Decreased medial temporal lobe activation in BDNF (66)Met allele carriers during memory encoding

The Met allele of the Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val(66)Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val(66)Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55-75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging. BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.