Eye movements reveal impaired inhibitory control in adult male fragile X premutation carriers asymptomatic for FXTAS.
OBJECTIVE
Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance.


METHODS
Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs (n = 21) and healthy age-matched controls (n = 22) performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks.


RESULTS
Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII.


CONCLUSIONS
Antisaccades require inhibitory control to inhibit reflexive eye movements. We found that eye movements are sensitive to impaired inhibitory control in fXPCs asymptomatic for FXTAS. Thus, eye movements may be useful in assessing FXTAS risk or disease progression.
Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center.
Ling M
0000-0002-6045-5344
LM
Wong
Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center.
Naomi J
NJ
Goodrich-Hunsaker
Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center.
Yingratana
Y
McLennan
Department of Biochemistry and Molecular Medicine, University of California, Davis Medical Center.
Flora
F
Tassone
Department of Neurobiology, Physiology, and Behavior, University of California, Davis.
Melody
M
Zhang
Department of Psychology, University of California, Davis.
Susan M
SM
Rivera
Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center.
Tony J
TJ
Simon
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000209:etiology; D002525:Cerebellar Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology; D056344:Executive Function / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007266:Inhibition, Psychological; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000209:etiology*; D016649:Primary Ovarian Insufficiency / Q000150:complications* / Q000235:genetics*; D011581:Psychological Tests; D011930:Reaction Time / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D055815:Young Adult
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human