Using multimodal human brain imaging to investigate reward circuit deficits in addiction

Addiction is a brain disorder which is characterised by engagement of an individual in rewarding activities, despite the adverse personal and physiological consequences. It's estimated that in Europe and the United States that up to 5-6 % of the population suffer from a substance-use disorder. Much of research into the mechanisms of addiction centre on the role of dopamine within the mesocorticolimbic system. Studies have found dopamine to be key for reward, with roles in motivation and incentive. To understand the neural correlates to addiction, neuroimaging tools such as positron emission tomography (PET), used to measure dopamine receptor availability and release, as well as functional magnetic resonance imaging (fMRI), a tool used to capture cerebral blood oxygenation activity in response to tasks have been employed. Specifically, fMRI imaging in Gambling disorders have proven to be inconsistent in findings related to the brains reward circuitry. Here we validate two novel fMRI paradigms, the 7-arm cue reactivity test and the reward enriched roulette paradigm to assess striatal activation patterns within gambling disorder. It is the hope to validate and use the RER in future multi-model (combined PHNO-PET-fMRI) neuroimaging addiction studies, and to test 7-ACR pre- and post-psychedelic therapy in populations suffering addiction. Recent research into brain mechanisms related to reward processing has focused on the role of the dopamine D3 receptor (D3-R). Research has implicated that antagonism of this receptor may restore reward deficits in addicted populations. Here, fMRI monetary incentive delay task data pre and post D3-R block will be compared with PET measures of D3-R densities in the same individuals allowing for investigation of the molecular foundation for previously reported normalisation of striatal fMRI response following a D3-R blockade. Utilising multi-modal neuroimaging tools will allow us to legitimately dissect the processes of addiction paving the way for more effective treatment.