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 in | Cerebral cortex (New York, N.Y. 1991) Vol. 23; no. 11; pp. 2657 - 2666 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
Oxford University Press
01.11.2013
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Online Access | Get full text |
ISSN | 1047-3211 1460-2199 1460-2199 |
DOI | 10.1093/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. |
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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 – name: 2 Department of Neurology, University of California Davis, Sacramento, CA,USA – name: 3 English Department , National Taiwan Normal University , Taipei , Taiwan – name: 5 M.I.N.D. Institute, University of California Davis, Sacramento, CA,USA – name: 8 Department of Biochemistry and Molecular Medicine , University of California Davis , Davis, CA , USA, and – name: 1 Center for Mind and Brain, University of California Davis, Davis, CA,USA – name: 7 Department of Psychiatry and Behavioral Sciences , University of California Davis , Sacramento, CA , USA – name: 4 Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA,USA – name: 9 Department of Medicine , University of Colorado at Denver and Health Sciences Center , Aurora, CO , USA |
Author_xml | – sequence: 1 givenname: J.-C. surname: Yang fullname: Yang, J.-C. – sequence: 2 givenname: S.-H. surname: Chan fullname: Chan, S.-H. – sequence: 3 givenname: S. surname: Khan fullname: Khan, S. – sequence: 4 givenname: A. surname: Schneider fullname: Schneider, A. – sequence: 5 givenname: R. surname: Nanakul fullname: Nanakul, R. – sequence: 6 givenname: S. surname: Teichholtz fullname: Teichholtz, S. – sequence: 7 givenname: Y.-Q. surname: Niu fullname: Niu, Y.-Q. – sequence: 8 givenname: A. surname: Seritan fullname: Seritan, A. – sequence: 9 givenname: F. surname: Tassone fullname: Tassone, F. – sequence: 10 givenname: J. surname: Grigsby fullname: Grigsby, J. – sequence: 11 givenname: P. J. surname: Hagerman fullname: Hagerman, P. J. – sequence: 12 givenname: R. J. surname: Hagerman fullname: Hagerman, R. J. – sequence: 13 givenname: J. M. surname: Olichney fullname: Olichney, J. M. |
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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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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 |
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