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The occurrence of debilitating chronic persistent (24/7) headache after mild traumatic brain injury (MTBI) represents a central neuropathic pain state. Previous studies suggest that this chronic headache (HA) state can be attributed to altered supraspinal modulatory functional connectivity in both resting and evoked pain states. Abnormalities in the myelin sheaths along the supraspinal Superior Longitudinal Fasciculus (SLF) and Anterior Thalamic Radiation (ATR) are frequently associated with alteration in pain modulation related to functional connectivity deficit with the prefrontal cortex. This study assessed the correlated axonal injury related white matter tract abnormality underlying these previously observed prefrontal functional connectivity deficits by comparing the fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) of brain white matter in patients with MTBI related headache (MTBI-HA) to healthy controls. Diffusion tensor imaging (DTI) data from patients (N=12, average ageSD=35.08.0 year-old, 10 male) with MTBI-HA were compared with images acquired from healthy controls. The MTBI cohort demonstrated two areas of significant (P<0.01, F-value >16, cluster size >50 voxels) white matter tract abnormalities closely related to pain affective and modulatory functions in: 1) the Left SLF which connects the prefrontal cortices with the parietal cortices; and 2) the Right ATR connecting the prefrontal cortices with the anterior cingulate cortex. In addition, a significant (P<0.01) decrease in AD and increase in RD at the SLF cluster was noted in the MTBI cohort. The identified white matter tract abnormalities may represent a state of Wallerian degeneration which correlates with the functional connectivity deficit in pain modulation and can contribute to the development of the chronic persistent headache in the patients with MTBI.

Pain-related white matter tract abnormalities in mild traumatic brain injury patients with persistent headache