Cortico-fugal regulation of predictive coding

  1. Alexandria MH Lesicko
  2. Christopher F Angeloni
  3. Jennifer M Blackwell
  4. Mariella De Biasi
  5. Maria N Geffen  Is a corresponding author
  1. University of Pennsylvania, United States
  2. Stony Brook University, United States

Abstract

Sensory systems must account for both contextual factors and prior experience to adaptively engage with the dynamic external environment. In the central auditory system, neurons modulate their responses to sounds based on statistical context. These response modulations can be understood through a hierarchical predictive coding lens: responses to repeated stimuli are progressively decreased, in a process known as repetition suppression, whereas unexpected stimuli produce a prediction error signal. Prediction error incrementally increases along the auditory hierarchy from the inferior colliculus (IC) to the auditory cortex (AC), suggesting that these regions may engage in hierarchical predictive coding. A potential substrate for top-down predictive cues is the massive set of descending projections from the auditory cortex to subcortical structures, although the role of this system in predictive processing has never been directly assessed. We tested the effect of optogenetic inactivation of the auditory cortico-collicular feedback in awake mice on responses of IC neurons to stimuli designed to test prediction error and repetition suppression. Inactivation of the cortico-collicular pathway led to a decrease in prediction error in IC. Repetition suppression was unaffected by cortico-collicular inactivation, suggesting that this metric may reflect fatigue of bottom-up sensory inputs rather than predictive processing. We also discovered populations of IC units that exhibit repetition enhancement, a sequential increase in firing with stimulus repetition. Cortico-collicular inactivation led to a decrease in repetition enhancement in the central nucleus of IC, suggesting that it is a top-down phenomenon. Negative prediction error, a stronger response to a tone in a predictable rather than unpredictable sequence, was suppressed in shell IC units during cortico-collicular inactivation. These changes in predictive coding metrics arose from bidirectional modulations in the response to the standard and deviant contexts, such that units in IC responded more similarly to each context in the absence of cortical input. We also investigated how these metrics compare between the anesthetized and awake states by recording from the same units under both conditions. We found that metrics of predictive coding and deviance detection differ depending on the anesthetic state of the animal, with negative prediction error emerging in the central IC and repetition enhancement and prediction error being more prevalent in the absence of anesthesia. Overall, our results demonstrate that the auditory cortex provides cues about the statistical context of sound to subcortical brain regions via direct feedback, regulating processing of both prediction and repetition.

Data availability

The data is available for review on the dryad depository, https://doi.org/10.5061/dryad.m905qfv13

The following data sets were generated

Article and author information

Author details

  1. Alexandria MH Lesicko

    Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Christopher F Angeloni

    Department of Psychology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jennifer M Blackwell

    Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mariella De Biasi

    Department of Psychiatry, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Maria N Geffen

    Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, United States
    For correspondence
    mgeffen@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3022-2993

Funding

National Institute on Deafness and Other Communication Disorders (F32MH120890)

  • Alexandria MH Lesicko

National Institute on Deafness and Other Communication Disorders (R01DC015527)

  • Maria N Geffen

National Institute on Deafness and Other Communication Disorders (R01DC014479)

  • Maria N Geffen

National Institute of Neurological Disorders and Stroke (R01NS113241)

  • Maria N Geffen

National Institute on Deafness and Other Communication Disorders (F31DC016524)

  • Christopher F Angeloni

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

Ethics

Animal experimentation: Animals were housed on a reversed 12-hour light-dark cycle with water and food available ad libitum. All procedures were approved by the University of Pennsylvania IACUC (protocol number 803266) and the AALAC Guide on Animal Research. We made every attempt to minimize the number of animals used and to reduce pain or discomfort.

Reviewing Editor

  1. Jennifer M Groh, Duke University, United States

Publication history

  1. Preprint posted: April 14, 2021 (view preprint)
  2. Received: August 24, 2021
  3. Accepted: March 12, 2022
  4. Accepted Manuscript published: March 15, 2022 (version 1)
  5. Version of Record published: April 5, 2022 (version 2)

Copyright

© 2022, Lesicko 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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  1. Alexandria MH Lesicko
  2. Christopher F Angeloni
  3. Jennifer M Blackwell
  4. Mariella De Biasi
  5. Maria N Geffen
(2022)
Cortico-fugal regulation of predictive coding
eLife 11:e73289.
https://doi.org/10.7554/eLife.73289

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