Figures and data
Demographic and clinical information of participants
Descriptive statistics for motor outcome measures
Volumetric differences in the basal ganglia and thalamus between HD-gene positive (HD) individuals and healthy controls (HC).
Regions-of-interest (ROIs) were segmented using FreeSurfer v6. All ROIs, except the left thalamus, showed significantly smaller volumes in the HD cohort after FDR correction for multiple comparisons. Colours indicate the strength of rank-biserial correlations (rrb) from Mann-Whitney U tests: Red = strong effect (rrb ≥ 0.5), Yellow = medium effect (0.3 ≤ rrb < 0.5), White = small effect (rrb < 0.3). Raincloud plots show the distribution of the volumetric measures in each ROI per group with orange (HD gene=1) for HD-gene positive and green (HD gene=0) for HD-gene negative participants. * p < 0.05; *** p < 0.001
Descriptive and Mann-Whitney Statistics for Intracranial Volume-Normalised Regions of Interest
Microstructural differences in ROIs between HD-gene positive (HD) and healthy control (HC) groups.
Median values of each microstructural measure were extracted per ROI. A) HD individuals show reduced soma density (fis) in the basal ganglia (BG). B) Soma radius (rs) is elevated in the caudate and putamen but reduced in the pallidum. C) Extracellular water fraction (fec) is increased in BG regions in the HD group. D) Extracellular diffusivity (De) is higher in the putamen and pallidum. E) Fractional anisotropy (FA) is elevated in the BG, and F) mean diffusivity (MD) is increased in the striatum. Colours indicate the strength of rank-biserial correlations (rrb) from Mann-Whitney U tests: Red = strong effect (rrb ≥ 0.5), Yellow = medium effect (0.3 ≤ rrb < 0.5), White = small effect (rrb < 0.3). Raincloud plots show the distribution of the microstructural measures in each ROI per group with orange (HD gene=1) for HD-gene positive and green (HD gene=0) for HD-gene negative participants. * p < 0.05; ** p < 0.01; *** p < 0.001
Descriptive and Mann-Whitney Statistics for Microstructural Measures in Regions of Interest
Scatterplot showing positive relationship between the Q-Motor principal component and the disease burden measure (CAP100) with the Spearman’s rho (ρ) test.
Rotated Component Loadings on the Q-motor Outcome Measures
A) Correlation matrix and B-G) selected scatter plots illustrating Spearman’s rho correlations between SANDI measures and the Q-Motor principal component.
A) Each cell represents the Spearman’s rho correlation strength, with pink indicating negative and green positive correlations. B-G) Each plot includes a best-fit least squares linear regression line with standard error indicated by the grey shaded area, along with the Spearman’s rho (ρ) and the corresponding FDR-p value. Scatter dot colours represent participants’ HD-ISS stage and those who were not classified due to having CAG<40 or incomplete clinical data. Abbreviations: De: Extracellular diffusivity; fec: Extracellular signal fraction; fin: Neurite density signal fraction; fis: Soma density signal fraction; PC: Principal component; rs: Soma radius; TFC: Total functional capacity.
A) Correlation matrix and B-D) selected scatter plots illustrating Spearman’s rho correlations between DTI, volumetric measures and the Q-Motor principal component.
A) Each cell represents the Spearman’s rho correlation strength, with pink indicating negative and green positive correlations. B-D) Each plot includes a best-fit least squares linear regression line with standard error indicated by the grey shaded area, along with the Spearman’s rho (ρ) and the corresponding FDR-p value. Scatter dot colours represent participants’ HD-ISS stage and those who were not classified due to having CAG<40 or incomplete clinical data. Abbreviations: FA: Fractional anisotropy; MD: Mean diffusivity.
Standardised beta coefficients of SANDI microstructural metrics predicting volume (normalised for intracranial volume) in regions of interest in the healthy control group.
Abbreviations: De: Extracellular diffusivity; fis: Soma density signal fraction; rs: Soma radius; TFC: Total functional capacity. * p < 0.05; ** p < 0.01; *** p < 0.001.
Hierarchical Linear Regression Predicting Normalised Volumes from SANDI Microstructural Metrics, Controlling for Age in the Healthy Control Participants
Hierarchical Linear Regression Models Predicting Normalised Volumes in each Region of Interest from SANDI Microstructural Metrics, Controlling for Age and TFC in HD Gene-Positive Participants
Standardised beta coefficients of SANDI microstructural metrics predicting volume (normalised for intracranial volume) in left hemisphere regions of interest in Huntington’s disease patients.
Abbreviations: De: Extracellular diffusivity; fec: Extracellular signal fraction; fis: Soma density signal fraction; rs: Soma radius. * p < 0.05; ** p < 0.01; *** p < 0.001.
Standardised beta coefficients of SANDI microstructural metrics predicting volume (normalised for intracranial volume) in right hemisphere regions of interest in Huntington’s disease patients.
Abbreviations: fec: Extracellular signal fraction; fis: Soma density signal fraction; rs: Soma radius; TFC: Total functional capacity. * p < 0.05; ** p < 0.01; *** p < 0.001.
A) Correlation matrix and B-J) selected scatter plots illustrating Spearman’s rho correlations between SANDI, DTI, and volumetric measures with CAP100. Each scatter plot includes a best-fit least squares linear regression line with standard error indicated by the grey shaded area, along with the Spearman’s rho (ρ) and the corresponding FDR-p value. Scatter dot colours represent participants’ HD-ISS stage and those who were not classified due to having CAG < 40 or incomplete clinical data. Abbreviations: De: Extracellular diffusivity; FA: Fractional anisotropy; fec: Extracellular signal fraction; fin: Neurite density signal fraction; fis: Soma density signal fraction; MD: Mean diffusivity; rs: Soma radius; vol: Normalised volume.
Bar plot showing the effect sizes and 95% confidence intervals for all the exploratory pairwise comparisons between premanifest, manifest and control groups.
Significant comparisons are marked with * (p < 0.05), ** (p < 0.01), and *** (p < 0.001).
Demographic and clinical information per HD-ISS stage.
