Development and validation of a new approach to testing reward processing and apathy

processing and apathy in patients with psychiatric and

neurodegenerative disorders

Chief Investigator	Institution	Dates	Funding Stream	Amount
Emma Robinson	University Hospitals Bristol NHS Foundation Trust	Mar-2016 to Feb-2018	Above and Beyond Autumn 2015	£19,000

 

Summary

Despite the discovery, more than 60 years ago, of drugs which improve the symptoms of depression, we still do not really know what causes this disease or why so many people do not respond to treatment. Depression is the major psychiatric disorder affecting modern society but it is also highly co-morbid with all chronic illnesses. Low mood, loss of motivation, anhedonia (loss of the experience of pleasure) and apathy are all commonly seen symptoms in diseases such as chronic pain, dementia, Parkinson's disease and stroke. As an animal researcher, I have focused on the development of improved methods to study psychiatric symptoms in non-human species. Our work has led to important developments in the area of emotional behaviour and reward and we are now seeking support to take these ideas forward into human studies. We have shown that many different factors linked to inducing depressive symptoms in people, cause negative biases in the way an animal learns and remembers rewarding experiences it has encountered. We have now developed a novel hypothesis which proposes that low mood, anhedonia and apathy are all related to the neurobiological processes we have been studying in rats. We now seek funding to help us to set-up a new approach to studying similar behaviours in human subjects. Our project has the potential to provide new insight into a common psychological basis for depression-related symptoms in a multitude of diseases and provide an objective and translational method to identify and develop improved treatments.

Work to date

We have commissioned the manufacture of the customised apparatus for the neuropsychological testing and this has been delivered and installed. The person who will undertake the testing has been appointed and has started the pilot testing of the task. We have so far run two pilot experiments. Our collaborator from King's College London has visited twice to help with the project planning. Testing in healthy volunteers was due to start early Dec 2016 with the aim to run patients end of 2017.

Update Dec 2019: The PhD student working on the project has successfully completed two studies and the results are in preparation for publication.  We have also been able to run two student projects using the task although the results from this are still preliminary.  We are currently recruiting for a study in people with anxiety and MDD and will be running a full analysis using the task from this project alongside other measures of reward processing.  It is hoped that this work will lead to a much larger application for funding to either MRC or BBSRC.

Main findings

This study aimed to develop a method to study reward motivation in people which did not depend on the person making a subjective assessment.   The task uses a joystick and on screen target and measures how much effort a person will exert to obtain rewards of different values.  The proof of concept studies have been successful and has led to a PhD studentship to carry on the work.  The project will now progress and test patients with mental health conditions where we hypothesise that we will see a deficit reflecting loss of interest in reward.

Update Dec 2019: As predicted, effort expenditure for reward using the joy-stick operated runway task (JORT) which we developed in this project, shows a very clear association with reward magnitude.  Individuals expend more effort for higher value rewards and these effects do not correlate with conventional measures of anhedonia.  Alongside the joy stick operated runway task, we have been able to develop a test battery designed to also look at changes in reward sensitivity (a sweet taste threshold test) and reward learning using a novel online associative learning task. From Jan 2020 we will be running a study where all three tasks are tested in patients with anxiety and MDD and compared to healthy controls.

Impact

This study aimed to develop a method to study reward motivation in people which did not depend on the person making a subjective assessment.   The task uses a joystick and on screen target and measures how much effort a person will exert to obtain rewards of different values.  The proof of concept studies have been successful and has led to a PhD studentship to carry on the work.  The project will now progress and test patients with mental health conditions where we hypothesise that we will see a deficit reflecting loss of interest in reward.

Update Dec 2019: The PhD student working on the project will finish at the end of 2020 and we are planning on submitting grant applications to progress the work and use the data from these initial studies to support a wider programme investigating reward deficits in MDD using objective methods.  Alongside our animal studies, the work we have carried out so far suggests that reward deficits in MDD occurring in a very specific domain and previous work using questionnaire-based methods provide a poor method of assessment.  We have also been developing a learning model of depression which integrates some of the work from this project into a wider model. 

Outputs

Update Dec 2019:

We have published and presented at meetings 3 abstracts based on this work including a poster at the 2019 Society for Neuroscience conference.  We are currently preparing the data from the first pilot studies (supported by this grant) for publication and anticipate this should be completed early 2020.

Further funding applications

 

Other project outcomes

Collaboration established with:

• Ian Penton-Voak, Experimental Psychology who will co-supervise the PhD student who is continuing this work.
• David Kessler, Social and Community medicine who will support the studies in clinical populations which will commence autumn 2018

Update Dec 2019: We are now also collaborating with Conor Hougton (Computer Science) and Nina Kazinina (Experimental Psychology) bringing in mathematical and EEG expertise.  We plan to further develop the JORT task and analysis with these collaborators and this has including making an EEG compatible version on the equipment needed. 

Updated 06/12/2019