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COMT Genotype Affects Language Processing in Children Sugiura et al. | 113

task, whereas superoptimal coupling at rest in Met carriers of 6–10 years. The slower language development in Val homozy-
may detrimentally affect the brain’s ability to uncouple task- gotes compared with Met carriers in the early elementary school
positive and task-negative regions during task performance. years appeared to be due to decreased dopaminergic neurotrans-
Therefore, the increased activation in the posterior cortical mission. In contrast, an increase in D1 receptor density around
regions in Met carriers relative to Val homozygotes demon- preadolescence would be of particular relevance to the genotype
strated in the present study may be a result of increased by age interactions on language performance and processing
resting-state connectivity and switching failure between task- around this age. Although previous studies have provided evi-
negative and task-positive states or a failure to suppress the dence for the COMT genotype effects on prefrontally mediated
DMN because of excessive dopamine. cognitive functions, the impact of the COMT genotype on cognition
was not limited to the PFC but extended to the posterior cortical
regions. The present study also suggests the possibility of direct or
Strengths and Limitations of the Study
indirect modulation of posterior activation without innervation of
Few genetic studies have examined language development in the PFC and the interplay of task-relevant (task-positive) and task-
children with a relatively large sample of brain-based intermedi- irrelevant (task-negative) activation mediated by DMN.
ate phenotype data. In general, functional neuroimaging studies
of children using fMRI, positron emission tomography, and other Supplementary Material
approaches pose technical challenges because the head position
must be strictly fixed and vocalization may induce severe motion Supplementary data are available at Cerebral Cortex online.
artifacts. Thus, the cognitive tasks used during the measurement
of brain functions are limited, and data affected by motion arti- Funding
facts cannotbeused, which makes thesamplesizesmall. By con-
This work was supported by research grants for priority areas,
trast, fNIRS is completely noninvasive, and a participant’smotion the New Leading Project for the Metropolis Fund from Tokyo
during measurement is tolerated to a higher degree. This
Metropolitan University, and a Grant-in-Aid for the promotion
approach enabled us to achieve long-duration, real-time monitor- of “Brain Science and Education, Type II” from the Research
ing of brain hemodynamics of active and restless healthy young
Institute of Science and Technology for Society, Japan Science
children using a language task with articulation and obtain a rela- and Technology Agency (RISTEX, JST) (to H.H.). In addition, this
tively large sample of cortical language function. However, the
research was partially supported by the Strategic Research
current study has several limitations: 1) fNIRS cannot measure Program for Brain Sciences from the Japan Agency for Medical
responses in deep brain or subcortical structures. Therefore, the
Research and Development (AMED) (to T.Y.), and by RIKEN BSI
effects of the COMT genotype that may exist in subcortical regions fund (to R.M. and T.Y.).
could not be detected. 2) The present study demonstrated the
effects of the COMT genotype on cortical responses during word Downloaded from https://academic.oup.com/cercor/article-abstract/27/1/104/2617708 by guest on 24 November 2018
processing. However, language is complex and consists of more Notes
than only a collection of disconnected words; it also consists of We thank all the children and their families who participated
different systems, such as phonology, semantics, and syntax. in this study, as well as the elementary school teachers for
Further studies are necessary to clarify the effects of the COMT their support. We are grateful to Dr Shiro Ojima for his consid-
genotype on both discrete and integrated components of lan- erable effort in preparing and collecting fNIRS data, Dr Ippeita
guage. 3) The present study demonstrated age-dependent COMT Dan and Dr Daisuke Tsuzuki for contributing to the spatial
genotype effects on language functions. However, the age range registration of fNIRS data, and Dr Takusige Katura for providing
investigated was very narrow. Future studies using a wider age fNIRS preprocessing analysis tools (Platform for Optical
range of children will identify a more detailed description of the Topography Analysis Tools). We thank Ms Naoko Nakamura,
effects. 4) Only a single COMT SNP (rs4680: Val 158 Met) was evalu- Dr Fumitaka Homae, Dr Atsushi Maki, and Dr Hideaki Koizumi
ated in this study. In the COMT gene, the Val 158 Met is the most for their continuous support. We also appreciate the Bennese
investigated genetic variant in terms of verbal/language ability, Cooperation for compiling and scoring the Japanese language
perception, or processing; however, there are other functionally test data. Conflict of Interest: None declared.
important polymorphisms, including rs4818, that have substan-
tial effects on the free energy of mRNA secondary structures References
(Nackley et al., 2006). In future studies, assessing the effects of
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cussed by considering dopaminergic neuronal modulation; how- Goitokusei: lexical properties of Japanese. Vol. 7. Tokyo:
ever, the COMT polymorphism may also affect cortical activity in Sanseido-shoten.
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Conclusions
Barnett JH, Heron J, Ring SM, Golding J, Goldman D, Xu K,
The present study demonstrated that COMT influences language Jones PB. 2007a. Gender-specific effects of the catechol-O-
performance and cortical responses during language processing methyltransferase Val108/158Met polymorphism on cognitive
that engages posterior language regions in children. Importantly, function in children. Am J Psychiatry. 164:142–149.
the COMT genotype effects on language performance and cortical Barnett JH, Jones PB, Robbins TW, Muller U. 2007b. Effects of the
responses were found to vary even within a narrow age window catechol-O-methyltransferase Val158Met polymorphism on