Evidence linking FMR1 mRNA and attentional demands of stepping and postural control in women with the premutation

Darren Robert Hocking, Claudine Kraan, David Eugeni Godler, Quang M Bui, Xin Li, John Lockyer Bradshaw, Nellie Georgiou-Karistianis, Sylvia Ann Metcalfe, Alison D Archibald, Erin Turbitt, Joanne Fielding, Julian Norman Trollor, Jonathon Cohen, Kim Marie Cornish

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Recent studies in young adult females with the fragile X mental retardation 1 (FMR1) gene premutation (PM) have shown subtle but significant impairments in executive control and postural stability. Less is known about the influence of age and FMR1 gene expression on executive control and postural stability in females with the PM. Here, we examined the attentional demands of reactive stepping using a well-validated measure of choice stepping reaction time under dual-task interference. We explored the interrelationships between step initiation times during a concurrent verbal fluency task and specific impairments in executive control previously reported in females with the PM. Our results showed increased dual-task interference on step initiation times and variability in female PM compared with control subjects. In addition, we observed greater choice stepping reaction time dual-task costs above the breakpoint of 81 CGG repeats relative to below this CGG range. Dual-task interference on both reaction time and movement time were significantly predicted by low working memory capacity in female PM carriers. Importantly, we revealed that FMR1 messenger RNA level is the most significant predictor accounting for dual-task stepping variability in both reaction time and movement time in PM females. These findings for the first time provide evidence linking elevated FMR1 messenger RNA levels that have been previously associated with FMR1 RNA toxicity and deficits in cerebellar motor and cognitive networks in a subgroup of at-risk PM women
Original languageEnglish
Pages (from-to)1400 - 1408
Number of pages9
JournalNeurobiology of Aging
Volume36
Issue number3
DOIs
Publication statusPublished - 2015

Cite this

Hocking, Darren Robert ; Kraan, Claudine ; Godler, David Eugeni ; Bui, Quang M ; Li, Xin ; Bradshaw, John Lockyer ; Georgiou-Karistianis, Nellie ; Metcalfe, Sylvia Ann ; Archibald, Alison D ; Turbitt, Erin ; Fielding, Joanne ; Trollor, Julian Norman ; Cohen, Jonathon ; Cornish, Kim Marie. / Evidence linking FMR1 mRNA and attentional demands of stepping and postural control in women with the premutation. In: Neurobiology of Aging. 2015 ; Vol. 36, No. 3. pp. 1400 - 1408.
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abstract = "Recent studies in young adult females with the fragile X mental retardation 1 (FMR1) gene premutation (PM) have shown subtle but significant impairments in executive control and postural stability. Less is known about the influence of age and FMR1 gene expression on executive control and postural stability in females with the PM. Here, we examined the attentional demands of reactive stepping using a well-validated measure of choice stepping reaction time under dual-task interference. We explored the interrelationships between step initiation times during a concurrent verbal fluency task and specific impairments in executive control previously reported in females with the PM. Our results showed increased dual-task interference on step initiation times and variability in female PM compared with control subjects. In addition, we observed greater choice stepping reaction time dual-task costs above the breakpoint of 81 CGG repeats relative to below this CGG range. Dual-task interference on both reaction time and movement time were significantly predicted by low working memory capacity in female PM carriers. Importantly, we revealed that FMR1 messenger RNA level is the most significant predictor accounting for dual-task stepping variability in both reaction time and movement time in PM females. These findings for the first time provide evidence linking elevated FMR1 messenger RNA levels that have been previously associated with FMR1 RNA toxicity and deficits in cerebellar motor and cognitive networks in a subgroup of at-risk PM women",
author = "Hocking, {Darren Robert} and Claudine Kraan and Godler, {David Eugeni} and Bui, {Quang M} and Xin Li and Bradshaw, {John Lockyer} and Nellie Georgiou-Karistianis and Metcalfe, {Sylvia Ann} and Archibald, {Alison D} and Erin Turbitt and Joanne Fielding and Trollor, {Julian Norman} and Jonathon Cohen and Cornish, {Kim Marie}",
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Evidence linking FMR1 mRNA and attentional demands of stepping and postural control in women with the premutation. / Hocking, Darren Robert; Kraan, Claudine; Godler, David Eugeni; Bui, Quang M; Li, Xin; Bradshaw, John Lockyer; Georgiou-Karistianis, Nellie; Metcalfe, Sylvia Ann; Archibald, Alison D; Turbitt, Erin; Fielding, Joanne; Trollor, Julian Norman; Cohen, Jonathon; Cornish, Kim Marie.

In: Neurobiology of Aging, Vol. 36, No. 3, 2015, p. 1400 - 1408.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Evidence linking FMR1 mRNA and attentional demands of stepping and postural control in women with the premutation

AU - Hocking, Darren Robert

AU - Kraan, Claudine

AU - Godler, David Eugeni

AU - Bui, Quang M

AU - Li, Xin

AU - Bradshaw, John Lockyer

AU - Georgiou-Karistianis, Nellie

AU - Metcalfe, Sylvia Ann

AU - Archibald, Alison D

AU - Turbitt, Erin

AU - Fielding, Joanne

AU - Trollor, Julian Norman

AU - Cohen, Jonathon

AU - Cornish, Kim Marie

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AB - Recent studies in young adult females with the fragile X mental retardation 1 (FMR1) gene premutation (PM) have shown subtle but significant impairments in executive control and postural stability. Less is known about the influence of age and FMR1 gene expression on executive control and postural stability in females with the PM. Here, we examined the attentional demands of reactive stepping using a well-validated measure of choice stepping reaction time under dual-task interference. We explored the interrelationships between step initiation times during a concurrent verbal fluency task and specific impairments in executive control previously reported in females with the PM. Our results showed increased dual-task interference on step initiation times and variability in female PM compared with control subjects. In addition, we observed greater choice stepping reaction time dual-task costs above the breakpoint of 81 CGG repeats relative to below this CGG range. Dual-task interference on both reaction time and movement time were significantly predicted by low working memory capacity in female PM carriers. Importantly, we revealed that FMR1 messenger RNA level is the most significant predictor accounting for dual-task stepping variability in both reaction time and movement time in PM females. These findings for the first time provide evidence linking elevated FMR1 messenger RNA levels that have been previously associated with FMR1 RNA toxicity and deficits in cerebellar motor and cognitive networks in a subgroup of at-risk PM women

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