Huntington's Disease Participants Research Articles

Closing-in Phenomenon in Huntington's Disease: A Neuropsychological Marker of Frontal/Executive Dysfunction.

In visuo-constructional tasks, patients may reproduce drawings near-to or superimposed on a model, showing the so-called "Closing-in" (CI), often ascribed to a defect in inhibitory control. CI has been described in neurological conditions, but no studies have explored CI in Huntington's disease (HD), a neurodegenerative disorder often involving the frontal cortical-subcortical circuits. We searched for the occurrence of CI in HD patients and systematically investigated its correlates to find a clinical marker of the frontal/executive dysfunctions in the early examination of HD patients. We assessed 130 HD participants, who performed a graphic coping task and a neuropsychological, psychiatric, motor, and functional assessment. CI occurred in 52/130 (40%) HD patients, with 43/52 (82.7%) superimposing their copy directly on the model. MANOVA showed that HD patients with CI scored significantly poorer on Symbol digit modality test, Stroop-color word - reading test, Stroop-color word - interference test, Trail making test - part B, and Phonological verbal fluency test. However, a logistic regression analysis revealed that the significant predictor of the occurrence of CI was the score on Stroop-color word - interference test. HD patients may show CI in graphic tasks, and it could be related to a defect in inhibitory control impeding the switch of attention from the model to the copying space, and releasing a default tendency which causes an attraction of hand movement towards the focus of visual attention. CI might be a useful clinical marker for the early detection of frontal/executive defects in HD patients.

Visual scanning of the eye region of human faces predicts emotion recognition performance in Huntington's disease.

Previous research has consistently shown that the ability to recognize emotions from facial expressions is impaired in Huntington's disease (HD). The aim of this study was to examine whether people with the gene expansion for HD visually scan the most emotionally informative features of human faces less than unaffected individuals, and whether altered visual scanning predicts emotion recognition in HD beyond general disease-related decline. We recorded eye movements of 25 participants either in the late premanifest or early stage of HD and 25 age-matched healthy control participants during a face-viewing task. The task involved the viewing of pictures depicting human faces with angry, disgusted, fearful, happy, and neutral expressions, and evaluating each face on a valence rating scale. For data analysis, we defined 2 regions of interest (ROIs) on each picture, including an eye-ROI and a nose/mouth-ROI. Emotion recognition abilities were measured using an established emotion-recognition task and general disease-related decline was measured using the UHDRS motor score. Compared to the control participants, the HD participants spent less time looking at the ROIs relative to the total time spent looking at the pictures (partial η2 = 0.10), and made fewer fixations on the ROIs (partial η2 = 0.16). Furthermore, visual scanning of the eye-ROI, but not the nose/mouth-ROI, predicted emotion recognition performance in the HD group, over and beyond general disease-related decline. The emotion recognition deficit in HD may partly be explained by general disease-related decline in cognition and motor functioning and partly by a social-emotional deficit, which is reflected in reduced eye-viewing. (PsycINFO Database Record

Motor cortex synchronization influences the rhythm of motor performance in premanifest huntington's disease.

In Huntington's disease there is evidence of structural damage in the motor system, but it is still unclear how to link this to the behavioral disorder of movement. One feature of choreic movement is variable timing and coordination between sequences of actions. We postulate this results from desynchronization of neural activity in cortical motor areas. The objective of this study was to explore the ability to synchronize activity in a motor network using transcranial magnetic stimulation and to relate this to timing of motor performance. We examined synchronization in oscillatory activity of cortical motor areas in response to an external input produced by a pulse of transcranial magnetic stimulation. We combined this with EEG to compare the response of 16 presymptomatic Huntington's disease participants with 16 age-matched healthy volunteers to test whether the strength of synchronization relates to the variability of motor performance at the following 2 tasks: a grip force task and a speeded-tapping task. Phase synchronization in response to M1 stimulation was lower in Huntington's disease than healthy volunteers (P < .01), resulting in a reduced cortical activity at global (P < .02) and local levels (P < .01). Participants who showed better timed motor performance also showed stronger oscillatory synchronization (r = -0.356; P < .05) and higher cortical activity (r = -0.393; P < .05). Our data may model the ability of the motor command to respond to more subtle, physiological inputs from other brain areas. This novel insight indicates that impairments of the timing accuracy of synchronization and desynchronization could be a physiological basis for some key clinical features of Huntington's disease. © 2018 International Parkinson and Movement Disorder Society.

