BDNF ValMet polymorphism tunes frontolimbic circuitry during affective contextual learning

Abstract

Adaptive learning impairments are common in cognitive and behavioral disorders, but the neurogenetic mechanisms supporting human affective learning are poorly understood. We designed a higher-order contextual learning task in which healthy participants genotyped for the Val66Met polymorphism of the brain derived neurotropic factor gene (BDNF) were required to choose the member of a picture pair most congruent with the emotion in a previously-viewed facial expression video in order to produce an advantageous monetary outcome. Functional magnetic resonance imaging (fMRI) identified frontolimbic blood oxygenation level dependent (BOLD) reactivity that was associated with BDNF Val66Met genotype during all three phases of the learning task: aversive and reward-predictive learning, contextually-challenging decision-making, and choice-related monetary loss-avoidance and gain outcomes. Relative to Val homozygotes, Met carriers showed attenuated ventromedial prefrontal response to predictive affective cues, dorsolateral prefrontal signaling that depended on decision difficulty, and enhanced ventromedial prefrontal reactivity that was specific to loss-avoidance. These findings indicate that the BDNF Val66Met polymorphism is associated with functional tuning of behaviorally-relevant frontolimbic circuitry, particularly involving the ventromedial prefrontal cortex, during higher-order learning.

Brain-Derived Neurotrophic Factor Genotype–Specific Differences in Cortical Activation in Chronic Aphasia

“…Correspondingly, the atypical genotype group was found to be more severely affected by aphasia as indicated by poorer performance on the WAB-R and the PNT. These results are consistent with studies in healthy individuals (W. Chen et al, 2016;Jabbi et al, 2017;McHughen et al, 2010) and the general stroke population (Kim et al, 2016) where decreased task-related functional brain activation has been reported for individuals carrying the BDNF Met allele polymorphism. Notably, McHughen et al (2010) observed smaller activation volume in a broad sensorimotor network in individuals with the Met allele present in response to right index finger movement.…”

A review of current research on genetic factors associated with the functioning of the perceptual and emotional systems of the brain

“…Regarding the Val homozygous genotype, Met carriers showed a weakened prefrontal response of the ventromedial system to predictive affective signals, dorsolateral prefrontal signaling, which depended on the difficulty of decision-making, and increased prefrontal reactivity of the ventromedial system, which is associated with modulating the decision to avoid failure to complete the task and associated with this loss of money. The data obtained indicate that the Val66Met gene BDNF polymorphism is associated with the functional adjustment of behaviorally significant schemes of the frontolimbic region, especially with the participation of the ventromedial prefrontal cortex, during affective learning of a higher order [5].…”