Abstract
BACKGROUND: Fragile X syndrome (FXS), a leading genetic cause of intellectual disability and autism, is characterized by marked social communication deficits, yet the neural underpinnings of these challenges remain poorly understood. METHODS: We employed a functional near-infrared spectroscopy(fNIRS) hyperscanning technique to investigate inter-brain synchrony (IBS) during naturalistic mother-child interactions in girls with FXS (n = 33), compared to age- and verbal IQ-matched controls (n=18)and typically developing (TD) peers (n=12). Dyads engaged in a cooperative tangram task and a free-talk conversation, while fNIRS measured neural activity across prefrontal, temporal, and parietal regions. RESULTS: During a tangram task, the FXS dyads showed distinct IBS patterns, including significantly enhanced IBS in the frontopolar area and reduced IBS in left Broca's area and dorsolateral prefrontal cortex. In the conversation, FXS dyads showed significantly reduced IBS in the frontal eye field and superior temporal gyrus but enhanced IBS in the right supramarginal gyrus (SMG), a region linked to phonological processing. Linguistically, children with FXS demonstrated significantly lower lexical richness and syntactic complexity compared to their peers. Stronger IBS in the right SMG correlated with better verbal performance (r = 0.267~0.401, p < 0.05) and higher autism severity (r = 0.276, p = 0.035). CONCLUSIONS: By integrating neural and linguistic metrics, our study pioneers an effective framework for FXS social dysfunction, underscoring IBS as a potential biomarker for FXS and informing targeted interventions leveraging dyadic synchrony to enhance communication outcomes.