Figure 4 – Lesion network mapping identified three brains regions with consistent negative functional connectivity to tuber distributions associated with infantile spasms.

The 74 tuber distributions associated with infantile spasms were registered to a standardized MNI brain template (A). Brain regions functionally connected to each tuber distribution were identified using a large-scale functional connectivity database of young adult participants (B). Overlap of these functional connectivity maps identified three brain regions connected to >95% of tuber distributions associated with infantile spasms: the left and right globus palladi and the cerebellar vermis (C). Consistent connected regions were also identified in two independent subsets (D). Of note, overlap of functional connectivity maps from the 49 children without infantile spasms did not reveal any consistently connected regions. Regions where connectivity was specific to infantile spasms were then identified by voxel-wise two-sample t-test between children with infantile spasms and those without. The conjunction of a mask of these significant voxels and the lesion network mapping analysis above generated a map of regions both sensitive and specific for infantile spams, here shown controlling for genetic etiology as a covariate (E). This process was repeated with an alternate large-scale functional connectivity database of 9-year-old participants identifying consistent results (F).