Temporal imprecision of the self in drug-free psychosis: Abnormal infraslow phase dynamics and brain complexity

Self-disturbance is a core feature of schizophrenia (SCZ) and may emerge during the prodromal phase. Temporal imprecision has recently been proposed as a core neural mechanism in schizophrenia, primarily demonstrated in faster EEG frequency ranges. Whether such imprecision extends to infraslow brain dynamics in functional magnetic resonance imaging (fMRI) and relates to self-disturbance in early psychosis remains unknown.

Here, we examined resting-state fMRI data from drug-free early psychosis patients (EPdrug-free, n = 31, scanned before and after medication) and 31 healthy controls (HC). Brain dynamics were quantified using sample entropy (SampEn) and instantaneous peak frequency (PF) in regions associated with different layers of self-processing (interoceptive, exteroceptive, and mental). Compared to controls, EPdrug-free showed higher SampEn and slower mean PF with greater variability than HC, particularly in the regions of the exteroceptive self.

Moreover, EPdrug-free exhibited a decoupling between SampEn and PF, whereas HC showed strong correlations. Both SampEn and PF significantly contributed to diagnostic classification, and increased SampEn was associated with greater severity of negative, disorganized, and anxiety/depression symptoms. Together, these findings indicate abnormal infraslow brain dynamics in early psychosis, characterized by increased neural complexity and disrupted temporal organization.

This temporal imprecision, particularly within the exteroceptive self, may represent a key mechanism linking altered brain dynamics to self-disturbance and psychopathology in early psychosis. We would like to thank all the members of the Department of Psychiatry and the staff of Department of Medical Research at National Taiwan University Hospital and the National Science and Technology Council, Taiwan, for their valuable administrative support. We also sincerely appreciate all the participants for their time, effort, and dedication to this study.

This study was supported by grants from National Science and Technology Council, Taiwan (MOST 111-2314-B-002-101-MY3) and National Taiwan University Hospital (NTUH 111-S0203; 112-S0148). School of Psychology, University of Ottawa, Ottawa, ON, Canada Mind, Brain Imaging and Neuroethics Unit, University of Ottawa Institute of Mental Health Research at The Royal, Ottawa, ON, Canada I-Fei Chen, Yujia Ao, Stephan Lechner & Georg Northoff Brain and Cognition Research Center, BEYKOG, İstanbul Medipol University, Istanbul, Türkiye Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Chen-Chung Liu, Tzung-Jeng Hwang, Yi-Ting Lin, Ming H. Hsieh, Yi-Ling Chien, Hai-Gwo Hwu & Chih-Min Liu Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan Department of Psychiatry, School of Medicine, Tzu Chi University, Hualien, Taiwan Correspondence to Chih-Min Liu or Georg Northoff.

The authors declare no competing interest. This study was approved by the National Taiwan University Hospital Institutional Review Board (IRB number: 201006054R). All methods were performed in accordance with the relevant guidelines and regulations.