The Relationship Between Plasma Oxytocin and Executive Functioning in Huntington’s Disease: A Pilot Study

2021 ◽  
pp. 1-6
Author(s):  
Emily R. Fisher ◽  
Natalia P. Rocha ◽  
Diego A. Morales-Scheihing ◽  
Venugopal Reddy Venna ◽  
Erin E. Furr-Stimming ◽  
...  
Keyword(s):  
Executive Functioning ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Potential Role ◽  
Group Differences ◽  
Significant Group ◽  
Plasma Measurement ◽  
The Relationship ◽  
Functioning Assessment

The role of oxytocin (OT) in social cognition of patients with Huntington’s disease (HD) has been studied, but its impact on executive functioning has not been explored yet. Healthy controls, premanifest HD, and manifest HD participants underwent executive functioning assessment and OT plasma measurement. There were no significant group differences in plasma OT levels. Higher OT levels were associated with better executive functioning in premanifest HD participants. Our findings revealed an association between OT levels and depressive symptoms in premanifest and manifest HD participants. The potential role of OT in HD deserves further investigation.

Presynaptic dysfunction in Huntington's disease

2010 ◽  
Vol 38 (2) ◽  
pp. 488-492 ◽  
Author(s):  
José L. Rozas ◽  
Leonardo Gómez-Sánchez ◽  
Cristina Tomás-Zapico ◽  
José J. Lucas ◽  
Rafael Fernández-Chacón
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Motor Dysfunction ◽  
Drosophila Model ◽  
Glutamine Repeat ◽  
Mutant Forms ◽  
The Relationship

HD (Huntington's disease) is produced by the expression of mutant forms of the protein htt (huntingtin) containing a pathologically expanded poly-glutamine repeat. For unknown reasons, in HD patients and HD mouse models, neurons from the striatum and cerebral cortex degenerate and lead to motor dysfunction and dementia. Synaptic transmission in those neurons becomes progressively altered during the course of the disease. However, the relationship between synaptic dysfunction and neurodegeneration in HD is not yet clear. Are there early specific functional synaptic changes preceding symptoms and neurodegeneration? What is the role of those changes in neuronal damage? Recent experiments in a Drosophila model of HD have showed that abnormally increased neurotransmitter release might be a leading cause of neurodegeneration. In the present review, we summarize recently described synaptic alterations in HD animal models and discuss potential underlying molecular mechanisms.

scholarly journals Impairments in Spatiotemporal Gait Adaptation During Obstacle Navigation in Huntington’s Disease

2017 ◽  
Vol 31 (10-11) ◽  
pp. 934-943 ◽  
Author(s):  
Naznine Anwar ◽  
Izelle Labuschagne ◽  
Katrina Simpson ◽  
Luke Smith ◽  
Nellie Georgiou-Karistianis
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Berg Balance Scale ◽  
Group Differences ◽  
Risk Of Falling ◽  
Experimental Conditions ◽  
Timed Up And Go ◽  
Significant Group ◽  
Gait Adaptation ◽  
Increased Risk

Background. Navigating obstacles whilst walking might be associated with poorer balance and a higher risk of falling in individuals with symptomatic Huntington’s disease (symp-HD). However, this issue has not been investigated within the literature. Objective. A unique obstacle navigation experiment was designed to examine adaptive gait patterns in order to identify spatiotemporal gait characteristics that might be associated with poorer balance and a higher risk of falling in symp-HD. Method. Sixteen diagnosed symp-HD participants and 16 age- and sex-matched healthy controls were included. Gait was examined in 3 experimental conditions: baseline walking, walking while navigating around 1 obstacle, and walking while navigating around 2 obstacles. Navigation around obstacle walks was divided into three step phases (approach, navigation, recovery). Group differences in gait variables were analyzed at baseline and during walking for each obstacle condition respectively. Gait variables were also correlated with the Berg Balance Scale (BBS) and Timed Up and Go (TUG) test. Results. Symp-HD participants, compared with controls, performed significantly poorer on most gait variables during baseline walking. Symp-HD participants significantly decreased their step-length while navigating around 1 obstacle, and increased their step-time while navigating around 1 and 2 obstacles. There were no significant group differences in step-width. Variables associated with navigating around obstacles correlated significantly with BBS and TUG clinical tools, which have been associated in the literature with an increased risk of falling in symp-HD. Conclusion. These findings could aid clinicians in better managing risk of falls in people with Huntington’s disease through targeted and effective strategies.

