Variant brain-derived neurotrophic factor val66met polymorphism engages memory-associated systems to augment olfaction

Abstract

The neurogenetic basis of variability in human olfactory function remains elusive. This study examined olfactory performance and resting-state functional neuroimaging results from healthy volunteers within the context of the brain-derived neurotrophic factor (BDNF) val66met polymorphism with the aim of unraveling the genotype-associated intrinsic reorganization of the olfactory network. We found that the presence of the Met allele is associated with better olfactory identification and additional engagement of semantic memory system within the olfactory network, in an allele dosage-dependent manner. This suggests that the Met allele may promote adaptive neural reorganization to augment olfactory capacity.

Figure 1

Differences in olfactory performance (by Sniffin’ Sticks test) among the three genotype groups in the olfaction cohort (n = 47). (A,B,D) No differences were noted in terms of odor detection threshold, discrimination, or composite TDI score. (C) The Met/Met group out-performed the Val/Val group in odor identification (post hoc Bonferroni test, *P = 0.023). A Met-allele dosage effect was observed (linear regression, r = 0.45, beta = 0.61, t = 3.02, P = 0.004, Supplementary Table 2). The bar graphs show the means and standard deviations of olfactory scores, and the scatter plots demonstrate all data points.

Figure 2

Representations of BDNF gene-informed piriform cortex (PC)-seeded olfactory network (olfaction cohort, n = 47). (A) The between-group comparison of olfactory networks in the Met/Met and Val/Val group exhibited stronger links to the semantic (middle/inferior temporal gyrus, MTG/ITG) and autobiographical (retrosplenial cortex, RSC; posterior cingulate cortex, PCC) memory areas, visual cortex (superior occipital lobule, SOL), gustatory area (insula, INS) and somatosensory area (postcentral gyrus, PostCG). (B) Met-allele dosage effect on the PC-seeded functional connectivity (FC). Note that in the linear regression model, Met/Met was defined as “2”, Val/Met as “1”, and Val/Val as “0”. The peak coordinates and the linear regression results for the Met-allele dosage effect can be found in Table 1.

Figure 3

BDNF gene-informed piriform cortex (PC, in the green sphere)-seeded olfactory network (PDM cohort n = 145). (A) The between-group comparison of olfactory networks in the Met/Met and Val/Val groups exhibited hyper-connectivity to a confluent cluster including the retrosplenial cortex (RSC), posterior cingulate cortex (PCC), precuneus and cuneus (P_FWE-corr. < 0.001, in red). (B) The between-group comparison of olfactory networks among the Met carriers and Val/Val groups converged to the RSC and cuneus (P_FWE-corr. < 0.001). (C) The between-group comparison of olfactory networks in the Val/Met and Val/Val groups displayed sub-significant clusters in the cuneus (P_FWE-corr. = 0.471 and 0.464 as seeded from the left and right PC respectively, in violet). (D) Met-allele dosage effects were observed in all aforementioned PC-seeded neurodynamics. The peak coordinates and linear regression results for the Met-allele dosage effect can be found in Supplementary Table 3.