Wayfinding
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In recent years some of the most stunning images of the hippocampus have emerged from Harvard University’s Center for Brain Science. There the neuroscientist Jeff Lichtman has pioneered a way of using microscopes to map neural connections in the brains of mice. By fiddling with genes, Lichtman causes mice to express different fluorescent proteins in individual neurons, which appear under magnification in bursts of beautiful pinks, blues, and greens. These “brainbow” photographs show how cells in the hippocampus are condensed into single orderly layers. Whereas neurons of the cortex look like a galaxy of randomly strewn stars, those in the hippocampus are aligned in elegant curving arcs.
These are the cells, called pyramidal neurons, that Jeffery and so many other neuroscientists are fascinated by. And they are a key to understanding the phenomenon of amnesia in our early lives.
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Sigmund Freud coined the term “infant amnesia” and explained it in terms of repression; the brain was hiding the desires and emotions of infancy from the adult psyche, and these could be accessed through psychotherapy. “Hitherto it has not occurred to us to feel any astonishment at the fact of this amnesia, though we might have had good grounds for doing so,” Freud wrote in 1910. “For we learn from other people that during these years, of which at a later date we retain nothing but a few unintelligible and fragmentary recollections, we reacted in a lively manner to impressions, that we were capable of expressing pain and joy in human fashion, that we gave evidence of love, jealousy, and other passionate feelings by which we were strongly moved at the time, and even that we gave utterance to remarks which were regarded by adults as good evidence of our possessing insight and the beginnings of a capacity for judgment. And of all this we, when we are grown up, have no knowledge on our own! Why should our memory lag so far behind the other activities of our minds?” Freud thought of memory as a permanent storage system that enacts a lasting influence over our behavior into adulthood, even if our conscious minds can’t unlock it. What he didn’t know is that this period of infant amnesia until the age of two—followed by childhood amnesia until the age of six or so—is not only universal among humans but some mammals as well. All altricial species who raise their young, including rats and monkeys, experience a period of amnesia, hinting at a potential evolutionarily conserved necessity for this developmental period.
From the 1970s to the 1990s, another explanation for infant amnesia was a child’s lack of language: early memories become inaccessible once babies transition from nonverbal to verbal communication. It’s precisely around the age of eighteen months that there is an explosion of language in infants, and shortly thereafter infant amnesia dissipates. As Nora Newcombe, founder of the Spatial Intelligence and Learning Center at Temple University, explained to me, “[They believed] that the advent of memories has to do with both language acquisition and is then tied up with cultural norms about the importance of remembering unique events. These are obviously not unimportant; we speak, we live in social groups. But that idea wasn’t going to be enough. It wasn’t going to be the only explanation.” Further complicating the language hypothesis was the fact that so many animal species that never develop language nevertheless seem to remember events in their lives.
It’s only more recently that scientists have uncovered connections between the development of spatial representation in children, amnesia, and memory, connections that might illuminate how these cognitive abilities evolved in humans in the first place. The ability of the human mind to engage in mental time travel—the ability to recall the past and imagine the future—and grammatical language may have evolved during the Pleistocene, the epoch that began 2.6 million years ago. This was also the period that it seems children, an Old English word that means “recently born,” emerged as a new, prolonged stage of biological and social development in our species. As several researchers explain in the book Predictions in the Brain, edited by the neuroscientist Moshe Bar, “This emergence of the genus Homo was accompanied by a prolongation of the period of development from infancy to adulthood, and that extra stage, known as childhood, was inserted into the sequence of developmental stages. Childhood lasts from 2½ to about age 7, roughly the period during which both mental time travel and grammatical language develop.”
Are children the result of a novel evolutionary stage in our species’ development, one that was needed in order for our brains to be able to fully develop our spatial and episodic memory systems? “Everyone thinks the first two years are so important, but if we can’t remember them, how are they important?” said Newcombe. “There are some answers, but if we can’t answer it crisply, that tells us we don’t really understand anything about the brain.”
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When Jon was prematurely born at twenty-six weeks, he weighed around two pounds. He had trouble breathing on his own, and for the next two months he lived in an incubator and was hooked to a ventilator. But he grew into a healthy baby and toddler until the age of four, when he had two epileptic seizures. It was about a year later that his parents began to notice that Jon couldn’t remember things that happened in his daily life. He didn’t remember watching television or what had happened at school or what book he had read the night before. When a team of neuroscientists evaluated Jon, they discovered other impairments. He couldn’t find his way anywhere, remember familiar environments, or locate objects or belongings. Remarkably, Jon’s IQ was normal, he could read and write and spell, and he did well at school. His semantic memory, the recollection of facts unbound from personal experience, was intact.
