Differential excitatory-inhibitory balance within dorsolateral prefrontal cortex links inter-network interactions in working memory

Working memory involves complex activity and interactions across multiple brain areas. However, little is known about how these large-scale activity and interaction patterns relate to resting-state activity and to excitatory and inhibitory interactions within localized brain regions. Here we show, using multimodal neuroimaging and large-scale neural network modelling, that excitatory and inhibitory neuronal activities within the dorsolateral prefrontal cortex (DLPFC) are linked to inter-network interactions during working memory.

We generate testable predictions by perturbing a resting-state functional magnetic resonance imaging (fMRI)-constrained neural network model and by performing molecular-enriched analyses using fMRI and positron emission tomography (PET) receptor maps. We then show that frontoparietal and default-mode network activity, which differs between resting state and working memory, covaries with DLPFC activity and its functional interactions with these networks. These findings provide a mechanistic account of how local excitatory and inhibitory activity may support large-scale network dynamics involved in working memory.

We appreciate the suggestions on writing the manuscript from Prof. Stefano Panzeri and Prof. This work was supported in part by the National Natural Science Foundation of China under Grant 62306083, in part by Heilongjiang Provincial Natural Science Foundation, Youth Project B (YQ2025F009), in part by Young Science and Technology Talents of Heilongjiang Province (RC2025QN107), in part by Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, and in part by the National Social Science Fund of China (24CYY089).

School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, China Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Beijing, China School of Medicine and Health, Harbin Institute of Technology, Harbin, China Haiqi Zhu, Zehua Lv, Shijie Zhou, Baichun Wei & Chunzhi Yi School of Foreign Studies, Xi’an Jiao Tong University, Xi’an, China School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China Zhengzhou Advanced Research Institute, Harbin Institute of Technology, Zhengzhou, China Suzhou Research Institute, Harbin Institute of Technology, Suzhou, China Correspondence to Baichun Wei or Chunzhi Yi. The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Xu, Z., Zhu, H., Li, Y. et al. Differential excitatory-inhibitory balance within dorsolateral prefrontal cortex links inter-network interactions in working memory.