The type of concurrent task affects dual-task performance in Huntington's disease

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Effects of task difficulty during dual-task circle tracing in Huntington's disease

YesHuntington’s disease (HD) is associated with impairments in dual-task performance. Despite that, only a few studies have investigated dual-tasking in HD. We examined dual-task performance in 15 participants in the early stages of HD and 15 healthy controls. Participants performed direct circle tracing (able to view arm) and indirect circle tracing (arm obscured) either on their own (single tasks) or paired with serial subtraction by twos or threes (dual tasks). Overall, our results suggested that HD participants were significantly slower and less accurate than controls. Both groups were slower and less accurate when performing indirect circle tracing compared with direct circle tracing. HD participants experienced greater dual-task interference in terms of accuracy when performing direct circle tracing compared with indirect circle tracing. Despite that, controls were more inclined to speed–accuracy trade-offs compared with HD participants. Importantly, unlike controls, HD participants were not disproportionately faster when performing direct circle tracing as a single task compared with the dual-task conditions. Our results suggest that simple tasks place greater attentional demands on HD participants compared with controls. These findings support that impaired automaticity may be responsible for some of the attentional deficits manifested in HD.Supported by the School of Psychological Sciences, Monash University

A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington's Disease

Understanding the order and progression of change in biomarkers of neurodegeneration is essential to detect the effects of pharmacological interventions on these biomarkers. In Huntington’s disease (HD), motor, cognitive and MRI biomarkers are currently used in clinical trials of drug efficacy. Here for the first time we use directly compare data from three large observational studies of HD (total N = 532) using a probabilistic event-based model (EBM) to characterise the order in which motor, cognitive and MRI biomarkers become abnormal. We also investigate the impact of the genetic cause of HD, cytosine-adenine-guanine (CAG) repeat length, on progression through these stages. We find that EBM uncovers a broadly consistent order of events across all three studies; that EBM stage reflects clinical stage; and that EBM stage is related to age and genetic burden. Our findings indicate that measures of subcortical and white matter volume become abnormal prior to clinical and cognitive biomarkers. Importantly, CAG repeat length has a large impact on the timing of onset of each stage and progression through the stages, with a longer repeat length resulting in earlier onset and faster progression. Our results can be used to help design clinical trials of treatments for Huntington’s disease, influencing the choice of biomarkers and the recruitment of participants

Robust markers and sample sizes for multi‐centre trials of Huntington's disease

Objective: The identification of sensitive biomarkers is essential to validate therapeutics for Huntington disease (HD). We directly compare structural imaging markers across the largest collective imaging HD dataset to identify a set of imaging markers robust to multicenter variation and to derive upper estimates on sample sizes for clinical trials in HD. Methods: We used 1 postprocessing pipeline to retrospectively analyze T1-weighted magnetic resonance imaging (MRI) scans from 624 participants at 3 time points, from the PREDICT-HD, TRACK-HD, and IMAGE-HD studies. We used mixed effects models to adjust regional brain volumes for covariates, calculate effect sizes, and simulate possible treatment effects in disease-affected anatomical regions. We used our model to estimate the statistical power of possible treatment effects for anatomical regions and clinical markers. Results: We identified a set of common anatomical regions that have similarly large standardized effect sizes (>0.5) between healthy control and premanifest HD (PreHD) groups. These included subcortical, white matter, and cortical regions and nonventricular cerebrospinal fluid (CSF). We also observed a consistent spatial distribution of effect size by region across the whole brain. We found that multicenter studies were necessary to capture treatment effect variance; for a 20% treatment effect, power of >80% was achieved for the caudate (n = 661), pallidum (n = 687), and nonventricular CSF (n = 939), and, crucially, these imaging markers provided greater power than standard clinical markers. Interpretation: Our findings provide the first cross-study validation of structural imaging markers in HD, supporting the use of these measurements as endpoints for both observational studies and clinical trial

Magnetic Resonance Imaging in Huntington's Disease.

