Evidence for the contribution of COMT gene Val158/108Met polymorphism (rs4680) to working memory training‐related prefrontal plasticity

Abstract

Background: Genetic factors have been suggested to affect the efficacy of working memory training. However, few studies have attempted to identify the relevant genes. Methods:In this study, we first performed a randomized controlled trial (RCT) to identify brain regions that were specifically affected by working memory training.Sixty undergraduate students were randomly assigned to either the adaptive training group (N = 30) or the active control group (N = 30). Both groups were trained for 20 sessions during 4 weeks and received fMRI scans before and after the training.Afterward, we combined the data from the 30 participants in the RCT study who received adaptive training with data from 71 additional participants who also received the same adaptive training but were not part of the RCT study (total N = 101) to test the contribution of the COMT Val158/108Met polymorphism to the interindividual difference in the training effect within the identified brain regions. Results:In the RCT study, we found that the adaptive training significantly decreased brain activation in the left prefrontal cortex (TFCE-FWE corrected p = .030). In the genetic study, we found that compared with the Val allele homozygotes, the Met allele carriers' brain activation decreased more after the training at the left prefrontal cortex (TFCE-FWE corrected p = .025). Conclusions:This study provided evidence for the neural effect of a visual-spatial span training and suggested that genetic factors such as the COMT Val158/108Met polymorphism may have to be considered in future studies of such training. K E Y W O R D SCOMT, fMRI, gene polymorphism, randomized controlled trial, working memory training

Working Memory Training in Amnestic and Non-amnestic Patients With Mild Cognitive Impairment: Preliminary Findings From Genotype Variants on Training Effects

“…In our study, we were only able to find a training gain for verbal learning in the naMCI LMX1A-AA group 1-month after WM training. Lastly, similar to our study, carriers of the val allele of the COMT Val 158 Met polymorphism, another gene that regulates the dopaminergic system, also showed lower baseline performance but greater plasticity of working memory ( Bellander et al, 2015 ), and showed greater WM training-related prefrontal plasticity ( Zhao et al, 2020 ). Future studies should include the evaluation of COMT polymorphism.…”

Change by challenge: A common genetic basis behind childhood cognitive development and cognitive training

“…The second problem is that genetic studies with cognitive interventions have all looked at only a few candidate genes or DNA markers (e.g., refs. 18 – 21 ). General cognition is a complex polygenic trait, influenced by thousands of genetic regions, so those past studies cannot give us a full and reliable genetic picture.…”

Review of the Neural Processes of Working Memory Training: Controlling the Impulse to Throw the Baby Out With the Bathwater

“…This suggests that prefrontal cortex dopaminergic synaptic plasticity associated with WMT is significantly influenced by COMT polymorphisms, particularly in older adults. Similarly, in the fMRI study by Zhao and collegues, WMT led to significantly reduced activation in the left prefrontal cortex, but especially for the Met (hetero – and homozygous) versus Val allele carriers, in that neural activation in the left prefrontal cortex of Val/Val carriers was unaltered between pre- and post-training ( 65 ). Conversely, the tDCS study examining the influence of COMT showed that those with the val/val COMT genotype gained most from 1.5 mA tDCS during visual WMT and from 1 mA tDCS during spatial WMT.…”

“…The authors’ concluded that variations in COMT val158met may predict the nature of WM improvement after initial and longitudinal tDCS. It is important to note that in the previous fMRI study that examined the contribution of COMT polymorphisms to WMT-related neuroplasticity, it was conversely found that neural activation in the val/val polymorphism group was least influenced by training ( 65 ). The discrepancy between the two studies could be due to the differences associated with encouraging neuroplasticity effects via WMT, versus brief neurostimulation via tDCS.…”

“…Finally, in the most recent fMRI study (a randomized control trial), there is some evidence for the contribution of the catechol-O-methyltransferase (COMT) (Val-158/108-Met) polymorphism (rs4680) to WMT related prefrontal cortex plasticity ( 65 ). This COMT gene polymorphism results in a valine to methionine mutation, whereby three possible outcomes occur: homozygous met (met/met); homozygous Val (Val/Val) or heterozygous (Val/Met).…”