Brain function and gaze fixation during facial-emotion processing in fragile X and autism

Abstract

Fragile X syndrome (FXS) is the most commonly known genetic disorder associated with autism spectrum disorder (ASD). Overlapping features in these populations include gaze aversion, communication deficits, and social withdrawal. Although the association between FXS and ASD has been well documented at the behavioral level, the underlying neural mechanisms associated with the social/emotional deficits in these groups remain unclear. We collected functional brain images and eye-gaze fixations from 9 individuals with FXS and 14 individuals with idiopathic ASD, as well as 15 typically developing (TD) individuals, while they performed a facial-emotion discrimination task. The FXS group showed a similar yet less aberrant pattern of gaze fixations compared with the ASD group. The FXS group also showed fusiform gyrus (FG) hypoactivation compared with the TD control group. Activation in FG was strongly and positively associated with average eye fixation and negatively associated with ASD characteristics in the FXS group. The FXS group displayed significantly greater activation than both the TD control and ASD groups in the left hippocampus (HIPP), left superior temporal gyrus (STG), right insula (INS), and left postcentral gyrus (PCG). These group differences in brain activation are important as they suggest unique underlying face-processing neural circuitry in FXS versus idiopathic ASD, largely supporting the hypothesis that ASD characteristics in FXS and idiopathic ASD reflect partially divergent impairments at the neural level, at least in FXS individuals without a co-morbid diagnosis of ASD.

Figure 1

Average fixation durations. Average duration of fixation on the mouth and eye region and face in general split by group. Error bars index the SEM.

Figure 2

Brain cluster with significant greater brain activation across all faces in the TD versus ASD and FXS group: (a) Right Fusiform Gyrus (FG): x = 20, y = −70, z = −2; 172 voxels. Brain clusters with significantly greater brain activation across all faces in the FXS versus versus TD control and ASD groups: (b) Left Hippocampus (HIPP): x = −19, y = −13, z = −15; 116 voxels, (c) Right Insula (INS): x = 39, y = −4, z = −6; 277 voxels, (d) Left Post Central Gyrus (PCG): x = −36, y = −28, z = 48; 402 voxels, (e) Left Superior Temporal Gyrus (STG): x = −45, y = −21, z = 11; 905 voxels. All images are presented in radiological convention such that the right hemisphere is displayed on the left of each coronal image. The clusters are color- coded based on the TD control and ASD minus fragile X t-statistic values (positive values indicate TD & ASD > FXS). Averaged MR time series are presented below each cluster for the 14 seconds post stimulus onset.

Figure 3

Scatter plot of the correlations between left HIPP cluster activation and SCQ (a) and general IQ (b) for the FXS group.

Figure 4

Brain activation clusters associated with average eye-fixation time for the FXS group. (a) Right FG: x = 33, y = −51, z = −8; 70 voxels, (b) Left FG: x = −34, y = −62, z = −8; 239 voxels. Scatter plots depicting the relationship between brain activation and average eye-fixation are presented below each cluster. Brain activation clusters associated with AUT characteristics (SCQ score) for the FXS group. (c) Right FG: x = 29, y = −72, z = −3; 103 voxels;. (d) Left Amygdala: x = −23, y = −7, z = −18; 82 voxels. Scatter plots depicting the relationship between brain activation and average autism characteristics are presented below each cluster.