Periodic Reporting for period 3 - Brain2Bee (How dopamine affects social and motor ability - from the human brain to the honey bee) Reporting period: 2021-07-01 to 2022-12-31 Summary of the context and overall objectives of the project Parkinson’s Disease is usually characterised by motor impairment, and Autism by social difficulties. However, the co-occurrence of social and motor symptoms is critically underappreciated; Parkinson’s Disease patients exhibit social symptoms, and motor difficulties are common in Autism. At present, the biological basis of co-occurring social and motor impairment is unclear. Notably, both Autism and Parkinson’s Disease have been associated with dopamine system dysfunction and, in non-clinical populations, dopamine has been linked with social and motor ability. These disparate strands of research have never been combined. Brain2Bee will use psychopharmacology in typical individuals to develop a model of the relationship between Dopamine (DA), Motor, and Social behaviour – the DAMS model. Brain2Bee will use sophisticated genetic analysis to refine DAMS, elucidating the contributions of dopamine-related biological processes (e.g. synthesis, receptor expression, reuptake). Brain2Bee will then test DAMS’ predictions in patients with Parkinson’s Disease and Autism. Finally, Brain2Bee will investigate whether DAMS generalises to an animal model, the honey bee, enabling future research to unpack the cascade of biological events linking DOPAMINE-related genes with social and motor behaviour. Brain2Bee will unite disparate research fields and establish the DAMS model. The causal structure of DAMS will identify the impact of dopaminergic variation on social and motor function in clinical and non- clinical populations, elucidating, for example, whether social difficulties in Parkinson’s Disease are a product of the motor difficulties caused by dopamine dysfunction. DAMS’ biological specificity will provide unique insight into the dopamine-related processes linking social and motor difficulties in Autism. Thus, Brain2Bee will determine the type of dopaminergic drugs (e.g. receptor blockers, reuptake inhibitors) most likely to improve both social and motor function. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Brain2Bee has had a highly successful start. Four members of staff have been appointed (Sowden, Schuster, Fraser, Traniello), all are carrying out their assigned projects with excellent progress. The project has so far led to nine published papers with a further six currently under review. In addition, work has been presented nationally and internationally via 12 conference/departmental talks and 18 poster presentations. Our first deliverable, to publish at least two papers reporting on the development of the Brain2Bee social and motor task battery was exceeded and achieved ahead of time. The Brain2Bee task battery, and a corresponding analysis pipeline, has been fully developed and pilot tested. During the development of this task battery we made some important psychological insights regarding a) emotion perception from facial motion cues (Sowden et al., 2021, Emotion; Sowden et al., 2019, Frontiers in Behavioural Neuroscience), b) kinematic markers of emotion-related body movements (Schuster et al., 2019, Frontiers in Behavioural Neuroscience), c) visual and motor cues which contribute to the ability to accurately estimate mental states (Schuster et al., under revision, Scientific Reports). Data collection for EXPT 1 (Haloperidol study) has been completed and three related manuscripts are currently in preparation. In addition to our research achievements, we have also developed procedures for indexing sociability in honeybees and algorithms to detect kinematic markers which separate autistic and non-autistic individuals. Our work on the link between social and motor function in members of the general population has resulted in important insights for emotion perception in clinical conditions such as autism. Furthermore, we are making cross-disciplinary developments regarding the human and honey bee genetics of social behaviour. To date we have been successful in communicating our research within academia, to industry and to the members of the general public via publications in peer-reviewed journals, conference presentations, industry placement schemes, public interest articles and videos and a public interest event. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The first part of the Brain2Bee project focused on the development of our Brain2Bee task battery which provides an easy, quick and effective way to measure individual differences in both the production and perception of social cues (i.e. in social and motor function). During the development of this task battery we made some important psychological insights regarding a) emotion perception from facial motion cues (Sowden et al., 2021, Emotion; Sowden et al., 2019, Frontiers in Behavioural Neuroscience), b) kinematic markers of emotion-related body movements (Schuster et al., 2019, Frontiers in Behavioural Neuroscience), c) visual and motor cues which contribute to the ability to accurately estimate mental states (Schuster et al., under revision, Scientific Reports). For example, in Sowden et al. (2021; https://psycnet.apa.org/fulltext/2021-22419-001.html; https://youtu.be/sbDq9qUVz_Y) we demonstrated that people move their face at different speeds when making happy, angry and sad emotional expressions. We also showed that the speed of our facial expressions is an important cue that other people use to help them figure out how we are feeling. These findings have attracted a lot of attention from other groups around the world. In Schuster et al., (under review; https://www.researchsquare.com/article/rs-208776/v2) we show that movement similarity is important in estimating others’ mental states. That is, it is easier for you to guess what another person is thinking if they move their body in a way that is similar to your own body movements. We are currently using our task battery to explore the production and perception of social cues in autism and Parkinson’s disease.After developing the task battery, we used it to unpack the role of dopamine in social and motor function (EXPT 1). To achieve this, we asked participants to complete the task battery once after they have taken a dopamine blocker (Haloperidol) and once after placebo (the order of Haloperidol and placebo was counterbalanced between people). We found that manipulating dopamine affected both social and motor function. For example, we saw that participants moved more slowly and in a less jerky fashion when they had taken haloperidol (Sowden et al., in prep; https://youtu.be/6vcYiW_8B6U) and we also observed effects on participants’ ability to estimate others’ mental states and infer others’ emotions (Schuster et al., in prep; https://youtu.be/t9vuihmsl6o). However, effects on motor and social function were largely independent of each other. These results raise the hypothesis that dopamine degradation in conditions like Parkinson’s disease has separable effects on social and motor ability. In other words, differences in social behaviour in Parkinson’s disease may be unrelated to differences in body movement. We are currently setting up studies specifically designed to test this hypothesis.
