Abstract
Fluent speech production is mediated by serially ordering and preparing motor plans corresponding to target speech sounds, a process known as speech-motor sequencing. Here we used high-density direct cortical recordings while 14 participants spoke utterances with varying phonemic and syllabic sequence complexity after reading a target sequence and a delay period. Phasic activations corresponding to speech production and auditory feedback were observed, but also sustained neural activity that persisted throughout all task phases including the target presentation, the delay period and production of the sequence. Furthermore, sustained activity in a specific area, the middle precentral gyrus (mPrCG), was both modulated by sequence complexity and predicted reaction time, suggesting a role in speech-motor sequencing. Electrocortical stimulation of the mPrCG caused speech disfluencies resembling those seen in apraxia of speech. These results suggest that speech-motor sequencing is mediated by a distributed cortical network in which the mPrCG plays a central role.
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Data availability
Data that support the main conclusions of the paper are available via Zenodo at https://doi.org/10.5281/zenodo.15346719 (ref. 78). Source data are provided with this paper. Specific statistical data is also provided in the Supplementary Data.
Code availability
Code for relevant analyses and figure creation is available via GitHub at https://github.com/ChangLabUcsf/Liu2025_Sequencing.
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Acknowledgements
We thank all the participants who generously donated their time and effort to the collection of these data. We also thank the Chang Lab for helpful feedback and clinical support, in particular M. K. Leonard, D. F. Levy, A. B. Silva, Q. Greicius, C. Wang and M. P. Seaton, as well as R. C. Knowlton and J. K. Kleen. J.R.L. was supported by the National Institutes of Health grant no. U01 DC018671-01A1. L.Z. was supported by the National Institute on Deafness and Other Communication Disorders grant no. K99 DC020235. P.W.H. was supported by the National Center for Advancing Translational Sciences grant no. 5TL1TR001871-05.
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J.R.L. and E.F.C. conceptualized the research and designed the experiments. J.R.L., L.Z. and others collected the ECoG data. P.W.H. and J.R.L. collected the stimulation data. J.R.L. and L.Z. analysed the data. J.R.L., L.Z. and E.F.C. wrote the paper with input from all authors. E.F.C. supervised the project.
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J.R.L. and E.F.C. are inventors of pending provisional University of California, San Francisco patent applications relevant to neural decoding approaches. EFC is co-founder of Echo Neurotechnologies, LLC.
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Liu, J.R., Zhao, L., Hullett, P.W. et al. Speech sequencing in the human precentral gyrus. Nat Hum Behav 9, 2327–2344 (2025). https://doi.org/10.1038/s41562-025-02250-1
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DOI: https://doi.org/10.1038/s41562-025-02250-1


