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A statistical method for detecting activated pixels in functional MRI (fMRI) data is presented. In this method, the fMRI time series measured at each pixel is modeled as the sum of a response signal which arises due to the experimentally controlled activation-baseline pattern, a nuisance component representing effects of no interest, and Gaussian white noise. For periodic activation-baseline patterns, the response signal is modeled by a truncated Fourier series with a known fundamental frequency but unknown Fourier coefficients. The nuisance subspace is assumed to be unknown. A maximum likelihood estimate is derived for the component of the nuisance subspace which is orthogonal to the response signal subspace. An estimate for the order of the nuisance subspace is obtained from an information theoretic criterion. A statistical test is derived and shown to be the uniformly most powerful (UMP) test invariant to a group of transformations which are natural to the hypothesis testing problem. The maximal invariant statistic used in this test has an F distribution. The theoretical F distribution under the null hypothesis strongly concurred with the experimental frequency distribution obtained by performing null experiments in which the subjects did not perform any activation task. Applications of the theory to motor activation and visual stimulation fMRI studies are presented.