The emergence of functional MRI (fMRI) techniques did not only revolutionize neuroscience research but also initiated the standardization of functional brain mapping methods to facilitate reliable comparisons across subjects and experiments. Wide-field optical imaging techniques, such as optical intrinsic signal (OIS) imaging, measure similar hemodynamic contrasts to fMRI, providing the opportunity to perform functional brain mapping in small animals under systematic protocols and controlled environments. The development and validation of robust image analysis pipelines for OIS imaging data is a fundamental step towards the advancement of small animal neuroimaging studies. The paper by Padawer-Curry et al. performs a systematic evaluation of the errors introduced after registering individual OIS images to a common spatial template (known as an atlas) in preparation for comparisons across subjects. Similar to fMRI methods, the authors propose to use a high-resolution anatomical image to improve the registration accuracy of the functional images, showing improved results from previous methods. While the main focus of the study is to improve the reliability of resting-state functional connectivity mapping using OIS imaging data, other wide–field optical imaging modalities (e.g. calcium imaging) and experimental paradigms (e.g. task activation mapping) can greatly benefit from this new approach.  

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