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    Area of Science:

    • Neuroscience
    • Computational Neuroscience
    • Biomedical Engineering

    Background:

    • Spike prediction models are vital for neural prostheses to restore communication by predicting downstream neural activity from upstream signals.
    • Reinforcement learning (RL) is necessary for training these models when ground truth is unavailable, but existing methods lack constraints, leading to unrealistic outputs.
    • Current models neglect neural firing pattern constraints and correlations, raising concerns for clinical applications.

    Purpose of the Study:

    • To introduce and evaluate a neural manifold constraint for shaping RL-generated spike trains in feature space.
    • To improve the biological plausibility and clinical viability of spike prediction models for neural prostheses.
    • To ensure that predicted neural activity remains within natural ranges and maintains realistic correlations.

    Main Methods:

    • Proposed a neural manifold constraint using first and second-order statistics from neural recordings during free movement.
    • Integrated constraint terms into RL optimization for models predicting primary motor cortex (M1) spikes from medial prefrontal cortex (mPFC) spikes in rats performing a discrimination task.
    • Trained models using behavioral reinforcement within the estimated neural manifold.

    Main Results:

    • Constrained models generated M1 spike trains that closely resembled real recordings.
    • Achieved comparable behavioral success rates to unconstrained models while reducing mean squared error of neural firing by 61%.
    • Demonstrated increased model robustness across data segments and induced realistic neural correlations.

    Conclusions:

    • The neural manifold constraint is a promising tool for enhancing spike prediction models in neural prostheses.
    • This approach enables the restoration of transregional neural communication with high behavioral performance and realistic microscopic neural patterns.
    • The method addresses limitations of existing models by incorporating biological constraints for more clinically relevant predictions.