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

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...

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Published inCerebral cortex (New York, N.Y. 1991) Vol. 23; no. 11; pp. 2657 - 2666
Main Authors 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.
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.11.2013
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Online AccessGet full text
ISSN1047-3211
1460-2199
1460-2199
DOI10.1093/cercor/bhs251

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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.
AbstractList 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.
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.
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 ( similar to 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.
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.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.
Author Niu, Y.-Q.
Tassone, F.
Chan, S.-H.
Nanakul, R.
Grigsby, J.
Hagerman, R. J.
Olichney, J. M.
Hagerman, P. J.
Khan, S.
Yang, J.-C.
Seritan, A.
Teichholtz, S.
Schneider, A.
AuthorAffiliation 3 English Department , National Taiwan Normal University , Taipei , Taiwan
8 Department of Biochemistry and Molecular Medicine , University of California Davis , Davis, CA , USA, and
5 M.I.N.D. Institute, University of California Davis, Sacramento, CA,USA
2 Department of Neurology, University of California Davis, Sacramento, CA,USA
6 Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA,USA
9 Department of Medicine , University of Colorado at Denver and Health Sciences Center , Aurora, CO , USA
7 Department of Psychiatry and Behavioral Sciences , University of California Davis , Sacramento, CA , USA
1 Center for Mind and Brain, University of California Davis, Davis, CA,USA
4 Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA,USA
AuthorAffiliation_xml – name: 6 Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA,USA
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Snippet Executive dysfunction in fragile X-associated tremor/ataxia syndrome (FXTAS) has been suggested to mediate other cognitive impairments. In the present study,...
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StartPage 2657
SubjectTerms Acoustic Stimulation
Attention - physiology
Cerebellar Diseases - physiopathology
Cerebral Cortex - physiopathology
Electroencephalography
Evoked Potentials, Auditory
Executive Function - physiology
Female
Fragile X Mental Retardation Protein - genetics
Fragile X Mental Retardation Protein - metabolism
Humans
Male
Memory, Short-Term - physiology
Middle Aged
Neuropsychological Tests
Title Neural Substrates of Executive Dysfunction in Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): a Brain Potential Study
URI https://www.ncbi.nlm.nih.gov/pubmed/22918986
https://www.proquest.com/docview/1443420981
https://www.proquest.com/docview/1492613046
https://pubmed.ncbi.nlm.nih.gov/PMC3792740
Volume 23
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