Abstract
The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system. However, whether this variant also contributes to TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. In this investigation, we applied rTMS during encoding of a visual memory task either over the left frontal cortex (LFC; experimental condition) or the cranial vertex (control condition). Subsequently, individuals underwent a recognition memory phase during a functional MRI acquisition. We included 43 young volunteers and classified them as 19 Met allele carriers and 24 as Val/Val individuals. The results revealed that rTMS delivered over LFC compared to vertex stimulation resulted in reduced memory performance only amongst Val/Val allele carriers. This genetic group also exhibited greater fMRI brain activity during memory recognition, mainly over frontal regions, which was positively associated with cognitive performance. We concluded that BDNF Val66Met gene polymorphism, known to exert a significant effect on neuroplasticity, modulates the impact of rTMS both at the cognitive as well as at the associated brain networks expression levels. This data provides new insights on the brain mechanisms explaining cognitive inter-individual differences to TMS, and may inform future, more individually-tailored rTMS interventions.
Highlights
The brain-derived neurotrophic factor (BDNF) Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to Transcranial magnetic stimulation (TMS) responses in studies of the motor system
In the present report we focused on functional MRI activation changes during the recognition phase as a function of the BDNF Val66Met gene variation
Following independent t-test analyses showed no differences in each experimental condition when comparing the BDNF polymorphisms both regarding accuracy and hits (accuracy, left frontal cortex (LFC): t(38) = − 1.744, p = 0.089; vertex: t(38) = 1.873, p = 0.069. hits, LFC: t(41) = − 0.327, p = 0.756; vertex: t(41) = 0.226, p = 0.822)
Summary
The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system Whether this variant contributes to TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. The results revealed that rTMS delivered over LFC compared to vertex stimulation resulted in reduced memory performance only amongst Val/Val allele carriers This genetic group exhibited greater fMRI brain activity during memory recognition, mainly over frontal regions, which was positively associated with cognitive performance. Within the framework of a European Initiative (https://www.imi.europa.eu/projects-results/project-factsheets/pharma-cog), we previously provided first evidence of the replicability across centers of the effects of such a cognitive interference protocol using r TMS10 These results confirmed the potentiality of rTMS as a standardized replicable memory interference paradigm, within multicentric and large clinical trials. Despite the roles of this neurotrophin in synaptic plasticity and activitydependent learning[30,31,32], whether this polymorphism contributes to the individual differences observed in TMSinduced cognitive outcomes and its associated underlying brain mechanisms remains unexplored
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