TRANSIENT ALTERATIONS IN THALAMO-CEREBELLAR FUNCTIONAL CONNECTIVITY IN PREMANIFEST HUNTINGTON’S DISEASE
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
There are no disease modifying therapies for Huntington’s disease (HD), a rare but fatal genetic neurodegenerative condition. To develop and test new management strategies, a better understanding of the mechanisms underlying HD progression is needed. Aberrant changes in thalamo-cortical and striato-cerebellar circuitry have been observed in asymptomatic HD, along with transient enlargement of the dentate nucleus.
Purpose
To evaluate the relationship between thalamo-cerebellar connectivity and HD progression.
Study Type
Prospective and retrospective.
Population
Patients with HD and healthy controls from a single-center dataset (n=34), and patients from the public TRACK-HD dataset (n=91).
Field strength/Sequence
3T and 7T.
Assessment
Thalamo-cerebellar connectivity was compared across patients and controls and related to motor scores and predicted years to symptom onset. Cross-sectional findings were validated within-patient by mapping changes in individual connectivity over time. HD effects on cognitive performance were also explored and related to connectivity.
Statistical Tests
Kruskal-Wallis with post hoc Dunn’s tests and Pearson correlations (p significant <0.05).
Results
In the 7T cohort, significant premanifest and control group differences in thalamo-dentate connectivity were observed (p Dunn <0.05, η 2 =.19-.22), with manifest HD connectivity approaching normative values. Thalamic connectivity with the dentate nucleus and anterior cerebellum also correlated with years to onset (p Den =0.06, r=0.42, p Ant <0.05, r=-0.45), together indicating potential transient functional alterations in premanifest HD. Similar patterns were observed between connectivity (thalamus to dentate nucleus and anterior lobe) and cognitive performance scores across all subjects (p<0.05, r Den =-0.17, r Ant =-0.18). In the premanifest TRACK-HD cohort, connectivity of multiple thalamo-cerebellar connections correlated with years to onset, revealing distinct patterns for patients with low versus high motor scores, again indicative of potential transient alterations. Exploratory non-parametric regression of serial imaging data further supported these findings.
Data conclusion
Transient changes in thalamo-cerebellar connectivity are seen in premanifest HD with increasing progression. More studies are needed to validate this potentially useful biomarker.
