Functional magnetic resonance imaging (fMRI) is one of the popular tools to study human brain functions. High-quality experimental designs are crucial to the success of fMRI experiments as they allow the collection of informative data for making precise and valid inference with minimum cost. The primary goal of this study is on identifying the best sequence of mental stimuli (i.e. fMRI design) with respect to some statistically meaningful optimality criteria. This work focuses on two related topics in this research field. The first topic is on finding optimal designs for fMRI when the design matrix is uncertain. This challenging design issue occurs in many modern fMRI experiments, in which the design matrix of the statistical model depends on both the selected design and the experimental subject's uncertain behavior during the experiment. As a result, the design matrix cannot be fully determined at the design stage that makes it difficult to select a good design. For the commonly used linear model with autoregressive errors, this study proposes a very efficient approach for obtaining high-quality fMRI designs for such experiments. The proposed approach is built upon an analytical result, and an efficient computer algorithm. It is shown through case studies that our proposed approach can outperform the existing method in terms of computing time, and the quality of the obtained designs. The second topic of the research is to find optimal designs for fMRI when a wavelet-based technique is considered in the fMRI data analysis. An efficient computer algorithm to search for optimal fMRI designs for such cases is developed. This algorithm is inspired by simulated annealing and a recently proposed algorithm by Saleh et al. (2017). As demonstrated in the case studies, the proposed approach makes it possible to efficiently obtain high-quality designs for fMRI studies, and is practically useful.