Simulating Human L2/3 Cortical Microcircuit Aging Cellular and Synaptic Mechanisms and Associated EEG Biomarkers

Abstract

This is the readme for the model associated with the paper: Guet-McCreight A, Tripathy S, Sibille E, Hay E. Linking age changes in human cortical microcircuits to impaired brain function and EEG biomarkers UPDATE: Added "Circuit_Simulation_NEURON9" folder for code updated to work in NEURON 9.0.2 and LFPy 2.3.5, including mod files (Modified 2026-09-24 by Valis Sowilo - github.com/ValisSowilo), circuit.py, and circuit_functions.py. Network Simulations: Simulation code associated with the L2/3 circuit used throughout the manuscript is in the /Circuit_Simulation/ directory. Note that this circuit model is adapted from https://doi.org/10.5281/zenodo.5770999. To run simulations, install all of the necessary python modules (see lfpy_env.yml), compile the mod files within the mod folder, and submit the simulations in parallel (e.g., see job_multirun_loop.sh). In job_multirun_loop.sh, the number at the end of the mpiexec command (see below - 1234) controls the random seed used for both the circuit variance (i.e., connection matrix, synapse placement, etc.) and the stimulus variance (i.e. Ornstein Uhlenbeck noise and stimulus presynaptic spike train timing). mpiexec -n 400 python circuit.py 1234 Here are some of the different configurations of parameters in circuit.py that we change to look at different conditions and levels of analysis. EEG simulations: tstop = 25000. rec_LFP = True rec_DIPOLES = True stimulate = 0 Brief stimulus simulations: tstop = 4500. rec_LFP = False rec_DIPOLES = False stimulate = 1 Stronger stimulus simulations: tstop = 4500. rec_LFP = False rec_DIPOLES = False stimulate = 2 Aging Parameters: OLDER_NMDA = 0 or 20 # Alters NMDA conductance (enter age in years relative to 50yrs) OLDER_SynLoss = 0 or 20 # Reduces PN2PN connection probability (enter age in years relative to 50yrs) OLDER_Proportion = 0 or 20 # Alters proportions (interneuron loss; enter age in years relative to 50yrs) Analysis and Dose Prediction: All code used for analysis and plotting of the circuit simulation results is found in the /Analysis_and_Plotting/ directory. Creation of subfolders for plots and analysis results may be necessary to run this code. In addition to spike simulation analysis, this folder also includes analysis of EEG power spectra (requires PSD generation by first running Plot_PSD_SavePSD2NPY_nperseg_80000.py) and oscillatory events (requires oscillatory event analysis generation by first running Plot_PSD_OEvents_thresh4.py).