Experimental design issues in functional brain imaging with high temporal resolution

Functional brain imaging experiments are widely conducted in many fields for study- ing the underlying brain activity in response to mental stimuli. For such experiments, it is crucial to select a good sequence of mental stimuli that allow researchers to collect informative data for making precise and valid statistical inferences at minimum cost. In contrast to most existing studies, the aim of this study is to obtain optimal designs for brain mapping technology with an ultra-high temporal resolution with respect to some common statistical optimality criteria. The first topic of this work is on finding optimal designs when the primary interest is in estimating the Hemodynamic Response Function (HRF), a function of time describing the effect of a mental stimulus to the brain. A major challenge here is that the design matrix of the statistical model is greatly enlarged. As a result, it is very difficult, if not infeasible, to compute and compare the statistical efficiencies of competing designs. For tackling this issue, an efficient approach is built on subsampling the design matrix and the use of an efficient computer algorithm is proposed. It is demonstrated through the analytical and simulation results that the proposed approach can outperform the existing methods in terms of computing time, and the quality of the obtained designs. The second topic of this work is to find optimal designs when another set of popularly used basis functions is considered for modeling the HRF, e.g., to detect brain activations. Although the statistical model for analyzing the data remains linear, the parametric functions of interest under this setting are often nonlinear. The quality of the de- sign will then depend on the true value of some unknown parameters. To address this issue, the maximin approach is considered to identify designs that maximize the relative efficiencies over the parameter space. As shown in the case studies, these maximin designs yield high performance for detecting brain activation compared to the traditional designs that are widely used in practice.