Brain-derived neurotrophic factor gene polymorphisms shape cortical plasticity in humans

The brain-derived neurotrophic factor (BDNF) gene is involved in mechanisms of synaptic plasticity in the adult brain. Recently it has been demonstrated that BDNF also plays a significant role in shaping externally induced human brain plasticity. Plasticity induced in the human motor cortex by intermittent theta-burst stimulation (iTBS) was impaired in individuals expressing the Val66Met polymorphism.

To explore whether this polymorphism is also important for other neuroplasticity-inducing tools in humans with modes of action differing from that of iTBS, namely transcranial direct current (tDCS) and random noise (tRNS) stimulation, we re-analysed the data of 64 subjects (87 measurements) studied in our laboratory with regard to BDNF genotype.

15 subjects with Val66Met allele, 46 subjects with Val66Val allele and 3 Met66Met carriers were identified. The response of the Val66Met allele carriers to stimulation differed in all protocols compared with the response of Val66Val individuals. For iTBS, plasticity could be only induced in the Val66Val allele carriers. However, for facilitatory tDCS and tRNS as well as for inhibitory tDCS, carriers of the Val66Met allele displayed enhanced plasticity.

BDNF polymorphism has a definite impact on plasticity in humans, which might differ according to the mechanism of plasticity induction. This impact of BDNF on plasticity should be taken into account for future studies with brain stimulation techniques, as well as having wider ranging implications for the treatment of neuropsychiatric disorders with transcranial stimulation tools, as it may predetermine their efficacy for the treatment of injury, disease and rehabilitation.