Turning back the learning clock

Neurologist and molecular biologist Takao Hensch discusses possible ways of reopening windows of heightened brain plasticity and making up for lost learning opportunities

I met Dr. Takao Hensch in the lobby of Boston Children’s Hospital, where he runs a neuroscience lab. The baseball World Series championship was halfway over, and Hensch was wearing a Chicago Cubs baseball hat over his close-cropped hair.

As we entered the elevator, I admitted that, as a child of immigrants who never watched American team sports, I never developed an allegiance to a baseball team. He smiled and explained why that doesn’t surprise him. According to a recent study, people are most likely to develop team loyalty between the ages of 8 and 12. “If their team had won a championship at that time in their life,” Hensch explained, “then they’re hooked forever.” But if they had no exposure to team sports during that window, they’d be more indifferent, like me.

I had accidentally hit upon one of the more practical applications of Hensch’s research. The Harvard University molecular biologist is one of the leaders in the field of ‘critical periods’ — windows of development when our brains are most susceptible to change and adept at learning. During these periods, when the brain is building new neural connections and eliminating unnecessary ones, it is at optimal “plasticity.”

Scientists are eager to understand when those periods open and close in a normal brain – to help understand language acquisition, visual acuity, and other skills thought to peak at certain ages.

But Hensch has also focused on ways to intentionally manipulate those periods, in rodent models as well as humans, for a variety of reasons: to make up for lost learning opportunities, to heal neurodevelopmental disorders, and to understand variations in developmental trajectories. For instance, how does experience – both good and bad, stressful or traumatic – interfere with basic critical periods by closing them early or late? And how can you reopen them to turn back the developmental clock?

Hensch studies the different kinds of cells that turn on and off critical periods (which are also called “sensitive periods.”) He talks about molecular “brakes” that rein in the brain’s plasticity, thereby ending a critical period. That discovery has helped him and his collaborators look for drugs that interfere with those brake-like behaviors, as tools to reopen a critical period.

For instance, in 2013, Hensch and his colleagues decided to see if they could teach “perfect pitch” to a group of adults, even though the window when humans learn to identify musical notes was thought to close by the age of 7. In Hensch’s study, participants were given valproic acid – a drug already used clinically for mood-stabilization – that he hypothesized would work directly on the brain cells responsible for opening and closing critical periods.

“What we found is that it’s generally hard to change the adult brain in two weeks, but we had improvement on the pitch naming task,” Hensch said, “and so this was very exciting because it was indeed just two weeks of time and they were able to then do better on this kind of absolute pitch performance.”

That’s just one way manipulating critical periods can create new learning opportunities.

I asked Hensch to talk about this field of research, how experience can change the brain’s plasticity, and how close we are to a world in which a bit of chemical tweaking can make a developed brain as pliable as a young child’s.

Karen Brown: What are some things we’ve assumed as a culture about the brain’s ability to change that we no longer believe? Is the brain more plastic longer than we thought?

Takao Hensch: It was long thought that these critical periods were very strict and set in stone, such that if you passed a particular chronological age the window was over. It’s becoming increasingly clear that plasticity is possible throughout life. Take language, for example. There’s been a long standing debate whether there’s a critical period for learning language or not. And while it’s possible that having complete lack of experience or exposure to language is detrimental, it’s also true that we can learn a new language later in life.

“What we can say at this point is that stress, like any other experience early in life, is tapping into this heightened moment of plasticity in the nervous system.”

Understanding a little bit more about what turns on and what turns off these windows of early plasticity has explained how windows may be shifted into older ages, or happen too soon, or may even be reopened later in life. We now have a sense of what kinds of cells are pivotal for timing the onset of these windows, and what events are involved in closing them.

KB: How does stress or trauma play a part with critical periods? Can negative experiences move the sensitive periods one way or another?

TH: We’re very much interested in the details of how stress might influence critical periods, but this is actively ongoing work. What we can say at this point is that stress, like any other experience early in life, is tapping into this heightened moment of plasticity in the nervous system. And so if you give an individual or an animal good or bad experiences early in life, either one will alter the brain circuitry to suit that environment. What we’ve realized more recently is that the very timing of these critical periods can change.

KB: Does that mean that someone who was raised in a stressful environment is going to have trouble learning? Will they have less plasticity or will their sensitive period for learning close earlier?

