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Modulation of brain complexity in schizophrenia patients with auditory verbal hallucinations by low-frequency rTMS stimulation

Clin Neurophysiol. 2025 May 17;175:2110752. doi: 10.1016/j.clinph.2025.2110752. Online ahead of print.

ABSTRACT

BACKGROUND: Entropy is a critical measure for assessing the complexity and irregularity of brain signals. Understanding how brain entropy can be influenced by non-invasive neurostimulation in psychiatric patients remains a clinically relevant issue.

OBJECTIVE: This study aims to explore whether low-frequency repetitive transcranial magnetic stimulation (rTMS) can modulate brain entropy in schizophrenia patient with auditory verbal hallucinations (AVH).

METHODS: A case-control design was employed in this study. Low-frequency (1 Hz) rTMS targeting at left temporoparietal junction was administered to schizophrenia patients with AVH. Brain entropy (sample entropy) was calculated from resting-state functional magnetic resonance imaging (fMRI) data. Comparisons of sample entropy were made between the schizophrenia patients and healthy controls, as well as within the patient group pre- and post-rTMS.

RESULTS: Following rTMS treatment, patients showed a reduction in clinical symptoms, including positive symptoms and AVH. Neurocognitive improvements were also observed in domains such as verbal and visual memory. Furthermore, patients exhibited increased sample entropy in regions including the prefrontal cortices and temporal lobes compared to healthy controls. However, this elevated entropy was reduced post-rTMS, particularly in areas associated with AVH. The language network and default model network, initially showing high mean sample entropy, demonstrated a significant decrease after rTMS treatment. These changes in brain entropy were correlated with clinical improvements.

CONCLUSION: This modulation of neural activity complexity induced by the low-frequency rTMS may underlie the observed clinical and cognitive improvement in schizophrenia.

PMID:40413810 | DOI:10.1016/j.clinph.2025.2110752

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