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 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.
Center for Mind and Brain, University of California Davis, Davis, CA,USA.
Jin-Chen
JC
Yang
Shiao-Hui
SH
Chan
Sara
S
Khan
Andrea
A
Schneider
Rawi
R
Nanakul
Sara
S
Teichholtz
Yu-Qiong
YQ
Niu
Andreea
A
Seritan
Flora
F
Tassone
Jim
J
Grigsby
Paul J
PJ
Hagerman
Randi J
RJ
Hagerman
John M
JM
Olichney
D000161:Acoustic Stimulation; D001288:Attention / Q000502:physiology; D002526:Cerebellar Diseases / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology*; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory; D056344:Executive Function / Q000502:physiology*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human