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<p>Schizophrenia involves well-documented disruptions of large-scale brain coordination, but how strongly networks engage one another, and how that engagement recovers when disrupted, remains poorly understood. We identify amplitude proportionality, the maintenance and recovery of matched engagement strength between networks, as a core dimension of coordination, largely obscured by intrinsic timescale differences. We developed a timescale-aligned, time-resolved amplitude framework that isolates amplitude differences from temporal misalignments, applied to a multi-site schizophrenia cohort (160 controls, 151 patients) with test-retest validation in the Human Connectome Project (<i>n</i> = 827). Patients with schizophrenia showed greater amplitude imbalance, especially during fast fluctuations, along with more frequent re-entry into unbalanced states and slower recovery to stable amplitude coordination. The imbalance carried symptom-specific signatures: cerebellar amplitude abnormalities scaled with positive symptoms, while cognitive control and default-mode imbalance scaled with negative symptoms. Slower recovery was also associated with poorer reasoning and problem-solving. These findings identify aberrant amplitude proportionality and impaired recovery to magnitude balance as a core dynamic feature of schizophrenia, with circuit-resolved signatures mapping onto distinct symptom dimensions, providing individual-level metrics as candidate biomarkers and hypothesis-generating targets for future neuromodulation studies.</p>

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Aberrant recovery of timescale-aligned amplitude balance links to symptoms and cognition in schizophrenia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月10日

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  • Sir-Lord Wiafe,
  • Spencer Kinsey,
  • Najme Soleimani,
  • Raymond O. Nsafoa,
  • Nigar Khasayeva,
  • Amritha Harikumar,
  • Robyn Miller,
  • Vince D. Calhoun

摘要

Schizophrenia involves well-documented disruptions of large-scale brain coordination, but how strongly networks engage one another, and how that engagement recovers when disrupted, remains poorly understood. We identify amplitude proportionality, the maintenance and recovery of matched engagement strength between networks, as a core dimension of coordination, largely obscured by intrinsic timescale differences. We developed a timescale-aligned, time-resolved amplitude framework that isolates amplitude differences from temporal misalignments, applied to a multi-site schizophrenia cohort (160 controls, 151 patients) with test-retest validation in the Human Connectome Project (n = 827). Patients with schizophrenia showed greater amplitude imbalance, especially during fast fluctuations, along with more frequent re-entry into unbalanced states and slower recovery to stable amplitude coordination. The imbalance carried symptom-specific signatures: cerebellar amplitude abnormalities scaled with positive symptoms, while cognitive control and default-mode imbalance scaled with negative symptoms. Slower recovery was also associated with poorer reasoning and problem-solving. These findings identify aberrant amplitude proportionality and impaired recovery to magnitude balance as a core dynamic feature of schizophrenia, with circuit-resolved signatures mapping onto distinct symptom dimensions, providing individual-level metrics as candidate biomarkers and hypothesis-generating targets for future neuromodulation studies.