Functional MRI and resting state connectivity in white matter - a mini-review.

Functional MRI (fMRI) signals are robustly detectable in white matter (WM) but they have been largely ignored in the fMRI literature. Their nature, interpretation, and relevance as potential indicators of brain function remain under explored and even controversial. Blood oxygenation level dependent (BOLD) contrast has for over 25 years been exploited for detecting localized neural activity in the cortex using fMRI. While BOLD signals have been reliably detected in grey matter (GM) in a very large number of studies, such signals have rarely been reported from WM. However, it is clear from our own and other studies that although BOLD effects are weaker in WM, using appropriate detection and analysis methods they are robustly detectable both in response to stimuli and in a resting state. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both GM and WM, and their relative low frequency (0.01-0.1 Hz) signal powers are comparable. They also vary with baseline neural activity e.g. as induced by different levels of anesthesia, and alter in response to a stimulus. In previous work we reported that BOLD signals in WM in a resting state exhibit anisotropic temporal correlations with neighboring voxels. On the basis of these findings, we derived functional correlation tensors that quantify the correlational anisotropy in WM BOLD signals. We found that, along many WM tracts, the directional preferences of these functional correlation tensors in a resting state are grossly consistent with those revealed by diffusion tensors, and that external stimuli tend to enhance visualization of specific and relevant fiber pathways. These findings support the proposition that variations in WM BOLD signals represent tract-specific responses to neural activity. We have more recently shown that sensory stimulations induce explicit BOLD responses along parts of the projection fiber pathways, and that task-related BOLD changes in WM occur synchronously with the temporal pattern of stimuli. WM tracts also show a transient signal response following short stimuli analogous to but different from the hemodynamic response function (HRF) characteristic of GM. Thus there is converging and compelling evidence that WM exhibits both resting state fluctuations and stimulus-evoked BOLD signals very similar (albeit weaker) to those in GM. A number of studies from other laboratories have also reported reliable observations of WM activations. Detection of BOLD signals in WM has been enhanced by using specialized tasks or modified data analysis methods. In this mini-review we report summaries of some of our recent studies that provide evidence that BOLD signals in WM are related to brain functional activity and deserve greater attention by the neuroimaging community.