Toward a pill that helps us learn

Shannon, a 14-year-old who lives in Massachusetts, has amblyopia, a condition sometimes referred to as “lazy eye.”

You can’t tell by looking at her, though. Unlike some amblyopic patients, whose eyes visibly wander, Shannon simply has extremely poor eyesight.

Patients’ best hope for correcting amblyopia is before they turn about 8 years old. Those who don’t get treatment early enough—or for whom treatment doesn’t work—usually end up living with the problem forever.

Shannon is one of those people. Her entire life, she’s worn glasses with a thin non-prescription lens on one side, and a thick corrective lens on the other. As a toddler, her parents tried to make her wear therapeutic eye patches, but she would fling them off.

A few months ago, Shannon enrolled in a clinical study at Boston Children’s Hospital for which she’s taking donepezil, a drug that’s typically used to treat Alzheimer’s. Donepezil is a cholinesterase inhibitor, meaning itincreases the amount of acetylcholine circulating around nerve endings. It’s been shown to improve memory function in some patients with dementia.

But of course, Shannon doesn’t have memory problems. Her team of doctors is instead using the donepezil to encourage her brain to learn new skills as quickly and nimbly as an infant’s would. Shannon’s vision has improved markedly over the past four months, her mother told me by phone.

Takao Hensch, a Harvard professor of cellular biology who is part of the Boston Children’s team, has found that behavioral drugs like donepezil can help return the chemistry of the brain to so-called “critical periods” in its development—the times during early childhood when the brain was rapidly growing. Critical periods help explain why children younger than about 7 can pick up new skills, like language and music, much faster than adults can. This is why you see parents attempting to plant foreign languages in their kids while they’re still in Pampers. It’s much easier than trying to conjugate French verbs for the first time when you’re 30.

Hensch and his colleagues have already found that valproate, an epilepsy drug, can help tone-deaf adults learn to differentiate music notes. In a study published in December in the journal Frontiers in Systems Neuroscience, a team of researchers including Hensch administered valproate or a placebo to 24 men with no music experience and then trained them to label music notes. Those who took the valproate were later able to correctly identify 5.09 music notes on average, compared with 3.5 in the control group.

There were several flaws in the study—the sample size was small, and it’s possible that some of the men had a genetic predisposition toward music.

Still, the effect size was promising enough for Hensch to attempt new experiments with other drugs and different types of traits.

In Shannon’s case, the donepezil helped her mis-wired brain learn how to process visual stimuli from the amblyopic eye, just like a newborn’s would.

“Our main interest is not really to create super humans but to help with developmental disorders or brain injury in adulthood,” he told me.

Hensch’s research is one of the more intriguing recent examples of how our understanding of neuroplasticity has evolved. Until about 20 years ago, scientists thought that after we reached puberty the structure of our brains more or less froze. But more recent studies have shown that our brains continue to transform throughout our lives, though not to the extent they did when we were children.

What Hensch hopes to do is to induce time-travel for our brains—to return them to their ultra-flexible younger years.

“The brain is not losing its plasticity forever as we grow older,” Hensch explained. Instead, it just throws on the brakes at certain times. “It’s the brain’s job to be elastic, and it wants to rewire. But through evolution, it’s created a lot of molecules to make sure it doesn’t rewire too much.”  

The psych meds work by boosting the molecules, such as serotonin and acetylcholine, that are normally dampened during adulthood. The extra surge of chemicals aids in the rewiring process.

One concern Hensch hears often is that the brain might then rewire too much, essentially wiping away the patient’s personality in the process. But that didn’t happen in the perfect-pitch study, he said—music was the only thing the subjects became better at. Though Hensch’s studies involve sub-clinical doses of the psych medications, he said eventually there may be video-game training or other stimuli that could create these critical periods without drugs.

Nafissa Ismail, an assistant professor in psychology at the University of Ottawa, says this type of critical-period-hacking should arouse both hope and caution. The young brain’s plasticity is a double-edged sword: though skills like language and music come much more naturally to children, environmental and social stress can also harm them much more profoundly.

“It’s during these times that the brain opens itself up to external factors, for better or worse,” she said. “Certain environmental factors that are adverse could come and interfere in brain development.”

Ismail has studied female mice who, when injected with a bacteria during a critical period, are less sexually receptive, more anxious, and more depressed as adults. In human females, being exposed to a major stressor during puberty could similarly hurt mood and libido in adulthood.

She cautions that even as drugs like valproate open up the brain to new skills and experiences, they could also make it more sensitive to environmental stressors.

It’s still too early in Hensch’s experiments to know whether that will be the case for the patients taking the Alzheimer’s medications. For the treatment to become widespread, the benefits would have to outweigh the costs. It’s unlikely that those of us without serious health conditions would want to pop heavy-duty drugs just for the chance to play sparkling piano sonatas. But Hensch said he’s been getting emails from stroke victims and others who are eager to try anything that might give their brains a second chance.

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