Windows on the brain : functional neuroimaging studies in obsessive-compulsive disorder

Just as in many other major psychiatric disorders, in OCD the advent of neuroimaging techniques has brought new opportunities for research into its neurobiology. In the research for this thesis two functional neuroimaging techniques, functional magnetic resonance imaging (fMRI) and Single Photon Emission Tomography (SPECT) were used to further explore neuropsychological functioning and neurochemistry in OCD. Neuropsychological functioning Chapter II describes the results of the first study to examine whether antisaccadic abnormalities in OCD represent a stable feature of the disorder or a feature that normalizes with treatment, i.e. are a state dependent phenomenon. In the first part of the study we found that patients with OCD have normal error rates on the antisaccade and fixation tasks, but need more time to initiate antisaccades. This finding indicates that patients with OCD have no gross impairment of oculomotor inhibitory capacities and does not support the notion of impaired inhibition being a common denominator of cognitive disturbances in OCD In the second part of the study we found no effects of pharmacotherapy or response on performance on the three oculomotor tasks, indicating that the specific pattern of oculomotor performance in OCD seems to constitute a state-independent phenomenon, i.e. a stable feature of the disorder. Chapter III presents a functional MRI study in which performance on a working memory task with increasing levels of difficulty (n-back), as well as the underlying neuronal substrate and its dynamics, were assessed in treatment-free patients with OCD with no comorbidity and pair-wise matched healthy controls. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions during the task as the matched healthy controls. Only in a region covering the anterior cingulate the activity was significantly elevated in patients with OCD at all levels of the task. The activity pattern in the other brain regions was comparable to that in controls. These findings do not provide evidence for a deficit of the spatial working memory system proper. Interestingly, studies examining the role of the anterior cingulate in executive functioning in healthy volunteers and non-human primates have led to hypotheses that the anterior cingulate plays a key role in the implementation or evaluation of a strategy. In chapter IV we demonstrated that that spatial working memory deficits in OCD and their functional anatomical correlates are, at least to some extent, related to OCD symptomatology, i.e. state dependent. Neurochemistry In Chapter IV and V two studies are described that examined the serotonergic and domainergic system in OCD by means of [123 I]beta-CIT SPECT or [123 I] IBZM, in combination with an MRI for delineation of the regions of interest. Patients with OCD showed increased densities of dopamine transporters and decreased densities of D2 receptors in the basal ganglia, supporting the notion of an increased striatal dopaminergic transmission as postulated in the fronto-thalamo-striatal model for OCD