Gradient of White Matter Functional Variability via fALFF Differential Identifiability

Abstract

Functional variability in both gray matter (GM) and white matter (WM) is closely associated with human brain cognitive and developmental processes, and is commonly assessed using functional connectivity (FC). However, as a correlation-based approach, FC captures the co-fluctuation between brain regions rather than the intensity of neural activity in each region. Consequently, FC provides only a partial view of functional variability, and this limitation is particularly pronounced in WM, where functional signals are weaker and more susceptible to noise. To tackle this limitation, we introduce fractional amplitude of low-frequency fluctuation (fALFF) to measure the intensity of spontaneous neural activity and analyze functional variability in WM. Specifically, we propose a novel method to quantify WM functional variability by estimating the differential identifiability of fALFF. Higher differential identifiability is observed in WM fALFF compared to FC, which indicates that fALFF is more sensitive to WM functional variability. Through fALFF differential identifiability, we evaluate the functional variabilities of both WM and GM, and find the overall functional variability pattern is similar although WM shows slightly lower variability than GM. The regional functional variabilities of WM are associated with structural connectivity, where commissural fiber regions generally exhibit higher variability than projection fiber regions. Furthermore, we discover that WM functional variability demonstrates a spatial gradient ascending from the brainstem to the cortex by hypothesis testing, which aligns well with the evolutionary expansion. The gradient of functional variability in WM provides novel insights for understanding WM function. To the best of our knowledge, this is the first attempt to investigate WM functional variability via fALFF.