Can a pill make you a singing star by rewiring your brain?

Justin Timberlake


I am a terrible singer.

I can’t sing a very good range, and I can’t sing notes within that range very well.

When I try to hold a note for longer than a nanosecond, it ends up being not one note but many notes as I wobble erratically around the intended pitch, and it’s so bad it makes small children cry.

The perfect pitch fairy never waved her wand at me. For that matter, neither did the regal nose, chiselled chin or piercing look fairies but that’s another story.

Researchers would say that perfect pitch is partly inherited, but mostly the result of early and frequent exposure and training in music (effort), during the critical learning period (timing), before the age of six. Two things to note here.

You’ll already know that the more effort we put into an endeavor, the more connections we can grow, and the more brain space is devoted to that endeavor. People with perfect, or absolute, pitch, show an increase in the size of their planum temporale, with both right and left structures enlarged, and the left planum temporale being larger than the right.

Critical periods are fixed windows of time in which we learn different skills easily and quickly, the effects of which long outlast the window. They usually occur early in life, and rely on the brain’s plasticity, or malleability, which enables swift and smooth reorganization to accommodate new information and experience.

Question is…

can you re-open them, for absolute pitch, and then other things?

Language for example, is learned most easily as a child, before about 8 years old. Learning a second language is the same. Move to another country with kids and they can pick up the language, and dialects, in no time at all with no effort, and no trace of an accent. They sound like natives.

Parents, on the other hand, carry the accent of their mother tongue into the newly acquired language, which they had to try much harder to learn. It’s not that they can’t learn it, it just seems so much more difficult. Wouldn’t it be great to absorb Spanish like a seven year old? (By the way, there’s a quick phonetics explanation and test after the guff at the bottom.)

Visual and auditory systems have critical periods, and the brain as a whole has periods of cell proliferation followed by cell pruning, so windows of development are a familiar concept.

Opening and closing them at will however, is a different story.

Recent proof of concept work by Takao Hensch, Professor of Molecular and Cellular Biology, and Professor of Neurology, at Harvard University’s Department of Molecular and Cellular Biology, sought to discover whether opening these periods back up again might be possible. The implications of such a find are intriguing.

Neuroplasticity allows us to learn easily. A malleable brain can more quickly and easily adapt and incorporate new information. If we’re able to augment our abilities through manipulating neuroplasticity, after the period of plasticity has closed, then what might be possible? If one window opens, can we open others? Can we learn languages? Can we acquire other skills effortlessly? Can we learn more easily?

Critical periods

From birth, when the brain is overloaded with synapses (the connections between brain cells), the brain grows swiftly through to about age five, then slows to about age 20, carefully pruning as it goes, and discarding unnecessary connections. Critical periods occur during these early years, and are shaped by growth and pruning.

Chemically, BDNF (brain-derived neurotrophic factor), a nerve growth chemical, operates like fertilizer on tomatoes, generating growth. Particularly, this protein activates the nucleus basalis, a small brain structure that sharpens attention, and stays switched on throughout the critical period. BDNF also consolidates connections between cells, which is crucial for memory. Once the critical period ends, the nucleus basalis is switched off.

Hensch notes that “behaviorally induced plasticity in the healthy brain, typically after the end of the relevant critical period, can lead to improvement beyond normal or average performance levels”.

He would add that this usually involves specifically targeted training, beyond what we would consider regular use. The training needs to be repetitive, intense, and relevant.

So what if there were another way?

Hensch also knew that growing older, along with experiential events, conspire to close the windows of critical periods. One of these changes involves an enzyme known as HDAC (histone-deacetylase) which halts critical period learning, much like putting on a hand brake stops a car. Research in mice had already shown that inhibiting HDAC could remove the brake in the visual and auditory systems. Could it work in humans? Could Hensch teach absolute pitch beyond the critical period by chemically releasing the brain’s learning hand brake?

Could I be a singing star after all?


In a randomized, double-blind, placebo-controlled study, 24 males received either placebo, or VPA treatment. None of the men had musical training as children. Variations of VPA, or valproate, are commonly used for reducing seizures in epilepsy, stabilizing mood in bipolar disorder, and in other psychiatric conditions. It’s also a HDAC inhibitor.

Following a period of online ear training, Hensch tested the men on how well they could discriminate between tones. If the experimental group outperformed the placebo group, then there would be evidence that the window had opened.

And it had.

Confirming their hypothesis, performance varied by experimental group. In Hensch’s words “Normal male volunteers performed significantly better on a test of AP (absolute pitch) after 2 weeks of VPA treatment than after 2 weeks of placebo”.

As he should be, Hensch is cautious. This doesn’t open the floodgates for massive-scale pharmo-educational snake oil, biotech commercialization, super soldiers, overnight geniuses, or anything.


So here’s the take home bit

Specific skills like this don’t necessarily translate to improvements in other areas so, for example, general intelligence doesn’t necessarily improve. Transfer to related areas is possible, but not automatic.

Hensch notes his small sample size, and that the work needs to be replicated before we get carried away. Others note the potential side effects of chemicals. Hensch sees the crudeness of this approach but opines that, if replicated, their “study will provide a behavioral paradigm for the assessment of the potential of psychiatric drugs to induce plasticity”.

The subtext is that psychiatric conditions can be overcome by harnessing the power of plasticity, however that plasticity is unlocked. Already, cognitive behavioral therapy re-sculpts the brain and chemicals can open critical windows.

Can newer work in optics switch on the nucleus basalis. It’s the BDNF gene that maps BDNF. Could we turn this on through transcranial electrical stimulation thereby turning on the nucleus basalis.

We don’t know. But we can tell that the ground is moving.

As for absolute pitch and my latent signing career, I’m still waiting for the fairy.

Impressive words to drop into the morning coffee chat

Brain-derived neurotrophic factor (BDNF)

What do you think?

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Learning languages

By way of illustrating critical periods and learning languages, English has 44 sounds. Other languages have more, or fewer.

Say ‘tip’ aloud. Phonetically, the opening ‘t’ sound in the word tip, is represented as /t/. Structurally, your mouth and tongue make the same movements for /t/ as for ‘d’ in dip, represented as /d/. Remember this symbol represents the sound, not the letter. The difference is that to make /d/, you have to add voice. Same goes for /p/ and /b/.

Here’s a test. Put your fingers on your voicebox and say ‘pump’ followed by ‘bump’. Feel your voicebox vibrate for the /b/ sound, but not the /p/ sound? Other pairs are /f/ and /v/, /k/ and /g/ and so on. We also have diphthongs, which are sound combinations; the ‘dg’ sound in ‘judge’, the ‘ch’ of church’ and so forth. And by the way, ‘phonetics’ in phonetics, is /fəˈnɛtɪks/.

We learn our native sounds easily, and once they’re learned, we lose the ability to learn new ones as easily, as the ability to make them disappears with the closing of the critical window. Most of us don’t use the click consonants of the Bantu, or the ‘ll’ sound found in Welsh, or the back of the mouth sounds found in Arabic, and would have to learn to master them, mashing our mouth around the necessary tongue, lip and teeth positions, let alone adding voice.

A young child, within the window, with nucleus basalis switched on, would pick them up quickly, regardless of the language.


About brendonbclark

Hi, I’m Brendon, but people usually call me B. I’ve a Masters degree in psychology, postgraduate qualification in mental health, and qualifications in counselling, professional supervision and adult education. I consult, speak and blog. Join me, you can subscribe for free.
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