PET and MR brain imaging study in gambling disorder
File(s)
Author(s)
Lan, Chen-Chia
Type
Thesis
Abstract
Gambling disorder is the first recognised behavioural addiction in clinical psychiatry. Both the DSM-5 and the ICD-11 categorised gambling disorder as one of the addictive disorders rather than impulse control disorders in the previous editions. Without the confounding toxic effects of chronic substance use, brain imaging studies on gambling disorder may reveal the core psychopathology of addiction.
Positron emission tomography (PET) and magnetic resonance imaging (MR) are non-invasive tools to study the human brain. The former excels in quantitatively measure the molecular changes of various neurochemical mechanisms, and the latter provides detailed structural and dynamic functional information. By combining the two modalities, the pathophysiology of various neuropsychiatric disorders could be studied comprehensively to devise novel therapeutics and preventive measures.
Gambling disorder patients have exhibited molecular aberrations in the mu-opioid and GABA neurotransmitter systems in PET studies and functional abnormalities during the resting-state or reward-processing and response inhibition tasks in fMRI studies. This thesis aims to maximise PET and MR imaging potentials by conducting combination analysis and developing a novel tracer kinetic model to detect neurotransmitter release under simultaneous PET/MR acquisitions.
In gambling disorder patients, the [11C]carfentanil binding potential in the posterior cingulate cortex (PCC) was reduced and correlated negatively with the resting-state functional connectivity between PCC and the other default-mode network hubs, the PCC amplitude of low-frequency fluctuations and the intrinsic connectivity. The mu-opioid receptor availability over the nucleus accumbens (NAcc) was negatively associated with its functional connectivity to the anterior and posterior insula during the Monetary Incentive Delay task in gambling disorder participants. The caudate [11C]Ro15-4513 volume of distribution correlated with its activation during the Go/Nogo task in healthy volunteers.
Finally, the novel kinetic model demonstrated good neurotransmitter release detectability and parameter estimation accuracy via computerised simulations with real-world tracer parameters and noise profiles from [11C]raclopride and [11C]-(+)-PHNO.
Positron emission tomography (PET) and magnetic resonance imaging (MR) are non-invasive tools to study the human brain. The former excels in quantitatively measure the molecular changes of various neurochemical mechanisms, and the latter provides detailed structural and dynamic functional information. By combining the two modalities, the pathophysiology of various neuropsychiatric disorders could be studied comprehensively to devise novel therapeutics and preventive measures.
Gambling disorder patients have exhibited molecular aberrations in the mu-opioid and GABA neurotransmitter systems in PET studies and functional abnormalities during the resting-state or reward-processing and response inhibition tasks in fMRI studies. This thesis aims to maximise PET and MR imaging potentials by conducting combination analysis and developing a novel tracer kinetic model to detect neurotransmitter release under simultaneous PET/MR acquisitions.
In gambling disorder patients, the [11C]carfentanil binding potential in the posterior cingulate cortex (PCC) was reduced and correlated negatively with the resting-state functional connectivity between PCC and the other default-mode network hubs, the PCC amplitude of low-frequency fluctuations and the intrinsic connectivity. The mu-opioid receptor availability over the nucleus accumbens (NAcc) was negatively associated with its functional connectivity to the anterior and posterior insula during the Monetary Incentive Delay task in gambling disorder participants. The caudate [11C]Ro15-4513 volume of distribution correlated with its activation during the Go/Nogo task in healthy volunteers.
Finally, the novel kinetic model demonstrated good neurotransmitter release detectability and parameter estimation accuracy via computerised simulations with real-world tracer parameters and noise profiles from [11C]raclopride and [11C]-(+)-PHNO.
Version
Open Access
Date Issued
2022-09-30
Date Awarded
01/08/2024
License URL
Advisor
Nutt, David
Wall, Matthew
Myers, James
Publisher Department
Department of Brain Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)