TH: Yes, the plasticity would wind down earlier than normal. This can be seen as adaptive. If you’re raised in an unstable environment, then you probably want to adjust to it very quickly and then not change circuitry too much more after that. Individuals who are raised in a stressful environment have a much shorter window of time to learn about their environment, and then they become refractory to change much sooner than normal.

KB: How is that applicable to schools or communities, especially where you might have a large number of kids who are living in chronic stress or poverty or violence?

TH: It’s difficult to make blanket statements because there’s great individual variability. But it is important for educators and clinicians and parents to be aware that the time windows for the milestones of development may actually be skewed in kids who’ve been raised under these kinds of traumatic environments, and the general direction of skew is that they become less plastic earlier. And so we might need to think of other ways to reopen such a critical period or to get them out of the stress early.

KB: How far away are we from developing a drug to re-open critical periods?

TH: To be honest, I don’t think we’re that far at all. We’ve been looking for these mechanisms that close critical periods for many many decades, but it’s only in the last five to ten years that we’ve realized the existence of molecular brakes that close critical periods. In other words, the nervous system is actively making factors to prevent rewiring and stabilize circuitry. And so there are in fact drugs that can counteract brake-like factors already being used for other purposes, clinically. It’s highly likely that the beneficial effects of some of these drugs are through a reopening of brain plasticity.

“Well I think the science fiction has become reality, and we need to be very careful about reopening brain plasticity willy-nilly.”

KB: What is a scenario in which somebody would seek out and take such a drug?

TH: If, for some reason, someone suffered a brain injury, or had a stroke in adulthood, when the circuitry is largely stable at that age, it might be desirable to reopen a critical period and allow for new learning, maybe training of a different part of the brain to take over the functions that were lost by the brain damage. Another example is the vast number of neurodevelopmental disorders, where we’re learning that these kids are going off the trajectory of normal development but ​are only recognized as such after they’ve deviated. So it might be useful then to reopen a critical period or allow a second chance for these people to acquire skills they might not have otherwise.

KB: What are the dangers of overusing this reopening of the critical period? Is there a trade off between plasticity and stability?

TH: Well I think the science fiction has become reality, and we need to be very careful about reopening brain plasticity willy-nilly. Just because we can do it doesn’t mean that it’s a good idea necessarily. And I think the evidence that it might not be a good idea comes from mental illnesses and neurological disorders. As we became aware of these molecular brakes, many were disrupted in mental illnesses, suggesting that perhaps one aspect of schizophrenia, for example, might be the failure to appropriately close a window of plasticity, rendering circuitry slightly more plastic, or less stable, for a longer period of time.

“Our critical periods have closed for a reason, and evolution has created these biologically costly mechanisms to maintain our individual identities and differences.”

KB: I can imagine there being a parent of a child with severe learning challenges who thinks – maybe I can give them this chemical, this drug – but am I going to create schizophrenia? Is that a danger?

TH: In the extreme, that might be a real concern. But even normal kids don’t learn things overnight. They have to work at it. And it’s the same with these manipulations thankfully. Someday soon, however, we may have other ways to more directly unleash brain plasticity, and in that case, we do worry about irretrievably losing something that we’ve acquired while growing up. Our critical periods have closed for a reason, and evolution has created these biologically costly mechanisms to maintain our individual identities and differences. Going in there and tampering with that seems like a risky proposition.

KB: In other words, we’ve all developed personalities, and the more plastic your brain is, the more your very personality could keep shifting?

TH: Potentially. If we could make the brain plastic all at once, then it would be a way to erase our identities — this is the stuff of movies. But we’re finding that the nervous system is not that easy to change. And the ways that have been identified are windows of opportunity that still require considerable effort on the individual’s part.

Takao K. Hensch, PhD, is joint professor of Neurology, Harvard Medical School at Boston Children’s Hospital, and professor of Molecular and Cellular Biology at Harvard’s Center for Brain Science. Professor Hensch’s research focuses on critical periods in brain development. By applying cellular and molecular biology techniques to neural systems, his lab identified pivotal inhibitory circuits that orchestrate structural and functional rewiring of connections in response to early sensory experience. His work affects not only the basic understanding of brain development, but also therapeutic approaches to devastating cognitive disorders later in life.