General reviewBrain connectivity and auditory hallucinations: In search of novel noninvasive brain stimulation therapeutic approaches for schizophrenia

Auditory verbal hallucinations (AVH) are among the most characteristic symptoms of schizophrenia and have been linked to likely disturbances of structural and functional connectivity within frontal, temporal, parietal and subcortical networks involved in language and auditory functions. Resting-state functional magnetic resonance imaging (fMRI) has shown that alterations in the functional connectivity activity of the default-mode network (DMN) may also subtend hallucinations. Noninvasive neurostimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) have the ability to modulate activity of targeted cortical sites and their associated networks, showing a high potential for modulating altered connectivity subtending schizophrenia. Notwithstanding, the clinical benefit of these approaches remains weak and variable. Further studies in the field should foster a better understanding concerning the status of networks subtending AVH and the neural impact of rTMS in relation with symptom improvement. Additionally, the identification and characterization of clinical biomarkers able to predict response to treatment would be a critical asset allowing better care for patients with schizophrenia.