Neural variability in the prefrontal cortex as a reflection of neural flexibility and stability in patients with Parkinson Disease

Abstract

__Background and Objectives:__ Functional near-infrared spectroscopy (fNIRS) studies provide direct evidence of the important role of the prefrontal cortex (PFC) during walking in aging and Parkinson disease (PD). Most studies explored mean hemoglobin (HbO2) levels, while moment-to-moment variability measures have rarely been investigated. Variability measures can inform on flexibility, which is imperative for adaptive function. We hypothesized that patients with PD will show less variability in HbO2 signals during walking compared to healthy controls. __Methods:__ Two hundred six participants, 57 healthy controls (age 68.9 ± 1.0 years, 27 women) and 149 patients with idiopathic PD (age 69.8 ± 0.6 years, 50 women, disease duration 8.27 ± 5.51 years), performed usual walking and dual-task walking (serial 3 subtractions) with an fNIRS sensor placed on the forehead. HbO2 variability was calculated from the SD, range, and mean detrended time series of fNIRS-derived HbO2 signal evaluated during each walking task. HbO2 variability was compared between groups and between walking tasks with mixed model analyses. __Results:__ Higher variability (SD, range, mean detrended time series) was observed during dual-task walking compared to usual walking ( p < 0.025), but this was derived from the differences within the healthy control group (group × task interaction p < 0.007). On the other hand, task repetition demonstrated reduced variability in healthy controls but increased variability in patients with PD (interaction group × walk repetition p < 0.048). The Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score correlated with HbO2 range ( r = 0.142, p = 0.050) and HbO2 SD ( r = 0.173, p = 0.018) during usual walking among all participants. __Discussion:__ In this study, we suggest a new way to interpret changes in HbO2 variability. We relate increased HbO2 variability to flexible adaptation to environmental challenges and decreased HbO2 variability to the stability of performance. Our results show that both are limited in PD; however, further investigation of these concepts is required. Moreover, HbO2 variability measures are an important aspect of brain function that add new insights into the role of PFC during walking with aging and PD. __Trial Registration Information:__ ClinicalTrials.gov Identifier: NCT01732653. __Classification of Evidence:__ This study provides Class III evidence that patients with PD have more variability within HbO2 signals during usual walking compared to healthy controls but not during dual-task walking. (© 2021 American Academy of Neurology.)