Characterising Upper Limb Movements in Huntington's Disease and the Impact of Restricted Visual Cues
August
Characterising Upper Limb Movements in Huntington's Disease and the Impact of Restricted Visual Cues
Jessica Despard 0 1 2
Anne-Marie Ternes 0 1 2
Bleydy Dimech-Betancourt 0 1 2
Govinda Poudel 0 1 2
Andrew Churchyard 0 1 2
Nellie Georgiou-Karistianis 0 1 2
0 Funding: This research was supported by funds from the School of Psychological Sciences, Monash University
1 Editor: Alfonso Fasano, University of Toronto , CANADA
2 1 School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton, Victoria , Australia , 2 Monash Biomedical Imaging , Monash University , Melbourne, Victoria , Australia , 3 Victorian Life Sciences Computation Initiative, Life Sciences Computation Centre , Melbourne, Victoria , Australia , 4 Department of Neurology, Monash Medical Centre , Clayton, Victoria , Australia
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Nine premanifest HD (pre-HD), nine early symptomatic HD (symp-HD) and nine matched
controls completed a motor task incorporating Fitts' law, a model of human movement
enabling the quantification of movement timing, via the manipulation of task difficulty (i.e.,
target size, and distance between targets). The task required participants to make
reciprocal movements under cued and blind conditions. Dwell times (time stationary between
movements), speed, accuracy and variability of movements were compared between
groups.
Symp-HD showed significantly prolonged and less consistent movement times, compared
with controls and pre-HD. Furthermore, movement planning and online control were
significantly impaired in symp-HD, compared with controls and pre-HD, evidenced by prolonged
dwell times and deceleration times. Speed and accuracy were comparable across groups,
suggesting that group differences observed in movement time, variability, dwell time and
deceleration time were evident over and above simple performance measures. The
presence of cues resulted in greater movement time variability in symp-HD, compared with
pre-HD and controls, suggesting that the deficit in movement consistency manifested only
in response to targeted movements.
Collectively, these findings provide evidence of a deficiency in both motor planning,
particularly in relation to movement timing and online control, which became exacerbated as a
function of task difficulty during symp-HD stages. These variables may provide a more
sensitive measure of motor dysfunction than speed and/or accuracy alone in symp-HD.
Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder caused by
the pathological expansion of a CAG trinucleotide repeat, disrupting cognitive, affective and
motor functions [1–3]. A major focus of current research is to identify specific deficits early in
the disease, in order to develop targeted treatment protocols that may delay disease progression
[4]. The premanifest stage of HD (pre-HD) [5] provides an unprecedented opportunity to
characterize deficits and ultimately encapsulate sensitive markers of disease progression from
premanifest to symptomatic stages for potential use in clinical interventions [4,6,7]. While the
focus of recent research has predominantly entailed the use of advanced neuroimaging
technologies to track neuronal activity [7–9], their functional relevance has been less well understood
[4]. Importantly, it is the behavioural impact at a functional level that renders an individual
incapable of living independently Although many studies have characterised motor deficits in
HD [10–29], most notably focus on rudimentary measures, such as speed and accuracy, and
often comprise of simple finger tapping tasks [11,30]. As such, there is paucity in the literature
as to how this translates into more complex motor behaviours.
The basal ganglia are the main site of neurodegeneration in HD and have previously been
implicated in motor preparation and planning, thereby regulating the phasic timing of
movements [16,31–36]. This considered, underlying dysfunction in the organisation of movement
may persist, over and above the observed deficit of speed and accuracy. For this reason, we
aimed to characterize the kinematic profile of more complex movement at different stages of
disease, to gain a more comprehensive understanding of how motor dysfunction may translate
into functional incapacity.
Studies probing the finer kinematic components of movement in healthy individuals have
uncovered that goal-directed aiming requires distinct, yet integrated motor components to
achieve a targeted end goal [37–40]. Historically, and based on Woodworth’s model [40],
goaldirected aiming of movements comprise of two separate actions. The first, a rapid ballistic
burst, orients the limb toward a target [37–41], followed by an ‘online’ control phase
incorporating visual and proprioceptive feedback to effectively detect and correct for errors in order
for the limb to accurately reach the target [26,37–40]. The initial component (measured as time
spent accelerating to reach peak speed) (...truncated)