new experiences. Can you discuss your work that has demonstrated this?

George Dragoi (GD): There are a couple of studies where we showed this neuronal organization and its predictive power. First, in Cell Press, we showed that neurons are functionally organized in clusters of neuronal triplets (two to four neurons, called tuplets) that are activated in a particular order repeatedly in time (e.g., one-two-three).

There is large repertoire of distinct tuplets in the network, similar to the existence of a repertoire of words (vocabulary) in a language. These tuplets are subsequently multiplexed and combined in multiple distinct extended sequences that can be expressed spontaneously during slow-wave sleep, and during various spatial sequential experiences. The neuronal sequences expressed during a novel experience are built on the framework of these multiplexed prior tuplets that are expressed during the preceding sleep session. In this sense, the sleep tuplets gain predictive power (probabilistic, higher than chance).

Second, during the first stage of neurodevelopment (out of three that are detailed in Science), there are groups (clusters) of neurons depicting together individual locations in space. Only later, in stages two to three, do these clusters of neurons become organized sequentially during sleep and are subsequently played in the same (or about the same) order during future experiences.

MC: So, the new theory suggests that there is a template that is effectively ready and waiting to be activated by, well – the experience of life. Is that correct?

GD: Yes, there is a repertoire of templates that are being used and partially modified during novel experiences. The modified sequences (post-experience sleep) do retain a relatively high correlation with the pre-experience ones, as shown in our study published in Hippocampus.

MC: Can you talk about why, historically it has been said that the human mind is a “blank slate” at birth, and why this has gained popularity as a theory in neurobiology? What are its flaws?

GD: In philosophy, the British empiricists have argued that, at birth, the human mind is a blank slate. I suppose part of the reason was their emphasis on experience-driven learning and the belief that one cannot acquire knowledge beyond the direct experience, even in adulthood. Some theories of learning also focused on the process of learning itself (ignoring the role of prior knowledge), which refers to acquiring new information through new experiences. The main flaw is that, in reality, learning appears to be merely a modification and use of prior knowledge onto which the newly acquired knowledge is incorporated, rather than a pure acquisition of new knowledge on an empty framework of mind. I also explain this older view in neurobiology in the article.

MC: If environmental stimuli is not the major dictator of how the brain processes and stores information, as is believed by many life scientists, what might this mean for our understanding of the early stages of neurodevelopment and how to nurture it?

GD: Both nature and nurture contribute to normal brain development, in different ways. Nature provides innate competence to fully develop and process certain features of the world, while early-life nurture increases the brain performance to fully exert its role in processing information about the world (pattern separation, specificity and capacity).

MC: Have you explored whether this kind of neural “template” exists in any other locations within the brain?

GD: I did not, but other researchers have reported similar correlations between neural responses to new sensory stimuli and preceding spontaneous neural activity in sensory (visual, auditory) and motor systems.

MC: Your research has been conducted in rodents. Can you talk about how the findings might translate to humans?

GD: Similar patterns of neuronal network pre-configuration and internally generated sequential activity (i.e., pre-play) have been reported in the human hippocampus and human neocortex-derived brain organoids.

MC: If this neural template exists in humans as it does in rodents, do you have any thoughts about its potential origins?

GD: The full spectrum of pre-configuration at the level of pre-existing sequences would serve rapid learning of sequential experiences. I would predict that sequence pre-play would exist in evolutionary earlier species, for which such experience is important. For instance, the motor network important for singing behavior in adult birds, such as zebra finch, has been shown to express a form of pre-play.

MC: Having now shared your theory as a published piece of work, has it been challenged at all?

GD: I have not received any challenge since its publication, but I received challenges roughly a decade ago after I first demonstrated the phenomenon of pre-play in mice and rats. The main challenge was on the statistical analysis employed to demonstrate pre-play. In a number of subsequent studies, most notably our research in Neuron and the current article, we debunked several pitfalls that prevented researchers from reporting network pre-configuration in the past, which included two classes of statistical fallacies, namely circularity and inadequacy.

MC: How are you going to continue this research?

GD: We are working on several directions. First, exploring the mechanisms leading to the emergence of network pre-configuration in the early postnatal life. Second, how prior knowledge accelerates new, related animal learning. Third, further exploration of the rules and principles of this neural grammar via interventional approaches.

MC: Can you share your thoughts on Dragoi’s perspective piece – are there any limitations to this theory?

Antonio Fernandez-Ruiz (AFR):  Dragoi's paper starts by describing how there has been a paradigm shift in recent years in the study of how the brain represents the external world.

According to his view, there has been a transition from thinking the brain is a “blank slate” in which experience is imprinted de novo, towards an emphasis on pre-existing dynamics that precede any experience and shape how brains represent and learn about the world.

Dragoi focused on the recent developments in the field on memory, many of them from his own group, that have contributed to this new view of the fundamental role of pre-existing neural patterns as a scaffold for cognition, or a generative grammar. He made compelling parallelisms between the syntactic structure of language, the clonal selection of antibodies in the immune system and the mechanisms of memory encoding.

He concludes by proposing that this generative grammar (or repertoire of pre-existing neural patterns) has several fundamental advantages over the alternative view that poses memories are formed completely de novo in the brain. These advantages are the ability to support rapid learning by assigning pre-existing neural patterns to encode new experiences, supporting imagination, planning and inferences.

This is still a very controversial topic in the field of neuroscience and, although the debate is far from over, this piece is an important milestone that crystalizes one of the leading views about neural representations.

Further experiments are still needed in order to understand whether and how this generative grammar contributes to cognition and behavior. Fundamentally, selective manipulations of these neural patterns are necessary to causally prove their functional roles, something that has been elusive so far due to technical challenges. 

Dr. George Dragoi and Dr. Antonio Fernandez-Ruiz were speaking to Molly Campbell, Senior Science Writer for Technology Networks.

About the interviewees: 

Dr. George Dragoi is associate professor of psychiatry and of neuroscience in the Department of Psychiatry at Yale University School of Medicine in New Haven, CT. He holds an M.D. degree from the Gr. T. Popa University of Medicine and Pharmacy of Iasi, Romania and a PhD in behavioral and neural science from Rutgers University where he worked in the laboratory of Dr. Gyorgy Buzsaki. Dragoi’s current research focuses on the role of neuronal activity and prior experience in cellular assembly organization and animal learning with implications for our better understanding of neuropsychiatric diseases.

Dr. Antonio Fernandez-Ruiz is the Nancy and Peter Meinig Family Investigator in the Life Sciences and an assistant professor in the department of neurobiology and behavior at Cornell University. He studied biology and physics in the Universities of Sevilla and Madrid (Spain). He earned his PhD at the Complutense University of Madrid in 2015 investigating the biophysical basis of brain oscillations and developing mathematical tools to analyze them. The main goal of Fernandez-Ruiz's research is to understand how neuronal dynamics support complex cognitive functions.