Reproducible protocol to obtain and measure first-order relay human thalamic white-matter tracts

Available online 13 August 2022The “primary ”or “first-order relay ”nuclei of the thalamus feed the cerebral cortex with information about on- going activity in the environment or the subcortical motor systems. Because of the small size of these nuclei and the high specificity of their input and output pathways, new imaging protocols are required to investigate thala- mocortical interactions in human perception, cognition and language. The goal of the present study was twofold: I) to develop a reconstruction protocol based on in vivo diffusion MRI to extract and measure the axonal fiber tracts that originate or terminate specifically in individual first-order relay nuclei; and, II) to test the reliability of this reconstruction protocol. In left and right hemispheres, we investigated the thalamocortical/corticothalamic axon bundles linking each of the first-order relay nuclei and their main cortical target areas, namely, the lateral geniculate nucleus (optic radiation), the medial geniculate nucleus (acoustic radiation), the ventral posterior nu- cleus (somatosensory radiation) and the ventral lateral nucleus (motor radiation). In addition, we examined the main subcortical input pathway to the ventral lateral posterior nucleus, which originates in the dentate nucleus of the cerebellum. Our protocol comprised three components: defining regions-of-interest; preprocessing diffu- sion data; and modeling white-matter tracts and tractometry. We then used computation and test-retest methods to check whether our protocol could reliably reconstruct these tracts of interest and their profiles. Our results demonstrated that the protocol had nearly perfect computational reproducibility and good-to-excellent test-retest reproducibility. This new protocol may be of interest for both basic human brain neuroscience and clinical studies and has been made publicly available to the scientific community.This work was supported by grants from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (grant agreement No. 713673 ), and from “la Caixa ”Foundation (grant No. 11660016 ) to M.L.; grants from the Span- ish Ministerio de Ciencia e Innovación ( IJC2020-042887-I ; PID2021- 123577NA-I00 ) to G.L.-U.; grants from the European Union ’s Horizon 2020 Research and Innovation Program, European Commission (grant agreement No. 945539 - HBP SGA3 ) and from the Ministerio de Ciencia e Innovación FLAG-ERA grant NeuronsReunited ( MICINN-AEI PCI2019-111900-2 ) to F.C.; and grants from the Ministerio de Ciencia e Innovación ( PGC2018-093408-B-I00 ; PID2021-123574NB-I00 ), Neuro- science projects from the Fundación Tatiana Pérez de Guzmán el Bueno , Basque Government ( PIBA-2021-1-0003 ), and a grant from “la Caixa ”Banking Foundation under the project code LCF/PR/HR19/52160002 to P.M.P.-A. BCBL acknowledges support by the Basque Government through the BERC 2022-2025 program and by the S panish State Re- search Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010-S