Reduced amygdala volumes are related to motor and cognitive signs in Huntington's disease: The IMAGE-HD study.

In Huntington's disease (HD), the presence of neurodegeneration in brain regions other than the striatum has been recently gaining attention. The amygdala is one such area, which has been investigated in only eight structural magnetic resonance imaging studies to date, but with inconsistent findings. This is the largest MRI study to date examining manually traced amygdala volumes in HD participants and the relationship of amygdala volumes to clinical measures of HD. Our study included 35 healthy control participants, and groups of 35 pre-symptomatic, and 36 symptomatic HD participants. When comparing the pre-symptomatic and symptomatic HD groups together against the control group, amygdala volumes were significantly lower in HD than controls and in symptomatic HD than pre-symptomatic HD. When examining relationships between amygdala volumes and clinical measures of HD, significantly smaller amygdala volumes were associated with worse motor and cognitive signs. For pre-symptomatic HD participants who were close to disease onset, smaller amygdala volumes were also associated with higher levels of anxiety symptoms. These findings suggest that the amygdala is affected in pre-symptomatic and symptomatic HD, and that the amygdala is related to the clinical profile of HD before onset of motor symptoms.

Evaluating cognition in individuals with Huntington disease: Neuro-QoL cognitive functioning measures.

Cognitive functioning impacts health-related quality of life (HRQOL) for individuals with Huntington disease (HD). The Neuro-QoL includes two patient-reported outcome (PRO) measures of cognition-Executive Function (EF) and General Concerns (GC). These measures have not previously been validated for use in HD. The purpose of this analysis is to evaluate the reliability and validity of the Neuro-QoL Cognitive Function measures for use in HD. Five hundred ten individuals with prodromal or manifest HD completed the Neuro-QoL Cognition measures, two other PRO measures of HRQOL (WHODAS 2.0 and EQ5D), and a depression measure (PROMIS Depression). Measures of functioning The Total Functional Capacity and behavior (Problem Behaviors Assessment) were completed by clinician interview. Objective measures of cognition were obtained using clinician-administered Symbol Digit Modalities Test and the Stroop Test (Word, Color, and Interference). Self-rated, clinician-rated, and objective composite scores were developed. We examined the Neuro-QoL measures for reliability, convergent validity, discriminant validity, and known-groups validity. Excellent reliabilities (Cronbach's alphas ≥ 0.94) were found. Convergent validity was supported, with strong relationships between self-reported measures of cognition. Discriminant validity was supported by less robust correlations between self-reported cognition and other constructs. Prodromal participants reported fewer cognitive problems than manifest groups, and early-stage HD participants reported fewer problems than late-stage HD participants. The Neuro-QoL Cognition measures provide reliable and valid assessments of self-reported cognitive functioning for individuals with HD. Findings support the utility of these measures for assessing self-reported cognition.

Absence of Acanthocytosis in Huntington’s Disease-like 2: A Prospective Comparison with Huntington’s Disease

<strong>Background:</strong> Huntington’s Disease-like 2 (HDL2) is classified as a neuroacanthocytosis; however, this remains unverified. We aim to determine if acanthocytes are present in HDL2 and whether acanthocytes can differentiate HDL2 from Huntington’s disease (HD). <strong>Methods:</strong> We prospectively compared 13 HD and 12 HDL2 cases against 21 unaffected controls in Johannesburg. Blood smears were prepared using international standards and reviewed by at least two blinded reviewers. An acanthocytosis rate of greater than 1.2% in the dry smear or greater than 3.7% in the wet smear was designated a priori as the threshold for clinical significance based on previously established standards. Flow cytometry was performed on all but four of the cases. Red cell membrane protein analysis was performed on all participants. <strong>Results:</strong> There were 12 HDL2, 13 HD, and 21 controls enrolled. None of the HD or HDL2 participants had defined acanthocytosis or other morphological abnormalities. None of the HD or HDL2 cases had evidence of an abnormal band 3. <strong>Discussion:</strong> Acanthocytosis was not identified in either HDL2 or HD in our patient population. Our results, based on the first prospective study of acanthocytes in HDL2 or HD, suggest that screening for acanthocytes will not help establish the diagnosis of HD or HDL2, nor differentiate between the two disorders and raises the question if HDL2 should be placed within the neuroacanthocytosis syndromes.

Recommendations for the Use of Automated Gray Matter Segmentation Tools: Evidence from Huntington's Disease.

