Dynamic Connectivity between Brain Networks Supports Working Memory: Relationships to Dopamine Release and Schizophrenia

作者：Cassidy Clifford M^*; Van Snellenberg Jared X; Benavides Caridad; Slifstein Mark; Wang Zhishun; Moore Holly; Abi Dargham Anissa; Horga Guillermo^*

来源：Journal of Neuroscience, 2016, 36(15): 4377-4388.

DOI：10.1523/JNEUROSCI.3296-15.2016

• dopamine
• multimodal imaging
• network functional connectivity
• positron emission tomography
• schizophrenia
• working memory

Connectivity between brain networks may adapt flexibly to cognitive demand, a process that could underlie adaptive behaviors and cognitive deficits, such as those observed in neuropsychiatric conditions like schizophrenia. Dopamine signaling is critical for working memory but its influence on internetwork connectivity is relatively unknown. We addressed these questions in healthy humans using functional magnetic resonance imaging (during an n-back working-memory task) and positron emission tomography using the radiotracer [C-11]FLB457 before and after amphetamine to measure the capacity for dopamine release in extrastriatal brain regions. Brain networks were defined by spatial independent component analysis (ICA) and working-memory-load-dependent connectivity between task-relevant pairs of networks was determined via a modified psychophysiological interaction analysis. For most pairs of task-relevant networks, connectivity significantly changed as a function of working-memory load. Moreover, load-dependent changes in connectivity between left and right frontoparietal networks (Delta connectivity lFPN-rFPN) predicted interindividual differences in task performance more accurately than other fMRI and PET imaging measures. Delta Connectivity lFPN-rFPN was not related to cortical dopamine release capacity. A second study in unmedicated patients with schizophrenia showed no abnormalities in load-dependent connectivity but showed a weaker relationship between Delta connectivity lFPN-rFPN and working memory performance in patients compared with matched healthy individuals. Poor working memory performance in patients was, in contrast, related to deficient cortical dopamine release. Our findings indicate that interactions between brain networks dynamically adapt to fluctuating environmental demands. These dynamic adaptations underlie successful working memory performance in healthy individuals and are not well predicted by amphetamine-induced dopamine release capacity.

• 出版日期2016-4-13