Enhancement of the left frontoparietal network through real-time functional magnetic resonance imaging functional connectivity-informed neurofeedback and its impact on working memory in schizophrenia: A pilot study.

Aim: Cognitive impairment in schizophrenia shows limited improvement with pharmacotherapy, indicating a need for effective treatment. The frontoparietal network supports working memory, and a biomarker has successfully predicted performance in patients, with the left frontoparietal network contributing the most to working memory. We hypothesized that enhancing functional connectivity in this network through real-time neurofeedback (NF) will improve working memory in patients with schizophrenia.

Methods: We conducted a two-arm, nonrandomized pilot study in patients with schizophrenia, with a NF group (N = 11) and a control N-back training group (N = 11). The NF training lasted 5 days (one session per day). The first session included baseline measurements, while the next four sessions involved training. The participants completed cognitive and clinical assessments and resting-state scans preintervention and postintervention. Our primary neural outcome was increased functional connectivity during NF, and the behavioral outcome was improvement in working memory, as indicated by scores on the digit-span backward task and working memory capability measured by the N-back task.

Results: The NF group showed increased functional connectivity within the left frontoparietal network during the final session. A significant correlation existed between functional connectivity and the improvement in the mean N-back level, indicating that enhancing this network can boost working memory. A group-by-time interaction effect improved postintervention task score on the digit-span backward task in the NF group. In addition, post-NF scans indicated an enhanced resting-state functional connectivity within the left frontoparietal network.

Conclusion: These results highlight the potential of functional connectivity-informed NF as a novel therapeutic approach for improving working memory in schizophrenia.

Clinical trial registration: Japan Registry of Clinical Trials (UMIN000024831, jRCTs052180168, jRCTs032190244).