Aberrant Emotion-Cognition Integration in <i>FMR1</i> Premutation Carriers: a fNIRS Study

Carriers of the FMR1 (Fragile X Messenger Ribonucleoprotein 1) premutation (55–200 CGG repeats on the X chromosome), known as premutation carriers (PMCs), often exhibit executive dysfunction. Yet, the neural mechanism of cognitive and executive dysfunction in PMCs remains underexplored. This study investigated the neural alterations associated with the inhibitory control and conflict processing of PMCs using functional near-infrared spectroscopy (fNIRS) technique. We recruited 31 participants, including 14 participants with the FMR1 premutation (all females, mean age: 36.93±8.06 years) and 17 controls (3 male and 14 females, mean age: 30.86±5.90 years). Hemodynamic activity of the participants during emotional Go/No-Go and Stroop tasks was recorded using a fNIRS system. The neural activation in response to different tasks was examined. Compared to the control group, the PMCs group exhibited decreased activation in the left dorsolateral prefrontal cortex (DLPFC, p = 0.03) during the Stroop task. They also revealed increased activation in the right DLPFC ( p = 0.015), right frontopolar cortex (FPC, p = 0.027), right Broca’s area ( p = 0.013), left pre-motor and supplementary motor area (SMA, p = 0.013), and visual association cortex ( p = 0.044) during the Go/No-Go task. Conversely, the PMCs group exhibited decreased activation in the right pre-motor and SMA ( p = 0.018) and the right somatosensory association cortex ( p = 0.013). Our findings revealed atypical neural patterns in response to the Stroop and Go/No-Go tasks, suggesting the underlying neurobiological mechanisms of inhibitory control and conflict processing are disrupted in PMCs, potentially guiding targeted interventions. Significance Statement This study investigated the neural mechanisms underlying executive dysfunction, specifically inhibitory control and conflict processing, in FMR1 premutation carriers using fNIRS. The findings revealed atypical neural activation patterns in premutation carriers compared to controls. During the Stroop task, the premutation carrier group showed decreased activation in the left dorsolateral prefrontal cortex. During the Go/No-Go task, they exhibited a mixed pattern, including increased activation in right-hemisphere regions and decreased activation in the right pre-motor and supplementary motor area. This study identifies distinct neural patterns associated with inhibitory control and conflict processing in premutation carriers, suggesting that the underlying neurobiological mechanisms governing these processes are disrupted, which could potentially guide future targeted interventions.