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Abstract Functional magnetic resonance imaging (fMRI) has become an indispensable tool for investigating the human brain. However, the inherently poor signal-to-noise-ratio (SNR) of the fMRI measurement represents a major barrier to expanding its spatiotemporal scale as well as its utility and ultimate impact. Here we introduce a denoising technique that selectively suppresses the thermal noise contribution to the fMRI experiment. Using 7-Tesla, high-resolution human brain data, we demonstrate improvements in key metrics of functional mapping (temporal-SNR, the detection and reproducibility of stimulus-induced signal changes, and accuracy of functional maps) while leaving the amplitude of the stimulus-induced signal changes, spatial precision, and functional point-spread-function unaltered. We demonstrate that the method enables the acquisition of ultrahigh resolution (0.5 mm isotropic) functional maps but is also equally beneficial for a large variety of fMRI applications, including supra-millimeter resolution 3- and 7-Tesla data obtained over different cortical regions with different stimulation/task paradigms and acquisition strategies. 

Magnetic resonance imaging (MRI) is a technique that scans the anatomical structure of the brain, whereas functional magnetic resonance imaging (fMRI) uses the same basic principles of atomic physics as MRI scans but image metabolic function. A major goal of MRI and fMRI study is to precisely delineate various types of tissues, anatomical structure, pathologies, and detect the brain regions that react to outer stimuli (e.g., viewing an image). As a key feature of these MRI‐based neuroimaging data, voxels (cubic pixels of the brain volume) are highly correlated. However, the associations between voxels are often overlooked in the statistical analysis. We adapt a recently proposed dimension reduction method called the envelope method to analyze neuoimaging data taking into account correlation among voxels. We refer to the modified procedure the envelope chain procedure. Because the envelope chain procedure has not been employed before, we demonstrate in simulations the empirical performance of estimator, and examine its sensitivity when our assumptions are violated. We use the estimator to analyze the MRI data from ADHD‐200 study. Data analyses demonstrate that leveraging the correlations among voxels can significantly increase the efficiency of the regression analysis, thus achieving higher detection power with small sample sizes.