Probing white matter microstructure in youth with chronic pain

Alterations in white matter (WM) have been reported in individuals with chronic pain, although findings are inconsistent, and mostly derived using the limited Diffusion Tensor Imaging (DTI) model. Going beyond DTI, one study reported lower WM complexity in corpus callosum, internal capsule and a hippocampus tract. In youth with chronic pain, no studies have examined WM changes, except in headache. The current study therefore examined potential WM alterations in youth with chronic pain using DTI as well as Neurite Orientation Dispersion and Density Imaging (NODDI), allowing more specific interrogation of WM microstructure. Multi-shell diffusion-weighted MR images were analyzed in 45 youth with chronic pain (age M=15.8±2.5, 41 females) and 25 controls (age M=16.0±3.2, 18 females). Preprocessing included estimation and correction of susceptibility-, eddy current-, and motion-induced distortions (FSL). DTI and NODDI models were fit, deriving indices of fractional anisotropy (FA/DTI), neurite density (NDI/NODDI) and orientation dispersion (ODI/NODDI). Data was spatially aligned using tensor-based alignment (DTI-TK), followed by tract-based spatial statistics (TBSS; TFCE-corrected). Group contrasts showed that while there were no group differences in FA and NDI, patients showed increased ODI in several tracts, including the corticospinal tract, corpus callosum and forceps minor (connecting medial and lateral frontal lobe), uncinate fasciculus (connecting frontal and temporal lobe), internal capsule (connecting subcortical structures) and fornix (a hippocampus tract). Our findings reveal specific WM alterations in several tracts that are implicated in (chronic) pain. In particular, the dispersion in fiber orientation was increased, reflective of less coherently organized fibers. This may indicate possible delayed pruning in these tracts. Neurite density indices were not different, reflective of similar amounts of fibers and myelin. Taken together, youth with chronic pain showed specific alterations in fiber dispersion of several WM tracts in cortico-limbic circuitry. Future work will examine associations with individual difference factors. NIH R01HD083270 to LE Simons.