PET studies of the dopamine system in relation to cognitive functions
Year: 2007
Type: dissertation
Abstract: The human brain is intricately designed to execute cognitive functions\nsuch as perception, attention, memory and learning. Deficits in cognitive\nfunctions accompany major psychiatric disorders such as schizophrenia,\nattention deficit hyperactivity disorder and Parkinson s disease. The\nbiological underpinnings of cognitive functions, is however poorly\nunderstood. One of the neurotransmitters proposed to play a central role\nin cognition is dopamine (DA).\n\nPositron emission tomography (PET) is a non-invasive molecular imaging\ntechnique by which biomarkers for neurotransmission systems can be\nexamined in the human brain in vivo and related to higher brain\nfunctions. Development of new tests based on advances in cognitive\nscience provides tools to identify basic elements of cognition.\n\nThe first aim of the present thesis was to develop improved\nmethodologies, both for molecular imaging and cognitive testing. The\nsecond aim was to apply these methods in a combined fashion with the\nintention to increase understanding of the organization of the DA system\nin the human brain and its role in cognitive functions. In the first\nstudy, a new selective radioligand for the dopamine transporter (DAT) was\ndeveloped. [11C]PE2I binding was characterized in four non-human primates\nand in one human control subject, showing better selectivity for the DAT\nwhen compared to previously developed radioligands. In addition, the\ndistinctive contrast of this radioligand demonstrated sufficient signal\nnot only in striatum, but also in substantia nigra.\n\nThe relationship between the presynaptic DAT and the mainly postsynaptic\nDA D2 receptor was examined in a double-tracer PET study (Study II). The\nresults from 17 human subjects demonstrated a lack of a correlation,\nsuggesting independent regulation of the two DA biomarkers in the human\nstriatum. The results suggest that these two biomarkers may not be\nmutually interchangeable when assessing the DAergic system in the healthy\nbrain.\n\nVisuospatial working memory (VSWM) is commonly impaired in patients with\nschizophrenia resulting in disorganization in both thoughts and behavior.\nIn Study III, a standard VSWM-test was modified to reduce ceiling effects\namong control subjects, thus allowing for a less biased comparison\nbetween patients with schizophrenia and controls. In addition, during\nhigh WM load the control group showed improved performance when the\nstimulus arrangement invited the use of cognitive strategies, as compared\nto an arrangement with random location of the target stimulus. This\nimprovement was not present in the patient group. The results indicate\nthat patients with schizophrenia do not make use of, or generate\nstrategies to the same extent as control subjects.\n\nIn the final study, the role of the DAT was examined in relation to\ncognitive aging. Cognitive performance was assessed in 12 human subjects,\nranging from 34-81 years of age, and DAT density was quantified using\nPET. The results indicate that DAT may serve as a biomarker of\nage-related deficits in episodic memory and executive function, and that\nDAT is implicated in cognitive performance irrespective of age.\n\nIn conclusion the present thesis, based on a combination of molecular\nimaging and cognitive assessment, corroborates a role for the DA system\nin higher brain functions in man.
Source: Figshare
Author: Nina Erixon-Lindroth
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2133976385