Common and distinct global functional connectivity density alterations in patients with bipolar disorder with and without auditory verbal hallucination during major depressive episodes

Although an increasing number of studies has explored the neural mechanisms of auditory verbal hallucination (AVH) using many modalities, including neuroimaging, neurotransmitters, and electroencephalography, the etiology of AVH remains unclear. In this study, we investigated the neuroimaging characteristics of AVH in patients with bipolar disorder (BD) experiencing depressive episodes with and without AVH. For this study, we recruited 80 patients with BD and depressive status (40 with and 40 without AVH), and 40 healthy individuals. Their global functional connectivity density (gFCD) was screened by functional magnetic resonance imaging. Differences in gFCD among the three groups were tested using voxel-wise one-way analysis of covariance. Patients in both BD groups demonstrated increased gFCD in the central parietal lobe, insular lobe, and middle cingulate cortex, and decreased gFCD in the posterior parietal cortex, lateral prefrontal cortex, and occipital lobe (all bilateral). We defined these alterations as the common aberrant gFCD pattern for BD with and without AVH. Compared with the other two groups, patients in the BD with AVH group demonstrated increased gFCD in the Broca and Wernicke regions, and decreased gFCD in the hippocampus (all bilateral). We defined these alterations as the distinct aberrant gFCD pattern for BD with AVH. To our knowledge, this report is the first to date to describe gFCD alterations in patients with BD with and without AVH. Our findings suggest that disturbances in brain activity and information communication capacity in patients with BD and AVH are located mainly in the left frontoparietal network, control network, and memory circuit. However, these observations were made only in patients with BD during depressive episodes, and without consideration of many factors, such as the treatment mode, symptom relapse, and BD subtype. Hence, the conclusions of this study merely provide clues for further study, and do not fully represent brain alterations in patients with BD and AVH. Further large-sample cohort studies are needed to clarify and expand on these findings.