Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease

Abstract

Structural and functional changes attributable to the neurodegenerative process in Huntington’s disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls). There were no significant differences in white matter macro- and microstructure between far from onset preHD participants and controls. Functional connectivity in a basal ganglia-thalamic and motor networks, all measures of the motor efferent and sensory afferent pathways as well as sensory-motor integration were also similar in far from onset preHD and controls. With the methods used in far from onset preHD sensory-motor neural macro- or micro-structure and brain function were similar to healthy controls. This suggests that any observable structural and functional change in preHD nearer to onset, or in manifest HD, at least using comparable techniques such as in this study, most likely reflects an ongoing neurodegenerative process.

Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

“…A third independent study reported decreased connectivity in thalamus and temporal gyrus of subcortical network, whereas increased connectivity was observed within the frontal gyrus (Wolf, Sambataro, Vasic, Depping, et al, ). In pre‐HD, two independent studies, implementing a seed‐based connectivity approach, failed to report network changes (Gorges et al, ; Seibert et al, ).…”

Resting-state connectivity stratifies premanifest Huntington’s disease by longitudinal cognitive decline rate

“…Classification based on presence or absence of mutated HTT gene is ideal to study within-subject reliability: genetic labels have virtually no associated noise, and are strictly stable across visits. Moreover, because functional differences are mild in gene-carriers far from symptom onset 21 , the sensitivity to test-retest fluctuations is expected to be higher than for strong neurological signatures. We trained binary classifiers using sex-and age-corrected FCD maps validated using LOSO-CV to ensure robustness to site differences.…”

“…Images are accompanied by a wealth of cognitive and motor measures, most also acquired during preceding TRACK-HD visits, in combination spanning up to 7 yearly measurements. Such a rich dataset allows for the estimation of subtle longitudinal changes in cognition and motor control, allowing subjects to be compared to their own performance baselines, and enabling analyses of population heterogeneity for a stage at which systematic brain differences from controls are mild 21 . In addition, because performance on different tasks might rely on the same affected neural systems, it is possible to identify combinations of measures for which longitudinal changes covary, potentially boosting behavioural signal-to-noise and isolating common brain structures responsible for cognitive decline.…”

Structural and Functional Brain Mapping Correlates of Impaired Eye Movement Control in Parkinsonian Syndromes: A Systems-Based Concept

“…And which diseased brain regions are suspect to be associated with a particular pattern of eye movement disturbances? These questions cannot be fully addressed yet, but systematic studies investigating eye movement control and brain connectivity ( 75 , 76 ) may indicate that network-based functional connectivity alterations are associated with worsened executive oculomotor function and that functional abnormalities may precede microstructural and macrostructural changes. Although the primary visual cortex in PD appears to be spared by the pathological process ( 60 ), a broad spectrum of visuo-oculomotor dysfunctions including color vision ( 77 ) and diplopia have been reported ( 78 ).…”