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BackgroundHuntington’s disease (HD) is associated with a range of cognitive deficits including problems with executive function. In the absence of a disease modifying treatment, cognitive training has been proposed as a means of slowing cognitive decline; however, the impact of cognitive training in HD patient populations remains unclear. The CogTrainHD study assessed the feasibility and acceptability of home-based computerised executive function training, for people impacted by HD.MethodsThirty HD gene carriers were recruited and randomised to either executive function training or non-intervention control groups. Participants allocated to the intervention group were asked to complete executive function training three times a week for 30 min for 12 weeks in their own homes. Semi-structured interviews were conducted with participants and friends, family or carers, to determine their views on the study.Results26 out of 30 participants completed the baseline assessments and were subsequently randomised: 13 to the control group and 13 to the intervention group. 23 of the 30 participants were retained until study completion: 10/13 in the intervention group and 13/13 in the control group. 4/10 participants fully adhered to the executive function training. All participants in the control group 13/13 completed the study as intended. Interview data suggested several key facilitators including participant determination, motivation, incorporation of the intervention into routine and support from friends and family members. Practical limitations, including lack of time, difficulty and frustration in completing the intervention, were identified as barriers to study completion.ConclusionsThe CogTrainHD feasibility study provides important evidence regarding the feasibility and acceptability of a home-based cognitive training intervention for people with HD. Variable adherence to the cognitive training implies that the intervention is not feasible to all participants in its current form. The study has highlighted important aspects in relation to both the study and intervention design that require consideration, and these include the design of games in the executive function training software, logistical considerations such as lack of time, the limited time participants had to complete the intervention and the number of study visits required. Further studies are necessary before computerised executive function training can be recommended routinely for people with HD.Trial registrationClinicalTrials.gov, Registry numberNCT02990676.

The #WhyWeDoResearch campaign was set up in 2014 and was originally planned to run locally, in Norfolk, at the James Paget University Hospitals NHS Foundation Trust (JPUH) for 12 days in December. Within four days, the campaign was being utilized nationally by other trusts and charities. By the New Year of 2015 it became international and had reached Australia and Canada. The intended audience for the campaign is broad and includes: patients, the general public, all staff working in health care and/or research including (but not limited to) National Health Service (NHS), commercial companies, charities and schools. The campaign has become a community where patients, staff and public alike can share their voices about health research on an equal playing field. Each year, to coincide with International Clinical Trials Day (ICTD) on 20 May, a #WhyWeDoResearch 'Tweetfest' is hosted. This includes a number of 'tweetchats' at set times throughout the Tweetfest. Tweetchats are hosted by experts in particular diseases or other areas. Patients and patient groups are included in this group of experts. This article uses the #WhyWeDoResearch campaign annual Tweetfest to demonstrate how social media can be utilized to raise awareness of health research around the world.

Background: Huntington’s disease (HD) is a rare, incurable neurodegenerative disorder caused by a CAG trinucleotide expansion with the first exon of the huntingtin gene. Numerous knock-in mouse models are currently available for modelling HD. However, before their use in scientific research, these models must be characterised to determine their face and predictive validity as models of the disease and their reliability in recapitulating HD symptoms.\ud Objective: Manifest HD is currently diagnosed upon the onset of motor symptoms, thus we sought to longitudinally characterise the progression and severity of motor signs in the HdhQ111 knock-in mouse model of HD, in heterozygous mice.\ud Methods: An extensive battery of motor tests including: rotarod, inverted lid test, balance beam, spontaneous locomotor activity and gait analysis were applied longitudinally to a cohort of HdhQ111 heterozygous mice in order to progressively assess motor function.\ud Results: A progressive failure to gain body weight was demonstrated from 11 months of age and motor problems in all measures of balance beam performance were shown in HdhQ111 heterozygous animals in comparison to wild type control animals from 9 months of age. A decreased latency to fall from the rotarod was demonstrated in HdhQ111 heterozygous animals in comparison to wild type animals, although this was not progressive with time. No genotype specific differences were demonstrated in any of the other motor tests included in the test battery.\ud Conclusions: The HdhQ111 heterozygous mouse demonstrates a subtle and progressive motor phenotype that begins at 9 months of age. This mouse model represents an early disease stage and would be ideal for testing therapeutic strategies that require elongated lead-in times, such as viral gene therapies or striatal transplantation.

