Neuronal timescales are functionally dynamic and shaped by cortical microarchitecture
- University of California, San Diego, United States
- University Medical Center Hamburg-Eppendorf, Germany
Abstract
Complex cognitive functions such as working memory and decision-making require information maintenance over seconds to years, from transient sensory stimuli to long-term contextual cues. While theoretical accounts predict the emergence of a corresponding hierarchy of neuronal timescales, direct electrophysiological evidence across the human cortex is lacking. Here, we infer neuronal timescales from invasive intracranial recordings. Timescales increase along the principal sensorimotor-to-association axis across the entire human cortex, and scale with single-unit timescales within macaques. Cortex-wide transcriptomic analysis shows direct alignment between timescales and expression of excitation- and inhibition-related genes, as well as genes specific to voltage-gated transmembrane ion transporters. Finally, neuronal timescales are functionally dynamic: prefrontal cortex timescales expand during working memory maintenance and predict individual performance, while cortex-wide timescales compress with aging. Thus, neuronal timescales follow cytoarchitectonic gradients across the human cortex, and are relevant for cognition in both short- and long-terms, bridging microcircuit physiology with macroscale dynamics and behavior.
Data availability
All raw data are previously published and taken from publicly available repositories (see Table 1), all intermediate data produced from this manuscript are available on Github, with the associated analysis and visualization code
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MNI Open iEEGMNI, https://mni-open-ieegatlas.research.mcgill.ca/.
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Human Connectome Project S1200 ReleaseHCP, https://www.humanconnectome.org/study/hcp-young-adult/document/1200-subjects-data-release.
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Neurotycho Anesthesia and Sleep TaskNeurotycho, Anesthesia and Sleep.
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Whole brain gene expressionhttp://www.meduniwien.ac.at/neuroimaging/mRNA.html.
Article and author information
Author details
Ruud L van den Brink
Funding
Natural Sciences and Engineering Research Council of Canada (CGSD3-488052-2016)
- Richard Gao
Katzin Prize
- Richard Gao
Alexander von Humboldt-Stiftung
- Ruud L van den Brink
Alfred P. Sloan Foundation (FG-2015-66057)
- Bradley Voytek
Whitehall Foundation (2017-12-73)
- Bradley Voytek
National Science Foundation (BCS-1736028)
- Bradley Voytek
National Institutes of Health (R01GM134363-01)
- Bradley Voytek
Shiley-Marcos Alzheimer's Disease Research Center
- Bradley Voytek
Halicioglu Data Science Institute Fellowship
- Bradley Voytek
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Martin Vinck, Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Germany
Version history
- Received: July 21, 2020
- Accepted: November 22, 2020
- Accepted Manuscript published: November 23, 2020 (version 1)
- Version of Record published: December 22, 2020 (version 2)
Copyright
© 2020, Gao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Neuronal timescales are functionally dynamic and shaped by cortical microarchitecture
eLife 9:e61277.
https://doi.org/10.7554/eLife.61277
Further reading
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Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model and provides a 2.24 Å average RMSDCα between predicted and experimentally determined CDR-H3 loops, thus outperforming other current computational methods in our non-redundant high-quality dataset. The model was validated by experimentally solving three structures of anti-VEGF nanobodies predicted by H3-OPT. We examined the potential applications of H3-OPT through analyzing antibody surface properties and antibody–antigen interactions. This structural prediction tool can be used to optimize antibody–antigen binding and engineer therapeutic antibodies with biophysical properties for specialized drug administration route.
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Background:
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB.
Methods:
Vaginal swabs were collected across gestation from pregnant women who ultimately underwent term birth, sPTL, or PPROM. Cytokines, chemokines, growth factors, and antimicrobial peptides in the samples were quantified via specific and sensitive immunoassays. Predictive models were constructed from immune mediator concentrations.
Results:
Throughout uncomplicated gestation, the vaginal immunoproteome harbors a cytokine network with a homeostatic profile. Yet, the vaginal immunoproteome is skewed toward a pro-inflammatory state in pregnant women who ultimately experience sPTL and PPROM. Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative of macrophage and T-cell activation, and reduced antimicrobial proteins/peptides. The vaginal immunoproteome has improved predictive value over maternal characteristics alone for identifying women at risk for early (<34 weeks) sPTB.
Conclusions:
The vaginal immunoproteome undergoes homeostatic changes throughout gestation and deviations from this shift are associated with sPTB. Furthermore, the vaginal immunoproteome can be leveraged as a potential biomarker for early sPTB, a subset of sPTB associated with extremely adverse neonatal outcomes.
Funding:
This research was conducted by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, and NGL were supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.
