a-protocol-for-uncovering-neural-mechanisms-neurotherapeutic-effects

A Protocol For Uncovering Neural Mechanisms Of Neurotherapeutic Effects On Electroencephalography Using The Human Neocortical Neurosolver

Electroencephalography (EEG) and electrophysiological methods provide millisecond-resolution biomarkers for central nervous system disorders and are ...

Brown University

Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.brown.edu) software. HNN has a graphical user interface designed to help researchers and clinicians interpret the neural origins of MEG/EEG. HNN's core is a neocortical circuit model that accounts for biophysical origins of electrical currents generating MEG/EEG. Data can be directly compared to simulated signals and parameters easily manipulated to develop/test hypotheses on a signal's origin. Tutorials teach users to simulate commonly measured signals, including event related potentials and brain rhythms. HNN's ability to associate signals across scales makes it a unique tool for translational neuroscience research.

Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data.

Electroencephalography (EEG) and electrophysiology methods provide millisecond resolution biomarkers for central nervous system disorders and are used to assess treatment-related effects. However, lack of understanding about the neural mechanisms generating such biomarkers impedes the development of diagnostics and therapeutics based on these signals. The Human Neocortical Neurosolver (HNN) is an open-source biophysical modeling software that connects localized EEG biomarkers to their multi-scale neural generators. This protocol demonstrates a hypothesis-driven workflow using HNN to test possible neural mechanisms of neurotherapy-induced EEG biomarkers by optimizing parameters to achieve a fit between simulated and empirical current source waveforms. Corresponding multi-scale cell- and circuit-level activity can then be visualized and quantified, providing validation targets for model predictions in follow up empirical studies. An example is provided which shows how to examine the generating mechanisms of the early event-related potential (ERP) components of an auditory evoked response (P1, N1 and P2) and to assess changes following neural circuit modification due to neurotherapeutic administration. This protocol demonstration enables scientists to design simulation experiments to develop testable predictions on how EEG biomarkers reflect neural circuit mechanisms of example therapeutics. A similar protocol can be applied to study disease mechanisms or other therapies.

Article	Year
Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data. eLife\| PubMed ID: 31967544	2020
Uncovering putative neural mechanisms of neurotherapeutic impacts on EEG using the Human Neocortical Neurosolver. bioRxiv : the preprint server for biology\| PubMed ID: 42039506	2026

Dylan S. Daniels

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