Aberrant Neural Function During Emotion Attribution in Female Subjects With Fragile X Syndrome

Abstract

Objective Fragile X (FraX) syndrome is caused by mutations of the FraX mental retardation–1 gene—a gene responsible for producing FraX mental retardation protein. The neurocognitive phenotype associated with FraX in female subjects includes increased risk for emotional disorders including social anxiety, depression, and attention deficit. Here, the authors investigated the neurobiological systems underlying emotion attribution in female subjects with FraX syndrome. Method While undergoing functional magnetic resonance imaging, 10 high-functioning female subjects with FraX syndrome and 10 typically developing (TD) female subjects were presented with photographs of happy, sad, and neutral faces and instructed to determine the facial emotion. Results No significant group differences were found for the recognition of happy faces, although the FraX group showed a trend toward a significant difference for the recognition of sad faces and significantly poorer recognition of neutral faces. Controlling for between-group differences in IQ and performance accuracy, the TD group had greater activation than the FraX group in the anterior cingulate cortex (ACC) for neutral faces compared with scrambled faces and the caudate for sad faces compared with scrambled faces (but not for sad faces compared with neutral faces). In the FraX group, FraX mental retardation protein levels positively correlated with activation in the dorsal ACC for neutral, happy, and sad faces when independently compared with scrambled faces. Significantly greater negative correlation between IQ and insula activation for neutral faces relative to scrambled faces was observed in the FraX group compared with the TD group. Significantly greater positive correlation between IQ and ACC activation for neutral faces relative to scrambled faces was observed in the TD group compared with the FraX group. Conclusions Although emotion recognition is generally spared in FraX syndrome, the emotion circuit (i.e., ACC, caudate, insula) that modulates emotional responses to facial stimuli may be disrupted.

Fragile X syndrome—From genes to cognition

“…Recent fMRI studies in FXS have begun to focus on the social-emotional deficits which are prominent features of the phenotype, such as eye gaze avoidance, anxiety and hyperarousal. All four of these fMRI studies used human faces as the relevant stimuli of interest, two investigating the effect of direct versus averted gaze [Garrett et al, 2004;Watson et al, 2008] and two examining emotional faces, one focused on emotion attribution [Hagan et al, 2008] and one focused on face encoding [Holsen et al, 2008]. Females with FXS have difficulty determining the direction of social gaze which appears to be mediated by deficits in activation of the fusiform gyrus, a brain region known to be critical for recognition of faces and other highly salient visual stimuli.…”

NIRS-based hyperscanning reveals increased interpersonal coherence in superior frontal cortex during cooperation

“…Understanding the dynamics of brain activity during social interaction is important for understanding our social nature and in turn for improving the life quality of people with social deficits, such as children with autism. Development of neuroimaging technologies, especially fMRI, has enabled noninvasive measurement of brain activity and has dramatically deepened our understanding of the neural basis of cognitive processes contributing to social behavior, including emotion (Phan et al, 2002; Hagan et al, 2008), theory of mind (Gallagher and Frith, 2003), moral judgment (Greene et al, 2001), trust (King-Casas et al, 2005), and agency (Tomlin et al, 2006). These technologies also enable us to better understand the structural and functional differences in the brains of people who have deficits in social cognition such as children with autism (Chiu et al, 2008; Piggot et al, 2004), fragile X syndrome (Watson et al, 2008), and Williams syndrome (Reiss et al, 2004).…”

Emotion Potentiated Startle in Fragile X Syndrome

“…Using functional brain resonance imaging (fMRI) techniques, Watson et al showed that the amygdala became abnormally sensitized in male adolescents with FXS upon repeated exposure to direct gaze faces (Watson et al 2008). In an fMRI study of facial processing in females with FXS, however, Hagan et al did not report any differences in amygdala activation, though significantly reduced anterior cingulate activation was documented (Hagan et al 2008). We documented reduced amygdalar activation in response to social stimuli among individuals who carry the FMR1 premutation (50 to 200 CGG repeats), females with FXS and males with mosaic expression of the FXS allele as compared to controls with normal FMR1 alleles (Hessl et al 2007; Hessl et al 2011; Kim et al 2012).…”