Voxel-wise detection of functional networks in white matter

Functional magnetic resonance imaging (fMRI) depicts neural activity in the brain indirectly by measuring blood oxygenation level dependent (BOLD) signals. The majority of fMRI studies have focused on detecting cortical activity in gray matter (GM), but whether functional BOLD signal changes also arise in white matter (WM), and whether neural activities trigger hemodynamic changes in WM similarly to GM, remain controversial, particularly in light of the much lower vascular density in WM. However, BOLD effects in WM are readily detected under hypercapnic challenges, and the number of reports supporting reliable detections of stimulus-induced activations in WM continues to grow. Rather than assume a particular hemodynamic response function, we used a voxel-byvoxel analysis of frequency spectra in WM to detect WM activations under visual stimulation, whose locations were validated with fiber tractography using diffusion tensor imaging (DTI). We demonstrate that specific WM regions are robustly activated in response to visual stimulation, and that regional distributions of WM activation are consistent with fiber pathways reconstructed using DTI. We further examined the variation in the concordance between WM activation and fiber density in groups of different sample sizes, and compared the signal profiles of BOLD time series between resting state and visual stimulation conditions in activated GM as well as activated and non-activated WM regions. Our findings confirm that BOLD signal variations in WM are modulated by neural activity and are detectable with conventional fMRI using appropriate methods, thus offering the potential of expanding functional connectivity measurements throughout the brain.