A team led by Professor Zhen Yuan with Centre for Cognitive and Brain Sciences (CCBS) at the University of Macau UM) has made new progress in identifying the key brain networks underlying Language Deficits in Schizophrenia. The research results were published by the internationally renowned journal Translational Psychiatry (5 year IF=7.0, Nature sister journal).
Language impairment manifests as disorganized speech, difficulty in understanding nuance, and reduced verbal fluency. The impaired language function is a core but untreatable aspect of schizophrenia, severely impacting patients’ quality of life. While antipsychotics manage positive symptoms like hallucinations, they do little to improve these cognitive-linguistic deficits. The neural mechanisms behind these deficits have remained elusive, with individual studies reporting conflicting results.
By employing robust activation likelihood estimation (ALE) algorithms, the team detected two brain regions consistently implicated across all language tasks: the left middle frontal gyrus (MFG) and the left inferior frontal gyrus (IFG). Crucially, the study discovered that activity in the left MFG was consistently increased in patients with schizophrenia, demonstrating a potential compensatory mechanism or neural inefficiency.
“For the first time, we have a clear, quantitative picture of the dysfunctional language network in schizophrenia,” said Prof. Yuan. “We’ve moved from a long list of candidate regions to a focused set of core hubs that are reliably altered. This gives us a solid foundation for developing biomarkers and new treatment targets.”
Fig.1 A) the brain regions (the left MFG and the left IFG) with altered brain activations related to language processing across all modalities and all contrasts in patients with schizophrenia compared to healthy controls; B) the increased activations in the left MFG were convergently found in patients with schizophrenia across all modalities. Denotes: lMFG: left middle frontal gyrus; lIFG: left inferior frontal gyrus.
Fig 2. A) The convergently decreased activations in the right MFG related to language comprehension in schizophrenia; B) The convergently increased activations in the left IFG related to language production in schizophrenia. Denotes: lIFG: left inferior frontal gyrus; rMFG: right middle frontal gyrus.
More importantly, this work provides a much-needed neural framework for understanding language deficits in schizophrenia. By identifying consistent brain targets and clarifying the sources of heterogeneity (modality, age), it paves the way for:
- Targeted Interventions:Neuromodulation techniques like TMS or tDCS could be precisely aimed at the left MFG or IFG to normalize activity.
- Stratified Clinical Trials:Patients can be grouped based on their specific language deficit profile (comprehension vs. production) and age, leading to more personalized and effective clinical trials.
- Benchmarking:The identified patterns serve as a benchmark for measuring the efficacy of future cognitive rehabilitation therapies or novel pharmaceuticals.
This study marks a significant leap forward, transforming our understanding of a neglected yet devastating aspect of schizophrenia and offering a clear path toward finally addressing it.
The research was led by Prof. Yuan and his previous PhD student Dr. Yuwen He is the key member of this project. This work received joint support from multiple funding sources including RSKTO with University of Macau (MYRG-GRG2024-00259-FHS, MYRG2022-00054-FHS, and MYRG-GRG2023-00038-FHS-UMDF), and Macau Science and Technology Development Fund (FDCT 0014/2024/RIB1) .
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