Brain‐derived neurotrophic factor val66met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

Abstract

Brain-derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long-term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype and functional activity in the hippocampus during episodic and working memory tasks in healthy young adults. Specifically, studies have found that met carriers exhibit both poorer performance and reduced neural activity within the medial temporal lobe (MTL) when performing episodic memory tasks. However, these studies have not been well replicated and have not considered the role of behavioral differences in the interpretation of neural differences. The current study sought to control for cognitive performance in investigating the role of the BDNF val66met genotype on neural activity associated with episodic memory. Across item and relational memory tests, met carriers exhibited increased MTL activation during both encoding and retrieval stages, compared to non-carriers. The results suggest that met carriers are able to recruit MTL activity to support successful memory processes, and reductions in cognitive performance observed in prior studies are not a ubiquitous effect associated with variants of the BDNF val66met genotype.The medial temporal lobe (MTL), including the hippocampus, is one of the key brain regions associated with both the encoding and retrieval of episodic memories (Dobbins and Davachi, 2006). Moreover, the involvement of the hippocampus in successful memory processing increases as the complexity of the episodic memory task increases. For example, item memory, which refers to remembering individual features or items associated with what occurred in the past, involves both hippocampal and surrounding MTL activity (e.g., Eldridge et al., 2000; Prince et al., in press;Wagner et al., 1998). However, relational memory, which refers to memory for associations amongst the items and the context in which they were presented (for a review see Johnson et al., 1993), has been shown to necessitate greater hippocampal activity than simple item memory (e.g., Davachi, 2006;Davachi and Wagner, 2002;Dennis et al., 2008;Eichenbaum et al., 2007;Prince et al., 2005). Moreover, patients with hippocampal damage exhibit deficits on both item and NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript relational memory tasks, with greater deficits found in relational memories (Giovanello et al., 2003;Kan et al., 2007;Kroll et al., 1996;Turriziani et al., 2004). Such evidence supports a role of the hippocampus in the binding of relational memories (e.g., item and contextual information) (e.g., Diana et al., 2007;Mitchell et al., 2006). Furthermore, it has been suggested that, during retrieval, anterior hipp...

BDNF val66met affects hippocampal volume and emotion-related hippocampal memory activity

“…This effect was not observed in other brain areas than the hippocampus and is consistent with studies in which emotional stimuli were used, 24, 25 but not with studies in which neutral stimuli were used. 50 We could not replicate the finding of higher hippocampal activation in carriers of a met allele in response to neutral stimuli as is reported in the seminal study by Egan et al.…”

Impact of the BDNF Val66Met Polymorphism on Cognition

“…A study of young adults with a history of childhood-onset mood disorder did not find an association of Val66Met polymorphism and declarative memory function on sub-tests of the WMS (Strauss and others 2004). The BDNF Met allele was found not to be associated with alterations in hippocampal structure and performance on four memory tasks in healthy individuals (Karnik and others 2010), and BDNF Met carriers exhibited increased medial temporal lobe activation in memory tests during encoding and retrieval compared to controls (Dennis and others 2010). The discrepancies between findings could be due to a number of variables.…”

Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder

“…While there is limited evidence for a role of the Val66Met polymorphism in PTSD, the Val66Met polymorphism may also result in altered memory function 50–55 . BDNF (met/met) carriers showed increased medial temporal lobe activation during episodic and encoding retrieval tasks 52 . Another study described greater recruitment of amygdala and PFC activity in Met/Met carriers during memory formation and retrieval of biologically relevant stimuli 53 .…”

“…Met/met carriers showed increased medial temporal lobe activation (perhaps compensatory) during episodic and encoding retrieval tasks 52 .…”