Background. Parkinson’s disease (PD) causes difficulties with hand movements, which few studies have addressed therapeutically. Training with action observation (AO) and motor imagery (MI) improves performance in healthy individuals, particularly when the techniques are applied simultaneously (AO + MI). Both AO and MI have shown promising effects in people with PD, but previous studies have only used these separately. Objective. This article describes the development and pilot testing of an intervention combining AO + MI and physical practice to improve functional manual actions in people with PD. Methods. The home-based intervention, delivered using a tablet computer app, was iteratively designed by an interdisciplinary team, including people with PD, and further developed through focus groups and initial field testing. Preliminary data on feasibility were obtained via a six-week pilot randomised controlled trial (ISRCTN 11184024) of 10 participants with mild to moderate PD (6 intervention; 4 treatment as usual). Usage and adherence data were recorded during training, and semistructured interviews were conducted with participants. Exploratory outcome measures included dexterity and timed action performance. Results. Usage and qualitative data provided preliminary evidence of acceptability and usability. Exploratory outcomes also suggested that subjective and objective performance of manual actions should be tested in a larger trial. The importance of personalisation, choice, and motivation was highlighted, as well as the need to facilitate engagement in motor imagery. Conclusions. The results indicate that a larger RCT is warranted, and the findings also have broader relevance for the feasibility and development of AO + MI interventions for PD and other conditions.

Background. Action observation and motor imagery activate neural structures involved in action execution, thereby facilitating movement and learning. Although some benefits of action observation and motor imagery have been reported in Parkinson's disease (PD), methods have been based on stroke rehabilitation and may be less suitable for PD. Moreover, previous studies have focused on either observation or imagery, yet combining these enhances effects in healthy participants. The present study explores the feasibility of a PD-specific home-based intervention combining observation, imagery, and imitation of meaningful everyday actions. Methods. A focus group was conducted with six people with mild to moderate PD and two companions, exploring topics relating to the utility and feasibility of a home-based observation and imagery intervention. Results. Five themes were identified. Participants reported their experiences of exercise and use of action observation and motor imagery in everyday activities, and the need for strategies to improve movement was expressed. Motivational factors including feedback, challenge, and social support were identified as key issues. The importance of offering a broad range of actions and flexible training was also highlighted. Conclusions. A home-based intervention utilising action observation and motor imagery would be useful and feasible in mild to moderate PD.

Homeodomain proteins constitute one of the largest families of metazoan transcription factors. Genetic studies have demonstrated that homeodomain proteins regulate many developmental processes. Yet, biochemical data reveal that most bind highly similar DNA sequences. Defining how homeodomain proteins achieve DNA binding specificity has therefore been a long-standing goal. Here, we developed a novel computational approach to predict cooperative dimeric binding of homeodomain proteins using High-Throughput (HT) SELEX data. Importantly, we found that 15 of 88 homeodomain factors form cooperative homodimer complexes on DNA sites with precise spacing requirements. Approximately one third of the paired-like homeodomain proteins cooperatively bind palindromic sequences spaced 3 bp apart, whereas other homeodomain proteins cooperatively bind sites with distinct orientation and spacing requirements. Combining structural models of a paired-like factor with our cooperativity predictions identified key amino acid differences that help differentiate between cooperative and non-cooperative factors. Finally, we confirmed predicted cooperative dimer sites in vivo using available genomic data for a subset of factors. These findings demonstrate how HT-SELEX data can be computationally mined to predict cooperativity. In addition, the binding site spacing requirements of select homeodomain proteins provide a mechanism by which seemingly similar AT-rich DNA sequences can preferentially recruit specific homeodomain factors.

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