Neuronal timescales are functionally dynamic and shaped by cortical microarchitecture
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
-
MNI Open iEEGMNI, https://mni-open-ieegatlas.research.mcgill.ca/.
-
Human Connectome Project S1200 ReleaseHCP, https://www.humanconnectome.org/study/hcp-young-adult/document/1200-subjects-data-release.
-
Neurotycho Anesthesia and Sleep TaskNeurotycho, Anesthesia and Sleep.
-
Whole brain gene expressionhttp://www.meduniwien.ac.at/neuroimaging/mRNA.html.
Article and author information
Author details
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.
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.
Metrics
-
- 11,194
- views
-
- 1,218
- downloads
-
- 183
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Computational and Systems Biology
- Physics of Living Systems
Planar cell polarity (PCP) – tissue-scale alignment of the direction of asymmetric localization of proteins at the cell-cell interface – is essential for embryonic development and physiological functions. Abnormalities in PCP can result in developmental imperfections, including neural tube closure defects and misaligned hair follicles. Decoding the mechanisms responsible for PCP establishment and maintenance remains a fundamental open question. While the roles of various molecules – broadly classified into ‘global’ and ‘local’ modules – have been well-studied, their necessity and sufficiency in explaining PCP and connecting their perturbations to experimentally observed patterns have not been examined. Here, we develop a minimal model that captures the proposed features of PCP establishment – a global tissue-level gradient and local asymmetric distribution of protein complexes. The proposed model suggests that while polarity can emerge without a gradient, the gradient not only acts as a global cue but also increases the robustness of PCP against stochastic perturbations. We also recapitulated and quantified the experimentally observed features of swirling patterns and domineering non-autonomy, using only three free model parameters - rate of protein binding to membrane, the concentration of PCP proteins, and the gradient steepness. We explain how self-stabilizing asymmetric protein localizations in the presence of tissue-level gradient can lead to robust PCP patterns and reveal minimal design principles for a polarized system.
-
- Computational and Systems Biology
- Neuroscience
The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (~3–6 Hz), high theta (~6–12 Hz), and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it is not understood what role these rhythms play in supporting the plasticity. Here, we create a biophysically detailed model of the BLA circuit to show that several classes of interneurons (PV, SOM, and VIP) in the BLA can be critically involved in producing the rhythms; these rhythms promote the formation of a dedicated fear circuit shaped through spike-timing-dependent plasticity. Each class of interneurons is necessary for the plasticity. We find that the low theta rhythm is a biomarker of successful fear conditioning. The model makes use of interneurons commonly found in the cortex and, hence, may apply to a wide variety of associative learning situations.