In vivo imaging of dopamine and serotonin release: response to psychopharmacological challenges

De neurotransmitters dopamine en serotonine zijn betrokken bij vele processen waaronder de regulatie van beloningsmechanismen (dopamine) en de stemming (serotonine). Ook is gevonden dat deze neurotransmitters betrokken zijn bij het ontstaan en de behandeling van verschillende psychiatrische en neurologische ziektebeelden. Het is echter nog steeds niet bekend wat de precieze rol van deze neurotransmitters hierbij is. Met behulp van neuroimaging technieken zoals PET (positron emission tomography) is het mogelijk om hierin meer inzicht te krijgen. In dit proefschrift werden een aantal methoden onderzocht die gericht zijn op het meten van de serotonerge en dopaminerge transmissie. In de eerste studies van dit proefschrift werd onderzocht of PET gebruikt kan worden om veranderingen in serotonine afgifte te meten. Hierbij werd gebruik gemaakt van de serotonine-1A ligand 18F-MPPF. Het principe van deze methode berust op het gegeven dat de binding van een radioligand wordt beïnvloed door veranderingen in de neurotransmitterconcentratie. Deze studies werden uitgevoerd bij gezonde vrijwilligers en proefdieren. Helaas bleek de binding van 18F-MPPF niet gevoelig voor veranderingen in de serotonineconcentratie. In een volgende studie werd het effect van een verhoging van de dopamineconcentratie onderzocht met behulp van de dopamine D2 ligand 11C-raclopride, bij gezonde vrijwilligers. Hierbij werd ondermeer een verband gevonden tussen de mate van dopamineafgifte en emoties zoals angst en euforie. In de laatste studie werd het effect van een dopamine toename op de hersenactiviteit gemeten met behulp van 15O-H2O PET. In deze studie werd een relatie gevonden tussen de dopamine-geïnduceerde toename in activiteit in de “anterior cingulate cortex” en de mate van euforie. Deze laatste twee methoden kunnen mogelijk worden toegepast bij patiëntenonderzoek en onderzoek naar het werkingsmechanisme van geneesmiddelen.

Neuroanatomy of the bipolar brain: from brain structure to treatment

In this thesis, I summarized results from researches done during my PhD course, organizing them in a brief introduction and five chapters. Specifically, the first chapter of this work is dedicated to the progress made during the past years in neuroimaging technologies and techniques, with a focus on structural Magnetic Resonance Imaging techniques and their employment into the neuropsychiatric research. The following three chapters are dedicated to the three studies, all developed though a specific research topic and directed to the understanding of the neural basis of Bipolar Disorder and its clinical implications

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

The effects of structural and functional damage to limbic structures on cognitive abilities

Functional and degenerative damage to regions of the limbic system are often associated with cognitive impairments in different aspects of memory. Neuroimaging studies in post-traumatic stress disorder (PTSD) and Alzheimer’s disease (AD) have reported selective hippocampal atrophy. Neuroimaging studies in panic disorder have also suggested reduced functional activity in the right parahippocampal gyrus. It is unclear whether this hippocampal damage is responsible for the emergence of selective neuropsychological deficits. Abnormal activity in limbic structures has also been reported in PTSD patients exposed to trauma-related stimuli. This thesis was concerned with examining the effects of structural and functional damage to the limbic system on selective cognitive abilities. The limbic structures under investigation included the hippocampus, parahippocampal gyrus, anterior cingulate cortex and amygdala. In order to investigate this issue, a series of neuropsychological and neuroimaging experiments were carried out using groups of patient populations, such as panic disorder, PTSD and AD, known to exhibit abnormalities to the limbic structures. An fMRI study, using the Color Stroop and Emotional Stroop task was also administered to PTSD patients and healthy controls.Results from the neuropsychological studies showed greater impairments in topographical/spatial memory compared to verbal memory in all groups of patients. In addition, voxel-based correlation analyses found that both PTSD and AD are associated with neuropsychological deficits in the area of visuo-spatial and topographical memory that may be explained by the regional brain atrophy in limbic structures. Abnormalities of the parahippocampal gyri and cingulate cortex and possibly the amygdalae in the fMRI study also suggested a dysregulation in limbic-cortical networks in PTSD. This thesis has demonstrated that damage to limbic structures might contribute to the cognitive abnormalities of panic disorder, PTSD and AD