The selection of an appropriate segmentation tool is a challenge facing any researcher aiming to measure gray matter (GM) volume. Many tools have been compared, yet there is currently no method that can be recommended above all others; in particular, there is a lack of validation in disease cohorts. This work utilizes a clinical dataset to conduct an extensive comparison of segmentation tools. Our results confirm that all tools have advantages and disadvantages, and we present a series of considerations that may be of use when selecting a GM segmentation method, rather than a ranking of these tools. Seven segmentation tools were compared using 3 T MRI data from 20 controls, 40 premanifest Huntington’s disease (HD), and 40 early HD participants. Segmented volumes underwent detailed visual quality control. Reliability and repeatability of total, cortical, and lobular GM were investigated in repeated baseline scans. The relationship between each tool was also examined. Longitudinal within-group change over 3 years was assessed via generalized least squares regression to determine sensitivity of each tool to disease effects. Visual quality control and raw volumes highlighted large variability between tools, especially in occipital and temporal regions. Most tools showed reliable performance and the volumes were generally correlated. Results for longitudinal within-group change varied between tools, especially within lobular regions. These differences highlight the need for careful selection of segmentation methods in clinical neuroimaging studies. This guide acts as a primer aimed at the novice or non-technical imaging scientist providing recommendations for the selection of cohort-appropriate GM segmentation software.

Families Affected by Huntington's Disease Report Difficulties in Communication, Emotional Involvement, and Problem Solving.

Background:Family functioning in Huntington’s disease (HD) is known from previous studies to be adversely affected. However, which aspects of family functioning are disrupted is unknown, limiting the empirical basis around which to create supportive interventions.Objective:The aim of the current study was to assess family functioning in HD families.Methods:We assessed family functioning in 61 participants (38 HD gene-expanded participants and 23 family members) using the McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), which provides scores for seven domains of functioning: Problem Solving; Communication; Affective Involvement; Affective Responsiveness; Behavior Control; Roles; and General Family Functioning.Results:The most commonly reported disrupted domain for HD participants was Affective Involvement, which was reported by 39.5% of HD participants, followed closely by General Family Functioning (36.8%). For family members, the most commonly reported dysfunctional domains were Affective Involvement and Communication (both 52.2%). Furthermore, symptomatic HD participants reported more disruption to Problem Solving than pre-symptomatic HD participants. In terms of agreement between pre-symptomatic and symptomatic HD participants and their family members, all domains showed moderate to very good agreement. However, on average, family members rated Communication as more disrupted than their HD affected family member.Conclusion:These findings highlight the need to target areas of emotional engagement, communication skills and problem solving in family interventions in HD.

Reliability and Validity of the HD-PRO-TriadTM, a Health-Related Quality of Life Measure Designed to Assess the Symptom Triad of Huntington's Disease.

Huntington's disease (HD), is a neurodegenerative disorder that is associated with cognitive, behavioral, and motor impairments that diminish health related quality of life (HRQOL). The HD-PRO-TRIADTM is a quality of life measure that assesses health concerns specific to individuals with HD. Preliminary psychometric characterization was limited to a convenience sample of HD participants who completed measures at home so clinician-ratings were unavailable. The current study evaluates the reliability and validity of the HD-PRO-TRIADTM in a well-characterized sample of individuals with HD. Four-hundred and eighty-two individuals with HD (n = 192 prodromal, n = 193 early, and n = 97 late) completed the HD-PRO-TRIADTM questionnaire. Clinician-rated assessments from the Unified Huntington Disease Rating Scales, the short Problem Behaviors Assessment, and three generic measures of HRQOL (WHODAS 2.0, RAND-12, and EQ-5D) were also examined. Internal reliability for all domains and the total HD-PRO-TRIADTM was excellent (all Cronbach's α >0.93). Convergent and discriminant validity were supported by significant associations between the HD-PRO-TRIADTM domains, and other patient reported outcome measures as well as clinician-rated measures. Known groups validity was supported as the HD-PRO-TRIADTM differentiated between stages of the disease. Floor and ceiling effects were generally within acceptable limits. There were small effect sizes for 12-month change over time and moderate effect sizes for 24-month change over time. Findings support excellent internal reliability, convergent and discriminant validity, known groups validity, and responsiveness to change over time. The current study supports the clinical efficacy of the HD-PRO-TRIADTM. Future research is needed to assess the test-retest reliability of this measure.

