Disrupted cortex-wide dynamics impair motor planning in Shank3-mutant mice

Coordinated cortical activity underlies voluntary movement planning, yet its disruption is implicated in neurodevelopmental disorders like autism spectrum disorder (ASD). Mutations in the SHANK3 gene, a key ASD risk factor, affect synaptic integrity and cortical network function, but their impact on preparatory cortical dynamics remains unclear. Here, we employed wide-field calcium imaging combined with motion tracking and computational motif analysis to examine cortex-wide activity in Shank3b + /- mice during spontaneous forepaw movements. We found reduced correlation between cortical activity and behavior preceding movement onset, alongside decreased expression of specific cortical motifs involving associative and motor areas. These changes contributed to global functional hyperconnectivity and impaired motor planning. Our findings reveal that disrupted spatiotemporal cortical dynamics in Shank3b + /- mice impair preparatory motor processes, providing insight into neural mechanisms underlying ASD-related motor deficits. Cortex-wide calcium imaging reveals impaired preparatory motor dynamics in Shank3b + /- mice, linking reduced expression of associative cortical motifs to disrupted movement planning and network hyperconnectivity.