Altered neural activity in the 'when' pathway during temporal processing in fragile X premutation carriers

Area of Science:

• Neuroscience
• Genetics
• Cognitive Psychology

Background:

• Fragile X syndrome (FXS) results from FMR1 gene mutations, causing FMRP deficiency.
• FXS infants show impaired temporal attention, while spatial attention remains intact.
• Premutation carriers may have altered FMRP levels and elevated FMR1 mRNA.

Purpose of the Study:

• To investigate atypical temporal processing in fragile X premutation carriers.
• To examine neural correlates of temporal processing using fMRI.
• To explore the relationship between FMR1 gene expression and temporal processing in carriers.

Main Methods:

• Utilized fMRI to assess brain activity during spatial and temporal working memory (SWM and TWM) tasks.
• Compared neural activation patterns between neurotypical adults and premutation carriers.
• Employed multiple regression to analyze the association between FMR1 gene expression and right TPJ activation.

Main Results:

• Neurotypical adults exhibited greater right TPJ activation during TWM retrieval compared to SWM retrieval.
• Premutation carriers failed to show increased right TPJ involvement during temporal information retrieval.
• Elevated FMR1 mRNA levels significantly predicted reduced right TPJ activation in carriers.

Conclusions:

• This study provides the first evidence of altered neural correlates of temporal processing in adults with the FMR1 premutation.
• The findings suggest that FMR1 gene expression, specifically elevated FMR1 mRNA, underlies atypical temporal processing in premutation carriers.
• These results highlight the impact of FMR1 gene expression on neural mechanisms of temporal cognition.