White matter microstructural changes in adult-onset idiopathic focal cervical dystonia using ultra-strong diffusion gradient MRI

Background and Objectives Adult-onset idiopathic focal cervical dystonia (AOIFCD) involves loss of co-ordinated contraction of the cervical musculature, resulting in pain, impaired function and in some individuals, an associated head tremor. Existing neuroimaging studies have implicated key motor networks. However, measures used to date lack specificity in detailing the underlying pathophysiological differences. Methods A cohort of individuals diagnosed with AOIFCD and an age- and sex-matched control group were prospectively recruited. All participants underwent MRI using structural and diffusion sequences with multiple b-values up to 30,000 s/mm2, coupled with motor and non-motor clinical phenotyping. Tractography was performed assessing whole tract median values, while tractometry was used for along tract analysis. Key white matter motor pathways were assessed initially using general measures (DTI/DKI: FA-fractional anisotropy; MD-mean diffusivity; MK-mean kurtosis; AK-axial kurtosis; RK-radial kurtosis) with subsequent microstructural white matter modelling approaches (NODDI: ODI-orientation distribution index, NDI-neurite density index, FWF-free water fraction; and standard model: f -intra-axonal signal fraction, D a -intra axonal diffusivity, D epar -extra axonal parallel diffusivity, D eperp -extra axonal perpendicular diffusivity, p 2 -orientation coherence) and unconstrained high b-value zero-order spherical harmonic signal (R0, related to intra-axonal signal) to assess differences within these tracts. Subgroup analyses were undertaken comparing those with and without associated head tremor to the control cohort. Results 50 AOIFCD and 30 healthy control participants underwent structural brain MRI, with 46 AOIFCD and 30 healthy controls included for analysis (33 without head tremor, 13 with head tremor). Significant differences were observed in the anterior thalamic radiations (lower mid tract FA, RK, f and p 2 and higher ODI), thalamopremotor tracts (mid tract higher MK and lower NDI, and distal tract lower ODI and higher f ) and striatopremotor tracts (proximal lower f and R0). These measures correlated with symptom severity across the spectrum with clinical measures, including psychiatric symptoms, sleep quality, pain and cognitive functioning. Discussion Overall, localised microstructural differences were identified within tracts linking the prefrontal cortex and premotor cortex with basal ganglia regions, suggesting microstructural aberrances of motor system modulatory pathways, particularly in relation to intra-axonal and fibre orientation dispersion measures.