Introduction: For those with weak cognitive skills, certain mathematical problem-solving strategies may be more difficult than others. Tailored mathematical instruction that recognizes cognitive load and incorporates ways to reduce this may help to overcome mathematical difficulties. To investigate the effects of different strategies and cognitive load we explored brain hemodynamic responses associated with the use of different strategies to solve subtraction of fractions. We focused on those born extremely preterm (EPT; less than 28 weeks gestation) as they are known to have cognitive challenges and struggle with mathematics in particular. We also included a group of full-term (FT) peers for comparison. Methods: Functional MRI was acquired while the participants mentally solved fraction equations using either an improper fractions strategy, where whole numbers are converted to improper fractions before solving, or a mixed fractions strategy, where computations are carried out separately for the whole numbers and fraction components. Different fraction item types were given, which affected respective required cognitive loads per strategy. Diffusion and T1-weighted structural images were also acquired. All imaging modalities were compared between the two groups. Results: The EPT and FT groups differed in terms of task-related hemodynamic responses, regional volumes, and white matter connectivity. Functional group differences varied with strategy and item type. These differences were greatest when the mixed fractions strategy was prompted for an item type that required relatively greater cognitive load and involved borrowing. Other findings showed reduced white and grey matter volume and reduced white matter connectivity in widespread areas in the EPT group compared to the FT group. Conclusion: Changes in the brain related to preterm birth are complex. The understanding of function and structure presented here may help inform pedagogical practices by allowing for tailoring of mathematical education through identifying suitable strategy adoption that depends on problem type, to circumvent weaknesses in cognitive skills.