BDNF Val66Met Polymorphism on Functional MRI During n-Back Working Memory Tasks

Val66Met polymorphism on the brain-derived neurotrophic factor (BDNF) gene is associated with hippocampal pathology and impaired episodic memory. However, the influence of this polymorphism on working memory (WM) performance and patterns of brain activation is controversial. This study investigated the effects of BDNF Val66Met polymorphism on functional magnetic resonance imaging (fMRI) during n-back WM tasks in healthy middle-aged adults. A total of 110 participants without subjective or objective cognitive impairment underwent BDNF genotyping. Eleven Met allele carriers and 9 noncarriers underwent fMRI during WM tasks. The WM performance was similar between the 2 groups. Increased brain activation in response to increases in WM loads was observed in both groups. The Met allele carrier group showed consistently lower brain activation in the right superior frontal gyrus (SFG) and the middle occipital gyrus than that of the noncarrier group (P < 0.001). No brain region showed increased activation during WM tasks in the Met allele group. BDNF Val66Met polymorphism may affect the WM network. Met allele carriers have lower brain activation in the right SFG and middle occipital gyrus than do noncarriers during WM tasks. Defective development of the WM network during brain maturation or differentiation is a possible mechanism. Additional studies with a larger sample and longer follow-up period are warranted.