Corticostriatal signatures of schadenfreude: evidence from Huntington’s disease

2017 ◽  
Vol 89 (1) ◽  
pp. 112-116 ◽  
Author(s):  
Sandra Baez ◽  
Mariana Pino ◽  
Mildred Berrío ◽  
Hernando Santamaría-García ◽  
Lucas Sedeño ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neural Correlates ◽  
Brain Regions ◽  
Reward Processing ◽  
Social Emotion ◽  
The Relationship ◽  
Regional Brain Atrophy ◽  
Shed Light

Schadenfreude—pleasure at others’ misfortunes—is a multidetermined social emotion which involves reward processing, mentalising and perspective-taking abilities. Patients with Huntington’s disease (HD) exhibit reductions of this experience, suggesting a role of striatal degeneration in such impairment. However, no study has directly assessed the relationship between regional brain atrophy in HD and reduced schadenfreude. Here, we assessed whether grey matter (GM) atrophy in patients with HD correlates with ratings of schadenfreude. First, we compared the performance of 20 patients with HD and 23 controls on an experimental task designed to trigger schadenfreude and envy (another social emotion acting as a control condition). Second, we compared GM volume between groups. Third, we examined brain regions where atrophy might be associated with specific impairments in the patients. While both groups showed similar ratings of envy, patients with HD reported lower schadenfreude. The latter pattern was related to atrophy in regions of the reward system (ventral striatum) and the mentalising network (precuneus and superior parietal lobule). Our results shed light on the intertwining of reward and socioemotional processes in schadenfreude, while offering novel evidence about their neural correlates.

scholarly journals Timing of selective basal ganglia white matter loss in Huntington’s disease

2021 ◽  
Author(s):  
Paul Zeun ◽  
Peter McColgan ◽  
Thijs Dhollander ◽  
Sarah Gregory ◽  
Eileanoir B Johnson ◽  
...  
Keyword(s):  
White Matter ◽  
Basal Ganglia ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Point Group ◽  
Disease Onset ◽  
Group Differences ◽  
Significant Group ◽  
Gene Carriers

AbstractObjectivesTo investigate the timeframe prior to symptom onset when cortico-basal ganglia white matter (WM) loss begins in premanifest Huntington’s disease (preHD), and which striatal and thalamic sub-region WM tracts are most vulnerable.MethodsWe performed fixel-based analysis, which allows resolution of crossing WM fibres at the voxel level, on diffusion tractography derived WM tracts of striatal and thalamic sub-regions in two independent cohorts; TrackON-HD, which included 72 preHD (approx. 11 years before disease onset) and 85 controls imaged at three time points over two years; and the HD young adult study (HD-YAS), which included 54 preHD (approx. 25 years before disease onset) and 53 controls, imaged at one time point. Group differences in fibre density and cross section (FDC) were investigated.ResultsWe found no significant group differences in cortico-basal ganglia sub-region FDC in preHD gene carriers 25 years before onset. In gene carriers 11 years before onset, there were reductions in striatal (limbic and caudal motor) and thalamic (premotor, motor and sensory) FDC at baseline, with no significant change over 2 years. Caudal motor-striatal, pre-motor-thalamic, and primary motor-thalamic FDC at baseline, showed significant correlations with the Unified Huntington’s disease rating scale (UHDRS) total motor score (TMS). Limbic cortico-striatal FDC and apathy were also significantly correlated.ConclusionsOur findings suggest that the initiation of disease modifying therapies 25 years before onset could protect these important brain networks from undergoing neurodegeneration and highlight selectively vulnerable sub-regions of the striatum and thalamus that may be important targets for future therapies.

scholarly journals Systematic genetic interaction studies identify histone demethylase Utx as potential target for ameliorating Huntington’s disease

2017 ◽  
Vol 27 (4) ◽  
pp. 649-666 ◽  
Author(s):  
Wan Song ◽  
Nóra Zsindely ◽  
Anikó Faragó ◽  
J Lawrence Marsh ◽  
László Bodai
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Potential Role ◽  
Genetic Interaction ◽  
Early Event ◽  
Protein Acetylation ◽  
Transcriptional Dysregulation ◽  
Specific Effects ◽  
Interaction Studies

Abstract Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease caused by alterations in the huntingtin gene (htt). Transcriptional dysregulation is an early event in HD progression. Protein acetylation and methylation particularly on histones regulates chromatin structure thereby preventing or facilitating transcription. Although protein acetylation has been found to affect HD symptoms, little is known about the potential role of protein methylation in HD pathology. In recent years, a series of proteins have been described that are responsible for methylating and demethylating histones as well as other proteins. We carried out systematic genetic interaction studies testing lysine and arginine methylases and demethylases in a Drosophila melanogaster HD model. We found that modulating methylation enzymes that typically affect histone positions H3K4, H3K36 or H3K79 had varying effects on HD pathology while modulating ones that typically affect constitutive heterochromatin marks at H3K9 and H4K20 generally had limited impact on HD pathology. In contrast, modulating enzymes acting on the facultative heterochromatin mark at H3K27 had specific effects on HD pathology, with reduction of the demethylase Utx rescuing HTT-induced pathology while reducing Polycomb Repressive Complex2 core methylase components led to more aggressive pathology. Further exploration of the mechanism underlying the methylation-specific interactions suggest that these lysine and arginine methylases and demethylases are likely exerting their influence through non-histone targets. These results highlight a novel therapeutic approach for HD in the form of Utx inhibition.

