Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia

Abstract Positive symptoms are a prominent feature of schizophrenia. Despite antipsychotic treatment, ~30% of patients develop refractory positive symptoms (RPSs). Current research fails to elucidate the potential neurophysiological mechanisms underlying RPSs, thereby hindering the development of ad...

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Main Authors: Xiaojuan Wang, Sitong Chen, Jie Li, Ying Gao, Shaobing Li, Meijuan Li, Xiaoya Liu, Shuang Liu, Dong Ming
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Schizophrenia
Online Access:https://doi.org/10.1038/s41537-025-00652-8
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author Xiaojuan Wang
Sitong Chen
Jie Li
Ying Gao
Shaobing Li
Meijuan Li
Xiaoya Liu
Shuang Liu
Dong Ming
author_facet Xiaojuan Wang
Sitong Chen
Jie Li
Ying Gao
Shaobing Li
Meijuan Li
Xiaoya Liu
Shuang Liu
Dong Ming
author_sort Xiaojuan Wang
collection DOAJ
description Abstract Positive symptoms are a prominent feature of schizophrenia. Despite antipsychotic treatment, ~30% of patients develop refractory positive symptoms (RPSs). Current research fails to elucidate the potential neurophysiological mechanisms underlying RPSs, thereby hindering the development of additional treatments. This study, which included 37 patients with RPSs and 40 with non-refractory positive symptoms (NRPSs), aimed to explore their underlying neural mechanisms. Outcome measures were relative power spectrum density and interregional synchronization across frequency bands and theta-gamma phase-amplitude coupling (θ-γ PAC). The single-frequency analysis indicated that RPSs exhibited elevated theta power and reduced lateralization in the left temporal lobe and temporo-parietal junction, along with enhanced functional connectivity in the left frontocentral region. The cross-frequency analysis revealed that RPSs exhibited slightly higher θ-γ coupling at the left temporo-parietal junction compared to NRPSs. Correlation analysis revealed significant associations among theta power, the lateralization index, functional connectivity, and the severity of positive symptoms. The aberrant activation of the theta rhythm in the left temporo-parietal region may lead to increased functional asymmetry in the brain, impeding interregional and inter-frequency information transmission and thus significantly impairing the normal processing of auditory information. These findings offer potential insights into the neurophysiological basis of positive symptoms in schizophrenia and may inform future clinical interventions.
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spelling doaj-art-452ce064ec4f4b09bf8be53bfdf372802025-08-20T03:45:52ZengNature PortfolioSchizophrenia2754-69932025-07-011111910.1038/s41537-025-00652-8Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophreniaXiaojuan Wang0Sitong Chen1Jie Li2Ying Gao3Shaobing Li4Meijuan Li5Xiaoya Liu6Shuang Liu7Dong Ming8Academy of Medical Engineering and Translational Medicine, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin UniversityInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical UniversityInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical UniversityInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical UniversityInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin UniversityAcademy of Medical Engineering and Translational Medicine, Tianjin UniversityAbstract Positive symptoms are a prominent feature of schizophrenia. Despite antipsychotic treatment, ~30% of patients develop refractory positive symptoms (RPSs). Current research fails to elucidate the potential neurophysiological mechanisms underlying RPSs, thereby hindering the development of additional treatments. This study, which included 37 patients with RPSs and 40 with non-refractory positive symptoms (NRPSs), aimed to explore their underlying neural mechanisms. Outcome measures were relative power spectrum density and interregional synchronization across frequency bands and theta-gamma phase-amplitude coupling (θ-γ PAC). The single-frequency analysis indicated that RPSs exhibited elevated theta power and reduced lateralization in the left temporal lobe and temporo-parietal junction, along with enhanced functional connectivity in the left frontocentral region. The cross-frequency analysis revealed that RPSs exhibited slightly higher θ-γ coupling at the left temporo-parietal junction compared to NRPSs. Correlation analysis revealed significant associations among theta power, the lateralization index, functional connectivity, and the severity of positive symptoms. The aberrant activation of the theta rhythm in the left temporo-parietal region may lead to increased functional asymmetry in the brain, impeding interregional and inter-frequency information transmission and thus significantly impairing the normal processing of auditory information. These findings offer potential insights into the neurophysiological basis of positive symptoms in schizophrenia and may inform future clinical interventions.https://doi.org/10.1038/s41537-025-00652-8
spellingShingle Xiaojuan Wang
Sitong Chen
Jie Li
Ying Gao
Shaobing Li
Meijuan Li
Xiaoya Liu
Shuang Liu
Dong Ming
Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia
Schizophrenia
title Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia
title_full Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia
title_fullStr Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia
title_full_unstemmed Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia
title_short Enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia
title_sort enhanced theta oscillations in the left temporoparietal region associated with refractory positive symptoms in schizophrenia
url https://doi.org/10.1038/s41537-025-00652-8
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