Real-time fMRI neurofeedback modulates auditory cortex activity and connectivity in schizophrenia patients with auditory hallucinations: A controlled study.
Clemens C C Bauer, Jiahe Zhang, Francesca Morfini, Oliver Hinds, Paul Wighton, Yoonji Lee, Lena Stone, Angelina Awad, Kana Okano, Melissa Hwang, Jude Hammoud, Paul G. Nestor, Susan Whitfield-Gabrieli, Ann K Shinn, Margaret Niznikiewicz
Psychiatry research. Neuroimaging October 1, 2025 DOI: 10.1016/j.pscychresns.2025.112050 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, sham-controlled trial Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Adults with schizophrenia/schizoaffective disorder and medication-resistant auditory hallucinations |
| Interventions | Real-time fMRI neurofeedback Mindfulness meditation |
| Topics | Default mode network Meditation |
| Keywords | Dorsolateral prefrontal cortex Superior temporal gyrus |
| Key findings | Real-time fMRI neurofeedback targeting the superior temporal gyrus, combined with mindfulness meditation, produced greater reductions in secondary auditory cortex activation and connectivity between auditory cortex and cognitive control regions than sham neurofeedback, but both groups showed similar symptom reduction. |
Abstract
Auditory hallucinations (AHs) affect 60-80 % of schizophrenia patients and often resist antipsychotic treatment. AHs involve superior temporal gyrus (STG) hyperactivity and disrupted auditory-cognitive control connectivity. Real-time fMRI neurofeedback (NFB) enables voluntary modulation of targeted brain regions. We previously showed STG-targeted NFB with mindfulness meditation reduced STG activation and AHs in one session. However, whether effects are specific to hallucination-related regions versus placebo, and whether NFB modulates broader networks, remained unclear. This randomized, sham-controlled trial examined NFB specificity and network effects. Twenty-three adults with schizophrenia/schizoaffective disorder and medication-resistant hallucinations practiced mindfulness meditation while receiving neurofeedback from either STG (n = 10, Real-NFB) or motor cortex (n = 13, Sham-NFB control). Sham participants subsequently received Real-NFB, providing within-subject comparison. Both groups showed reduced AHs post-NFB without group differences. However, compared to Sham-NFB, Real-NFB produced greater reductions in secondary auditory cortex activation and connectivity between auditory cortex and cognitive control regions (dorsolateral prefrontal cortex and anterior cingulate). These connectivity reductions persisted in the Real-after-Sham condition. Both groups showed reduced primary auditory cortex activation, suggesting mindfulness meditation independently regulates bottom-up hallucination processes. Region-specific NFB targeting produces distinct neural changes beyond symptom reduction. STG-targeted NFB differentially modulates auditory-cognitive control networks, potentially restoring the disrupted balance between bottom-up sensory processing and top-down control in AHs. These findings highlight the importance of anatomically-informed NFB targets and provide mechanistic insights for developing precision interventions for treatment-resistant psychiatric symptoms.