Morphometry of human insular cortex and insular volume reduction in Williams syndrome

Functional imaging in humans and anatomical data in monkeys have implicated the insula as a multimodal sensory integrative brain region. The topography of insular connections is organized by its cytoarchitectonic regions. Previous attempts to measure the insula have utilized either indirect or automated methods. This study was designed to develop a reliable method for obtaining volumetric magnetic resonance imaging (MRI) measurements of the human insular cortex, and to validate that method by examining the anatomy of insular cortex in adults with Williams syndrome (WS) and healthy age-matched controls. Statistical reliability was obtained among three raters for this method, supporting its reproducibility not only across raters, but within different software packages. The procedure described here utilizes native-space morphometry as well as a method for dividing the insula into connectivity-based sub-regions estimated from cytoarchitectonics. Reliability was calculated in both ANALYZE (N=3) and BrainImageJava (N=10) where brain scans were measured once in each hemisphere by each rater. This highly reliable method revealed total, anterior, and posterior insular volume reduction bilaterally (all p's<.002) in WS, after accounting for reduced total brain volumes in these participants. Although speculative, the reduced insular volumes in WS may represent a neural risk for the development of hyperaffiliative social behavior with increased specific phobias, and implicate the insula as a critical limbic integrative region. Native-space quantification of the insula may be valuable in the study of neurodevelopmental or neuropsychiatric disorders related to anxiety and social behavior.