White Matter Tract Integrity and Sexual Dimorphisms: A Mulitmodal Imaging Study of Dual-Task Walking in Older Adults

Abstract

Evidence of higher-order cortical control of locomotion is well-established and using functional Near Infrared Spectroscopy (fNIRS) we have demonstrated a key functional role of the Pre- Frontal Cortex (PFC) in gait. Dual-Task-Walking (DTW), requiring the individual to walk and talk at the same time, is an ecologically-valid paradigm in which older adults show robust increases in prefrontal oxygenated hemoglobin (HbO2) as measured by fNIRS when compared to Single-Task-Walking (STW). Increasing cortical activation is typically an adaptive function to meet increasing cognitive task demands, however, a more efficient brain utilizes fewer resources to cope with task demands. Alternative explanations suggest lower levels of cortical activation under increased executive demands demonstrate capacity limitations of an aging brain system. Age-related decline in microstructural white matter integrity (WMI) has been associated with cognitive decline, particularly in domains of attention and executive functioning. There is evidence that older men show greater PFC HbO2 during DTW, however, evidence of sex differences in WMI in aging is mixed. In the current study, we combined Diffusion Tensor Imaging (DTI) and fNIRS to examine differences in the moderating effects of white matter integrity (WMI) in select tracts on PFC HbO2 assessed during active walking under single- and dual-task conditions. We also explored sex differences in the moderating effects of WMI on PFC HbO2 during active walking conditions. A sample of 59 non-demented community-dwelling older adults (mean age 74.75 ± 5.08) underwent DTI to calculate fractional anisotropy as a gauge of WMI and fNIRS, which measured PFC HbO2 during walking tasks. Gait velocity was assessed using an instrumented walkway and included in statistical models. As expected, results indicated that gait velocity declined and PFC HbO2 increased in DTW compared to STW, given the increased cognitive demands of DTW. Results also indicated that WMI of the genu of the corpus callosum (GCC), bilateral superior longitudinal fasciculus (SLF), left inferior frontooccipital fasciculus (IFOF), and right uncinate fasciculus (UF) moderated the change in PFC HbO2 from STW to DTW. However, the directions of these relationships varied. Specifically, increased WMI of the GCC, left SLF and right UF was associated with an attenuated increase in PFC HbO2 from STW to DTW, while the inverse was true for the right SLF and left IFOF. Additionally, there were sex differences in the moderating relationships of WMI in the GCC, left SLF, left IFOF, right UF, and left corticospinal tract (CST) on PFC HbO2 during walking. Results were interpreted in the context of neural efficiency and capacity limitations models. Conclusion: These findings highlight the complex brain structure-function relationships underpinning locomotion. In the context of maintained behavioral performance, reduced WMI in healthy older adults resulted in alterations in prefrontal cortex activation during an attention demanding walking task with well-established links to falls, clinical outcomes and functional independence. Furthermore, we have highlighted variations in these structure-function relationships for older men and women. This work provides initial insights into the potentially modifiable factors underlying altered cortical activation patterns during locomotion in aging.