Action Potential

Learning from your horrible mistakes

Staying on the genetics theme, a recent Science article suggests that a particular variant of the dopamine receptor (D2) causes some people to poorly learn via negative reinforcement. The A1 allele, as this variant is known, has previously been linked to increased vulnerability of addiction.

The researchers recruited volunteers, who performed a learning task while lying in an fMRI machine. Individuals with the A1 allele (at least one copy) were equally successful at selecting a targeted “good” symbol reinforced with positive feedback (the display of a “smiley face”) as those individuals completely lacking the A1 allele. However, when the task was changed such that negative reinforcement drove the learning (subjects were asked to avoid the “bad symbol”), those individuals with the A1 allele failed to perform as well as their A1-lacking colleagues.

Examining the fMRI data, those with the A1 allele had less activity in the frontal cortex and hippocampus, two areas normally responsive during tasks involving negative reinforcement and memory. This reduction was thought to be because posessing the A1 allele can cause up to a 30% reduction in D2 receptor density in individuals, presumably affecting the neural circuitry, and likely influencing the activity within the reward signaling pathways.

With a variety of evidence suggesting that the A1 allele is more prevalent in alcoholics (although there is also plenty of evidence refuting this link), the authors are enthusiastic that they have uncovered an important bridge between addiction and reward reinforcement. Alcoholics tend to repeatedly experience strife, perhaps because they cannot learn from the negative consequences suffered as a result of their actions. Therefore, the thought is that this genetic inability to process negative experiences as learning opportunities can underlie the social and physical consequences of this disease. What a bunch of rubbish.

The current study is based on 26 German males, with 12 of them posessing the A1 allele. So it is not only small, but conducted in a very specific population. Positive reinforcement as the display of a smiley face? Negative reinforcement as the display of a “frowny” face? I bet every alcoholic, with or without the A1 allele, wishes that the worst that would happen to him/her at the end of a rough night of binging is that when they pressed a button, a frowny face would come up (usually that frowny face is attached to a policeman with a large nightstick and handcuffs…). This study seems to be stretching quite a bit, and looks to be more of a headline-grabber than anything. Tellingly, in an accompanying piece, geneticist Neil Risch states:

[The A1 allele] has been a candidate gene for every imaginable psychiatric phenotype for 18 years now, and to my knowledge none of the originally reported associations has held up.

I guess only time will tell whether this study holds true, or is swept into the research purgatory of “irreproducible”, or “controversial” (due to conflicting studies NOT demonstrating a link between A1 and negative reinforcement). Taking Risch at his word, it seems possible that many population genetics researchers studying A1 also possess a copy or two…

Klein, T., Neumann, J., Reuter, M., Hennig, J., von Cramon, D., & Ullsperger, M. (2007). Genetically Determined Differences in Learning from Errors Science, 318 (5856), 1642-1645 DOI: 10.1126/science.1145044


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