Neural Substrates of Executive Dysfunction in Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): A Brain Potential Study

Jin Chen Yang, Shiao Hui Chan, Sara Khan, Andrea Schneider, Rawi Nanakul, Sara Teichholtz, Yu Qiong Niu, Andreea Seritan, Flora Tassone, Jim Grigsby, Paul J. Hagerman, Randi J. Hagerman, John M. Olichney

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Executive dysfunction in fragile X-associated tremor/ataxia syndrome (FXTAS) has been suggested to mediate other cognitive impairments. In the present study, event-related potentials and neuropsychological testing were combined to investigate the brain mechanisms underlying the executive dysfunction in FXTAS. Thirty-two-channel electroencephalography was recorded during an auditory oddball task requiring dual responses. FXTAS patients (N= 41, mean age= 62) displayed prolonged latencies of N1 and P3 and reduced amplitudes of P2 and P3, whereas their N2 measures remained within the normal range, indicating relatively preserved early-stage auditory attention but markedly impaired late-stage attention and working memory updating processes (as indexed by P3). Topographical mapping revealed a typical parietal P3 peak preceded by a prominent fronto-central P3 in normal control subjects (N= 32), whereas FXTAS patients had decreased parietal P3 amplitude and diminished fronto-central positivities with a delayed onset (∼50 ms later than controls, P < 0.002). The P3 abnormalities were associated with lower executive function test (e.g., BDS-2) scores. Smaller P3 amplitudes also correlated with increased CGG repeat length of fragile X mental retardation 1 (FMR1) gene and higher FMR1 mRNA levels. These results indicate that abnormal fronto-parietal attentional network dynamics underlie executive dysfunction, the cardinal feature of cognitive impairment in FXTAS.

Original languageEnglish
Pages (from-to)2657-2666
Number of pages10
JournalCerebral Cortex
Volume23
Issue number11
DOIs
Publication statusPublished - 2013 Nov 1

Keywords

  • attention
  • executive function
  • FMR1
  • P300
  • working memory

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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    Yang, J. C., Chan, S. H., Khan, S., Schneider, A., Nanakul, R., Teichholtz, S., Niu, Y. Q., Seritan, A., Tassone, F., Grigsby, J., Hagerman, P. J., Hagerman, R. J., & Olichney, J. M. (2013). Neural Substrates of Executive Dysfunction in Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): A Brain Potential Study. Cerebral Cortex, 23(11), 2657-2666. https://doi.org/10.1093/cercor/bhs251