Mathematical competence is essential for an individual’s functioning in society and for societal prosperity and progress in general. Crucially, the specific cognitive and biological factors that determine high, average, or low mathematical achievement are still poorly understood. The current project aims to address this gap by examining the link between mathematical achievement (cognitive factors) and brain indices (biological factors) across the developmental trajectory and for different competency levels. Specifically, the projects objectives are: 1) identify the critical cognitive and biological components, as well as the dynamic developmental sequence, necessary for the normal development of mathematical abilities; 2) unravel the cognitive and biological factors that contribute to and/or restrict neuroplasticity in mathematical learning. This knowledge may be used in the future to improve prevention, identification, and classification of children with impaired numeracy such as developmental dyscalculia; and 3) develop and test well-defined, evidence-based methods for improving mathematical learning. In addition, one of the objectives of the proposed project is to provide experimental knowledge that will have high ecological validity, by examining mathematical learning and achievement while subjects are studying in a classroom setting. I will use an innovative multimethod approach that integrates cognitive and developmental psychology together with neuromodulation, neurophysiology, and neurochemistry, which will provide a comprehensive understanding of the cognitive and brain bases of mathematical learning and cognition. While such knowledge will offer substantive advances for the fields of psychology, education, and neuroscience, it also has broad societal implications, as the high ecological validity provides insights in translational approaches for improving the lives of children and adults with low mathematical abilities.