Targeted cortical reorganization using optogenetics in non-human primates

  1. Azadeh Yazdan-Shahmorad  Is a corresponding author
  2. Daniel B Silversmith  Is a corresponding author
  3. Viktor Kharazia
  4. Philip N Sabes
  1. University of California, San Francisco, United States

Abstract

Brain stimulation modulates the excitability of neural circuits and drives neuroplasticity. While the local effects of stimulation have been an active area of investigation, the effects on large-scale networks remain largely unexplored. We studied stimulation-induced changes in network dynamics in two macaques. A large-scale optogenetic interface enabled simultaneous stimulation of excitatory neurons and electrocorticographic recording across primary somatosensory (S1) and motor (M1) cortex (Yazdan-Shahmorad et al., 2016). We tracked two measures of network connectivity, the network response to focal stimulation and the baseline coherence between pairs of electrodes; these were strongly correlated before stimulation. Within minutes, stimulation in S1 or M1 significantly strengthened the gross functional connectivity between these areas. At a finer scale, stimulation led to heterogeneous connectivity changes across the network. These changes reflected the correlations introduced by stimulation-evoked activity, consistent with Hebbian plasticity models. This work extends Hebbian plasticity models to large-scale circuits, with significant implications for stimulation-based neurorehabilitation.

Data availability

We have provided the numerical data (.mat format) for all of the graphs in all of the figures except where images or raw data were presented. For each figure we are providing ReadMe files that include descriptions of the parameters used as well as the Matlab code for generating the figures. In addition, we have made the full dataset available via UCSF data share program: https://dash.berkeley.edu/stash/dataset/doi:10.7272/Q61834NF

The following data sets were generated

Article and author information

Author details

  1. Azadeh Yazdan-Shahmorad

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    For correspondence
    azadehy@uw.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5212-509X
  2. Daniel B Silversmith

    Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, United States
    For correspondence
    dsilversmith@berkeley.edu
    Competing interests
    No competing interests declared.
  3. Viktor Kharazia

    Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  4. Philip N Sabes

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    Philip N Sabes, has financial interest in Neuralink Corp., a company that is developing clinical therapies using brain stimulation.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8397-6225

Funding

Defense Advanced Research Projects Agency (W911NF-14-2-0043)

  • Azadeh Yazdan-Shahmorad
  • Daniel B Silversmith
  • Viktor Kharazia
  • Philip N Sabes

American Heart Association (Post-doctoral fellowship)

  • Azadeh Yazdan-Shahmorad

National Science Foundation (Graduate student fellowship)

  • Daniel B Silversmith

This research was partially funded by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-14-2-0043, issued by the Army Research Office contracting office in support of DARPA'S SUBNETS program. The views, opinions, and/or findings expressed are those of the author(s) and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. 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 procedures were performed under the approval of the University of California, San Francisco Institutional Animal Care and Use Committee (AN108552-03) and were compliant with the Guide for the Care and Use of Laboratory Animals.

Copyright

© 2018, Yazdan-Shahmorad 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

  • 3,473
    views
  • 547
    downloads
  • 46
    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. Azadeh Yazdan-Shahmorad
  2. Daniel B Silversmith
  3. Viktor Kharazia
  4. Philip N Sabes
(2018)
Targeted cortical reorganization using optogenetics in non-human primates
eLife 7:e31034.
https://doi.org/10.7554/eLife.31034

Share this article

https://doi.org/10.7554/eLife.31034

Further reading

    1. Neuroscience
    Masahiro Takigawa, Marta Huelin Gorriz ... Daniel Bendor
    Research Article

    During rest and sleep, memory traces replay in the brain. The dialogue between brain regions during replay is thought to stabilize labile memory traces for long-term storage. However, because replay is an internally-driven, spontaneous phenomenon, it does not have a ground truth - an external reference that can validate whether a memory has truly been replayed. Instead, replay detection is based on the similarity between the sequential neural activity comprising the replay event and the corresponding template of neural activity generated during active locomotion. If the statistical likelihood of observing such a match by chance is sufficiently low, the candidate replay event is inferred to be replaying that specific memory. However, without the ability to evaluate whether replay detection methods are successfully detecting true events and correctly rejecting non-events, the evaluation and comparison of different replay methods is challenging. To circumvent this problem, we present a new framework for evaluating replay, tested using hippocampal neural recordings from rats exploring two novel linear tracks. Using this two-track paradigm, our framework selects replay events based on their temporal fidelity (sequence-based detection), and evaluates the detection performance using each event's track discriminability, where sequenceless decoding across both tracks is used to quantify whether the track replaying is also the most likely track being reactivated.

    1. Neuroscience
    Nicolas Langer, Maurice Weber ... Ce Zhang
    Tools and Resources

    Memory deficits are a hallmark of many different neurological and psychiatric conditions. The Rey–Osterrieth complex figure (ROCF) is the state-of-the-art assessment tool for neuropsychologists across the globe to assess the degree of non-verbal visual memory deterioration. To obtain a score, a trained clinician inspects a patient’s ROCF drawing and quantifies deviations from the original figure. This manual procedure is time-consuming, slow and scores vary depending on the clinician’s experience, motivation, and tiredness. Here, we leverage novel deep learning architectures to automatize the rating of memory deficits. For this, we collected more than 20k hand-drawn ROCF drawings from patients with various neurological and psychiatric disorders as well as healthy participants. Unbiased ground truth ROCF scores were obtained from crowdsourced human intelligence. This dataset was used to train and evaluate a multihead convolutional neural network. The model performs highly unbiased as it yielded predictions very close to the ground truth and the error was similarly distributed around zero. The neural network outperforms both online raters and clinicians. The scoring system can reliably identify and accurately score individual figure elements in previously unseen ROCF drawings, which facilitates explainability of the AI-scoring system. To ensure generalizability and clinical utility, the model performance was successfully replicated in a large independent prospective validation study that was pre-registered prior to data collection. Our AI-powered scoring system provides healthcare institutions worldwide with a digital tool to assess objectively, reliably, and time-efficiently the performance in the ROCF test from hand-drawn images.