Effects of metacognitive training on the neurophysiological correlates of the jumping-to-conclusions bias in schizophrenia
Human Cognitive and Systems Neuroscience
Final Report Abstract
Reasoning biases such as the jumping-to-conclusions bias (JTC) are thought to significantly contribute to delusions in schizophrenia, and metacognitive interventions targeting these biases, such as metacognitive training (MCT), may improve delusions. So far, it is not clear whether JTC depends on dopaminergic reward areas that constitute the locus of action of antipsychotic drugs, or rather on dopamine-independent cortical areas. Activations across widely distributed brain areas including the prefrontal, parietal, medial temporal cortex, thalamic/striatal areas and the insula have been reported in connection with specific aspects of probabilistic reasoning, but previous findings are difficult to integrate into one coherent account. The objective of the present project was to investigate the neurophysiological correlates of probabilistic reasoning, and their changes following MCT, in patients with delusions. Functional MRI brain activation and functional connectivity patterns during a probabilistic reasoning paradigm (Box Task) were examined in 27 healthy controls and in 30 patients with delusions. Only medication-free or medication-resistant patients were included in the project in order to minimize antipsychotic medication effects. A second fMRI was carried out in patients after a course of MCT. In healthy controls, conclusion events were associated with extensive activations in widely distributed brain areas associated with the task-positive network (TPN), such as the dorsal anterior cingulate cortex, right prefrontal cortex, medial occipital areas, thalamus, bilateral (mainly inferior) parietal areas, and anterior insula. In contrast, draw events were characterized by higher activation in brain areas assumed to be part of the tasknegative network (TNN), i.e. inferior medial prefrontal cortex, ventral anterior cingulate cortex, posterior cingulate cortex, angular gyrus, and right posterior insula. There were no differences between patients and controls in brain activation and connectivity patterns. However, presence of JTC (irrespective of group) was associated with lower activity in the dorsal striatum, and lower connectivity between this area and inferior parietal cortex, during final conclusion events. In addition, MCT responders exhibited higher activity in areas of the taskpositive network and higher connectivity between inferior parietal cortex (BA40) and salience/reward areas. In summary, the present study indicates that probabilistic reasoning in the absence of a reward context is dependent on the balance between the task-positive and task-negative network, and that shifts in effective connectivity between the two networks may be crucial for data-gathering. Although JTC is associated with dysregulated activity in reward system areas that constitute the main target of antipsychotic drugs, its improvement may be dependent on cortical areas belonging to the task-positive network, and their ability to regulate the reward system. These findings point to additional pathophysiological mechanisms, supplementary to dopaminergic antagonism, which may help improve JTC and delusions.
Publications
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(2018) fMRI correlates of jumping-to-conclusions in patients with delusions: Connectivity patterns and effects of metacognitive training. NeuroImage: Clinical 20 119-127
Andreou, C., Steinmann, S., Leicht, G., Kolbeck, K., Moritz, S., Mulert, C.
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(2018) The role of effective connectivity between task-positive and task-negative network in evidence gathering and connectivity [Evidence gathering and connectivity]. NeuroImage 173 49–56
Andreou, Christina; Steinmann, Saskia; Kolbeck, Katharina; Rauh, Jonas; Leicht, Gregor; Moritz, Steffen; Mulert, Christoph
