RT Journal Article SR Electronic T1 Functional MRI of large scale activity in behaving mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.04.16.044941 DO 10.1101/2020.04.16.044941 A1 Madalena S. Fonseca A1 Mattia G. Bergomi A1 Zachary F. Mainen A1 Noam Shemesh YR 2020 UL http://biorxiv.org/content/early/2020/04/18/2020.04.16.044941.1.abstract AB Behaviour involves complex dynamic interactions across many brain regions. Detecting whole-brain activity in mice performing sophisticated behavioural tasks could facilitate insights into distributed processing underlying behaviour, guide local targeting, and help bridge the disparate spatial scales between rodent and human studies. Here, we present a comprehensive approach for recording brain-wide activity with functional magnetic resonance imaging (fMRI) compatible with a wide range of behavioural paradigms and neuroscience questions. We introduce hardware and procedural advances to allow multi-sensory, multi-action behavioural paradigms in the scanner. We identify signal artifacts arising from task-related body movements and propose novel strategies to suppress them. We validate and explore our approach in a 4-odour classical conditioning and a visually-guided operant task, illustrating how it can be used to extract information insofar intangible to rodent behaviour studies. Our work paves the way for future studies combining fMRI and local circuit techniques during complex behaviour to tackle multi-scale behavioural neuroscience questions.Competing Interest StatementThe authors have declared no competing interest.