Aberrant Face and Gaze Habituation in Fragile X Syndrome

Abstract

Objective We sought to investigate neural system habituation to face and eye gaze in fragile X syndrome (FXS), a disorder characterized by eye gaze aversion, among other social and cognitive deficits. Method Participants (age 15-25 years) included 30 individuals with FXS (14 females) and a comparison group of 25 individuals without FXS (12 females) matched for general cognitive ability and autism symptoms. We used fMRI to assess brain activation during a gaze habituation task. Participants viewed repeated presentations of 4 unique faces with either direct or averted eye gaze and judged the direction of eye gaze. Results Four participants (all males, 3 FXS) were excluded due to excessive head motion during fMRI scanning. Behavioral performance did not differ between groups. Less neural habituation (and significant sensitization) for the FXS group was found for all faces (direct and averted gaze) in cingulate gyrus, fusiform gyrus, and frontal cortex. Left fusiform habituation in female participants was directly correlated with higher, more typical, levels of fragile X mental retardation protein (r(10)=0.67, p=0.02), and inversely correlated with autism symptoms (rs(12)=−0.72, p<0.004). There was no evidence for differential habituation to direct versus averted gaze within or between groups. Conclusions Impaired habituation and accentuated sensitization 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 FXS modulate anxiety and arousal associated with eye gaze thereby improving social functioning.

Altered visual repetition suppression in Fragile X Syndrome: New evidence from ERPs and oscillatory activity

“…This increase shows an abnormal pattern of habituation as suggested by auditory studies. Also, it would be in line with (Bruno et al, 2014), who found sensitization in the FXS group, indicating deficient modulation of neural responses to repeated gaze stimuli. In visual sensory ERP and an oddball paradigm using smiley faces, larger N1 and N2b amplitudes and reduced P3b amplitudes are found in FXS patients (Knoth et al, 2014; Van der Molen et al, 2012b).…”

“…They found significantly greater decrease in N1 ERP component amplitude and inter‐trial coherence (ITC) in lower frequency bands with repetitions in controls than in patients, suggesting a stronger habituation for controls. Only Bruno and colleagues addressed this issue in the visual modality using fMRI (Bruno et al, 2014). They presented four unique repeated faces with either direct or averted eye gaze and participants (controls and patients) had to judge the direction of eye gaze.…”

Fragile X syndrome: A review of clinical management

“…Examples of the processing problem are difficulty tolerating bright lights and loud noises, crowded places overstimulation, difficulty making good eye contact, and trouble tolerating certain clothes. These problems are related to a lack of normal habituation to a sensory stimulus seen in both electrodermal studies (145) and even on Functional Magnetic Resonance Imaging (fMRI) studies to recurrent direct or indirect eye contact (146).…”

“…The team can be adjusted for each individual's problems. There are many tools that have been proven useful and reliable for assessing an individual's condition such as the Sensory Profile questionnaire, the Sensory Processing Measure questionnaire, the Movement Assessment Battery for Children, the Quick Neurological Screening Test and the Berg Balance Scale (146). It is recommended that children with FXS should receive routine assessments from occupational therapists and receive occupational therapy at least twice a week during early development (66).…”

Moving Toward Integrative, Multidimensional Research in Modern Psychiatry: Lessons Learned From Fragile X Syndrome

“…It is possible that these results were a reflection of compromised capacity in processing facial information, which is potentially consistent with the small size of the amygdala in individuals with FraX (15, 16). In addition to the amygdala, abnormal habituation was also found in the anterior cingulate, fusiform gyrus, as well as frontal cortex of young adults and adolescents with FraX when responding to face/eye gaze (37). Finally, individuals with FraX have decreased duration of eye fixation, which is putatively associated with decreased activation of FFA (38).…”