Mesoscale cortex-wide neural dynamics predict goal-directed, but not random actions in mice several seconds prior to movement

Volition - the sense of control or agency over one’s voluntary actions - is widely recognized as the basis of both human subjective experience and natural behavior in non-human animals. Several human studies have found peaks in neural activity preceding voluntary actions, e.g. the readiness potential (RP), and some have shown upcoming actions could be decoded even before awareness. Others propose that random processes underlie and explain pre-movement neural activity. Here we seek to address these issues by evaluating whether pre-movement neural activity in mice contains structure beyond that present in random neural activity. Implementing a self-initiated water-rewarded lever pull paradigm in mice while recording widefield [Ca++] neural activity we find that cortical activity changes in variance seconds prior to movement and that upcoming lever pulls could be predicted between 3 to 5 seconds (or more in some cases) prior to movement. We found inhibition of motor cortex starting at approximately - 5sec prior to lever pulls and activation of motor cortex starting at approximately 2sec prior to a random unrewarded left limb movement. We show that mice, like humans, are biased towards commencing self-initiated actions during specific phases of neural activity but that the pre-movement neural code changes over time in some mice and is widely distributed as behavior prediction improved when using all vs single cortical areas. These findings support the presence of structured multi-second neural dynamics preceding self-initiated action beyond that expected from random processes. Our results also suggest that neural mechanisms underlying self-initiated action could be preserved between mice and humans. ### Competing Interest Statement The authors have declared no competing interest.