Temporo-cerebellar connectivity underlies timing constraints in audition

  1. Anika Stockert
  2. Michael Schwartze
  3. David Poeppel
  4. Alfred Anwander
  5. Sonja Kotz  Is a corresponding author
  1. University of Leipzig, Germany
  2. Maastricht University, Netherlands
  3. Max Planck Institute for Empirical Aesthetics, Germany
  4. Max Planck Institute for Human Cognitive and Brain Sciences, Germany

Abstract

The flexible and efficient adaptation to dynamic, rapid changes in the auditory environment likely involves generating and updating of internal models. Such models arguably exploit connections between the neocortex and the cerebellum, supporting proactive adaptation. Here we tested whether temporo-cerebellar disconnection is associated with the processing of sound at short-timescales. First, we identify lesion-specific deficits for the encoding of short timescale spectro-temporal non-speech and speech properties in patients with left posterior temporal cortex stroke. Second, using lesion- guided probabilistic tractography in healthy participants, we revealed bidirectional temporo-cerebellar connectivity with cerebellar dentate nuclei and crura I/II. These findings support the view that the encoding and modeling of rapidly modulated auditory spectro-temporal properties can rely on a temporo-cerebellar interface. We discuss these findings in view of the conjecture that proactive adaptation to a dynamic environment via internal models is a generalizable principle.

Data availability

There is restricted access to the data due to German legal regulations of patient protection.We have made all data which we can legally share accessible via figure share (link is included in the resource statement). We have provided all data (lesion data, scripts, behavioral data that allowed lesion-symptom mapping) in our figure share account for reproduction of the critical seed region for a tracking analysis.Anonymisation of MRI/DTI data is not allowed either through the ethics agreement nor the participants' consent. We cannot do anything about this as these are the legal regulations that we have to deal with. We have made a clear statement that we seek open dialogue about how we have analysed our data. Further, given the data that we have provided, any interested researcher can (1) approach us about our analysis, (2) can take a set of open source age-matched structural MRI/DTI data to replicated our results

Article and author information

Author details

  1. Anika Stockert

    Department of Neurology, University of Leipzig, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael Schwartze

    Neuropsyhology and Psychopharmacology, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. David Poeppel

    Neuroscience, Max Planck Institute for Empirical Aesthetics, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Alfred Anwander

    Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4861-4808
  5. Sonja Kotz

    Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, Netherlands
    For correspondence
    sonja.kotz@maastrichtuniversity.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5894-4624

Funding

Deutsche Forschungsgemeinschaft (DFG KO 2268/6-1)

  • Sonja Kotz

Dissertation award University of Leipzig (none)

  • Anika Stockert

Max-Planck-Gesellschaft (none)

  • Sonja Kotz

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

Ethics

Human subjects: The protocol of the current research was approved by the ethics committee of the University of Leipzig, Germany (Protocol Number: 953). All participants provided written, informed consent before the start of data collection.

Reviewing Editor

  1. Timothy D Griffiths, University of Newcastle, United Kingdom

Publication history

  1. Preprint posted: February 7, 2021 (view preprint)
  2. Received: February 7, 2021
  3. Accepted: September 9, 2021
  4. Accepted Manuscript published: September 20, 2021 (version 1)
  5. Version of Record published: September 29, 2021 (version 2)
  6. Version of Record updated: September 30, 2021 (version 3)

Copyright

© 2021, Stockert 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

  • 708
    Page views
  • 122
    Downloads
  • 2
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. Anika Stockert
  2. Michael Schwartze
  3. David Poeppel
  4. Alfred Anwander
  5. Sonja Kotz
(2021)
Temporo-cerebellar connectivity underlies timing constraints in audition
eLife 10:e67303.
https://doi.org/10.7554/eLife.67303

Further reading

    1. Neuroscience
    Kasra Manoocheri, Adam G Carter
    Research Article

    Connections from the basolateral amygdala (BLA) to medial prefrontal cortex (PFC) regulate memory and emotion and become disrupted in neuropsychiatric disorders. The diverse roles attributed to interactions between the BLA and PFC may reflect multiple circuits nested within a wider network. To examine these circuits, we first used retrograde and anterograde anatomy to show that the rostral BLA (rBLA) and caudal BLA (cBLA) differentially project to prelimbic (PL) and infralimbic (IL) subregions of the mouse PFC. Using ex vivo whole-cell recordings and optogenetics, we then assessed which neuronal subtypes are targeted, showing that rBLA preferentially drives layer 2 (L2) cortico-amygdalar (CA) neurons in PL, whereas cBLA drives layer 5 (L5) pyramidal tract (PT) neurons in IL. We next combined in vivo silicon probe recordings and optogenetics to confirm that cBLA mainly influences IL L5, whereas rBLA primarily activates PL L2, but also evokes polysynaptic activity in PL L5. Lastly, we used soma-tagged optogenetics to explore the local circuits linking superficial and deep layers of PL, showing how rBLA can engage L2 CA neurons to impact L5 PT neuron activity. Together, our findings delineate how subregions of the BLA target distinct networks within the PFC and differentially influence output from PL and IL.

    1. Cell Biology
    2. Neuroscience
    Arnau Llobet Rosell, Maria Paglione ... Lukas Jakob Neukomm
    Research Article

    Axon degeneration contributes to the disruption of neuronal circuit function in diseased and injured nervous systems. Severed axons degenerate following the activation of an evolutionarily conserved signaling pathway, which culminates in the activation of SARM1 in mammals to execute the pathological depletion of the metabolite NAD+. SARM1 NADase activity is activated by the NAD+ precursor nicotinamide mononucleotide (NMN). In mammals, keeping NMN levels low potently preserves axons after injury. However, it remains unclear whether NMN is also a key mediator of axon degeneration and dSarm activation in flies. Here, we demonstrate that lowering NMN levels in Drosophila through the expression of a newly generated prokaryotic NMN-Deamidase (NMN-D) preserves severed axons for months and keeps them circuit-integrated for weeks. NMN-D alters the NAD+ metabolic flux by lowering NMN, while NAD+ remains unchanged in vivo. Increased NMN synthesis, by the expression of mouse nicotinamide phosphoribosyltransferase (mNAMPT), leads to faster axon degeneration after injury. We also show that NMN-induced activation of dSarm mediates axon degeneration in vivo. Finally, NMN-D delays neurodegeneration caused by loss of the sole NMN-consuming and NAD+-synthesizing enzyme dNmnat. Our results reveal a critical role for NMN in neurodegeneration in the fly, which extends beyond axonal injury. The potent neuroprotection by reducing NMN levels is similar to the interference with other essential mediators of axon degeneration in Drosophila.