Pilot Validation of Ambulatory Activity Monitors for Sleep Measurement in Huntington's Disease Gene Carriers.

Sleep disturbance occurs early in Huntington's disease (HD). Consumer- and research-grade activity monitors may enable routine assessment of sleep disturbances in HD. We compared Actiwatch Spectrum Pro, Jawbone UP2 and Fitbit One to the gold standard, polysomnography, in four late presymptomatic and three early HD participants. Compared to polysomnography, all ambulatory monitors overestimated total sleep time by >60 minutes and sleep efficiency by ∼15%. Thus, for assessment of specific sleep parameters in HD, none of the activity monitors are sufficiently accurate to replace polysomnography, although they may be sufficient for estimating overall sleep-wake patterns. Larger sample replication is required.

Abnormal Visual Scanning of Emotionally Evocative Natural Scenes in Huntington's Disease.

Huntington’s disease (HD) is a neurodegenerative movement disorder associated with deficits in the processing of emotional stimuli, including alterations in the self-reported subjective experience of emotion when presented with pictures of emotional scenes. The aim of this study was to determine whether individuals with HD, compared to unaffected controls, display abnormal visual scanning of emotionally evocative natural scenes. Using eye-tracking, we recorded eye-movements of 25 HD participants (advanced pre-symptomatic and early symptomatic) and 25 age-matched unaffected control participants during a picture viewing task. Participants viewed pictures of natural scenes associated with different emotions: anger, fear, disgust, happiness, or neutral, and evaluated those pictures on a valence rating scale. Individuals with HD displayed abnormal visual scanning patterns, but did not differ from controls with respect to their valence ratings. Specifically, compared to controls, HD participants spent less time fixating on the pictures and made longer scan paths. This finding highlights the importance of taking visual scanning behavior into account when investigating emotion processing in HD. The visual scanning patterns displayed by HD participants could reflect a heightened, but possibly unfocussed, search for information, and might be linked to attentional deficits or to altered subjective emotional experiences in HD. Another possibility is that HD participants may have found it more difficult than controls to evaluate the emotional valence of the scenes, and the heightened search for information was employed as a compensatory strategy.

Chapter 6 - Cognitive and behavioral changes in Huntington disease before diagnosis

Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The earliest detected cognitive changes are observed in the Symbol Digit Modalities Test, Stroop Interference, Stroop Color and Word Test-interference condition, and Trail Making Test. Cognitive changes in the middle and near motor diagnostic stages of prodromal HD involve nearly every cognitive test administered and the greatest changes over time (i.e., slopes) are found in those prodromal HD participants who are nearest to motor diagnosis. Psychiatric changes demonstrate significant worsening over time and remain elevated compared with healthy controls throughout the prodromal disease course. Psychiatric and behavior changes in prodromal HD are much lower than that obtained using cognitive assessment, although the psychiatric and behavioral changes represent symptoms most debilitating to independent capacity and wellness.

Identification of extreme motor phenotypes in Huntington's disease.

The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using quantile regression for longitudinal data. More than 15% of HD participants had an extreme TMS phenotype for at least one visit. In contrast, only about 4% of participants were consistent TMS extremes at two or more visits. Data from healthy controls revealed an upper cut-off of 13 for the TMS representing the extreme of motor ratings for a normal aging population. In HD, boundaries of motor age-at-onset based on diagnostic confidence or derived from the TMS data cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an individual carrying the HD mutation indicates a high likelihood of motor manifestations of HD irrespective of CAG repeat length or age. The identification of motor phenotype extremes can be useful in the search for disease modifiers, for example, genetic or environmental such as medication. © 2016 Wiley Periodicals, Inc.

Comparison of Huntington's Disease in Europe and North America.

In a rare disorder such as Huntington's disease (HD), a global network of clinical trial sites with access to patients speeds up recruitment into clinical trials. The objective was to test the hypothesis that demographics, HTT genotype, clinical spectrum, and progression are similar in HD participants of two large observational HD studies, the European Huntington's Disease Network's European REGISTRY study and the North American COHORT study. REGISTRY cross-sectional data were available from a total of 7,384 participants (1,125 [15.2%] premanifest and 6,259 [84.8%] manifest HD). COHORT cross-sectional data from 1,499 participants at 44 study sites were available (175 pre-HD [11.7%], 1,324 manifest HD [88.3%]). Participants were assessed clinically using the Unified Huntington's Disease Rating Scale (UHDRS). Longitudinal data were available for total motor score and cognitive performance in more than 50% of REGISTRY participants and more than 70% of COHORT participants. Demographics, HTT genotypes, phenotype, and progression were similar in the two studies. Patients in Europe were prescribed antidyskinetics more frequently, and antidepressants less frequently, than in North America. In either study, participants on antidyskinetic medication had higher UHDRS total motor scores, worse function assessment scores, and worse cognitive scores than those taking antidepressants or no medication. In contrast, motor, function assessment, and cognitive scores were broadly similar in participants taking antidepressants or no medication. The differences in cognitive performances between languages were small. Our data suggest that HD patients, and the way they are assessed, are similar across two continents with different cultures and languages.

