# Dynamic Brain Age Modeling Identifies Network-Specific Cognitive Deficits in Schizophrenia

**Authors:** Mohammad Sendi, Sabrina Edwards-Swart, Bradley Baker, Daniel Mathalon, Judith Ford, Adrian Preda, Theo van Erp, Godfrey Pearlson, Jessica Turner, Vince Calhoun

PMC · DOI: 10.21203/rs.3.rs-7336363/v1 · 2025-10-10

## TL;DR

This study shows that dynamic brain connectivity can reveal cognitive issues in schizophrenia, particularly in attention and memory.

## Contribution

The study introduces dynamic brain age modeling as a novel method to identify cognitive deficits in schizophrenia.

## Key findings

- Dynamic brain age gaps (BAGs) are strongly linked to attention and working memory deficits in schizophrenia.
- Network-specific BAGs in cognitive control and default mode networks are robust predictors of cognitive impairment.
- Dynamic connectivity models outperform static models in predicting cognitive dysfunction.

## Abstract

Schizophrenia is characterized by deficits in attention and working memory. The brain age gap (BAG), the difference between brain-predicted and chronological age, has emerged as a biomarker of brain dysfunction, but its association with dynamic brain function remains unclear. We developed brain age models using static (sFNC) and dynamic (dFNC) functional network connectivity from a large resting-state fMRI dataset (N = 22,569; UK Biobank, HCP-Young Adult, HCP-Aging) and validated them in an independent schizophrenia cohort (FBIRN; N = 153). Higher BAGs were significantly associated with lower attention and working memory performance (FDR p < 0.01), with dFNC-based models showing more potent effects than sFNC. Network-specific BAGs, particularly within cognitive control, default mode, and subcortical networks, were robust predictors of cognitive impairment. These findings establish dFNC-based BAG as a sensitive biomarker of cognitive dysfunction in schizophrenia and highlight the value of dynamic connectivity measures for advancing precision diagnostics and stratification.

## Linked entities

- **Diseases:** schizophrenia (MONDO:0005090)

## Full-text entities

- **Diseases:** brain dysfunction (MESH:D001927), Schizophrenia (MESH:D012559), deficits in attention and working memory (MESH:D001289), Cognitive Deficits (MESH:D003072)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12632720/full.md

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Source: https://tomesphere.com/paper/PMC12632720