Objective: Impaired nucleus accumbens (NAcc) activation is associated with amotivation and anhedonia, which are resistant to treatment with antipsychotics and antidepressants in schizophrenia. In this study, healthy participants were trained to self-regulate the activation of their NAcc, a brain region that plays an important role in motivation, using real-time functional magnetic resonance imaging (fMRI) neurofeedback. Method: The experimental group (N = 19) received feedback from the NAcc, whereas the control group (N = 5) received “sham” feedback from the posterior parahippocampal gyrus, a control brain region not normally related to motivation. All participants were trained to use mental strategies to regulate their NAcc activations in a 3T MRI scanner. Results: For the learning effect of NAcc regulation, we found that the majority of participants (74%) in the experimental group successfully learned to self-regulate the NAcc. They also showed improved behavioral performance in motivation and decreased functional connectivity between the NAcc and the ventral medial prefrontal cortex and an increase in small-world properties in the reward circuit after training, indicating improved information integration in reward processing. However, improvement in motivation and modification of function connectivity were not observed in the sham control group and the participants who failed to self-regulate the NAcc in the experimental group. Self-regulation was influenced by the baseline motivation. Conclusions: These findings suggest that the NAcc could be self-regulated using real-time fMRI neurofeedback and can result in improved motivation in cognitive tasks.