Little is known about the genetic contribution to individual differences in neural networks subserving cognition function. In this functional magnetic resonance imaging (fMRI) twin study, we found a significant genetic influence on brain activation in neural networks supporting digit working memory tasks. Participants activating frontal-parietal networks responded faster than individuals relying more on language-related brain networks. There were genetic influences on brain activation in language-relevant brain circuits that were atypical for numerical working memory tasks as such. This suggests that differences in cognition might be related to brain activation patterns that differ qualitatively among individuals.