Large-scale electrophysiology and deep learning reveal distorted neural signal dynamics after hearing loss
Abstract
Listeners with hearing loss often struggle to understand speech in noise, even with a hearing aid. To better understand the auditory processing deficits that underlie this problem, we made large-scale brain recordings from gerbils, a common animal model for human hearing, while presenting a large database of speech and noise sounds. We first used manifold learning to identify the neural subspace in which speech is encoded and found that it is low-dimensional and that the dynamics within it are profoundly distorted by hearing loss. We then trained a deep neural network (DNN) to replicate the neural coding of speech with and without hearing loss and analyzed the underlying network dynamics. We found that hearing loss primarily impacts spectral processing, creating nonlinear distortions in cross-frequency interactions that result in a hypersensitivity to background noise that persists even after amplification with a hearing aid. Our results identify a new focus for efforts to design improved hearing aids and demonstrate the power of DNNs as a tool for the study of central brain structures.
Data availability
The metadata, ABR recordings, and a subset of the IC recordings analyzed in this study are available on figshare (DOI:10.6084/m9.figshare.845654). We have made only a subset of the IC recordings available because they are also being used for commercial purposes. These purposes (to develop improved assistive listening technologies) are distinct from the purpose for which the recordings are used in this manuscript (to better understand the fundamentals of hearing loss). Researchers seeking access to the full set of neural recordings for research purposes should contact the corresponding author via e-mail to set up a material transfer agreement. The custom code used for training the deep neural network models for this study is available at github.com/nicklesica/dnn.
-
Data from Sabesan et al., 202310.6084/m9.figshare.845654.
Article and author information
Author details
Funding
Wellcome Trust (200942/Z/16/Z)
- Shievanie Sabesan
- Nicholas A Lesica
Engineering and Physical Sciences Research Council (EP/W004275/1)
- Ciaran Bench
- Fotios Drakopoulos
- Nicholas A Lesica
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental protocols were approved by the UK Home Office (PPL P56840C21). Every effort was made to minimize suffering.
Copyright
© 2023, Sabesan 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
-
- 811
- views
-
- 130
- downloads
-
- 3
- 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
-
- Neuroscience
Learning alters cortical representations and improves perception. Apical tuft dendrites in cortical layer 1, which are unique in their connectivity and biophysical properties, may be a key site of learning-induced plasticity. We used both two-photon and SCAPE microscopy to longitudinally track tuft-wide calcium spikes in apical dendrites of layer 5 pyramidal neurons in barrel cortex as mice learned a tactile behavior. Mice were trained to discriminate two orthogonal directions of whisker stimulation. Reinforcement learning, but not repeated stimulus exposure, enhanced tuft selectivity for both directions equally, even though only one was associated with reward. Selective tufts emerged from initially unresponsive or low-selectivity populations. Animal movement and choice did not account for changes in stimulus selectivity. Enhanced selectivity persisted even after rewards were removed and animals ceased performing the task. We conclude that learning produces long-lasting realignment of apical dendrite tuft responses to behaviorally relevant dimensions of a task.
-
- Neuroscience
Multiplexed error-robust fluorescence in situ hybridization (MERFISH) allows genome-scale imaging of RNAs in individual cells in intact tissues. To date, MERFISH has been applied to image thin-tissue samples of ~10 µm thickness. Here, we present a thick-tissue three-dimensional (3D) MERFISH imaging method, which uses confocal microscopy for optical sectioning, deep learning for increasing imaging speed and quality, as well as sample preparation and imaging protocol optimized for thick samples. We demonstrated 3D MERFISH on mouse brain tissue sections of up to 200 µm thickness with high detection efficiency and accuracy. We anticipate that 3D thick-tissue MERFISH imaging will broaden the scope of questions that can be addressed by spatial genomics.