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<p>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.</p><p></p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月13日

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  • Manuel Ambrosone,
  • Elena Montagni,
  • Timothy J. Buschman,
  • Anna Letizia Allegra Mascaro

摘要

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.