BDNF genotype modulates resting functional connectivity in children

Abstract

A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within both default-mode and executive networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because of the known association between the BDNF gene and neuropsychiatric disorder, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. In addition, we demonstrate that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.

Keywords: BDNF; adolescents; children; fMRI; functional connectivity; gene; resting-state.

Figure 1

Map of neural connectivity for the three major resting-state networks across all subjects (n = 38). p < 0.0001. Red circles denote approximate locations of seed-point ROIs.

Figure 2

One-sample t-tests within each genetic group depicting group effects for three major resting-state networks at p < 0.0001.

Figure 3

Two-sample t-tests for three major resting-state networks. BDNF gene group differences (val/val > val/met: blue; val/met > val/val: orange) across three resting networks. FG = fusiform gyrus, Ins = insula, Hip = hippocampus, IPL = inferior parietal lobule, PHG = parahippocampal gyrus, SPL = superiorparietal lobe, Pu = putamen, Am = amygdala; p < 0.01.

Figure 4

BDNF gene group differences (val/val > val/met: blue; val/met > val/val: yellow) for each of the three resting networks within hippocampal ROIs.