Intrinsic timescales as an organizational principle of neural processing across the whole rhesus macaque brain

Abstract

Hierarchical temporal dynamics are a fundamental computational property of the brain; however, there are no whole-brain, noninvasive investigations into timescales of neural processing in animal models. To that end, we used the spatial resolution and sensitivity of ultrahigh field fMRI performed at 10.5 Tesla to probe timescales across the whole macaque brain. We uncovered within-species consistency between timescales estimated from fMRI and electrophysiology. Crucially, we extended existing electrophysiological hierarchies to whole brain topographies. Our results validate the complementary use of hemodynamic and electrophysiological intrinsic timescales, establishing a basis for future translational work. Further, with these results in hand, we were able to show that one facet of the high-dimensional functional connectivity topography of any region in the brain is closely related to hierarchical temporal dynamics. We demonstrated that intrinsic timescales are organized along spatial gradients that closely match functional connectivity gradient topographies across the whole brain. We conclude that intrinsic timescales are a unifying organizational principle of neural processing across the whole brain.

Data availability

The functional connectivity gradient maps and the timescale maps have been uploaded to figshare.Functional connectivity gradients: https://doi.org/10.6084/m9.figshare.19189331Intrinsic neural timescales: https://doi.org/10.6084/m9.figshare.19197026

The following data sets were generated

Article and author information

Author details

  1. Ana MG Manea

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    For correspondence
    manea006@umn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4786-9657
  2. Anna Zilverstand

    Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4889-9700
  3. Kamil Ugurbil

    Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sarah Heilbronner

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jan Zimmermann

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

NIH (P41 EB027061)

  • Kamil Ugurbil
  • Jan Zimmermann

NIH (R01 MH118257)

  • Sarah Heilbronner

NIH (R56 EB031765)

  • Jan Zimmermann

NIH (R01 MH128177)

  • Jan Zimmermann

Digital Technologies Initiative

  • Jan Zimmermann

Minnesota Institute of Robotics

  • Jan Zimmermann

Young Investigator Awards from the Brain & Behavior Research Foundation

  • Anna Zilverstand
  • Sarah Heilbronner

NIH (P30DA048742)

  • Anna Zilverstand
  • Sarah Heilbronner
  • Jan Zimmermann

UMN AIRP award

  • Anna Zilverstand
  • Sarah Heilbronner
  • Jan Zimmermann

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experimental procedures were carried out in accordance with the University of Minnesota Institutional Animal Care and Use Committee and the National Institute of Health standards for the care and use of nonhuman primates. Protocol IDs: 2005-38127A 2005-38135A 1911-37623A

Copyright

© 2022, Manea 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

  • 3,703
    views
  • 374
    downloads
  • 31
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Ana MG Manea
  2. Anna Zilverstand
  3. Kamil Ugurbil
  4. Sarah Heilbronner
  5. Jan Zimmermann
(2022)
Intrinsic timescales as an organizational principle of neural processing across the whole rhesus macaque brain
eLife 11:e75540.
https://doi.org/10.7554/eLife.75540

Share this article

https://doi.org/10.7554/eLife.75540

Further reading

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.