scholarly journals Validating Automated Segmentation Tools in the Assessment of Caudate Atrophy in Huntington’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Nina M. Mansoor ◽  
Tishok Vanniyasingam ◽  
Ian Malone ◽  
Nicola Z. Hobbs ◽  
Elin Rees ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Outcome Measures ◽  
Group Differences ◽  
Automated Segmentation ◽  
Cross Sectional ◽  
Significant Group ◽  
Manual Delineation ◽  
Therapeutic Trials

Background: Neuroimaging shows considerable promise in generating sensitive and objective outcome measures for therapeutic trials across a range of neurodegenerative conditions. For volumetric measures the current gold standard is manual delineation, which is unfeasible for samples sizes required for large clinical trials.Methods: Using a cohort of early Huntington’s disease (HD) patients (n = 46) and controls (n = 35), we compared the performance of four automated segmentation tools (FIRST, FreeSurfer, STEPS, MALP-EM) with manual delineation for generating cross-sectional caudate volume, a region known to be vulnerable in HD. We then examined the effect of each of these baseline regions on the ability to detect change over 15 months using the established longitudinal Caudate Boundary Shift Integral (cBSI) method, an automated longitudinal pipeline requiring a baseline caudate region as an input.Results: All tools, except Freesurfer, generated significantly smaller caudate volumes than the manually derived regions. Jaccard indices showed poorer levels of overlap between each automated segmentation and manual delineation in the HD patients compared with controls. Nevertheless, each method was able to demonstrate significant group differences in volume (p < 0.001). STEPS performed best qualitatively as well as quantitively in the baseline analysis. Caudate atrophy measures generated by the cBSI using automated baseline regions were largely consistent with those derived from a manually segmented baseline, with STEPS providing the most robust cBSI values across both control and HD groups.Conclusions: Atrophy measures from the cBSI were relatively robust to differences in baseline segmentation technique, suggesting that fully automated pipelines could be used to generate outcome measures for clinical trials.

The Role of Melatonin in Multiple Sclerosis, Huntington's Disease and Cerebral Ischemia

2014 ◽  
Vol 13 (6) ◽  
pp. 1096-1119 ◽  
Author(s):  
Begona Escribano ◽  
Ana Colin-Gonzalez ◽  
Abel Santamaria ◽  
Isaac Tunez
Keyword(s):  
Multiple Sclerosis ◽  
Cerebral Ischemia ◽  
Huntington's Disease ◽  
Huntington’S Disease

Cardiac interoception in neurological conditions and its relevance for dimensional approaches

2018 ◽  
Author(s):  
Adrián Yoris ◽  
Adolfo M. García ◽  
Paula Celeste Salamone ◽  
Lucas Sedeño ◽  
Indira García-Cordero ◽  
...  
Keyword(s):  
Potential Role ◽  
Neurocognitive Deficits ◽  
Future Directions ◽  
Treatment And Prevention ◽  
Neurological Conditions ◽  
Key Aspects ◽  
The Relationship ◽  
General Source ◽  
Neuropsychiatric Conditions

Dimensional and transdiagnostic approaches have revealed multiple cognitive/emotional alterations shared by several neuropsychiatric conditions. While this has been shown for externally triggered neurocognitive processes, the disruption of interoception across neurological disorders remains poorly understood. This chapter aims to fill this gap while proposing cardiac interoception as a potential common biomarker across disorders. It focuses on key aspects of interoception, such as the mechanisms underlying different interoceptive dimensions; the relationship among interoception, emotion, and social cognition; and the roles of different interoceptive pathways. It considers behavioral and brain evidence in the context of an experimental and clinical agenda to evaluate the potential role of interoception as a predictor of clinical outcomes, a marker of neurocognitive deficits across diseases, and a general source of insights for breakthroughs in the treatment and prevention of multiple disorders. Finally, future directions to improve the dimensional and transdiagnostic assessment of interoception are outlined.

scholarly journals The Role of Pretraining on Skilled Forelimb Use in an Animal Model of Huntington's Disease

2003 ◽  
Vol 12 (3) ◽  
pp. 257-264 ◽  
Author(s):  
R. A. Fricker-Gates ◽  
R. Smith ◽  
J. Muhith ◽  
S. B. Dunnett
Keyword(s):  
Animal Model ◽  
Huntington's Disease ◽  
Huntington’S Disease
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