The provided code simulates the biophysical environment and neural responses to two types of extracellular electrical stimulation: intracortical microstimulation (ICMS) and a uniform electric field. Both these approaches are used to study the effects of electrical stimulation on neurons, an area of interest for understanding neural processing and for clinical applications such as neural prosthetics and brain–computer interfaces. ### Intracortical Microstimulation (ICMS) ICMS involves delivering current directly into the cortical tissue through a microelectrode. In the code, the ICMS mode is denoted by `stim_mode = 1`. The model calculates the extracellular potentials at neuronal compartments resulting from a point-source current injection from a microelectrode positioned at a specified point (x, y, z) in the cortical tissue. The following are key biological components modeled by ICMS in the code: 1. **Electrode Location**: The position of the electrode is defined in micrometers (`xe`, `ye`, `ze`), reflective of precise, spatially localized stimulation typical in ICMS. 2. **Current Source**: The current injected by the electrode is assumed to be a point-source with a unit current of 1 μA, a typical setting for ICMS experiments to examine neuronal activation thresholds and spatial reach. 3. **Conductivity**: The electrical conductivity (`sigma_e`) of the surrounding tissue is modeled based on literature values, affecting how the current spreads through the extracellular space. 4. **Extracellular Potentials**: The code computes extracellular potentials (`Ve`) experienced by neuron compartments, using an inverse-square relationship typical in point-source stimulations. This reflects the biophysical effect of stimulation, where the potential diminishes with distance from the electrode. ### Uniform Electric Field Stimulation Uniform electric fields are sometimes used to simulate more diffuse stimulation paradigms, such as those experienced during transcranial electrical stimulation (tES). The code features a separate mode (`stim_mode = 2`) for simulating potentials resulting from a uniform electric field, characterized by: 1. **Field Orientation**: Parameters `theta` and `phi` describe the polar and azimuthal angles of the electric field, dictating its directional influence on brain tissue. 2. **Electric Field Components**: The code calculates the field components (`Ex`, `Ey`, `Ez`) based on these angles, affecting how neuronal structures, with their anisotropic electrical properties, might polarize or depolarize. 3. **Potential Calculation**: Similar to ICMS, extracellular potentials are computed but for each compartment based on the linear field influence, reflecting the larger, broadly distributed electric fields used in non-invasive brain stimulation techniques. ### Biological Relevance The primary biological aim of the code is to simulate how neurons react to different paradigms of external electrical stimulation. By calculating extracellular potentials that neurons experience, the model helps predict neuronal firing and network dynamics in response to varying stimulation types. This can be insightful for both basic neuroscience, in understanding neuronal excitability and synaptic integration, and for clinical applications, by informing stimulation parameters that optimize therapeutic outcomes while minimizing adverse effects.