ALTERED CORTEX-WIDE DYNAMICS DISRUPT MOTOR PLANNING IN SHANK3-MUTANT MICE

Coordinated activity across the cortex is essential for voluntary movement planning, and disruptions to this process have been linked to neurodevelopmental disorders such as autism spectrum disorder (ASD). Mutations in the SHANK3 gene, a major genetic risk factor for ASD, are known to alter synaptic structure and cortical network organization, yet their effects on preparatory cortical activity remain poorly understood. In this study, we combined wide-field calcium imaging, behavioral tracking, and computational motif analysis to investigate cortex-wide dynamics in Shank3b⁺/⁻ mice during spontaneous forepaw movements. We observed a weakened relationship between cortical activity and behavior prior to movement initiation, along with reduced expression of specific cortical motifs spanning associative and motor regions. These alterations were associated with widespread functional hyperconnectivity and deficits in motor planning. Together, our results demonstrate that disrupted spatiotemporal cortical dynamics in Shank3b⁺/⁻ mice compromise preparatory motor processes, offering mechanistic insight into motor impairments associated with ASD.