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Mapping human thalamocortical connectivity with electrical stimulation and recording

Nature Neuroscience volume 28, pages 1797–1809 (2025)Cite this article

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Abstract

The brain’s functional architecture is shaped by electrophysiological interactions between its components, encompassing both cortical and subcortical structures. In this study, we provide an atlas of electrophysiological causal connections across 4,864 brain sites in 27 human participants using repeated single-pulse electrical stimulations and recordings with intracranial electrodes implanted in cortical regions and multiple thalamic nuclei. We show distinct spectral signatures elicited by perturbations of specific brain areas. Identified features of causal connectivity exhibited highly organized yet distinct patterns, indicating that each feature may correspond to a separate mode of information transmission across brain regions. Notably, we report a new waveform with unique temporal and spatial characteristics specifically linked to thalamic stimulations, namely delayed-onset theta oscillations in both ipsilateral and contralateral cortical regions. These findings contribute to a more detailed understanding of the human brain’s functional architecture and offer valuable data for the development of biologically informed computational models.

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Fig. 1: Complex and variable electrophysiological responses (local field potential) evoked by the stimulation of a given site.
Fig. 2: Illustration of data processing pipeline.
Fig. 3: Spectrograms of stimulation-evoked power within and between UMAP localizers.
Fig. 4: Electrophysiological neural features indicating different types of connectivity and illustration of the decoding process.
Fig. 5: The timing of feature presence (that is, the latency of maximum representation of the feature).
Fig. 6: Anatomical landscapes of feature presence.
Fig. 7: Late thalamocortical compared with early thalamocortical/corticothalamic connections.

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Data availability

Preprocessed electrophysiological data for replicating the reported results are deposited at Zenodo and will be available upon publication (https://doi.org/10.5281/zenodo.15330862)62. The standard brain atlas used for group-level visualization is based on publicly available FS_LR brain surface: https://github.com/Washington-University/HCPpipelines/blob/master/global/templates/standard_mesh_atlases/. Source data are provided with this paper.

Code availability

All customized codes are deposited at Zenodo and will be available upon publication (https://doi.org/10.5281/zenodo.15330862)62. Any additional information about the current study can be requested from the corresponding author.

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Acknowledgements

We are grateful to the patients who agreed to participate in our research, as well as to the staff in the EEG lab, including clinical fellows and attending physicians, whose assistance enabled this research. We express our gratitude to our colleagues R. Matsumoto (University of Kyoto, Kyoto, Japan), C. Keller (Stanford University, Palo Alto, CA, USA), K. Körding (University of Pennsylvania, Philadelphia, PA, USA) and R. T. Knight (University of California, Berkeley, Berkeley, CA, USA) for their valuable feedback; and to L. McInnes (Ottawa, Canada) for running a sanity check on our UMAP analysis approach. This work was supported by research grants from the US National Institute of Neurological Disorders and Stroke (R01NS078396 and R21NS113024), US National Institute of Mental Health (1R01MH109954 and P50MH109429) and US National Science Foundation (BCS1358907 and BCS1850938 to J.P.).

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Authors and Affiliations

  1. Laboratory of Behavioral and Cognitive Neuroscience, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA

    Dian Lyu, James Robert Stiger, Zoe Lusk & Josef Parvizi

  2. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA

    Vivek Buch & Josef Parvizi

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  1. Dian Lyu
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Contributions

D.L. contributed to the conception, acquisition, analysis and interpretation of data, and creation of new codes and measures used in the work and writing of the manuscript. J.R.S. contributed to the analysis and interpretation of data. Z.L. contributed to the acquisition of data. V.B. performed surgeries and contributed to the acquisition and interpretation of data and the editing of the manuscript. J.P. contributed to the conception and design of the work, the acquisition and interpretation of data and the writing of the manuscript. All authors provided significant feedback throughout the study and manuscript preparation and have approved the submitted version.

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Correspondence to Josef Parvizi.

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Nature Neuroscience thanks Riki Matsumoto, Nicholas Schiff and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–10 and Supplementary Tables 1–9.

Reporting Summary

Supplementary Table 8

Significance testing results for all post hoc comparisons with either feature presentation (‘Fx_peak’) or feature latency (‘Fx_time’) as dependent variables (x being 1, 2 and 3).

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Source Data Fig. 5

Statistical source data.

Source Data Fig. 6

Statistical source data.

Source Data Fig. 7

Statistical source data.

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Lyu, D., Stiger, J.R., Lusk, Z. et al. Mapping human thalamocortical connectivity with electrical stimulation and recording. Nat Neurosci 28, 1797–1809 (2025). https://doi.org/10.1038/s41593-025-02009-x

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