Dr. Rihui Li, Assistant Professor at the Centre for Cognitive and Brain Sciences of the University of Macau (UM), in collaboration with Dr. Yuanyuan Gao from Stanford University, has made significant strides in understanding the neural underpinnings of face processing in girls with fragile X syndrome (FXS). This pioneering longitudinal research is the first to uncover abnormal patterns of neural activity changes during face processing in FXS girls as they progress through puberty. The study has been published in Biological Psychiatry (IF = 10.8, JCR Q1), a flagship journal in Psychiatry.

Fragile X syndrome, a genetic condition associated with intellectual disability and autism spectrum disorder (ASD), affects approximately 1 in 4000 males and 1 in 8000 females. Individuals with FXS often face social challenges such as anxiety and avoidance, particularly during social interaction. Despite the higher prevalence of research focusing on males with FXS, this study emphasizes the importance of examining the unique symptom profiles of females with the condition. Using portable functional near-infrared spectroscopy (fNIRS) and a facial processing paradigm, the research team tracked 65 girls with FXS and 52 developmental-matched girls for approximately three years (Figure 1).

The findings revealed that girls with FXS exhibited significantly higher neural activation in the right middle and superior frontal gyri when exposed to facial stimuli compared to the control group. Moreover, this abnormal activation pattern intensified over time. Notably, girls with FXS demonstrated aberrant neural sensitization in the superior frontal gyrus, characterized by an increased response to repeated facial stimuli (Figure 2). This abnormal sensitization positively correlated with worsening symptoms of social anxiety and avoidance over time (Figure 3).

The research sheds light on the neurobiological basis of social challenges often experienced by individuals with FXS. It suggests that inefficiencies in facial processing contribute to social anxiety and avoidance behaviors, pointing to abnormalities in neural systems responsible for interpreting facial expressions and emotions.

These findings offer new hope for improving the quality of life for FXS patients and provide potential biomarkers for evaluating treatment efficacy. Also, the study paves the way for developing more precise therapeutic approaches aimed at addressing the specific neural abnormalities observed in girls with FXS.

Prof. Rihui Li is the co-first author of the research, with Dr. Yuanyuan Gao as the co-first and corresponding author. The research received support from the National Institute of Mental Health (Grant Nos R01MH050047), the Kelvin Foundation, and the Canel Family Fund.

The full version of the article can be accessed at: https://doi.org/10.1016/j.biopsych.2024.06.020.

Figure 1. The experimental design. (A) This study included two neuroimaging assessment time points (Time 1 and Time 3). (B) The face processing task paradigm. (C) A picture showing a participant with the fNIRS montage. (D) The location of fNIRS measurement channels.

Figure 2. Changes in neural sensitization (represented by t-value) from the first time point (T1) to the third time point (T3) for each group.

Figure 3. The correlation model of initial brain sensitization at assessment time point 1 in the superior frontal gyrus and clinical rating changes over time. Association between initial sensitization and (A) ADAMS General Anxiety, (B) ADAMS Social Avoidance, and (C) SRS-2 Total Score.