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ORIGINAL RESEARCH article

Front. Neurosci.

Sec. Brain Imaging Methods

This article is part of the Research TopicExploring Neuropsychiatric Disorders Through Multimodal MRI: Network Analysis, Biomarker Discovery, and Clinical InsightsView all 4 articles

LLM-Based Feature Selection and Counterfactual Explanations Applied to Functional Connectivity Analysis in Schizophrenia

Provisionally accepted
Shaolong  WeiShaolong Wei1*Xinyan  YuanXinyan Yuan2Tiantian  ChenTiantian Chen2Yanyan  HeYanyan He2Lingling  GuLingling Gu2Ying  SunYing Sun2
  • 1School of Artificial Intelligence and Computer Science, Nantong University, Nantong, China
  • 2School of Electronics and Information, Jiangsu Vocational College of Business, Nantong, China

The final, formatted version of the article will be published soon.

ABSTRACT Schizophrenia (SZ) is a complex psychiatric disorder whose neural mechanisms are still unclear. Functional connectivity (FC) provides a unique perspective for understanding its pathology, but its high-dimensional nature poses significant challenges for feature selection and model interpretation. Traditional feature selection methods, while predictive, lack the integration of prior neuroscience knowledge, resulting in limited clinical relevance. To address this, we propose an innovative framework that combines feature selection guided by a large language model (LLM) with counterfactual explanation. This framework leverages brain disease knowledge encoded by the LLM to guide dimensionality reduction of high-dimensional FC, ensuring that selected features are both statistically significant and biologically plausible. Counterfactual explanations are then used to generate causal intervention examples, which are then translated by the LLM into intuitive explanations in natural language, providing understandable and actionable clinical insights for individual patients or physicians. We validate our approach on five real-world SZ datasets and demonstrate that it not only improves model classification performance but also provides new insights into SZ analysis.

Keywords: Counterfactual explanation, Feature Selection, functional connectivity, Large Language Model, Schizophrenia

Received: 25 Oct 2025; Accepted: 17 Dec 2025.

Copyright: © 2025 Wei, Yuan, Chen, He, Gu and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Shaolong Wei

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