Magnetic resonance imaging (MRI) is a noninvasive technique used routinely to image the body in both clinical and research settings. Through the manipulation of radio waves and static field gradients, MRI uses the principle of nuclear magnetic resonance to produce images with high spatial resolution, appropriate for the investigation of brain structure and function

A gyrification analysis approach based on Laplace Beltrami eigenfunction level sets

An accurate measure of the complexity of patterns of cortical folding or gyrification is necessary for understanding normal brain development and neurodevelopmental disorders. Conventional gyrification indices (GIs) are calculated based on surface curvature (curvature-based GI) or an outer hull surface of the cortex (outer surface-based GI). The latter is dependent on the definition of the outer hull surface and a corresponding function between surfaces. In the present study, we propose the Laplace Beltrami-based gyrification index (LB-GI). This is a new curvature-based local GI computed using the first three Laplace Beltrami eigenfunction level sets. As with outer surface-based GI methods, this method is based on the hypothesis that gyrification stems from a flat surface during development. However, instead of quantifying gyrification with reference to corresponding points on an outer hull surface, LB-GI quantifies the gyrification at each point on the cortical surface with reference to their surrounding gyral points, overcoming several shortcomings of existing methods. The LB-GI was applied to investigate the cortical maturation profile of the human brain from preschool to early adulthood using the PING database. The results revealed more detail in patterns of cortical folding than conventional curvature-based methods, especially on frontal and posterior tips of the brain, such as the frontal pole, lateral occipital, lateral cuneus, and lingual. Negative associations of cortical folding with age were observed at cortical regions, including bilateral lingual, lateral occipital, precentral gyrus, postcentral gyrus, and superior frontal gyrus. The results also indicated positive significant associations between age and the LB-GI of bilateral insula, the medial orbitofrontal, frontal pole and rostral anterior cingulate regions. It is anticipated that the LB-GI will be advantageous in providing further insights in the understanding of brain development and degeneration in large clinical neuroimaging studies

Dual task performance in Huntington's disease: a comparison of choice reaction time tasks

YesObjective: This study investigated whether dual tasks make disproportionately high demands in Huntington’s disease (HD) compared with controls, and also tested the Multiple Resources Theory. Method: Thirteen HD participants and 13 controls completed 2 dual task sets that varied in difficulty and complexity: Set 1 paired simple choice reaction time (RT) with digit forward, and Set 2 paired complex choice RT with digit backward. Results: We found that HD participants were overall slower; however, although they maintained similar levels of accuracy in the simple choice RT tasks with controls, their accuracy decreased in the complex choice RT tasks. In addition, we found that HD participants were more susceptible to speed-accuracy trade-offs. Despite that, they did not show greater dual task costs than controls. Conclusions: Overall, our findings do not support the Multiple Resources Theory, but they do provide some support for the Unitary Resource Theory and the attentional impairment hypothesis

The effects of age and attention on motor overflow production-a review

Motor overflow refers to overt involuntary movement, or covert muscle activity, that sometimes co-occurs with voluntary movement. Various clinical populations exhibit overflow. Motor overflow is also present in healthy children and the elderly, although in young adults, overt overflow is considered abnormal unless elicited under conditions of extreme force or muscle fatigue. Current theories of overflow imply that the corpus callosum may mediate production of this phenomenon. However, given that the corpus callosum is a conduit enabling the transfer of cortical information, surprisingly few studies have considered the cortical or subcortical structures underlying overflow. This review considers the developmental trend of motor overflow production, specifically in the upperlimbs, and the mechanisms thought to underlie this age-related phenomenon. Potential neurological correlates of motor overflow will be discussed in conjunction with higher order attentional processes which also regulate motor overflow production. Future research investigating the impact of attentional processes on overflow production may be particularly valuable for designing rehabilitation strategies for patients experiencing induced pathological overflow or conversely, to develop techniques to encourage the recovery of movement function in individuals with paretic limbs