The neuropsychology of first impressions: Evidence from Huntington's disease

Impairments of emotion recognition have been widely documented in Huntington's disease (HD), but little is known concerning how these relate to other aspects of social cognition, including first impressions of traits such as trustworthiness and dominance. Here, we introduce a novel and sensitive method to investigate the ability to evaluate trustworthiness and dominance from facial appearance, with control tasks measuring ability to perceive differences between comparable stimuli. We used this new method together with standard tests of face perception to investigate social cognition in HD. We found that a subgroup of people with HD was impaired at perceiving trustworthiness and dominance, and that perceiving trustworthiness and dominance were correlated with impaired facial expression recognition. In addition, we used diffusion tensor imaging (DTI) to provisionally identify candidate brain regions associated with social cognition by contrasting regional functional anisotropy (FA) measures between subgroups of HD participants showing normal or impaired perception of trustworthiness and dominance, and by correlating these regional brain abnormalities with behavioural performance on tests of emotion recognition. In this way we show for the first time alterations in perception of trustworthiness and dominance in people with HD and link these to regions which may map the boundaries of the social brain. The pattern of breakdown seen in this neurodegenerative disease can thus be used to explore potential inter-relationships between different components of social cognition.

Hypernasality associated with basal ganglia dysfunction: evidence from Parkinson's disease and Huntington's disease.

BackgroundAlthough increased nasality can originate from basal ganglia dysfunction, data regarding hypernasality in Parkinson’s disease (PD) and Huntington’s disease (HD) are very sparse. The aim of the current study was to analyze acoustic and perceptual correlates of velopharyngeal seal closure in 37 PD and 37 HD participants in comparison to 37 healthy control speakers.MethodsAcoustical analysis was based on sustained phonation of the vowel /i/ and perceptual analysis was based on monologue. Perceptual analysis was performed by 10 raters using The Great Ormond Street Speech Assessment ’98. Acoustic parameters related to changes in a 1/3-octave band centered on 1 kHz were proposed to reflect nasality level and behavior through utterance.ResultsPerceptual analysis showed the occurrence of mild to moderate hypernasality in 65% of PD, 89% of HD and 22% of control speakers. Based on acoustic analyses, 27% of PD, 54% of HD and 19% of control speakers showed an increased occurrence of hypernasality. In addition, 78% of HD patients demonstrated a high occurrence of intermittent hypernasality. Further results indicated relationships between the acoustic parameter representing fluctuation of nasality and perceptual assessment (r = 0.51, p < 0.001) as well as the Unified Huntington Disease Rating Scale chorea composite subscore (r = 0.42, p = 0.01).ConclusionsIn conclusion the acoustic assessment showed that abnormal nasality was not a common feature of PD, whereas patients with HD manifested intermittent hypernasality associated with chorea.

Cross-sectional and longitudinal multimodal structural imaging in prodromal Huntington's disease.

Diffusivity in white-matter tracts is abnormal throughout the brain in cross-sectional studies of prodromal Huntington's disease. To date, longitudinal changes have not been observed. The present study investigated cross-sectional and longitudinal changes in white-matter diffusivity in relationship to the phase of prodromal Huntington's progression, and compared them with changes in brain volumes and clinical variables that track disease progression. Diffusion MRI profiles were studied for 2 years in 37 gene-negative controls and 64 prodromal Huntington's disease participants in varied phases of disease progression. To estimate the relative importance of diffusivity metrics in the prodromal phase, group effects were rank ordered relative to those obtained from analyses of brain volumes, motor, cognitive, and sensory variables. First, at baseline diffusivity was abnormal throughout all tracts, especially as individuals approached a manifest Huntington's disease diagnosis. Baseline diffusivity metrics in 6 tracts and basal ganglia volumes best distinguished among the groups. Second, group differences in longitudinal change in diffusivity were localized to the superior fronto-occipital fasciculus, most prominently in individuals closer to a diagnosis. Group differences were also observed in longitudinal changes of most brain volumes, but not clinical variables. Last, increases in motor symptoms across time were associated with greater changes in the superior fronto-occipital fasciculus diffusivity and corpus callosum, cerebrospinal fluid, and lateral ventricle volumes. These novel findings provide new insights into changes within 2 years in different facets of brain structure and their clinical relevance to changes in symptomatology that is decisive for a manifest Huntington's diagnosis. © 2016 International Parkinson and Movement Disorder Society.

