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dc.contributor.authorMcKinney, Walker S.
dc.contributor.authorBartolotti, James
dc.contributor.authorKhemani, Pravin
dc.contributor.authorWang, Jun Yi
dc.contributor.authorHagerman, Randi J.
dc.contributor.authorMosconi, Matthew W.
dc.identifier.citationMcKinney, W. S., Bartolotti, J., Khemani, P., Wang, J. Y., Hagerman, R. J., & Mosconi, M. W. (2020). Cerebellar-cortical function and connectivity during sensorimotor behavior in aging FMR1 gene premutation carriers. NeuroImage. Clinical, 27, 102332.
dc.descriptionThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.en_US
dc.description.abstractIntroduction Premutation carriers of the FMR1 gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease characterized by motor, cognitive, and psychiatric decline as well as cerebellar and cerebral white matter pathology. Several studies have documented preclinical sensorimotor issues in aging premutation carriers, but the extent to which sensorimotor brain systems are affected and may represent early indicators of atypical neurodegeneration has not been determined.

Materials and methods Eighteen healthy controls and 16 FMR1 premutation carriers (including five with possible, probable, or definite FXTAS) group-matched on age, sex, and handedness completed a visually guided precision gripping task with their right hand during fMRI. During the test, they used a modified pinch grip to press at 60% of their maximum force against a custom fiber-optic transducer. Participants viewed a horizontal white force bar that moved upward with increased force and downward with decreased force and a static target bar that was red during rest and turned green to cue the participant to begin pressing at the beginning of each trial. Participants were instructed to press so that the white force bar stayed as steady as possible at the level of the green target bar. Trials were 2-sec in duration and alternated with 2-sec rest periods. Five 24-sec blocks consisting of six trials were presented. Participants’ reaction time, the accuracy of their force relative to the target force, and the variability of their force accuracy across trials were examined. BOLD signal change and task-based functional connectivity (FC) were examined during force vs. rest.

Results Relative to healthy controls, premutation carriers showed increased trial-to-trial variability of force output, though this was specific to younger premutation carriers in our sample. Relative to healthy controls, premutation carriers also showed reduced extrastriate activation during force relative to rest. FC between ipsilateral cerebellar Crus I and extrastriate cortex was reduced in premutation carriers compared to controls. Reduced Crus I-extrastriate FC was related to increased force accuracy variability in premutation carriers. Increased reaction time was associated with more severe clinically rated neurological abnormalities.

Conclusions Findings of reduced activation in extrastriate cortex and reduced Crus I-extrastriate FC implicate deficient visual feedback processing and reduced cerebellar modulation of corrective motor commands. Our results are consistent with documented cerebellar pathology and visual-spatial processing in FXTAS and pre-symptomatic premutation carriers, and suggest FC alterations of cerebellar-cortical networks during sensorimotor behavior may represent a “prodromal” feature associated with FXTAS degeneration.
dc.description.sponsorshipOnce Upon a Time Foundationen_US
dc.description.sponsorshipNIH U54 HD090216en_US
dc.rights© 2020 The Author(s). Published by Elsevier Inc.en_US
dc.subjectFragile X-associated tremor/ataxia syndrome (FXTAS)en_US
dc.subjectExtrastriate cortexen_US
dc.subjectCerebellar Crus Ien_US
dc.subjectFunctional connectivityen_US
dc.subjectFMR1 premutationen_US
dc.titleCerebellar-cortical function and connectivity during sensorimotor behavior in aging FMR1 gene premutation carriersen_US
kusw.kuauthorMcKinney, Walker S.
kusw.kuauthorBartolotti, James
kusw.kuauthorMosconi, Matthew W.
kusw.kudepartmentLife Span Instituteen_US
kusw.kudepartmentKansas Center for Autism Research and Training (K-CART)en_US
kusw.kudepartmentClinical Child Psychology Programen_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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© 2020 The Author(s). Published by Elsevier Inc.
Except where otherwise noted, this item's license is described as: © 2020 The Author(s). Published by Elsevier Inc.