Stefanie Jansen

Interaction of BDNF and COMT Polymorphisms on Paired-Associative Stimulation-Induced Cortical Plasticity

The common single-nucleotide polymorphism (SNP) brain-derived neurotrophic factor (BDNF) valine-to-methionine substitution at codon 66 (Val66Met) has been associated with differences in memory functions and cortical plasticity following brain stimulation. Other studies could not confirm these results, though, and potential interactions of BDNF carrier status with other learning-relevant SNPs are largely unknown. The present study aimed to evaluate the effects of BDNF Val66Met genotype on paired associative stimulation (PAS)-induced motor cortex plasticity, while additionally taking catechol-O-methyltransferase (COMT) Val158Met and kidney and brain (KIBRA) rs17070145 carrier status into account. Therefore, a cohort of 2 × 16 age- and education-matched healthy young females underwent transcranial magnetic stimulation using an excitatory PAS25 protocol to induce cortical plasticity. Cognitive performance was assessed using implicit grammar- and motor-learning tasks and a detailed neuropsychological test battery. While BDNF carrier status alone did not significantly influence PAS-induced cortical plasticity, we found a significant BDNF × COMT interaction, showing higher plasticity immediately following the PAS25 protocol for the BDNF Val/Val vs Met genotype in COMT Met homozygotes only (ANOVA, p = 0.027). A similar advantage for this group was noted for implicit grammar learning (ANOVA, p = 0.021). Accounting for KIBRA rs17070145 did not explain significant variance. Our findings for the first time demonstrate an interaction of BDNF by COMT on human cortical plasticity. Moreover, they show that genotype-related differences in neurophysiology translate into behavioral differences. These findings might contribute to a better understanding of the mechanisms of interindividual differences in cognition.

COMT Val158Met Polymorphism Modulates Cognitive Effects of Dietary Intervention

A common single nucleotide polymorphism (SNP) in the gene encoding catechol-O-methyltransferase (COMT), Val158Met, is thought to influence cognitive performance due to differences in prefrontal dopaminergic neurotransmission. Previous studies lend support for the hypothesis that the “at risk” genotype comprising two Val-alleles (low dopamine) might benefit more from plasticity-enhancing interventions than carriers of one or two Met-alleles. This study aimed to determine whether the response to dietary interventions, known to modulate cognition, is dependent on COMT genotype. Blood samples of 35 healthy elderly subjects (61.3 years ±8 SD; 19 women, 16 men, BMI: 28.2 kg/m2 ±4 SD) were genotyped for COMT Val158Met by standard procedures (Val/Val = 6; Val/Met = 20; Met/Met = 9). Subjects had previously completed a randomized controlled trial investigating the effects of caloric restriction (CR) or enhancement of unsaturated fatty acids (UFA) on immediate and delayed verbal recognition memory. Homozygous Val/Val-carriers had significantly lower memory scores than Met-carriers at baseline (p < 0.001). Significant interactions of genotype and dietary intervention with regard to cognition were found: CR- and UFA enhancement-induced memory improvements of Val/Val-carriers were considerably greater than those of Met-carriers (ANOVA ps < 0.02). The current study shows for the first time that cognitive effects of dietary interventions are dependent on COMT Val158Met genotype. Our findings lend further support to the hypothesis that an “at risk” genotype might benefit more from plasticity-enhancing interventions than the “not at risk” genotype. This might help to develop individualized therapies in future research based on genetic background.

Influences of semantic and syntactic incongruence on readiness potential in turn-end anticipation

Knowing when it is convenient to take a turn in a conversation is an important task for dialog partners. As it appears that this decision is made before the transition point has been reached, it seems to involve anticipation. There are a variety of studies in the literature that provide possible explanations for turn-end anticipation. This study particularly focuses on how turn-end anticipation relies on syntactic and/or semantic information during utterance processing, as tested with syntactically and semantically violated sentences. With a combination reaction time and EEG experiment, we used the onset latencies of the readiness potential (RP) to uncover possible differences in response preparation. Although the mean anticipation timing accuracy (ATA) values of the behavioral test were all within a similar time range (control sentences: 108 ms, syntactically violated sentences: 93 ms and semantically violated sentences: 116 ms), we found evidence that response preparation is indeed different for syntactically and semantically violated sentences in comparison with control sentences. Our preconscious EEG data, in the form of RP results, indicated a response preparation onset to sentence end interval of 1452 ms in normal sentences, 937 ms in sentences with syntactic violations and 944 ms in sentences with semantic violations. Compared with control sentences, these intervals resulted in a significant RP interruption for both sentence types and indicate an interruption of preconscious response preparation. However, the behavioral response to sentence types occurred at comparable time points.