Research progress of brain white matter based on functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI), a noninvasive imaging technology, measures metabolism and hemodynamics during brain activity based on blood oxygen level-dependent (BOLD) signals that indirectly reflect neural activity. Since the technique was proposed, it has been widely used in studies of cognitive neuroscience and clinical neuropsychiatry. The finding that BOLD signals between the bilateral sensorimotor cortices and other brain regions in the resting state had high temporal correlations led to the concept of functional connectivity being proposed. The functional connectivity method measures the degree of connection between different brain regions, revealing the functional integration of the brain, and has vigorously promoted the development of fMRI research. To date, however, fMRI applications usually focus on the cortical gray matter of the brain, in which blood vessels are relatively dense, rather than the deep white matter regions. The reasons are mainly attributed to the following two points. First, the vascular density, blood flow and blood volume are lower in white matter than in gray matter; thus, BOLD signal changes are much weaker. Second, white matter contains fewer postsynaptic potentials, which is the main source of BOLD signals. As a result, the reliability and biophysical origin of the white matter BOLD signal have always been controversial, and the BOLD signals from white matter have often been treated as noise in previous fMRI studies. In recent years, with the revelation of the physiological significance of BOLD signals in white matter, researchers have gradually turned their attention to fMRI studies of white matter. Through analysis, these studies have found that BOLD signals in white matter are generated by neural activity rather than by noise or artifacts and that white matter and gray matter have similar physiological origins and significance. It was demonstrated that external stimulation could activate white matter regions and that the white matter had functional networks similar to the gray matter cortex. Therefore, future studies should explore more activation patterns of white matter under tasks to further reveal the potential relationship between white matter function and individual’s behavior and cognition. In addition, the study of functional connectivity between white matter and gray matter further revealed functional interactions between them. Subsequent clinical studies found that patients generally showed abnormal white matter activity in the brain and pathological changes in its functional networks and that the dysfunctions in patients may also be related to abnormal communication between white matter and gray matter. Although white matter fMRI provides a direct method to investigate and evaluate white matter function, this research is still at a preliminary exploratory stage. At present, the function of deep brain white matter is rarely studied due to the limitations of analytic methods. Hence, future studies on white matter fMRI need to provide a set of normative and appropriate analytic methods to facilitate the in-depth development of related research.