The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced functional magnetic resonance imaging activity in the hippocampus and increased use of caudate nucleus-dependent strategies in a human virtual navigation task

Abstract

Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent ‘spatial’ navigation, which relies on knowledge of the relationship between landmarks in one’s environment to build a cognitive map, and habit-based ‘response’ learning, which requires the memorization of a series of actions and is mediated by the caudate nucleus. Studies have demonstrated that people spontaneously use one of these two alternative navigational strategies with almost equal frequency to solve a given navigation task, and that strategy correlates with functional magnetic resonance imaging (fMRI) activity and grey matter density. Although there is evidence for experience modulating grey matter in the hippocampus, genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has emerged as a possible inhibitor of hippocampal function. We have investigated the role of the BDNF Val66Met polymorphism on virtual navigation behaviour and brain activation during an fMRI navigation task. Our results demonstrate a genetic contribution to spontaneous strategies, where ‘Met’ carriers use a response strategy more frequently than individuals homozygous for the ‘Val’ allele. Additionally, we found increased hippocampal activation in the Val group relative to the Met group during performance of a virtual navigation task. Our results support the idea that the BDNF gene with the Val66Met polymorphism is a novel candidate gene involved in determining spontaneous strategies during navigation behaviour.

A secondary working memory challenge preserves primary place strategies despite overtraining

“…In rodents, a robust double dissociation is observed between a hippocampal-mediated place strategy and a dorsolateral striatalmediated response strategy (Packard et al 1989;Packard and McGaugh 1996;Packard 1999;Yin and Knowlton 2004); with similar dissociations noted in humans (Corkin 1968;Knowlton et al 1996;Hartley et al 2003;Squire 2004;Bohbot et al 2007;Balleine and O'Doherty 2010;Banner et al 2011;Wit et al 2012). Moreover, several factors that modulate strategy recruitment are shown to act differentially on neural structures implicated in place and response navigation (Packard 1987(Packard , 2009McDonald et al 2004).…”

“…Further work will need to clarify the degree to which secondary training can influence strategy reliance in subjects with a response predisposition, e.g., as a result of aging (Bohbot et al 2012), neuroanatomical variability (Bohbot et al 2007;Wit et al 2012), genetic polymorphism (Banner et al 2011), stress (Packard 2009;Schwabe et al 2010), and/or sleep deprivation (Hagewoud et al 2010), rather than repeated practice and experience. Nonetheless, this research opens a promising line of future investigation.…”

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

“…The resource-modulation hypothesis by Lindenberger and colleagues assumes that losses in neurochemical (Bäckman et al 2006(Bäckman et al , 2010 and anatomical (Raz et al 2005(Raz et al , 2008 brain resources in aging modulate the effects of common genetic variations on cognitive functioning (see Fig. 1): Whereas genetic effects in younger adults may be small or undetectable, these effects become stronger as people age.…”

“…In young adults, BDNF Met carriers have shown lower activity in hippocampus during encoding and retrieval of episodic memories (e.g., Egan et al 2003;Hariri et al 2003; for meta-analysis, see Kambeitz et al 2012) and during performance of a virtual navigation task (Banner et al 2011). However, note that others have failed to find effects of BDNF on hippocampal activations during encoding and retrieval of episodic information in young and middle-aged adults (Dodds et al 2013).…”

BDNF Val66Met polymorphism in patterns of neural activation in individuals with MDD and healthy controls

“…This suggests that bdnfval66met-or-bdnfmet66met patients with MDD experience stronger visceral reaction to emotional stimuli (Longstaff, 2005). The increase of activation in striatum (Banner et al, 2011) has been associated with vulnerability to MDD linked to methionine allele. A changed level of BDNF observed in the region can produce depressive-like symptoms (Berton et al, 2006;Eisch et al, 2003).…”