Complexity Based Measures of Postural Stability Provide Novel Evidence of Functional Decline in Fragile X Premutation Carriers

Overview

Journal J Neuroeng Rehabil

Publisher Biomed Central

Specialties Biomedical Engineering
Neurology
Rehabilitation Medicine

Date 2019 Jul 14

PMID 31299981

Citations 10

Authors

Clodagh OKeeffe

Laura P Taboada

Niamh Feerick

Louise Gallagher

Timothy Lynch

Richard B Reilly

Affiliations

Soon will be listed here.

Abstract

Background: Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative movement disorder characterized by tremor, ataxic gait, and balance issues resulting from a premutation of the Fragile X Mental Retardation 1 (FMR1) gene. No biomarkers have yet been identified to allow early diagnosis of FXTAS, however, recent studies have reported subtle issues in the stability of younger premutation carriers, before disease onset. This study investigates the efficacy of multiscale entropy analysis (MSE) in detecting early changes in the motor system of premutation carriers without FXTAS.

Methods: Sway complexity of 12 female Premutation carriers and 15 healthy Controls were measured under four conditions: eyes open, closed, and two dual-task conditions. A Sustained Attention Response Task (SART) and a working memory based N-Back task were employed to increase cognitive load while standing on the forceplate. A Complexity Index (Ci) was calculated for anterior-posterior (AP) and mediolateral (ML) sway. Independent t-tests were used to assess between-group differences and Oneway repeated measures ANOVA were used to assess within group differences with Bonferroni corrections to adjust for multiple comparisons.

Results: Group performances were comparable with eyes open and closed conditions. The Carrier group's Ci was consistent across tasks and conditions while the Control group's AP Ci increased significantly during the cognitive dual-task (p = 0.001). There was also a strong correlation between CGG repeat length and complexity for the Carrier group (p = 0.004).

Significance: Increased sway complexity is believed to stem from reallocation of attention to facilitate the increased cognitive demands of dual-tasks. Carriers' complexity did not change during dual-tasks, possibly indicating capacity interference and inefficient division of attention. Lower sway complexity in carriers suggests diminished adaptive capacity under stress as well as degradation of motor functioning. Therefore, sway complexity may be a useful tool in identifying early functional decline in FMR1 premutation carriers as well as monitoring progression towards disease onset.

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References

Goldberger A, Amaral L, Glass L, Hausdorff J, Ivanov P, Mark R . PhysioBank, PhysioToolkit, and PhysioNet: components of a new research resource for complex physiologic signals. Circulation. 2000; 101(23):E215-20. DOI: 10.1161/01.cir.101.23.e215. View

Lipsitz L . Dynamics of stability: the physiologic basis of functional health and frailty. J Gerontol A Biol Sci Med Sci. 2002; 57(3):B115-25. DOI: 10.1093/gerona/57.3.b115. View

Woollacott M, Shumway-Cook A . Attention and the control of posture and gait: a review of an emerging area of research. Gait Posture. 2002; 16(1):1-14. DOI: 10.1016/s0966-6362(01)00156-4. View

Costa M, Goldberger A, Peng C . Multiscale entropy analysis of complex physiologic time series. Phys Rev Lett. 2002; 89(6):068102. DOI: 10.1103/PhysRevLett.89.068102. View

Peterka R . Sensorimotor integration in human postural control. J Neurophysiol. 2002; 88(3):1097-118. DOI: 10.1152/jn.2002.88.3.1097. View

Sasaki O, Usami S, Gagey P, Martinerie J, Le Van Quyen M, Arranz P . Role of visual input in nonlinear postural control system. Exp Brain Res. 2002; 147(1):1-7. DOI: 10.1007/s00221-002-1170-1. View

KIRCHNER W . Age differences in short-term retention of rapidly changing information. J Exp Psychol. 1958; 55(4):352-8. DOI: 10.1037/h0043688. View

Jacquemont S, Hagerman R, Leehey M, Hall D, Levine R, Brunberg J . Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA. 2004; 291(4):460-9. DOI: 10.1001/jama.291.4.460. View

Lipsitz L, Goldberger A . Loss of 'complexity' and aging. Potential applications of fractals and chaos theory to senescence. JAMA. 1992; 267(13):1806-9. View

10.

Cohen S, Masyn K, Adams J, Hessl D, Rivera S, Tassone F . Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome. Neurology. 2006; 67(8):1426-31. DOI: 10.1212/01.wnl.0000239837.57475.3a. View

11.

Jacobs J, Horak F . Cortical control of postural responses. J Neural Transm (Vienna). 2007; 114(10):1339-48. PMC: 4382099. DOI: 10.1007/s00702-007-0657-0. View

12.

Leehey M, Berry-Kravis E, Goetz C, Zhang L, Hall D, Li L . FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology. 2007; 70(16 Pt 2):1397-402. PMC: 2685188. DOI: 10.1212/01.wnl.0000281692.98200.f5. View

13.

Allen E, Juncos J, Letz R, Rusin M, Hamilton D, Novak G . Detection of early FXTAS motor symptoms using the CATSYS computerised neuromotor test battery. J Med Genet. 2008; 45(5):290-7. PMC: 3696494. DOI: 10.1136/jmg.2007.054676. View

14.

Rodriguez-Revenga L, Madrigal I, Pagonabarraga J, Xuncla M, Badenas C, Kulisevsky J . Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur J Hum Genet. 2009; 17(10):1359-62. PMC: 2986640. DOI: 10.1038/ejhg.2009.51. View

15.

Kang H, Costa M, Priplata A, Starobinets O, Goldberger A, Peng C . Frailty and the degradation of complex balance dynamics during a dual-task protocol. J Gerontol A Biol Sci Med Sci. 2009; 64(12):1304-11. PMC: 2781784. DOI: 10.1093/gerona/glp113. View

16.

Manor B, Costa M, Hu K, Newton E, Starobinets O, Kang H . Physiological complexity and system adaptability: evidence from postural control dynamics of older adults. J Appl Physiol (1985). 2010; 109(6):1786-91. PMC: 3006415. DOI: 10.1152/japplphysiol.00390.2010. View

17.

Hocking D, Kogan C, Cornish K . Selective spatial processing deficits in an at-risk subgroup of the fragile X premutation. Brain Cogn. 2012; 79(1):39-44. DOI: 10.1016/j.bandc.2012.02.005. View

18.

Wang J, Hessl D, Hagerman R, Tassone F, Rivera S . Age-dependent structural connectivity effects in fragile x premutation. Arch Neurol. 2012; 69(4):482-9. PMC: 3979438. DOI: 10.1001/archneurol.2011.2023. View

19.

Scoppa F, Capra R, Gallamini M, Shiffer R . Clinical stabilometry standardization: basic definitions--acquisition interval--sampling frequency. Gait Posture. 2012; 37(2):290-2. DOI: 10.1016/j.gaitpost.2012.07.009. View

20.

Manor B, Lipsitz L . Physiologic complexity and aging: implications for physical function and rehabilitation. Prog Neuropsychopharmacol Biol Psychiatry. 2012; 45:287-93. PMC: 3568237. DOI: 10.1016/j.pnpbp.2012.08.020. View