Background Aberrant myelination may contribute or even precede neurodegeneration. White matter (WM) abnormalities have been widely reported in Huntington’s disease (HD), and are detectable in the pre-manifest stage, prior to symptom onset, using diffusion-weighted (DW) MRI. However, standard DW MRI metrics (e.g. fractional anisotropy (FA)) are non-specific indices of underlying biological changes. Quantitative magnetization transfer (qMT) imaging is a more sensitive measure of myelin content in white matter, as indexed by the macromolecular proton fraction (MPF). MPF is lower in early-stage HD and is related to WM abnormalities measured with DW MRI (Bourbon-Teles et al, 2017). Aims To assess whether myelin breakdown can be detected in pre-manifest HD gene carriers using qMT and DW MRI. Methods/techniques MRI was performed on a Siemens PRISMA 3T MRI Scanner at Cardiff University Brain Research Imaging Centre (CUBRIC). Eight pre-HD participants (Disease burden score; 229–299), and eight matched controls were recruited and scanned. A 3D MT-weighted fast spoiled gradient recalled-echo (SPGR) sequence was used to obtain qMT data for estimation of myelin. DW MRI was acquired and manual tractography of the cortico-spinal tract (CST), corpus callosum (CC), anterior thalamic radiation (ATR) and SMA-putamen was performed in Explore-DTI v 4.8.3. Results/outcome We will present a group-wise comparison between MPF and FA, radial and axial diffusivity (RD and AD) across all WM tracts, in line with the methods of (Bourbon-Teles et al, 2017). Planned analysis to assess group differences in diffusion metrics will be used to infer microstructural differences in WM properties including myelin content, white matter integrity and axonal damage in pre-manifest participants. Conclusions This is the first study to apply qMT MRI to measure myelin content in a pre-manifest cohort. Reduced myelination in this cohort could help inform the development of new drug treatments that aim to tackle HD in the earliest stages. Further analysis will combine this with volumetric data, to probe the early relationship between myelination and grey matter atrophy.

Huntington's disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD.

Huntington’s disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD.

Cognitive impairments, especially deficits of executive function, have been well documented as a core and early feature in Huntington’s disease (HD). Cognitive impairments represent considerable burden and can be devastating for people and families affected by HD. Computerised cognitive training interventions that focus on improving executive function present a possible non-pharmacological treatment option. We propose to determine the feasibility, acceptability, and appropriate outcome measures for use in a randomised controlled feasibility study. Participants will be randomised into either a computerised cognitive training group or a control group. Those randomised to the training group will be asked to complete a cognitive training intervention based on the HappyNeuron Pro software tasks of executive function, for a minimum of 30 min, three times a week for the 12-week study duration. Participants in the control group will not receive computerised cognitive training but will receive a similar degree of social interaction via equivalent study and home visits. We will explore quantitative outcome measures, including measures of cognitive performance, motor function, questionnaires and semi-structured interviews, as well as magnetic resonance imaging (MRI) measures in a subset of participants. Feasibility will be determined through assessment of recruitment, retention, adherence and acceptability of the intervention. The results of this study will provide crucial guidance and information regarding the feasibility of conducting a randomised controlled study into computerised cognitive training in HD. This study is crucial for the development of larger definitive randomised controlled trials which are powered to determine efficacy and for the development of future cognitive training programmes for people affected by HD. The study is registered on clinicaltrials.gov and has the unique identifier NCT02990676 .

