Cavitational Capacitive Drive (CCD) Model for Ultrasonic Neuromodulation

This repository package contains a standalone NEURON simulation demonstrating the Cavitational Capacitive Drive (CCD) model applied to a cortical Regular Spiking (RS) neuron model, with ultrasound stimulation intensity recorded in mW/cm².

Citation & Authorship

• Author: Dr. Mithun Padmakumar
• Publication Citation: Padmakumar, M., Rajan, D., & Steephen, J. E. (2026). Cavitational capacitive drive: A computationally efficient model for ultrasonic neuromodulation. Journal of Neural Engineering.

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Model Overview

Focused Ultrasound Stimulation (FUSS) induces high-frequency acoustic cavitation within lipid bilayers, periodically modulating membrane capacitance ($C_m$) and driving neuromodulatory responses.

The CCD model provides a computationally efficient alternative to differential-equation-based intramembrane cavitation models by utilizing pre-computed optimization parameter tables ($k$, $s_e$, $s_c$). It directly evaluates the time-varying capacitance waveform $c(t)$ and its derivative $\frac{dc}{dt}$, allowing efficient long-duration multi-frequency simulations.

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Parameter Ranges

Ultrasound intensity (usi) is specified in mW/cm². The parameter tables accept intensity values in the range 10 to 2000 mW/cm².

Ultrasound frequency (usf) is specified in kHz. The accepted frequency range is from 100 to 1000 kHz.

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File Manifest

• main.hoc: Primary HOC entry point script. Constructs the RS neuron model, loads parameter tables, initializes recording vectors, opens GUI panels, and sets up voltage visualization.
• ccd.mod: NMODL mechanism implementing the CCD variable capacitance model.
• ccd_tables.hoc: HOC script initializing optimized parameter lookup tables ($k$, $s_e$, $s_c$) across ultrasound intensities (10–2000 mW/cm²) and frequencies (100–1000 kHz).
• HH_traub.mod: Hodgkin-Huxley fast $Na^+$ and $K^+$ channels for hippocampal/cortical pyramidal cells (Traub & Miles, 1991; Destexhe, 1992).
• IM_cortex.mod: Slow non-inactivating $M$-current ($K^+$) responsible for spike-frequency adaptation (Yamada et al., 1989; Destexhe, 1995).
• GUI.hoc: Graphical User Interface for adjusting CCD parameters (usi in mW/cm²) and selecting output saving operations.
• processes.hoc: HOC helper functions managing mechanism insertion, parameter updates, signal pre-processing (window averaging & downsampling), and data exports.

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Prerequisites

• NEURON Simulation Environment (v7.8+ or v8.x) with Python support.
• C/C++ compiler (gcc / clang) for compiling NMODL mechanisms via nrnivmodl.

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How to Run the Demonstration

Step 1: Compile NMODL Mechanisms

Open a terminal in the ccd_model_demo directory and run:

nrnivmodl

This compiles ccd.mod, HH_traub.mod, and IM_cortex.mod, creating an x86_64 (or host architecture) binary library directory.

Step 2: Launch the Simulation GUI

Execute main.hoc using NEURON's GUI wrapper:

nrngui main.hoc

Upon launching:

1. The RunControl panel will automatically open.
2. The CCD Parameters panel will open with FUSS enabled (bFUSS = 1) and default intensity usi = 50 mW/cm².
3. The Manage Output panel and soma.v(0.5) voltage graph will be visible.
4. Click Init & Run in the RunControl panel to execute the simulation.

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Output Options in GUI

Clicking buttons in the Manage Output panel exports data files into the ./Results/ directory:

1. Save Raw Vm: Saves time (ts) and raw soma membrane potential (vsoma) recorded at the original simulation time step (dt = 0.025 / freq ms) to Results/ccd_<usi>_<freq>.dat (or Results/baseline.dat if FUSS is disabled).
2. Save Processed Vm: Applies a 40-point centered moving window average and downsamples by the frequency factor (freq) to convert the effective resolution to dt = 0.025 ms. Plots the processed trace in a new NEURON graph window and saves to Results/ccd_processed_<usi>_<freq>.dat along with metadata Results/ccd_processed_<usi>_<freq>_metadata.dat.
3. Save Cm Waveform: Exports the full membrane capacitance vector ($C_m(t)$) from $t=0$ to $t_{stop}$ to Results/ccd_Cm_<usi>_<freq>.dat.
4. Save AP Times: Saves the action potential firing timestamps to Results/APtimes_ccd_<usi>_<freq>.dat.

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How to Use the CCD Mechanism in Custom NEURON Scripts

To integrate the CCD mechanism into your own custom neuron or network models in NEURON:

1. Load Parameter Lookup Tables

Always load ccd_tables.hoc before inserting the ccd mechanism:

load_file("ccd_tables.hoc")

2. Insert Mechanism & Bind Pointer

Insert ccd into the target sections (e.g., soma) and immediately bind the mechanism's c pointer to NEURON's capacitance variable (cm) for all segments in the target section:

soma {
    insert ccd
    for (x, 0) {
        setpointer c_ccd(x), cm(x)
    }
}

3. Set Stimulation Parameters

Set the ultrasound stimulation parameters (intensity in mW/cm²):

usi_ccd = 100     // Ultrasound intensity in mW/cm2 (supported range: 10 to 2000 mW/cm2)
usf_ccd = 200     // Ultrasound frequency in kHz (supported range: 100 to 1000 kHz)
tbegin_ccd = 20   // FUSS start time in ms
tdur_ccd = 100    // FUSS duration in ms

Optionally, if it is intended to use pulse-width-modulation (PWM), set the following parameters also:

PWMperiod_ccd = 10  // PWM Period ( = 1000 / PRF) in ms, where PRF is the pulse-repetition frequency in Hz. 
PWMdc_ccd = 0.2     // Duty Cycle

4. Adjust Integration Time Step (dt) before running simulation

Because ultrasound oscillations occur at high frequencies (100–1000 kHz), the simulation time step dt MUST be scaled with frequency:

dt = 0.025 / usf_ccd