The Cavitational Capacitive Drive (CCD) model simulates the neuromodulatory effects of Focused Ultrasound Stimulation (FUSS) on excitable cells. Inspired from the NICE model (Plaksin et al., 2014; Tarnaud et al., 2019), this model simulates the periodical expansion and contraction of the cell membrane, modulating membrane capacitance (Cm) and driving capacitive currents. CCD model removes the computational complexity of the original NICE model and thereby achieves the capability to simulate ultrasonic stimulation on biophysically realistic, compartmentalized NEURON models. More details on how this can be found from the source paper of CCD (Padmakumar et al., 2026). Through this entry in ModelDB, we demonstrates the CCD model integrated into a cortical Regular Spiking (RS) neuron model (Pospischill et al., 2008 / Traub & Miles, 1991). IMPORTANT: 1. Usage of ultrasonic time step (dt = 0.025 / USF) for simulation: To simulate ultrasonic stimulation of frequency, say 500 kHz, it is required to use a dt = 0.00005 ms which will slow down the simulation. With the increased number of segments in the model, the simulation time increases propotionately. Once the simulation is completed, you may downsample and retain the biophysically relevant data in biophysically relevant dt. 2. Allowed parameter ranges: This model is tested to accurately reproduce FUSS-induced passive and active responses matching full intramembrane cavitation models across frequencies (100–1000 kHz) and intensities (10–2000 mW/cm2). 3. Insertion procedure: Insert the 'ccd' mechanism into a section of existing NEURON cell ( insert('ccd') ), followed by linking the 'ccd' mechanism pointer to every segment capacitances ('cm') belonging to that section. Detailed documentation is available in the README.md file.
Experimental motivation: Intramembrane cavitation models—such as the NICE (Neuronal Intramembrane Cavitation Excitation) and SONIC models—demonstrated that Focused Ultrasound Stimulation (FUSS) modulates neuronal excitability by driving periodic nanometer-scale cavitation within lipid bilayers, resulting in dynamic membrane capacitance (Cm) changes. This is one of the major mechanisms that can explain the ultrasonic neuromodulation, which can explain many of the experimental observations (King et al., 2013; Plaksin et al., 2014). However, implementing the NICE and SONIC models within standard NEURON simulation environments presents significant technical and computational challenges: 1. Solver Stiffness & High Overhead: They used a modified version of the differential equation formulations of bubble dynamics (Rayleigh-Plesset equation). Those are computationally stiff equations, requiring extremely fine time steps and specialized numerical integration routines. 2. Implementation Complexity: Integrating these cavitation models into generic, multi-compartmental NEURON cell models is cumbersome and computationally prohibitive. These limitations motivated the development of the Cavitational Capacitive Drive (CCD) model. The CCD model captures the exact capacitive drive mechanism of intramembrane cavitation through an explicit, parameter-optimized formulation (k, Se, Sc). It allows researchers to seamlessly apply ultrasonic neuromodulation to any standard NEURON cell model via a simple NMODL mechanism (ccd.mod) without numerical stiffness or prohibitive runtime overhead.
Model Type: Neuron or other electrically excitable cell
Region(s) or Organism(s):
Cell Type(s): Hodgkin-Huxley neuron; Neocortex spiking regular (RS) neuron
Currents: I C
Receptors:
Genes:
Transmitters:
Model Concept(s): Detailed Neuronal Models; Excitability; Impedance; Neuromodulation
Simulation Environment: NEURON
Implementer(s): Padmakumar, Mithun [mithun.padmakumar at duk.ac.in]
References:
Padmakumar M, Rajan D, Steephen JE. (2026). Cavitational capacitive drive: a computationally efficient model for ultrasonic neuromodulation. Journal of neural engineering. 23 [PubMed]