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Aberrant Face and Gaze Habituation in Fragile X Syndrome
Jennifer Lynn Bruno, Ph.D.; Amy S. Garrett, Ph.D.; Eve-Marie Quintin, Ph.D.; Paul K. Mazaika, Ph.D.; Allan L. Reiss, M.D.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.13111464
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From the Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, Calif.; the Departments of Radiology and Pediatrics, Stanford University; and the Center for Advanced Brain Imaging, Georgia Institute of Technology, Atlanta.

Previously presented in part at the 20th Annual Meeting of the Cognitive Neuroscience Society, April 13–16, 2013, San Francisco.

Address correspondence to Dr. Reiss (areiss1@stanford.edu).

Copyright © 2014 by the American Psychiatric Association

Received November 06, 2013; Revised March 20, 2014; Accepted April 10, 2014.

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Abstract

Objective  The authors sought to investigate neural system habituation to face and eye gaze in fragile X syndrome, a disorder characterized by eye-gaze aversion, among other social and cognitive deficits.

Method  Participants (ages 15–25 years) were 30 individuals with fragile X syndrome (females, N=14) and a comparison group of 25 individuals without fragile X syndrome (females, N=12) matched for general cognitive ability and autism symptoms. Functional MRI (fMRI) was used to assess brain activation during a gaze habituation task. Participants viewed repeated presentations of four unique faces with either direct or averted eye gaze and judged the direction of eye gaze.

Results  Four participants (males, N=4/4; fragile X syndrome, N=3) were excluded because of excessive head motion during fMRI scanning. Behavioral performance did not differ between the groups. Less neural habituation (and significant sensitization) in the fragile X syndrome group was found in the cingulate gyrus, fusiform gyrus, and frontal cortex in response to all faces (direct and averted gaze). Left fusiform habituation in female participants was directly correlated with higher, more typical levels of the fragile X mental retardation protein and inversely correlated with autism symptoms. There was no evidence for differential habituation to direct gaze compared with averted gaze within or between groups.

Conclusions  Impaired habituation and accentuated sensitization in response to face/eye gaze was distributed across multiple levels of neural processing. These results could help inform interventions, such as desensitization therapy, which may help patients with fragile X syndrome modulate anxiety and arousal associated with eye gaze, thereby improving social functioning.

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