DOI: 10.5061/dryad.qbzkh18cw
title: Abnormal Development of Cerebellar-Striatal Circuitry in Huntington’s Disease: Supplemental Figures

description: Objective: To test the hypothesis that the trajectory of functional
 connections over time of the striatum and the cerebellum differs between
 pre-symptomatic patients with the HD gene expansion (GE) and patients with
 a family history of HD but without the gene-expansion (GNE), we evaluated
 function MRI data from the Kids-HD study.  Methods: We utilized
 resting-state, functional MRI data from participants in the Kids-HD study
 between 6 to 18 years old.  Participants were divided into the GE
 (CAG 36-59) and GNE (CAG &lt;36) groups.  Seed to seed
 correlations were calculated between four regions that provide input
 signals to the anterior cerebellum: 1) dorsocaudal putamen; 2) globus
 pallidus externa; 3) subthalamic nucleus, and 4) pontine nuclei and two
 regions that represented output from the cerebellum, the dentate nucleus
 to the: 1) ventrolateral thalamus and 2) dorsocaudal putamen. Linear mixed
 effects regression models evaluated differences in developmental
 trajectories of these connections over time between groups. Results: Four
 of the six striatal-cerebellum correlations showed significantly different
 trajectories between groups.  All showed a pattern where in the
 early age ranges (6-12 years), there was hyperconnectivity in the GE
 compared to the GNE with those trajectories showing linear decline in the
 latter half of the age range. Conclusion: These results parallel previous
 findings showing striatal hypertrophy in GE children as early as age
 6.  These findings support the notion of developmentally higher
 connectivity between the striatum and cerebellum early in the life of the
 child with the HD gene expansion, possibly setting the stage for
 cerebellar compensatory mechanisms.
description: Supplemental Figure 1: Overview of how long participants were
 followed during the Kids-HD study.  Single data points represent
 participants who were only seen once.   Supplemental
 Figure 2: This figure represents the cross-sectional sex by group
 interaction (does not account for longitudinal changes by age).  Panel A
 outlines the differences in functional connectivity of the globus pallidus
 externa (GPE) to the anterior cerebellum (aCB) between the gene expanded
 (GE) and gene non-expanded (GNE) groups by sex.  Panel B shows similar
 results for functional connectivity between the subthalamic nucleus (STN)
 and the aCB.  Most notably in each panel, functional connectivity seems to
 be higher in GE boys relative to GNE boys. Supplemental
 Figure 3: This figure represents the triple interaction of age*group*sex,
 which allows us to investigate the differences in trajectory of functional
 connectivity strength between groups by sex.  This represents functional
 connectivity changes between the aCB to the GPE.  In both boys and girls,
 functional connectivity strength is higher earlier in life in the GE group
 with a steeper decline over time relative to the GNE group.
 Supplemental Figure 4: This figure represents the triple
 interaction of age*group*sex, which allows us to investigate the
 differences in trajectory of functional connectivity strength between
 groups by sex.  This represents functional connectivity changes between
 the aCB to the STN.  Again, in both boys and girls, functional
 connectivity strength is higher earlier in life in the GE group with a
 steeper decline over time relative to the GNE group.