Motivation in patients with neurological disease
Research type
Research Study
Full title
Motivation and decision-making in patients with neurological disease
IRAS ID
242551
Contact name
Sanjay Manohar
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
We are studying about how motivation and actions are influenced by diseases affecting the nervous system, and how it is altered by drugs that alter the concentrations of neurotransmitters in the brain. When you do something that you find rewarding, neurotransmitters such as dopamine are released in the brain. To date, most scientific research on the role of dopamine and other neurotransmitters has concentrated on learning. However, this ignores the fact that these transmitters during rewarding situations may have a motivating effect. For example, they may make us move more quickly, more accurately or letting us put in greater effort.
We wish to investigate how brain chemistry – such as dopamine levels – influences behaviour in healthy people, and in people with neurological disease. First we will measure cognitive process that are affected by motivation in healthy participants, and compare this to patients with neurological disorders that affect specific brain pathways. Then, we will study patients on their normal medication, and compare their performance when they omit a particular tablet for 12 hours. Finally, we will examine brain activity by two kinds of scan: MRI scanners use magnetic fields to produce images of brain activity, whereas EEG/MEG uses electrical contacts and sensitive coils to detect electrical fields produced by your brain.
We hope that the results of this study will help us better understand how dopamine directly influences motivation and may shed light on how apathy arises in diseases that disrupt these systems, especially Parkinson’s disease and stroke.
Lay summary of study results:
Patients with neurodegenerative disease and focal brain damage have reduced motivation, but it is unclear why. Through a series of studies, we showed that
1) Across a wide range of neurodegenerative diseases, including Parkinson’s disease, frontotemporal dementia, Alzheimer’s disease, patients are sometimes unaware of their apathy despite it causing significant problems for their lifestyle. This lack of insight is clear from caregiver reports (Zhao et al 2025).
2) Damage to a small region within the prefrontal cortex, an area at the very front of the brain, can cause changes in motivation. In particular, it reduces our ability to stick to our goals while we act (Holton et al 2024), reduces how much we feel like helping other people (Gueguen et al Brain 2025; Lockwood et al 2024), and changes how we evaluate our own choices (Manohar et al 2022).
3) Through careful review, we proposed a framework for thinking about apathy specifically in Parkinson’s disease. They can be apathetic on multiple dimensions, each of which may rely on a different brain mechanism (Le Heron et al 2025).REC name
London - Fulham Research Ethics Committee
REC reference
18/LO/2152
Date of REC Opinion
13 Feb 2019
REC opinion
Further Information Favourable Opinion