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Published in Neuroscience and biobehavioral reviews on January 26, 2026.

Unraveling the Brain's Hidden Circuits in Schizophrenia

Mapping intrinsic brain activity and multilevel mechanisms underlying auditory verbal hallucinations in schizophrenia: A systematic review and meta-analysis.

Neuroscience and biobehavioral reviews • January 26, 2026 • Review • Moderately Relevant

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AI Summary

This groundbreaking research delves into the complex neurological mechanisms behind auditory verbal hallucinations (AVH) in schizophrenia, revealing intricate brain activity patterns that have profound implications for understanding mental health disorders. Using advanced neuroimaging techniques like resting-state fMRI, researchers mapped brain activity and discovered significant neural network disruptions associated with these hallucinations.

The study uncovered a multilevel perspective on AVH, highlighting increased intrinsic brain activity in multiple neural networks, including auditory, language, reward, and executive control regions. Notably, the research found strong spatial correlations between AVH-related brain activity and neurotransmitter systems, particularly involving cannabinoid (CB1), dopaminergic, and glutamate receptors. This suggests a complex interplay between neurodevelopmental vulnerabilities, genetic factors, and neurochemical dysregulation that may contribute to the emergence of hallucinations.

By integrating neuroimaging, neurotransmitter analysis, and genetic research, the study proposes a sophisticated systems-level model that explains how early developmental and genetic factors interact with ongoing neural network dysfunction. The findings are crucial for developing more precise diagnostic and intervention strategies for schizophrenia, potentially opening new avenues for targeted treatments that address the underlying mechanisms of auditory verbal hallucinations.

📄 Original Abstract

Auditory verbal hallucinations (AVH) represent one of the most debilitating symptoms in schizophrenia. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF), derived from resting-state fMRI, serve as robust metrics for intrinsic brain activity; however, their network-level and biological correlates of AVH have yet to be systematically elucidated. We conducted a comprehensive systematic review and meta-analysis of ALFF/fALFF studies in schizophrenia with AVH, integrating neurochemical and genetic annotation to provide a multilevel perspective. Across studies, AVH was consistently associated with increased intrinsic activity in auditory and language networks, reward and motivation circuits, and executive control regions, along with decreased activity in sensorimotor network. While alternations within the default mode network were more heterogeneous. Meta-analysis further highlighted the involvement of thalamic-frontal network in distinguishing AVH from non-AVH patients. Spatial correlation analysis demonstrated strong associations between AVH-related activity changes and the distribution of cannabinoid (CB1), dopaminergic (D2), noradrenergic (NAT), and metabotropic glutamate (mGluR5) neurotransmitter systems. Gene enrichment analysis revealed that implicated regions were transcriptionally characterized by pathways related to neurodevelopment, neural circuit formation, and regulation of neural activity. By integrating these multilevel findings, we propose a systems-level model in which early neurodevelopmental and genetic vulnerabilities interact with ongoing neurotransmitter dysregulation and large-scale network dysfunction, ultimately driving the emergence and persistence of AVH in schizophrenia. These findings underscore the importance of developing multidimensional biomarkers and may inform the design of future precision interventions targeting AVH in schizophrenia.

Paper Type

📚 Review

Publication

Journal: Neuroscience and biobehavioral reviews
Published: January 26, 2026
PMID: 41605340
DOI: 10.1016/j.neubiorev.2026.106579

Authors (14)

Yuanjun Xie Department of Military Medical Psychology, Air Force Medical University, Xi'an, China. Electronic address: xieyuanj@gmail.com.
Tian Zhang Department of Military Medical Psychology, Air Force Medical University, Xi'an, China.
Anping Ouyang Department of Military Medical Psychology, Air Force Medical University, Xi'an, China.
Guan Muzhen Department of Mental Health, Xi'an Medical College, Xi'an, China.
Xinxin Lin Department of Military Medical Psychology, Air Force Medical University, Xi'an, China.
+9 more authors