A Biological Framework of Reduced Physical and Social Activity across the Lifespan

For decades, we have known that being physically and socially active can have major health benefits, including the prevention of later life ill-health and the improvement of symptoms when sick. Despite these benefits, many people do not engage in regular exercise and are socially dis-engaged. Such inactivity increases as people get older, leading to significant costs to health systems across the world, as well as major personal costs to the individual.

Why aren't people more active? A crucial factor that prevents an active life is motivation. People who are more motivated are more active. Even otherwise healthy people can suffer from high levels of motivation problems such as social apathy (people enjoy social interactions but simply don't have the will to engage in them) or fatigue (people who feeling exhausted after small levels of exertion). Moreover these motivational impairments increase as people get older. Yet, we understand very little about why people vary in motivation. Is there a biology of social apathy and fatigue?

The overarching aim of the proposed research is to identify how differences in how certain systems in the brain work, relates to differences in how socially apathetic or fatigued people are, and to examine how changes in the brain lead to reduced motivation as we get older. To do this I will extend recent advancements in basic neuroscience that has provided a rich understanding of how the brain motivates behaviour. Within this research it has been suggested that reduced motivation might be due to a heightened sensitivity to how effortful actions are. People who are more motivated find the same actions less effortful.

Here, I propose to examine how different aspects of effort sensitivity may be linked to fatigue and social apathy in healthy people as they get older. To do this, I will perform studies in healthy human volunteers using a number of techniques including brain imaging, brain stimulation and a mobile phone game, with effort sensitivity quantified using precise computational approaches. Using all of these approaches together I will be able to answer specific questions about the systems in the brain that motivate behaviour in social situations and when getting exhausted. By comparing the brain systems underlying effort sensitivity in young and older people, I will try and understand what changes in the brain may lead to higher levels of social apathy and fatigue as people get older. In summary, the key questions that the proposed research would examine are:

1) Can social apathy and fatigue be characterised as increased sensitivity to different aspects of effort in healthy people?
2) Do social apathy and fatigue increase across the lifespan because of heightened effort sensitivity?
3) What systems in the brain underlie different aspects of effort sensitivity and are they linked to social apathy and fatigue?
4) Are changes in these brain systems in older adults linked to increased effort sensitivity, social apathy and fatigue?
5) Can stimulating these brain areas in a unique sample of individuals with deep brain stimulators implanted into specific brain areas provide evidence of these regions being causally involved in effort sensitivity?

This work will be carried out in the Department of Experimental Psychology, at the University of Oxford. The principal investigator (Dr. Apps) will work in collaboration with a postdoctoral researcher, consultant surgeons in the Nuffield Department of Surgical Science, the Wellcome trust Centre for integrated neuroscience and a mobile brain training company.

Staying physically and socially active can have powerful protective effects for health and wellbeing across the lifespan. Yet, increasing levels of activity is a major public health challenge. One significant barrier is motivation. Social apathy - a reduced willingness to engage in social behaviours - and fatigue - a feeling of exhaustion that reduces activity - both reduce motivation, physical and social activity, and increase across the lifespan. Yet, the underlying neuro-computational mechanisms of such motivational impairments are poorly understood.

Here, I propose to develop novel, biological, causally linked accounts of social apathy and fatigue in healthy people by characterising them as heightened sensitivity to different components of effort. I will take a multimodal approach using brain imaging, computational modelling, testing the effects of deep-brain stimulation and a mobile app. In doing so I will characterise the systems in the brain that underlie effort sensitivity, their relation to social apathy and fatigue, and how they may change across the lifespan.

I will test specific hypotheses relating to the following questions:

(1) Can heightened sensitivity to exerting effort to benefit others (i.e. reduced "prosocial motivation") be used as a framework of social apathy and its changes across the lifespan?
(2) Can increased sensitivity to the history of exerted effort during a task be used as a framework of lifespan changes in different aspects of fatigue?
(3) What are the neuro-computational mechanisms underlying effort sensitivity and does variability in them relate to social apathy and fatigue?
(4) Do the same systems in the brain that are linked to effort sensitivity, social apathy and fatigue, also show differences in processing effort between younger and older adults?
(5) Does a causal manipulation of fronto-striatal circuits in the human brain in deep brain stimulation patients change sensitivity to effort

By 2060, age-related spending, such as spending on pensions and healthcare, is projected to rise to 26.3% of GDP, equivalent to a rise of around £79bn in the UK, and a rise of up to 29.8% of GDP in the EU. In a 2010 WHO report, reduced physical activity was highlighted as the fourth biggest cause of mortality worldwide. Yet, currently our understanding of why people vary in activity is poor. Apathy and fatigue - the key motivational impairments in this proposal - are known to have significant impacts on quality of life, well-being, levels of civic engagement and employment. In addition, they are significant secondary symptoms in many psychiatric and neurological conditions. As a result, the long-term goal of this research is to provide understanding reduced activity and find approaches that increase it by enhancing motivation, providing a significant improvement to national health and reduce public health spending.

(1) Who will benefit from this research?
Key beneficiaries include:
o Professionals working with young and older people such as doctors, nurses, clinical psychologists, neurologists, occupational therapists, professionals working in social care, individuals and groups working with the unemployed and people working in human resources department in industry
o Individuals with motivational problems: including young and old people themselves; patients with neurological and psychiatric disorders which lead to high levels of apathy and fatigue (e.g. Parkinson's Disease, Alzheimer's disease, Schizophrenia, Depression)
o Charities and policy makers: Age UK, Age Concern and the Center for Ageing Policy, policy makers in the Department of Health and Department of Work and Pensions
o Industry: Brain training company Peak and the brain training industry.
Although the focus here is UK based, similar beneficiaries also exist internationally.

(2) How will they benefit from this research?
The short-term aims of this specific grant is to develop an evidence based for understanding motivational impairments. Based on this evidence, medium and long-term potential impact may arise through the development of tools for increasing motivation.

Policy makers in the Department of Health and Work and Pensions: The evidence base provided could be used for informing policy. This would allow the departments to find new ways of encouraging the UK population to increase levels of activity and social engagement through public health campaigns that focus on increasing motivation.

Charities, practitioners and social workers: The research will be of benefit to these groups in the short to medium term. Providing an understanding that motivational impairments may have an underlying biology may significantly help individuals for whom high levels of fatigue and social apathy are stigmatized and poorly understood. This understanding may also guide charities, social workers and practitioners in their policies for interacting with service users.

Young and old people, patients and carers: In the short term, I aim to communicate with a broad demographic of society including young and older people and patients, particularly those for whom apathy and fatigue are a significant issue. In the longer term, it is hoped that these groups will benefit from improved evidence-based initiatives that scaffold healthy ageing. By increasing societal and individual awareness through direct channels with the researchers this may have a greater impact for individuals and carers.

Industry: Brain training is a growing industry - worth over £1bn in 2016. The collaboration with Peak has the potential in the medium/long term to develop tools that increase motivation. The brain training industry would therefore benefit through the development of such tools, assuming the efficacy is rigorously, empirically tested.