# Atypical Inter-Brain Synchrony and Social Communication Deficits in Girls with Fragile X Syndrome: Evidence from Functional Near-infrared Spectroscopy Hyperscanning

**Authors:** Rihui Li, Henrikke Dybvik, Danyong Feng, Cassie Eng, Cindy H. Lee, Kristi L. Bartholomay, Yingchun Zhang, Amy A. Lightbody, Allan L. Reiss

PMC · DOI: 10.21203/rs.3.rs-7541575/v1 · Research Square · 2025-10-17

## TL;DR

Girls with Fragile X Syndrome show unusual brain synchronization patterns during social interactions, which may explain their communication difficulties.

## Contribution

This study pioneers the use of fNIRS hyperscanning to explore inter-brain synchrony in FXS during naturalistic interactions.

## Key findings

- FXS dyads showed enhanced frontopolar IBS and reduced IBS in Broca’s area and DLPFC during a tangram task.
- During conversation, FXS dyads had reduced IBS in frontal eye field and STG but enhanced IBS in right SMG.
- Right SMG IBS correlated with better verbal performance and higher autism severity in FXS children.

## Abstract

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.

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.

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).

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.

## Linked entities

- **Genes:** FMR1 (fragile X messenger ribonucleoprotein 1) [NCBI Gene 2332]
- **Diseases:** Fragile X syndrome (MONDO:0010383), autism (MONDO:0005260)

## Full-text entities

- **Diseases:** social dysfunction (MESH:D000067404), Social Communication Deficits (MESH:D003147), autism (MESH:D001321), FXS (MESH:D005600), intellectual disability (MESH:D008607)

## Full text

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## Figures

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## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12633177/full.md

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Source: https://tomesphere.com/paper/PMC12633177