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The obsessed brain. functional and structural neural correlates in obsessive-compulsive disorder
The obsessed brain. functional and structural neural correlates in obsessive-compulsive disorder
A number of neuropsychological studies have evaluated the conspicuous features of obsessivecompulsive disorder (OCD), a heavily impairing psychiatric illness. While the neuropsychological model seems to be well understood and therefore the diagnose well established, the therapy effects are rather short term and go along with high relapse rates. This is probably the consequence of the still undetected disorder causes and therefore therapy is mainly symptom alleviation treatment, with only rarely lasting long term effects. Advances in research tools such as brain imaging have enabled the exploration of the coredriving organ in which OCD related processes take place, namely the brain. Against the background of findings from various OCD neuroimaging studies, a neurobiological model of the disorder has evolved including disturbances in cortico-striato-thalamo-cortical (CSTC) Areas and their functional circuits. Nevertheless, as there is a high inconsistency between study results and the analysis tools for brain imaging data are advancing fast, more recent studies reinforced the need for a revision of the OCD model by including additional areas. Thus, the integration of multiple variables from neuro-psychology, -biology as well as genetics and basic research, shifted the Research approach from a region-focused thinking to concepts of Network disruption in OCD. To disentangle the recent inconsistent neuroimaging findings, the aim of the current thesis was to investigate the neural patterns of brain function (e.g. activation, connectivity) and structure (e.g. measures of gray and white matter GM/WM), their associations with each other and their link to clinical characteristics such as symptom severity and duration of illness. The aim was accomplished in form of three recently published studies, in which we compared a large sample of OCD patients with age-, and gender- matched healthy controls. We examined brain function and structure using a 3T MRI, the functional images were acquired during OCD-sensitive tasks. Overall, in the three studies, we provided evidence for an overactive circuit during symptom provocation associated with structural impairments of underlying WM tracts. Moreover, we observed a globally decreased GM in patients in various properties of the cortical mantle, one of which has been associated with early brain development. Our results are partly in agreement with previous studies, but bring also additional evidence on interconnections between several neuronal measures. They as well suggest that in order to elucidate the neurobiological substrates of OCD, research questions need to be addressed on the network level rather than on regional dysfunctions. Furthermore, these findings should encourage future studies to replicate and validate existing results, ideally in the form of metaanalyses or multi-center studies. Valid and reliable Information about the interrelations of all measurable properties of the brain, but also their links to OCD onset and progression, will help in furthering our understanding about the neural mechanism of the disorder, but also in the clinical conceptualisation and categorisation. Moreover, this would enable future studies to investigate whether there is a trait-like neurobiological pattern common to all patients, or if the various symptom spectra are characterized by unique and partly distinct neural patterns. Answers to these questions might improve treatment and clinical handling of OCD, potentially leading to more individualized therapeutic interventions. These could also be of relevance for OCD drug-treatment research in detecting more specialized medication, with less side effects and fewer relapse rates, to be used as an additional supportive factor in therapy.
obsessive-compulsive disorder, fMRI, structural MRI, DTI, Freesurfer, functional connectivity, structural connectivity
Rus, Oana Georgiana
2017
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Rus, Oana Georgiana (2017): The obsessed brain: functional and structural neural correlates in obsessive-compulsive disorder. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)
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Abstract

A number of neuropsychological studies have evaluated the conspicuous features of obsessivecompulsive disorder (OCD), a heavily impairing psychiatric illness. While the neuropsychological model seems to be well understood and therefore the diagnose well established, the therapy effects are rather short term and go along with high relapse rates. This is probably the consequence of the still undetected disorder causes and therefore therapy is mainly symptom alleviation treatment, with only rarely lasting long term effects. Advances in research tools such as brain imaging have enabled the exploration of the coredriving organ in which OCD related processes take place, namely the brain. Against the background of findings from various OCD neuroimaging studies, a neurobiological model of the disorder has evolved including disturbances in cortico-striato-thalamo-cortical (CSTC) Areas and their functional circuits. Nevertheless, as there is a high inconsistency between study results and the analysis tools for brain imaging data are advancing fast, more recent studies reinforced the need for a revision of the OCD model by including additional areas. Thus, the integration of multiple variables from neuro-psychology, -biology as well as genetics and basic research, shifted the Research approach from a region-focused thinking to concepts of Network disruption in OCD. To disentangle the recent inconsistent neuroimaging findings, the aim of the current thesis was to investigate the neural patterns of brain function (e.g. activation, connectivity) and structure (e.g. measures of gray and white matter GM/WM), their associations with each other and their link to clinical characteristics such as symptom severity and duration of illness. The aim was accomplished in form of three recently published studies, in which we compared a large sample of OCD patients with age-, and gender- matched healthy controls. We examined brain function and structure using a 3T MRI, the functional images were acquired during OCD-sensitive tasks. Overall, in the three studies, we provided evidence for an overactive circuit during symptom provocation associated with structural impairments of underlying WM tracts. Moreover, we observed a globally decreased GM in patients in various properties of the cortical mantle, one of which has been associated with early brain development. Our results are partly in agreement with previous studies, but bring also additional evidence on interconnections between several neuronal measures. They as well suggest that in order to elucidate the neurobiological substrates of OCD, research questions need to be addressed on the network level rather than on regional dysfunctions. Furthermore, these findings should encourage future studies to replicate and validate existing results, ideally in the form of metaanalyses or multi-center studies. Valid and reliable Information about the interrelations of all measurable properties of the brain, but also their links to OCD onset and progression, will help in furthering our understanding about the neural mechanism of the disorder, but also in the clinical conceptualisation and categorisation. Moreover, this would enable future studies to investigate whether there is a trait-like neurobiological pattern common to all patients, or if the various symptom spectra are characterized by unique and partly distinct neural patterns. Answers to these questions might improve treatment and clinical handling of OCD, potentially leading to more individualized therapeutic interventions. These could also be of relevance for OCD drug-treatment research in detecting more specialized medication, with less side effects and fewer relapse rates, to be used as an additional supportive factor in therapy.