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Background Previous research has demonstrated an association between emotion recognition and apathy in a number of neurological conditions involving fronto-striatal pathology, including Parkinson’s disease and brain injury. Aims In line with these findings, we aimed to determine whether apathetic participants with early Huntington’s disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. Methods We included 43 HD participants from the TRACK-HD study who had an apathy score >1 on the Problem Behaviours Assessment – short version (PBA-S), 67 HD participants who reported no apathy, and 107 controls matched for age, sex and level of education. During their baseline visit, participants completed a battery of cognitive tests that include an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS), and the PBA-s. Results Compared to the non-apathetic HD group and the control group, the apathetic HD group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology (HADS) and general disease progression (UHDRS total motor score). This was despite no difference between the apathetic and non-apathetic groups on overall cognitive functioning assessed by a cognitive composite score. Conclusions Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on fronto-striatal pathways may broadly explain associations between emotion recognition and apathy found across a number of patient groups, further work is needed to determine what relationships exist between the recognition of specific emotions, distinct subtypes of apathy, and underlying neuropathology.

HD-YAS will study a cohort of young adult HD Gene Expansion Carriers (HDGEC) decades before expected symptom onset to characterize the very earliest signs of disease-related brain changes and identify whether there is any identifiable early functional impairment. Currently there is no detailed characterization of such a young adult HDGEC cohort and this represents the earliest time point after predictive genetic testing in which to gain disease insights. HD-YAS will be important in determining the earliest potential time window for therapeutic intervention. HD-YAS will recruit 120 participants-60 premanifest HDGECs and 60 gene negative or family controls-and will use a cross-sectional comparison with one visit per participant to assess the earliest time-point at which neurodegeneration can be detected. Participants will undergo 3T Volumetric MRI, rsfMRI and task fMRI, NODDI, and cognitive assessments including the CANTAB and EMOTICOM batteries, and biosamples such as CSF, blood and DNA will be collected to investigate biomarkers. Participants will be 18–40 years old and at-risk individuals must have a predictive genetic test; either carry the HD gene (gene-carrier) or not carry the HD gene (control). Individuals must not show any clinical symptoms of HD, have a disease burden score of ≤240, and must be willing and able to comply with the study visit and study procedures. HD-YAS began in August 2017 and is expected to complete by February 2019. HD-YAS collaborates with Enroll-HD, UK clinical genetics services and HD charity groups to identify potentially eligible participants throughout the UK. HD-YAS is funded by Wellcome, with CSF collection funded by CHDI. HD-YAS investigators – Participant Identification Site Investigators; Dr Oliver Quarrell, Dr Nayana Lahiri, Dr Andrea Nemeth, Dr Mary Porteous, Dr Elisabeth Rosser, Dr David Craufurd, Dr Rhona MacLeod, Dr Deborah Ruddy, Dr Roger Barker, Dr Simon Holden, Dr Hugh Rickards, Dr Anne Rosser, Dr Emma Hobson, Prof Angus Clarke, Dr Katherine Lachlan, Dr Reza Kiani, Dr Timothy Harrower. Thank you to the HDA, HDYO, SHA.

Introduction Disrupted gating of motor control through striatal pathways is thought to drive the development of motor symptoms in Huntington’s disease (HD). The range of motor symptoms, from chorea to bradykinesia, is thought to be driven by disruption in different striatal pathways. Aside from motor control, striatal pathways are also thought to play a key role in the expression of motivated behaviour. On this basis we asked whether the association between apathy and specific motor symptoms is in keeping with the hypothesis that apathy in HD is another manifestation of dysfunctional striatal gating. Methods Clinical data on 2608 patients with manifest HD disease was retrieved from the ENROLL-HD database. A linear mixed model was built to assess the relationship between motor symptoms and apathy (measured using the PBA and square root transformed) controlling for cognitive impairment, depression, medication use, disease duration, CAG repeat size and age. In a separate analysis the bradykinesia item was replaced by voluntary finger tapping performance. Results Although both bradykinesia and chorea were significantly associated with apathy, their effects were in opposite directions. Bradykinesia was associated with greater apathy (β=0.14, p Conclusion This analysis suggests that the processes driving distinct motor symptoms in HD may also underlie hard-to-treat psychiatric symptoms such as apathy. A common substrate and likely target for this shared mechanism is the disruption of specific striatal pathways that gate actions, decisions and motivated behaviour.