Abstract
During rest, a set of brain areas shows increased activity compared to when people are performing complex tasks. This network is commonly referred to as the default-mode network (DMN) and includes the ventral and dorsal medial prefrontal cortex, posterior cingulate cortex and lateral posterior cortices. Activity within these regions is
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highly correlated during resting-state and is thought to reflect self-referential processes important for social cognitive functioning.Abnormal functioning of the DMN is associated with various psychiatric disorders including schizophrenia. However, it is also suggested that activity and connectivity within the DMN is caused or confounded by non-neural noise such as cardiorespiratory processes. The aim of this thesis was to gain more insight in the function of the DMN in self-referential processing and social cognition using functional MRI. The first part of the thesis is focused on healthy volunteers, while the second part describes two studies in unaffected siblings of patients with schizophrenia. These siblings are at increased genetic risk of developing the disorder and exhibit difficulties in social functioning. In the first study of this thesis, we investigated whether resting-state and task-induced activity within the DMN could be explained by effects of cardiorespiratory processes. This study showed that activity within the DMN is highly interconnected during resting-state and cannot be explained by cardiorespiratory confounds alone. In the second study, the role of the DMN in self-referential processing was assessed by investigating connectivity and activity during a self-referential processing task. This study revealed increased activity during self-referential processing within the DMN in combination with decreased functional coupling between areas of the network, suggesting functional specialization within the DMN. After focusing on DMN function in healthy controls, the third study investigatedresting-state DMN connectivity in siblings of schizophrenia patients and whether this was related to the functioning of the network during self-referential processing. Compared with controls, siblings showed exaggerated connectivity during resting-state between the midline areas of the DMN and this was associated with aberrant interactions between these areas during self-referential processing. These findings suggest that the functional organization of the DMN is aberrant in subjects at increased risk of developing schizophrenia. Finally, the fourth study showed that the unaffected siblings exhibit abnormal activation within the DMN, the amygdala and hippocampus during another important aspect of social cognition, namely emotion processing. Together, the studies of this thesis confirmed that activity within the DMN reflects self-referential mental activity relevant for social cognitive functioning and does not merely reflect physiological noise. In addition, these studies suggest that the DMN is organized in highly interconnected but functionally specialized regions. Abnormalities within this organization of the DMN may contribute to difficulties in social cognitive functioning observed in schizophrenia
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