Altered reward-related effective connectivity in obsessive-compulsive disorder: an fMRI study

Background: Obsessive­compulsive disorder (OCD) is characterized by anxiety-provoking, obsessive thoughts. Patients usually react to these thoughts with repetitive behaviours that reduce anxiety and are perceived as rewarding. Hence, reward plays a major role in the psychopathology of OCD. Previous studies showed altered activation in frontostriatal networks, among others, in association with the processing of reward in patients with OCD. Potential alterations in connectivity within these networks have, however, barely been explored. Methods: We investigated a sample of patients with OCD and healthy controls using functional MRI and a reward learning task presented in an event-related design. Dynamic causal modelling (DCM) was used to estimate effective connectivity. Results: Our sample included 37 patients with OCD and 39 healthy controls. Analyses of task-related changes in connectivity showed a significantly altered effective connectivity between the ventromedial prefrontal cortex (vmPFC) and the orbitofrontal cortex (OFC), among others, both in terms of endogenous connectivity as well as modulatory effects under positive feedback. Clinical measures of compulsion correlated with the effect of feedback input on visual sensory areas. Limitations: The reported alterations should be interpreted within the context of the task and the a priori­defined network considered in the analysis. Conclusion: This disrupted connectivity in parts of the default mode network and the frontostriatal network may indicate increased rumination and self-related processing impairing the responsiveness toward external rewards. This, in turn, may underlie the general urge for reinforcement accompanying compulsive behaviours.

Network-based decoupling of local gyrification in obsessive-compulsive disorder.

Gyrification is associated with cortical maturation and closely linked to neurodevelopmental processes. Obsessive-compulsive disorder has previously been associated with neurodevelopmental risk factors. Using graph theoretical modeling we examined structural covariance patterns to assess potential disruptions in processes associated with neurodevelopment in OCD. In total 97 patients and 92 healthy controls underwent magnetic resonance imaging. Structural covariance networks based on local gyrification indices were constructed using an atlas-based parcellation scheme. Network properties were assessed using the network-based statistic as well as global and local graph theoretical measures. Correlations between gyrification and symptom severity as well as age of disease onset were examined. Network-based statistic analysis revealed one cluster with significantly decreased structural covariance in patients comprising mainly ventral brain regions (p = .041). Normalized characteristic path length was found to be impaired in patients (p = .051). On a nodal level, left middle frontal sulcus displayed a significantly decreased local clustering coefficient (p < .001). Finally, gyrification in several inferior frontal nodes significantly correlated with age of onset but not symptom severity. The decrease in a gyrification-based covariance network in OCD appears to be mostly confined to ventral areas in which gyrification starts the latest during development. This pattern may indicate that alterations taking place during development are potentially time locked to specific periods. Correlations between gyrification in inferio-frontal nodes and age of onset potentially indicate a structural trait rather than state marker for OCD. Finally, a trend in impaired global integration capabilities may point towards potentially widespread global alterations during neurodevelopment in patients.

Structural alterations in patients with obsessive-compulsive disorder: a surface-based analysis of cortical volume, surface area and thickness.

BACKGROUND: Mounting evidence indicates the presence of structural brain alterations in individuals with obsessive-compulsive disorder (OCD). Findings are, however, rather heterogeneous, which may be partly because of differences in methodological approaches or clinical sample characteristics. The aim of the present study was to analyze the whole brain cortical volume, surface area and thickness in a large sample of patients with OCD compared with age- and sex-matched healthy controls. METHODS: We conducted whole brain surface-based analyses of grey matter measures using the automated FreeSurfer software in patients with OCD and matched controls. Group analyses were performed and corrected for multiple testing using Monte Carlo simulations (p < 0.05). Altered brain regions and their average morphological values were associated to symptom severity and type (Yale-Brown Obsessive Compulsive Scale scores). RESULTS: We included 75 patients and 75 controls in our analyses. Patients with OCD showed decreases in both volume and surface area compared with healthy controls in inferior-superior parieto-occipital regions. In addition, the precuneus, posterior cingulate areas, middle frontal and orbitofrontal areas, and middle inferior temporal areas extending to the fusiform gyrus were characterized by a reduced surface area only. There were no differences in grey matter thickness between the groups. LIMITATIONS: The presence of comorbidities, medication usage and the multisymptomatic feature of OCD could have influenced our results to a certain degree. CONCLUSION: Our results suggest decreased grey matter volume and surface area in several key regions in patients with OCD. Parietal regions showed reductions in both volume and surface area, which underlines the potential relevance of these regions for the pathophysiology of the disorder.

Extensive learning is associated with gray matter changes in the right hippocampus.

Longitudinal voxel-based morphometry studies have demonstrated increases in gray matter volume in hippocampal areas following extensive cognitive learning. Moreover, there is increasing evidence for the relevance of the subiculum in the context of learning and memory. Using longitudinal FreeSurfer analyses and hippocampus subfield segmentation the present study investigated the effects of 14weeks of intensive learning on hippocampal and subicular gray matter volume in a sample of medical students compared to control subjects not engaged in any cognitive learning activities. We found that extensive learning resulted in a significant increase of right hippocampal volume. Volume of the left hippocampus and the subiculum remained unchanged. The current findings emphasize the role of the hippocampus in semantic learning and memory processes and provide further evidence for the neuroplastic ability of the hippocampus in the context of cognitive learning.

