A Neural Basis for Atypical Auditory Processing: A Williams Syndrome Model

Abstract

Williams syndrome (WS) is a rare, neurodevelopmental disorder caused by the deletion of 26 genes on chromosome 7q11.23. WS has a well-defined auditory phenotype, characterized by a strong attraction and emotional reactivity to music, abnormal sensitivity to sounds (hyperacusis) and an aversion to or avoidance of sounds (phonophobia). Auditory abnormalities reported in WS also affect a wide range of neurodevelopmental, neuropsychiatric and neurological disorders. Little is known about sensory modulation, or the demonstration of maladaptive emotional and behavioral responses to sensory stimuli in WS. This study aims to describe a neural basis for impaired sensory modulation in atypical auditory processing characteristic of the WS phenotype.

To define functional and structural connectivity between brain regions involved in auditory processing, we recruited 18 individuals with WS and 18 controls, ages 16-50, for neuroimaging. In the absence of external stimuli, “resting state” fMRI (rs-fMRI) measures blood oxygenation level dependent (BOLD) signal that reflects baseline neuronal activation in functionally connected networks of brain regions, including the auditory processing network. We used rs-fMRI to identify a network of functional brain regions involved in auditory processing in WS. White matter (WM) integrity was assessed by DTI parameters providing a quantitative measure of water diffusion through axonal membranes. We used DTI to identify structural integrity differences in WM fiber tracts underlying auditory processing in WS. To provide a basis for understanding sensory modulation impairments in WS, 56 caregivers of individuals with WS, ages 5-49, were recruited to quantitatively describe sensory processing patterns, independent of clinical diagnoses. Atypical auditory response patterns, based on a self-report of sensory processing, were correlated with group differences in functional and structural connectivity in WS. This study constitutes the most comprehensive investigation of patterns of sensory processing in WS, spanning a wide age range, and provides a uniquely developmentally-informed basis for understanding behavioral difficulties and the clinical interventions that could address them. Investigating the relationship between patterns of auditory sensory responses and functional and structural connectivity measures elucidates a brain-behavior relationship related to atypical auditory processing.