Salience network-midbrain dysconnectivity and blunted signals in schizophrenia

Theories of schizophrenia propose that abnormal functioning of the neural reward system
is linked to negative and psychotic symptoms, by disruption of reward processing and
promotion of context-independent false associations. Recently it has been argued that an
insula-anterior cingulate cortex (ACC) salience network system enables switching of
brain states from the default mode to a task-related activity mode. Abnormal interaction
between the insula-ACC system and reward processing regions may help explain
abnormal reinforcer processing and symptoms. Here we use fMRI to assess the neural
correlates of reward processing in schizophrenia. Furthermore we investigated functional
connectivity between the dopaminergic midbrain, a key region for the processing of
reinforcers, and other brain regions. In response to rewards, controls activated task
related regions (striatum, amygdala/hippocampus and midbrain) and the insula-ACC
salience network. Patients similarly activated the insula-ACC salience network system
but failed to activate task related regions. Reduced functional connectivity between the
midbrain and the insula was found in schizophrenia, with the extent of this abnormality
correlating with increased psychotic symptoms. The findings support the notion that
reward processing is abnormal in schizophrenia and highlight the potential role of
abnormal interactions between the insula-ACC salience network and reward regions.