2010). Activity-dependent secretion of BDNF is a necessary component for long-term potentiation (LTP) and depression processes (LTD), which are regarded as key elements of neural plasticity underlying learning and memory (Minichiello 2009). A click here common functional single nucleotide polymorphism (SNP) in the gene (rs6265), leading to an amino acid change in the pro-domain

of BDNF at codon 66 (Val66Met), occurs in about 30% of the human population of Caucasian ancestry (Egan et al. 2003; Hariri Inhibitors,research,lifescience,medical et al. 2003; Sen et al. 2003). The substitution of Val to Met in BDNF affects the intracellular trafficking and secretion of the BDNF protein and impairs the ability of BDNF to undergo activity-dependent Inhibitors,research,lifescience,medical release, but not general secretion (Egan et al. 2003; Hariri et al. 2003; Chen et al. 2004). Most research has focused on the effects of BDNF Val66Met on memory processes and related brain structures. Here, Met carriership has been associated with smaller hippocampal volumes (Pezawas et al. 2004; Bueller et al. 2006; Frodl et al. 2007; Karnik Inhibitors,research,lifescience,medical et al. 2010), decreased hippocampal activity, and lower declarative memory performance (Egan et al. 2003; Hariri et al. 2003). Research on the effects of BDNF in the brain has been extended into the motor system and motor learning. Using transcranial magnetic stimulation (TMS), it was shown that

BDNF Met carriers do not show the expansion of motor cortex surface area that is typically observed after a motor learning episode (Kleim et al. 2006). Cheeran et al. (2009) further elaborated on this study by showing that the LTP/LTD-like motor excitability induced with various TMS protocols is Inhibitors,research,lifescience,medical modulated by BDNF genotype, with Met carriers showing less motor cortex excitability. Met carriers were also shown to be more error prone when learning new motor skills during a delayed driving task (McHughen et al. 2010). Together, Inhibitors,research,lifescience,medical these TMS and behavioral studies

provide strong evidence that BDNF genotype indeed affects motor performance and motor learning. Recent evidence suggests that the effects of BDNF genotype may be influenced by sex (Fukumoto et al. 2010; Verhagen et al. 2010). However, a potential BDNF sex interaction in the motor domain has not yet been investigated. In this study, we next tested such an interaction. As BDNF Val66Met has been shown to influence both structural brain connectivity in the corpus callosum (CC) (Chiang et al. 2011) and functional connectivity as observed with resting-state fMRI (Thomason, Yoo, Glover, & Gotlib, 2009), we use a bimanual motor task to capture possible contributions from both motor and interhemispheric motor connectivity-related processes. Materials and Methods Subjects This study is part of the Brain Imaging Genetics (BIG) project running at the Radboud University Nijmegen (Medical Centre) (Franke et al. 2010), which is a collection of participants from (neuroimaging) studies that required genetic information.