Highlights • We compared delayed matching and non-matching to position (DMTP and DNMTP) tasks in two different operant apparatus, the 9-hole operant apparatus configuration and the Skinner-like operant apparatus configuration. • We determined that the DMTP and DNMTP operant tasks produce more efficient, robust and reliable results in the Skinner-like operant apparatus configuration. • We therefore used the Skinner-like operant apparatus configuration to test DMTP and DNMTP tasks in the HdhQ111 mouse model of HD. • We tested the DMTP and DNMTP tasks in the HdhQ111 knock-in mouse model of HD which revealed significant deficits in task acquisition and reversal learning in comparison to wildtype animals., Background Operant behavioural testing provides a highly sensitive and automated method of exploring the behavioural deficits seen in rodent models of neurodegenerative diseases, including Huntington's disease (HD). The delayed matching to position (DMTP) and delayed non-matching to position (DNMTP) tasks probe spatial learning and working memory and when applied serially they can be used to measure reversal learning, which has been shown to be an early symptom of executive dysfunction in HD. New method The DMTP and DNMTP tasks were conducted in two configurations of operant apparatus; the conventional 9-hole operant apparatus, and a Skinner-like operant apparatus, to compare, contrast and optimise the DMTP and DNMTP operant protocols for use in mice. The optimised tasks were then tested in the HdhQ111 mouse model of HD. Results Optimisation of the operant apparatus demonstrated that the mice learned the DMTP and DNMTP tasks more rapidly and effectively in the Skinner-like apparatus configuration in comparison to the conventional 9-hole apparatus configuration. When tested in the HdhQ111 mouse model of HD, the DMTP and DNMTP tasks revealed significant deficits in reversal learning. Comparison with existing method We found that mice were capable of performing the DMTP and DNMTP tasks in both apparatus configurations, but in comparison to the 9-hole configuration, the Skinner-like configuration produced more efficient, robust and reliable results. Conclusions The results presented here suggest that DMTP and DNMTP tasks, incorporating a reversal learning manipulation, are valid and robust methods for probing selected cognitive deficits in mouse models of neurodegenerative diseases.

The Science Communication Competition is now in its fifth year. As in previous years, it aims to find young talented science writers and give them the opportunity to have their work published in The Biochemist. In 2015, a new branch of the competition was launched to include video entries. Overall this year's competition attracted 47 entries and these were reviewed by our external panel of expert judges. The first prize in the written category was awarded to Emma Yhnell from Cardiff University, whose article is presented here; the winner of the video category was Chris Morgan from the University of Birmingham. Chris Morgan's winning video can be viewed on the Society's website: http://bit.ly/1kxt8eH

Background: Huntington’s disease (HD) can cause cognitive disturbances, including problems with attention, which can significantly affect the ability to manage independently and quality of life. Cognitive training interventions therefore offer a potential therapeutic intervention. Aim: To determine if cognitive training, that is focused on attention, can alter HD signs in a mouse model of HD. Methods: HdhQ111 heterozygous mice were given cognitive training in the 5-choice serial reaction time task (5-CSRTT) of attention, for 20 days at 4 months of age. Two age matched control groups were also used. One control group received training in a similar task with no attentional component for a comparable number of days, and the other group were cage controls. All animals were then tested in the 5-CSRTT at 12 months of age. Results: All cognitive training regimes had a positive effect on task performance in comparison to cage controls. Attentional cognitive training, improved attentional performance in all animals and specifically improved motor performance in HD animals. In the control group who received comparable training in a non-attentional task, a positive effect of training was seen, although, this type of training did not confer any specific advantage to HD animals in comparison to wildtype animals. Conclusion: The results demonstrate that attentional cognitive training implemented at a young age improves attentional performance at an older age in both wildtype and HD mice. Attentional cognitive training also specifically improved motor performance in HD mice. This leads to the exciting possibility that specific cognitive training may improve HD related disease symptoms later in life.

Background Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of a CAG polyglutamine repeat within the first exon of the huntingtingene. A range of mouse models are currently available for modelling HD, however these models must be characterised to determine their reliability in recapitulating HD symptoms. Knock-in mouse models have been previously shown to demonstrate subtle early cognitive phenotypes, followed by the appearance of motor disturbances which accurately reflect the symptom development of the human disease. Aims We sought to characterise the development of both motor and cognitive symptoms in HdhQ111 heterozygous mice to determine whether they recapitulate the core symptoms of the human disease. Methods The motor phenotype was investigated very three months using a battery of motor tests including; rotarod, balance beam, grip strength, locomotor activity and gait analysis. The cognitive phenotype was explored every six months utilising 9-hole operant boxes and an operant battery of tasks which included; fixed ratio, progressive ratio and the 5-choice serial reaction time task (5CSRTT). Results No significant differences were demonstrated in the fixed or progressive ratio tasks. However, HdhQ111 heterozygous animals were significantly impaired in the 5CSRTT at 6 and 12 months of age. Significant motor problems were observed in HdhQ111 heterozygous animals on the accelerating rotarod from 12 months of age. Balance beam results indicated motor deficits beginning at 9 months of age and additional problems with co-ordination from 12 months of age. No significant differences were observed in grip strength, general locomotor activity or gait analysis. Conclusions Deficits in the 5CSRTT, followed by motor problems which occur later in the disease accurately reflect the human condition and make the HdhQ111 mouse model an ideal model for testing novel therapeutics.