The Role of the BDNF Val66Met Polymorphism for the Synchronization of Error-Specific Neural Networks

Abstract

Behavioral adaptation depends on the recognition of response errors and processing of this error-information. Error processing is a specific cognitive function crucial for behavioral adaptation. Neurophysiologically, these processes are reflected by an event-related potential (ERP), the error negativity (Ne/ERN). Even though synchronization processes are important in information processing, its role and neurobiological foundation in behavioral adaptation are not understood. The brain-derived neurotrophic factor (BDNF) strongly modulates the establishment of neural connectivity that determines neural network dynamics and synchronization properties. Therefore altered synchronization processes may constitute a mechanism via which BDNF affects processes of error-induced behavioral adaptation. We investigate how variants of the BDNF gene regulate EEG-synchronization processes underlying error processing. Subjects (n ϭ 65) were genotyped for the functional BDNF Val66Met polymorphism (rs6265). We show that Val/Val genotype is associated with stronger error-specific phase-locking, compared with Met allele carriers. Posterror behavioral adaptation seems to be strongly dependent on these phase-locking processes and efficacy of EEG-phase-locking-behavioral coupling was genotype dependent. After correct responses, neurophysiological processes were not modulated by the polymorphism, underlining that BDNF becomes especially necessary in situations requiring behavioral adaptation. The results suggest that alterations in neural synchronization processes modulated by the genetic variants of BDNF Val66Met may be the mechanism by which cognitive functions are affected.

BDNF Val66Met polymorphism and goal-directed behavior in healthy elderly — evidence from auditory distraction

“…The current results add on recent studies providing evidence that BDNF modulates response selection and control processes (Gajewski et al, 2011;Beste et al, 2010aBeste et al, , 2010b and on studies reporting an advantage of the Met allele in elderly (Erickson et al, 2008;Matsushita et al, 2005;Ventriglia et al, 2002). For the current study we suggest two possible neuronal mechanisms that may underlie the effects observed.…”

“…Gale et al, 2008). Several results suggest that within this basal ganglia network the Met-allele may shift the balance between the direct and indirect pathway towards a predominating inhibitory effect (Beste et al, 2010a(Beste et al, , 2010bGajewski et al, 2011). Similar effects have also been suggested to emerge as an effect of aging per se (e.g.…”

“…However, the association pattern is not conclusive (review: Mandelman and Grigorenko, 2012), partly because of pleiotrophic effects (e.g. Beste et al, 2010aBeste et al, , 2010bKennedy et al, 2009;Thomason et al, 2009). In the elderly, previous results indicated compromised cognitive functions in Met-allele carriers (Miyajima et al, 2008).…”

BDNF polymorphism associates with decline in set shifting in Parkinson's disease

“…The explanation for the better preservation of this part of executive functioning in the Met-allele carriers is merely speculative. A change in the balance between the direct and indirect nigrostriatal pathways seems to be involved, as decreases in nigrostriatal activity are related to increases in response inhibitory performance, which might result in better set shifting (Beste et al, 2010a(Beste et al, , 2010b. Correspondingly, high midbrain D3 receptor availability (the expression of which is controlled by BDNF, Guillin et al, 2001) is associated with reduced functional connectivity between the orbitofrontal cortex and frontoparietal networks (Cole et al, 2012), which are implicated in executive function.…”

The Transcription Factor XBP1 in Memory and Cognition: implications in Alzheimer’s Disease

“…neuronal atrophy and synapse loss in aged rats and nonhuman primates (137). What is more, a human genetic polymorphism in the gene encoding BDNF has been linked to abnormal brain structure, hippocampal activity and memory in humans (138)(139)(140) and to several psychiatric disorders (141)(142)(143)(144)(145). On a similar note, a polymorphism in the XBP1 promoter has been linked to a risk of AD (146).…”