Epigenetic influence on Neuroplasticity

It appears that neuroplasticity is governed by epigenetic mechanisms, which can be modulated to allow learning of absolute pitch (a.k.a. perfect pitch) beyond the normal age window (4-6 years in humans).
Absolute pitch is thought to require specific training, with association of conceptual labels to specific pitches. In this experiment, the authors report treating young adult men with valproate improved their learning of absolute pitch outside the normal window of opportunity.

Valproate is a drug used primarily for anticonvulsant effects in generalised epilepsy, and it is a known inhibitor of HDAC. Histone deacetylase (HDAC) is an enzyme responsible for removing acetyl groups from histones. Acetylation of histones makes them bind their DNA less tightly, increasing the DNA's accessibility and promoting transcription.
It should be noted that this effect is generalised across all histones.

The study design was randomised, double blind, placebo controlled crossover. The subjects were, interestingly, asked whether they knew which treatment arm was the active substance. 17/18 knew. This is a perfect example of how psychoactive drugs cannot be blinded in the typical way. Essentially the study was un-blinded, making it liable to more confounds.

If we look at the results, after crossover the effect of valproate disappears. This is important, as it puts the validity of the conclusion into question. The authors do not seem concerned, (having got the result they want?), and suggest that the subjects experienced memory interference having already mis-learned that task once while on placebo. They rightly suggest a larger, single stage trial to reveal the truth.

The results are interesting and deserve further attention but are not conclusive, especially given the lack of effect after crossover, with no falsifiable explanation for it.


Valproate reopens critical-period learning of absolute pitch
Gervain Judit, Vines Bradley W., Chen Lawrence M., Seo Rubo J, Hensch Takao K., Werker Janet F, Young Allan H   
Frontiers in Systems Neuroscience
2013