For over a century, it has been the absence of memory in individuals like Jon that has given scientists a method for studying memory. Perhaps the most famous case of amnesia in the scientific literature is H.M., an epileptic who in the 1950s at the age of twenty-seven had part of his temporal lobes removed and lost his ability to acquire and recollect memories. H.M., whose real name was Henry Molaison, described his conscious existence as “like waking from a dream.” His surroundings always seemed unfamiliar to him, he was forever in a “new” place. It took him many years to eventually memorize the floor plan of his own house. For these reasons, he could never remember the people who spent decades testing his memory or his way around places he had been visiting for years. One of these was the Massachusetts Institute of Technology (MIT), where Molaison was often a subject at the Behavioral Neuroscience Laboratory between 1962 and his death in 2008.
It was H.M.’s case that led scientists to initially identify the hippocampus as the source of episodic memory—the ability to formulate and recall the places and events that make up our autobiographical past. And in Jon’s case, neuroscientists discovered the reason he couldn’t remember his past or reliably find his way when they used magnetic resonance imaging to look at his brain. The lack of oxygen to his brain as an infant, known as hypoxia, and the subsequent seizures had caused rare and severe damage to the cells in his hippocampus, stunting its growth. As a result, it was abnormally small, about half the size of a healthy hippocampus. Jon was one of several children who became part of ongoing studies into the nature of hippocampal amnesia. “These kids are really incredible,” Newcombe said. “There are only four or five of them, and their brain damage varies. But they are pretty normal: they go to school, they talk, they know facts, but they really don’t remember their lives—they don’t have autobiographical memory. And they can’t find their way to a school that they have attended for years and that’s two blocks away.”
As it turns out, there are interesting parallels between amnesiacs like Jon and all children in the early years of life. Children’s sense of space and memory for places and events is strange, far more emotionally vivid and sensitive than an adult’s yet confounding because it is so fleeting and fragmented. They are capable of forming memories, but they are highly vulnerable to forgetting; their memories are filamentlike and burn out quickly. Decades after the first scientific papers documenting H.M.’s condition and Jon’s case were published, the scientific u
nderstanding of the hippocampus and its importance to childhood development and memory is rapidly growing. Scientists have found multiple types of cells in the hippocampal circuit: head-direction cells discharge in relation to the way our head is pointed on the horizontal plane, and grid cells fire as we roam an environment, building a coordinate system for navigating. Place cells fire at a unique location in space, what is called the place field. Though the presence of these cells in the human brain is often inferred with brain scans, researchers have proven they exist by recording their activity during epileptic therapies, when electrodes can be directly implanted in the brain. Other spatial cell types are distinct to certain taxa. For instance, monkeys (but not rodents) possess gaze-direction cells that fire when a monkey is simply looking in a particular location.
All together, many now believe it’s the constellations of these cells blinking on and off in our brains that make self-localization and navigation possible. And there is evidence that infancy and toddlerhood are important periods in which cells in the hippocampus begin to encode space—as some say, map it—and mature. So, as babies explore their environment and create spatial representations, these experiences may be laying the neural foundation for episodic memory, our ability to remember the events of daily life.
The neuroscientist Lynn Nadel became interested in the developmental story of the hippocampus in the 1970s during the period he was researching and writing The Hippocampus as Cognitive Map with John O’Keefe, an eminent figure in the field of memory research. As they write, the hippocampus is a structure that matures at different times in different animals, unlike some other parts of the brain that are relatively mature at birth. In rats and mice, for instance, around 85 percent of the cells in the dentate gyrus—the sensory input region of the hippocampus—originate after birth in the days that correlate to the first two years of life for children. “The biggest surge in synaptic formation occurs in the period between postnatal days 4 and 11 when the number of synapses in the exposed blade doubles every day and the synaptic density increases 20 times.”
They proposed a fascinating trigger for the spatial mapping system in the brain to begin creating these representations—exploration. Animals are engaged in mixtures of activities: nesting, foraging, walking, swimming, flying, sleeping. They also explore, a behavior that occurs when an animal encounters a place that is unfamiliar or novel and begins to gather information about it by physically investigating. In the context of the cognitive map theory, Nadel and O’Keefe said that exploration is critical for building the map, for cells to encode space and make what is unknown familiar. Novelty is when an item or place “does not have a representation in the locale system and thus excites the mismatch cells in that system.” If the hippocampus disappeared, they predicted that exploratory behavior would also disappear in animals, and, in fact, lesion studies show this to be true. But what is the reason for this delayed maturation of the spatial mapping system? Perhaps it is to prevent young animals, who are still dependent on their mothers, from leaving their nest to explore and put themselves at risk.
After the book was published, Nadel continued to mull the implications of delayed maturation. “We had the theory of what the hippocampus did, but what does it mean if the hippocampus doesn’t work?” Nadel told me. “What’s it like if you don’t have it? What’s it like to be a relatively late-developing system? Does it make it more susceptible to plasticity in the environment?” Eventually he realized that the answer was amnesia. If the hippocampus wasn’t working, according to their theory of the cognitive map and its support for memory, there would be an inability to remember anything. Nadel had inadvertently found a neurobiological explanation for infant amnesia: like Jon, we can’t retain memories as children because we lack a fully functioning hippocampus.
