Impaired motivation is considered a fundamental aspect of the Avolition domain of negative symptoms. The ventral tegmental area (VTA) contains the highest number of DA neurons projecting to the brain areas involved in motivation-related processes.

The aim of our study was to investigate by functional MRI the resting-state functional connectivity (RS-FC) of the VTA in patients with schizophrenia and its relationships with real-life motivation and avolition.

The RS-FC was investigated in 22 healthy controls (HC) and in 26 schizophrenia patients (SCZ) treated with second generation antipsychotics only and divided in high (HA=13) and low avolition (LA=13) subgroups. We used the Quality of Life Scale and the Schedule for the Deficit Syndrome to assess real-life motivation and avolition, respectively.

HA, as compared to LA and HC, showed a reduced RS-FC of VTA with the right ventrolateral prefrontal cortex (R VLPFC), right posterior insula (R pINS) and right lateral occipital cortex (R LOC). The RS-FC for these regions was positively correlated with motivation in the whole sample and negatively correlated with avolition in schizophrenia patients.

Our findings demonstrate that motivational deficits in schizophrenia patients are linked to reduced functional connectivity in the DA circuit involved in retrieval of the outcome values of different actions to guide behavior. Further characterization of the factors modulating the functional connectivity in this circuit might foster the development of innovative treatments for avolition.