Variation in the gene coding for BDNF influences the integrity of white matter tracts within recognition memory circuits.

• ¹ University of Auckland, New Zealand

Background: Recognition memory allows for the discrimination of stimuli that have been previously encountered from those that have not. Previous research has suggested that performance on recognition memory tasks is influenced by a single nucleotide polymorphism (SNP) observed within the gene that codes for brain derived neurotrophic factor (BDNF). This SNP is known to affect the functional activity of BDNF and carriers of the BDNF Met allele have shown impaired performance on recognition memory tasks as well as reduced hippocampal volume compared to Val homozygotes. It is of interest to us to determine whether observed behavioural differences between Met allele carriers and Val homozygotes might be underpinned by white matter connectivity differences.

Methods: 30 healthy participants completed two behavioural tasks that were designed to examine familiarity and recollection based recognition memory performance. Diffusion weighted images were also collected for each participant and probabilistic tractography was used to trace out thalamo-cortical pathways of interest.

Results: Connectivity of thalamo-cortical pathways differed between the two genotype groups. Carriers of the Met allele were found to have reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in tracts seeded from the anterior and medial dorsal thalamic nuclei compared to Val homozygotes. Behavioural results showed no difference in accuracy between the two groups, however, connectivity measures were found to account for 60% of the variance in the recognition scores of our participants and therefore might indicate problems with the sensitivity of our behavioural tasks.

Discussion: We have found that across thalamo-cortical pathways implicated in recognition memory circuits, carriers of the BDNF Met allele have reduced connectivity as measured by FA and MD. This was particularly apparent in pathways seeded from the anterior thalamic nuclei, which is thought to be a critical component of the neural circuit for recollection-based recognition memory. These results are consistent with previous findings that Met allele carriers perform worse on recognition memory tasks. Our findings indicate that BDNF genotype influences white matter microstructure and we therefore propose that in Met allele carriers, this results in a loss of tract integrity and may underpin the decrease in recognition memory performance observed in previous studies.