A biological framework for understanding and modulating apathy in healthy people

As we get older our ability to do mentally and physically demanding tasks declines. However, research shows that we also lose motivation to complete mentally and physically demanding tasks through the effects of aging. Apathy - a reduction in the willingness to engage and perform mentally and physically demanding tasks - is widespread in mild forms in young adults, but crucially, it significantly increases as we age, hampering the daily lives of the elderly. Apathy in young adults may also have considerable long-term effects with significant costs, affecting education, employment and civic engagement.

Despite the importance of keeping motivated for healthy aging, very little is known about the biological processes that lead to apathy in the young or the elderly. In this research I aim to establish a biological model of apathy. I will test specific ideas developed from animal models of the processes in the brain that lead to reduced motivation. Using this models as a basis, I will test whether key pathways in the brain that lead animals to stop doing mentally and physically demanding tasks are also responsible for causing individual differences in how motivated people are . Using new mathematical approaches in conjunction with brain imaging techniques in healthy young adults I will build a biologically based model of apathy in the young and the elderly. Using modern non-invasive brain stimulation techniques I will then explore whether motivation can be increased by stimulating parts of the brain we predict are involved in motivation based on our animal model.
There are three key questions this research will address:

(1) To what extent is motivation reduced in the elderly?
Most research that has looked at motivation in aging, has used questionnaires, asking people about how motivated they feel. Unfortunately, these do not provide us with a model that can explain the biology behind apathy. Using two new tasks, the designs of which are based on tasks used to explore animal decision-making, I will examine how motivated the elderly are compared to young adults to do mentally and physically demanding tasks and how motivated they are to overcome fatigue.

(2) What is the biology of apathy
Research into the processes that underpin motivation in rats, birds and monkeys has provided us with a models of the pathwys in the brain that are crucial for keeping animals motivated. However, it is unknown what the links are between how these 'motivational circuits' work, apathy in humans, and changes in motivation through aging. Using functional Magnetic Resonance Imaging (which can tell us about whether an area is 'activated' by doing a task) and Diffusion Tensor Imaging (which can tell us about how strongly connected to each other brain areas are) I will test whether the same pathways in the brain that are responsible for motivating animals are also responsible for motivating humans. I will then test whether changes in these pathways in older people leads to them being less motivated.

(3) Can we increase motivation in the elderly and the apathetic young by stimulating the brain?
Once my proposed model of apathy has been tested, I will have identified I will have identified regions that can targeted by brain stimulation techniques. By stimulating these areas in a particular way, I predict that we can increase people's willingness to overcome cognitive and physical demands, and make people less influenced by fatigue. That is, I aim to try and increase how motivated people are, in order to develop potential techniques for ameliorating apathy.

This work will provide the first biological model of apathy and how changes in the brain can lead to greater levels of apathy in the elderly. This model will provide researchers, clinicians and industry with a framework on which to base therapeutic techniques and technologies aimed at increasing motivation.

Apathy - reduced motivation to initiate goal-directed behaviours - is present in a number of psychiatric and neurological disorders. In addition, apathy is widespread in a milder form in the healthy population and increases with ageing, causing significant disruptions to well being. However, there is currently no biological, mechanistic account of apathy. The aim of the proposed fellowship is to develop the first model of apathy in the young and the elderly.

Basic neuroscience research in animals is increasingly elucidating computational and neural models of motivation. In these models, motivation is cast as a decision-making problem. Behaviours are initiated following cost-benefit analyses, where beneficial outcomes (rewards) are discounted (devalued) by the costs (effort) of acting. Here, this framework will be used as a model of apathy, to inform the design of tasks and to derive hypotheses.

Two tasks will be used to test the relationship between apathy in young and the elderly, and cost-benefit decision-making. The first measures the sensitivity of subjects to cognitive or physical effort. The second measures the influence that fatigue has on cost-benefit decision-making. Using computational modeling approaches I can characterize individual differences in the sensitivity to cognitive and physical effort, and fatigue, in the young and the elderly. This approach can then be used to the test the notion that cost-benefit decision-making can be used as a model of apathy in humans.

To test cost-benefit decision-making as a biological model of apathy I will use functional magnetic resonance imaging and diffusion tensor imaging to test specific hypotheses about the neuroanatomical correlates of apathy, physical and cognitive effort, and fatigue sensitivity. Using Transcranial Magnetic Stimulation I will test the causality of activity in the hypothesised cortical regions, with the aim of increasing motivation in the apathetic.

Impact Summary

Who will benefit from the research?
Academic: This research has the potential to benefit academics across a broad range of disciplines, including ecology, neuroscience, sports psychology, aging psychology and neuroscience. It will also have considerable interest to those interested in health and well-being including clinical psychologists, neurologists and charitable organizations promoting healthy aging such as Age UK (Age Uk have been contacted regarding endorsement for this research fellowship). In addition, members of the public in whom apathy is highly prevelant (Levy, 2006) include:
- Alzheimer's disease (~60%)
- Parkinson's disease (~51%)
- Depression (~40%)
- Traumatic Brain Injury (~46%)
- As well as evidence in the long-term unemployed (Rodiguez, 1997)
In addition, motivation is crucial within the sporting industry for athletes to achieve high levels of performance.

How will they benefit?
Societal Impact: In 2011-2012 the UK spent £4bn on unemployment benefit. Whilst many of these individuals are motivated for searching for work, apathy is highly prevalent in the long-term unemployed. This can have considerable short-term and long-term consequences for well-being and mental health. Minimising the effects of apathy will therefore decrease the cost to society. By increasing awareness of the issues surrounding apathy I hope, in the long-term, to reduce the burden placed on society by apathetic individuals.

Clinical Impact (patients and practitioners): The absence of a mechanistic account of apathy has held back the development of therapeutic advances. I will develop a model that delineates components of apathy and identify potential avenues for patient-tailored care to be developed. Thus, clinical researchers will benefit from this research by having a framework which will inform therapeutic techniques. To increase engagement with clinical researchers and practitioners I will hold a round table meeting with the principal investigators at the head of the Oxford Dementia and Aging Research (OXDARE) network hold a motivational workshop and host website for raising awareness of the role of motivation for healthy aging. In addition, if this research highlights the efficacy of TMS as a treatment, follow-on funding would be applied for to develop an rTMS protocol to ameliorate the negative effects of apathy on longer time-scales.

Industry Impact: In this project I am hoping to use TMS to increase motivation. Whilst TMS has been used as a treatment technique, alternative techniques such as transcranial direct current stimulation (tDCS) are cheaper and preferable to TMS. However, currently tDCS is unlikely to be able to target the desired cortical zones we are highlighting as crucial for motivation (the supplementary motor area). Thus, if I were able to demonstrate efficacy for increasing motivation I would aim to contact industry leaders in brain stimulation techniques (e.g. Magstim) in order to apply for an industrial partnership award to develop more efficient methods of tDCS that could be used for the aim of stimulating SMA and increasing motivation. This would allow for more portable flexible techniques to be developed that would allow for use safe and prescribed use and potentially as a potential enhancement of sporting performance. Such processes will be in the long-term and these proposals are made with the awareness that considerable ethical and practical challenges will need to be solved before this is a possibility.