Objective: This study aimed to characterize cortical theta activity in Fragile X Premutation carriers during continuous balance.

Background: Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a degenerative movement disorder characterized by tremor and balance impairments, affecting up to 40% of FMR1 premutation carriers over 50 years[1]. While subtle changes in balance have been seen in younger carriers prior to a diagnosis of FXTAS, the neural mechanisms underlying these changes have not yet been explored. Research has linked increases in frontal and parietal theta spectral power with an error signal, caused by unstable balance [2,3]. This study investigated cortical theta activity during continuous balance and its relationship to balance performance in Fragile X premutation carriers.

Method: Four premutation carriers and 10 healthy controls stood on a forceplate with eyes open, closed (EO/EC) and while conducting two cognitive tasks (N-back and SART tasks). Postural Sway and high-density EEG data were simultaneously recorded to measure changes in theta power in response to balance task difficulty. Postural sway parameters included sway area, path length, and velocity, ROIs included frontal, fronto-medial, central, and parietal regions.

Results: The carrier group’s path length and velocity were greater than the control groups’ during the N-back task (p=.05 and p=.02, respectively), and carriers fronto-medial theta power reduced significantly during the task. Fronto-medial theta activity was also reduced under EO and central theta activity during the SART task compared to controls’. Path length and velocity were strongly negatively correlated with theta power across all four ROI during EC condition (p<.05 for all), as well as frontal and fronto medial theta during the SART task, whereas the control group showed a moderate positive correlation between theta activity and sway area.

Conclusion: The positive relationship between theta power and balance seen in the control group may indicate an increase in error detection caused by reduced visual input and greater discrepancies between expected and actual balance state. Negative relationships between theta power and stability in carriers may indicate reduced error detection and processing, resulting in an inability to compensate efficiently for challenges to stability. Such results provide new insight into the neural correlates of balance control in Fragile X premutation carriers.

References: [1] P. J. Hagerman, “The fragile X prevalence paradox,” Journal of medical genetics, vol. 45, pp. 498-499, 2008. [2] A. L. Adkin, S. Quant, B. E. Maki, and W. E. McIlroy, “Cortical responses associated with predictable and unpredictable compensatory balance reactions,” Experimental brain research, vol. 172, p. 85, 2006. [3] A. R. Sipp, J. T. Gwin, S. Makeig, and D. P. Ferris, “Loss of balance during balance beam walking elicits a multifocal theta band electrocortical response,” Journal of Neurophysiology, vol. 110, pp. 2050-2060, 2013.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/probing-error-signals-of-postural-control-in-fragile-x-premutation-carriers/