Human brain mechanisms underlying motivation and apathy

Motivation is a crucial feature of mental health, wellbeing and success. Yet we understand very little about the brain mechanisms underpinning it. Pathological loss of motivation manifests as the syndrome of apathy is a common symptom in many brain disorders but it has no established treatment. Here we test a new conceptual framework to provide an ambitious, transformational step change in this field. By bringing together the expertise of a diverse, multidisciplinary collaboration, we seek to:

1. Understand the variability of motivation in healthy people across different domains – behavioural, cognitive, social and emotional – at the level of behavioural and brain mechanisms.

2. Using a transdiagnostic approach, establish mechanisms underlying pathological apathy in patients with Parkinson’s disease (PD), small vessel cerebrovascular disease (SVD) and Alzheimer’s disease (AD).

3. Investigate modulation of motivation in healthy people and PD using drugs that target different neurotransmitter systems and deep brain stimulation (DBS) in PD.

We will deploy a common set of behavioural measures, computational modelling and neuroimaging analyses to provide a unifying platform for data integration across studies. This will provide a comprehensive understanding of human motivation and apathy, new behavioural tools and potential novel treatment approaches for loss of motivation and apathy in health and disease.