Claustrum Morphometry Reveals Spatially Heterogeneous Alterations in 22q11DS

The human claustrum is a small, irregular, and complexly positioned structure, yet it carries long range projections to most cortical regions responsible for executive functioning. Prior structural MRI research has largely relied on global volume as the metric of its morphology. Such measures may obscure regionally specific morphological changes relevant to developmental and pathological variation. We therefore addressed this limitation by applying longitudinal surface-based morphometry to 874 scans from 440 individuals aged 5-35 years, comparing typical development with 22q11.2 deletion syndrome (22q11DS), a genetic condition characterized by brain dysmaturation, and assessing associations with working memory performance. Our data show a significant age-related volumetric decline that is reduced in 22q11DS left claustra, while surface deformation and thickness analyses revealed spatial patterns unique to hemisphere, group, and developmental age. In controls, the claustrum surface deformed with age in clustered zones along a dorsoventral gradient, and the dorsal-anterior zone thinned across development while the ventral zone thickened. 22q11DS claustra showed less age-related deformation than controls, whose claustrum surface changes associated with verbal working memory. This structural correlate was statistically equivalent to zero in carriers, consistent with a disrupted claustral development to the working memory vulnerability of the syndrome. These findings show the value of surface-based morphometry over volume alone, highlight dysmaturation and regionally organized claustrum shape variation, and suggest that disrupted structural organization is accompanied by a weaker claustrum-working memory association.