Functional connectivity and grey matter volume of the striatum in schizophrenia.

BACKGROUND: Alterations in the dopaminergic reward system, predominantly the striatum, constitute core characteristics of schizophrenia. AIMS: Functional connectivity of the dorsal striatum during reward-related trial-and-error learning was investigated in 17 people with schizophrenia and 18 healthy volunteers and related to striatal grey matter volume and psychopathology. METHOD: We used voxel-based morphometry and psychophysiological interaction to examine striatal volume and connectivity. RESULTS: A reduced functional connectivity between left striatum and temporo-occipital areas, precuneus and insula could be detected in the schizophrenia group. The positive correlation between grey matter volume and functional connectivity of the left striatum yielded significant results in a very similar network. Connectivity of the left striatum was negatively correlated with negative symptoms. CONCLUSIONS: Present results suggest a disruption in striatal functional connectivity that is closely linked to grey matter morphometry of the striatum. Decreased connectivity between the striatum and psychopathologically relevant networks may explain the emergence of negative symptoms.

Checking and washing rituals are reflected in altered cortical thickness in obsessive-compulsive disorder.

There is growing evidence for structural brain alterations in obsessive-compulsive disorder (OCD). The overall picture is however rather heterogeneous. To detect meaningful associations between clinical symptom profiles and structural alterations, we applied a classification approach, the k-means cluster analysis on clinical data, i.e., the Obsessive Compulsive Inventory-Revised (OCI-R) questionnaire. 73 OCD patients were assigned to three distinct symptom profiles. Using structural MRI and surface-based morphometric analysis (SBM), we compared cortical thickness between all OCD patients and 69 matched healthy subjects as well as among patients according to three symptom profiles. The total sample of OCD patients exhibited a thicker cortex in the pre-supplementary motor cortex (pre-SMA), dorsomedial prefrontal (DMPFC), anterior cingulate cortex and in the right anterior insula. Comparing patients of the three symptom clusters, a subgroup of OCD patients with a specific symptom profile was identified, which showed a thicker cortex in pre-SMA/DMPFC and in the contralateral primary motor cortex. In contrast to both other subgroups, patients in this group were mainly characterized by the predominance of a combination of checking and washing rituals. The other two OCD symptom subgroups showed comparable cortical thickness to healthy controls. Higher cortical thickness in regions of the motor circuitry seems to be related to motor activity-induced neuroplasticity in a specific group of OCD patients. Thicker anterior insular cortex in the total sample of patients points toward a more general pathophysiological process in OCD and potentially indicates abnormal interoceptive processing in OCD.

Association between hippocampus volume and symptom profiles in obsessive-compulsive disorder.

BACKGROUND: The hippocampus has recently been identified to play a key role in the pathophysiology of adult obsessive-compulsive disorder (OCD). Surprisingly, there is only limited evidence regarding the potential relationships with symptom dimensions. Due to the heterogeneity of symptoms in OCD, we aimed at further examining, whether hippocampal volume differences might be related to symptom profiles instead of single symptom dimensions. METHODS: In order to find out more about the potential association between clinical symptom profiles and alterations in hippocampal volume we categorized a large sample of OCD patients (N = 66) into distinct symptom profile groups using K-means clustering. In addition, hippocampal volumes of the different symptom profile groups were compared with hippocampal volumes in a sample of 66 healthy controls. RESULTS: We found significant differences in hippocampal volume between the different symptom profile groups which remained significant after correcting for age, sex, total intracranial volume, OCI-total score, depression, medication, disease duration and scanner. The patient group characterized by overall lower symptom scores and without high symptom severity in any specific domain showed the highest hippocampal volume. Finally, the comparison with healthy controls demonstrated significantly lower hippocampal volumes in those patients whose symptom profile was characterized by a high severity of ordering and checking symptoms. CONCLUSIONS: Present results provide further confirmation for alterations in hippocampus structure in OCD and suggest that symptom profiles which take into account the multi-symptomatic character of the disorder should be given greater attention in this context.

Functional and structural connectivity of the amygdala in obsessive-compulsive disorder.

BACKGROUND: The amygdala is known to be involved in anxiety processing, but its role in the psychopathology of obsessive-compulsive disorder (OCD) is still unclear. AIMS: In this MRI study we investigated potential alterations in structural and functional connectivity of the amygdala in 42 adult patients with OCD and 37 healthy subjects. METHOD: Psychophysiological interaction analysis was used to explore amygdala functional connectivity during a negative affective task. Probabilistic tractography was then employed to study structural connectivity and integrity of underlying white matter fiber tracts. RESULTS: Compared to controls, OCD patients showed a significantly increased functional connectivity of the left amygdala with mostly parieto-occipital regions during task. No structural connectivity differences could be found between the groups. In addition, only patients showed a significant association between functional and structural connectivity of these regions. Moreover, symptom severity was negatively associated with structural integrity of the underlying white matter tracts. CONCLUSIONS: Present results emphasize the relevance of the amygdala for OCD and may reflect that neuronal alterations in structural connectivity could be associated with functional connectivity alterations in broader networks.