Significance
Functional MRI (fMRI) has proven valuable at mapping cortical activity in the brain. However, many fMRI studies may be underestimating the extent of activation due to low signal-to-noise-ratio or modeling assumptions. Further, fMRI signal in the white matter of the brain is often removed or treated as an artifact. In a complementary study to previous works which showed that nearly all cortex responds to a task, we show both white and gray matter show widespread blood oxygenation level–dependent signal changes. This suggests that many reports of fMRI studies may not only underestimate the true extent of brain activation but also exclude and/or neglect half of all brain tissue (white matter) and may miss crucial information from the MRI signal.
Abstract
Recent studies have revealed the production of time-locked blood oxygenation level–dependent (BOLD) functional MRI (fMRI) signals throughout the entire brain in response to tasks, challenging the existence of sparse and localized brain functions and highlighting the pervasiveness of potential false negative fMRI findings. “Whole-brain” actually refers to gray matter, the only tissue traditionally studied with fMRI. However, several reports have demonstrated reliable detection of BOLD signals in white matter, which have previously been largely ignored. Using simple tasks and analyses, we demonstrate BOLD signal changes across the whole brain, in both white and gray matters, in similar manner to previous reports of whole brain studies. We investigated whether white matter displays time-locked BOLD signals across multiple structural pathways in response to a stimulus in a similar manner to the cortex. We find that both white and gray matter show time-locked activations across the whole brain, with a majority of both tissue types showing statistically significant signal changes for all task stimuli investigated. We observed a wide range of signal responses to tasks, with different regions showing different BOLD signal changes to the same task. Moreover, we find that each region may display different BOLD responses to different stimuli. Overall, we present compelling evidence that, just like all gray matter, essentially all white matter in the brain shows time-locked BOLD signal changes in response to multiple stimuli, challenging the idea of sparse functional localization and the prevailing wisdom of treating white matter BOLD signals as artifacts to be removed.