Emotion Evaluation and Social Inference Impairments in Huntington's Disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by motor, cognitive and neuropsychiatric symptoms. Recent research has established that individuals with HD display reduced discrimination of emotional facial expressions and impaired higher-order social cognitive skills, including 'theory of mind'. This study aimed to further characterise the emotion evaluation and theory of mind deficits in HD in an ecologically-valid context, and determine their impact on socially-relevant functional abilities. A sample of 17 HD participants and 24 healthy controls were assessed using The Awareness of Social Inference Test (TASIT), together with additional self- and informant rated measures of cognition, social communication, empathy and neuropsychiatric symptoms. Participants with HD showed significant difficulties in evaluating negative emotions, and understanding sincere, sarcastic and 'paradoxical sarcastic' statements, compared with controls. The ability to evaluate positive emotions was negatively correlated with behavioural problems, but no other clinical, behavioural or communication measures correlated significantly with TASIT subscales. These findings suggest that social cognitive difficulties in symptomatic HD may be underpinned by more generalised impairments, related to deciphering social exchanges, as opposed to a selective theory of mind deficit. Such difficulties have the potential to place significant strain on interpersonal relationships, and thus warrant thorough clinical assessment, using ecologically-valid tools, to promote early detection and development of person-centred interventions.

The Allure of High-Risk Rewards in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder that produces a bias toward risky, reward-driven decisions in situations where the outcomes of decisions are uncertain and must be discovered. However, it is unclear whether HD patients show similar biases in decision-making when learning demands are minimized and prospective risks and outcomes are known explicitly. We investigated how risk decision-making strategies and adjustments are altered in HD patients when reward contingencies are explicit. HD (N=18) and healthy control (HC; N=17) participants completed a risk-taking task in which they made a series of independent choices between a low-risk/low reward and high-risk/high reward risk options. Computational modeling showed that compared to HC, who showed a clear preference for low-risk compared to high-risk decisions, the HD group valued high-risks more than low-risk decisions, especially when high-risks were rewarded. The strategy analysis indicated that when high-risk options were rewarded, HC adopted a conservative risk strategy on the next trial by preferring the low-risk option (i.e., they counted their blessings and then played the surer bet). In contrast, following a rewarded high-risk choice, HD patients showed a clear preference for repeating the high-risk choice. These results indicate a pattern of high-risk/high-reward decision bias in HD that persists when outcomes and risks are certain. The allure of high-risk/high-reward decisions in situations of risk certainty and uncertainty expands our insight into the dynamic decision-making deficits that create considerable clinical burden in HD.

Classification of Huntington's disease stage with support vector machines: A study on oculomotor performance.

Alterations in oculomotor performance are among the first observable physical alterations during presymptomatic stages of Huntington's disease (HD). Quantifiable measurements of oculomotor performance have been studied as possible markers of disease status and progression in presymptomaticand early symptomatic stages of HD, on the basis of traditional analysis methods. Whether oculomotor performance can be used to classify individuals according to HD disease stage has yet to be explored via the application of machine-learning methods. In the present study, we report the application of the support vector machine (SVM) algorithm to oculomotor features pooled from a four-task psychophysical experiment. We were able to automatically distinguish control participants from presymptomatic HD (pre-HD) participants with an accuracy of 73.47%, a sensitivity of 74.31%, and a specificity of 72.64%; to distinguish control participants from HD patients with an accuracy of 81.84%, a sensitivity of 76.19%, and a specificity of 87.48%; and to distinguish pre-HD participants from HD patients with an accuracy of 83.54%, a sensitivity of 92.62%, and a specificity of 74.45%. These results demonstrate that the application of supervised classification methods to oculomotor features is a valuable and promising approach to the automatic detection of disease stage in HD.