In 1984 Nadel published his hypothesis, which he rooted in the fact that the time during which children exhibit amnesia matches the postnatal maturation of the hippocampus in rats. With coauthor Stuart Zola-Morgan, he proposed that episodic memory is only possible after the brain is capable of place-learning and that infant amnesia is a period during which the hippocampal memory system for space is relatively undeveloped. Animals don’t explore haphazardly, they pointed out, but in a structured fashion, going one place and then another but only rarely returning to locations they have already visited until they have sampled widely. “This pattern suggests the existence of internal representations that capture the spatial structure of the environment,” they write. In rats, guinea pigs, and cats, exploratory behavior emerges just as the hippocampal system approaches maturity: “If the machinery is not there, the system will not function.” And in both young animals and children, the capacity to store information about environments for spatial exploration and place-learning allows the encoding of events and where they occur, increasing memory capacity.
Three decades after he published the idea, Nadel told me that he thinks it is probably too simplistic—in both its definition of infant amnesia and the nature of development in the hippocampus, which varies between species. “The hippocampus, it’s not like a structure that isn’t there and then is there the next day. There is a gradual emergence of its functions,” he said. “We now know more about the piecemeal nature of that. There’s a patchy developmental picture that has emerged. On top of that, we know now that good episodic memory requires more than the hippocampus. For four or five years we don’t have these memories, and it has more to do with the entire network, connections to prefrontal cortex and all the parts of the brain that are involved when we do fMRIs.* But the core idea that the first nine to eighteen months of life there is no episodic memory at all, that is still on the right track. It’s the maturation of the network and the connections between those parts that give you long-term memory.”
Nadel and Zola-Morgan articulated a central mystery of spatial cognition: are we born with a brain that is hardwired to develop spatial memory or is experience important for building its infrastructure? Since then, hippocampal development and its relationship to memory has remained one of the most intriguing issues in neuroscience. As Jeffery said, “People started to look at development, and there’s quite a bit of interesting work now suggesting head-direction cells come online first, then place cells come online, and then the grid cells.” Indeed the evidence suggests that while certain components of the cognitive map are innate to our brains, we undergo a period of acquiring spatial knowledge in early life that influences how well we perform these functions later on.
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In 2010 two different research teams did something amazing: they implanted electrodes into freely moving preweaned rats the size of quail eggs and recorded individual neurons in the hippocampus. The teams, one at the Norwegian University of Science and Technology and the other at University College London, were able to record hundreds of head-direction cells, place cells, and grid cells starting from the rats’ sixteenth day of life for two weeks. Both teams discovered that all three of the cell types were present in the young rats as early as two days after they opened their eyes, and before they began to leave the nest and explore their environment. But of these cell types, only the head-direction cells were fully mature. It took several weeks of exploring the environment for the place cells and grid cells to become adultlike. From these data, the teams concluded that spatial learning continues to improve long after the components of the cognitive map are in place. Furthermore, one of the most important factors for determining the number and maturation of neurons was the age at which the young rats were exposed to new places, rather than how often they were exposed. The younger the age, the more quickly and easily they seemed able to encode spatial cells and learn.
Research into primates and behavioral studies of children have given neuroscientists clues to how the same process might occur in young humans. The Swiss neuroscientists Pierre Lavenex and Pamela Banta Lavenex have proposed that around two years of age the CA1 region of the hippocampus, essential to object differentiation in long-ter
m memory, matures. Over the subsequent years of toddlerhood, the dentate gyrus, a remarkably plastic region of the brain that undergoes neurogenesis—the creation of new neurons—into adulthood, matures and supports the creation of new memories. By six, children show a strong positive relationship between hippocampal volume and their episodic memory—the bigger the volume, the greater the ability to recall details of an event—and six is the average age at which childhood amnesia diminishes.
Throughout this period, learning seems essential for the hippocampus to generate and condition neurons. Indeed, without sustained opportunities for children to experience what could be described as exploratory wayfinding, some researchers believe that there would be costs to cognition and memory. In 2016 researchers at New York University’s Center for Neural Science published findings that showed how susceptible the development of the hippocampus is to learning experience. The team chose two different developmental ages in infant rats: postnatal day seventeen, which roughly corresponds to the age of two years in humans, and postnatal day twenty-four, which roughly corresponds to between six and ten years of age. By measuring molecular markers in the hippocampus, they were able to show how experience impacted the maturation of the hippocampus during this period. Then they increased or decreased the level of these molecules, thereby manipulating the rat hippocampus to either speed up memory retention or lengthen the window of infantile amnesia. What they concluded is that infantile amnesia is a type of critical period—a window of plasticity when environmental stimulation actively shapes the brain.