Neuroscientists have long demonstrated that neuronal connections in the brain can be strengthened with neuronal activity in the process known as neuroplasticity, and that brain training can be the ideal remedy to sharpen the human mind and to slow down the progress of neurodegeneration. However, recent studies revealed that too much thinking can actually be detrimental to the brain, causing profound DNA damage often dubbed as the DNA double-stranded breakages (DSBs).

DSBs are identified by the accumulation of gH2A.X histone- a recruiter of the DNA-repair machinery- at the site of breakage, and are previously thought to be caused only by cell stress.

 According to the study by Suberbielle et al. published in this issue of Nature Neuroscience, DSBs are also produced when the brain is at work (during exploration tasks), or when neurons are aberrantly activated during an epileptic seizure or by artificial stimulation by optogenetic techniques. The authors further showed that the DSBs are not produced as a response to stress hormones, but are rather produced by the normal neuronal activation of the NMDA glutamate receptor; a key receptor involved in neuroplasticity.

The effect of neuronal activity on DSB production is further aggravated by the presence of amyloid-beta plaques in the brain of Alzheimer’s disease patients; an effect induced by aberrant neuronal activity or seizures associated with the disease. While DSBs are dangerous DNA lesions that can result in neuronal cell death and the loss of brain function, the DSBs are shown to be repaired within 24 hours, begging the question as to whether DSB represents a crucial and yet unknown genetic event in memory and cognition.

Indeed, this discovery has far-reaching implications in our understanding of the neurological consequences of brain training. With brain-training games supporting a growing multi-million dollar industry, the study by Suberbielle et al. is forcing scientists and brain-training consumers to question whether brain-training could potentially have negative consequences in the brain. The study could also explain why there is very little consensual scientific evidence showing the effectiveness brain-training games on improving the human mind.  

Lastly, as brain training is shown as an effective a remedy against the onset of Alzheimer’s disease, the aggravation of activity-induced DSBs in the Alzheimer’s brain is a ground-breaking discovery fostering questions as to whether brain-training is a safe remedy for Alzheimer’s disease. Further research into the role of activity-induced DSBs in memory and cognition would be crucial to answer this pressing question.


Suberbielle et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β. Nature Neuroscience. 2013 Mar 24. doi:10.1038/nn.3356