# Activating function

The activating function is a mathematical formalism that is used to approximate the influence of an extracellular field on an axon or neurons.[1][2][3][4][5][6] It was developed by Frank Rattay and is a useful tool to approximate the influence of functional electrical stimulation (FES) or neuromodulation techniques on target neurons.[7] It points out locations of high hyperpolarization and depolarization caused by the electrical field acting upon the nerve fiber. As a rule of thumb, the activating function is proportional to the second-order spatial derivative of the extracellular potential along the axon.

## Equations

In a compartment model of an axon, the activating function of compartment n, ${\displaystyle f_{n}}$, is derived from the driving term of the external potential, or the equivalent injected current

${\displaystyle f_{n}=1/c\left({\frac {V_{n-1}^{e}-V_{n}^{e}}{R_{n-1}/2+R_{n}/2}}+{\frac {V_{n+1}^{e}-V_{n}^{e}}{R_{n+1}/2+R_{n}/2}}+...\right)}$,

where ${\displaystyle c}$ is the membrane capacity, ${\displaystyle V_{n}^{e}}$ the extracellular voltage outside compartment ${\displaystyle n}$ relative to the ground and ${\displaystyle R_{n}}$ the axonal resistance of compartment ${\displaystyle n}$.

The activating function represents the rate of membrane potential change if the neuron is in resting state before the stimulation. Its physical dimensions are V/s or mV/ms. In other words, it represents the slope of the membrane voltage at the beginning of the stimulation.[8]

Following McNeal's[9] simplifications for long fibers of an ideal internode membrane, with both membrane capacity and conductance assumed to be 0 the differential equation determining the membrane potential ${\displaystyle V^{m}}$ for each node is:

${\displaystyle {\frac {dV_{n}^{m}}{dt}}=\left[-i_{ion,n}+{\frac {d\Delta x}{4\rho _{i}L}}\cdot \left({\frac {V_{n-1}^{m}-2V_{n}^{m}+V_{n+1}^{m}}{\Delta x^{2}}}+{\frac {V_{n-1}^{e}-2V_{n}^{e}+V_{n+1}^{e}}{\Delta x^{2}}}\right)\right]/c}$,

where ${\displaystyle d}$ is the constant fiber diameter, ${\displaystyle \Delta x}$ the node-to-node distance, ${\displaystyle L}$ the node length ${\displaystyle \rho _{i}}$ the axomplasmatic resistivity, ${\displaystyle c}$ the capacity and ${\displaystyle i_{ion}}$ the ionic currents. From this the activating function follows as:

${\displaystyle f_{n}={\frac {d\Delta x}{4\rho _{i}Lc}}{\frac {V_{n-1}^{e}-2V_{n}^{e}+V_{n+1}^{e}}{\Delta x^{2}}}}$.

In this case the activating function is proportional to the second order spatial difference of the extracellular potential along the fibers. If ${\displaystyle L=\Delta x}$ and ${\displaystyle \Delta x\to 0}$ then:

${\displaystyle f={\frac {d}{4\rho _{i}c}}\cdot {\frac {\delta ^{2}V^{e}}{\delta x^{2}}}}$.

Thus ${\displaystyle f}$ is proportional to the second order spatial differential along the fiber.

## Interpretation

Positive values of ${\displaystyle f}$ suggest a depolarization of the membrane potential and negative values a hyperpolarization of the membrane potential.

## References

1. ^ Rattay, F. (1986). "Analysis of Models for External Stimulation of Axons". IEEE Transactions on Biomedical Engineering (10): 974–977. doi:10.1109/TBME.1986.325670.
2. ^ Rattay, F. (1988). "Modeling the excitation of fibers under surface electrodes". IEEE Transactions on Biomedical Engineering. 35 (3): 199–202. doi:10.1109/10.1362. PMID 3350548.
3. ^ Rattay, F. (1989). "Analysis of models for extracellular fiber stimulation". IEEE Transactions on Biomedical Engineering. 36 (7): 676–682. doi:10.1109/10.32099. PMID 2744791.
4. ^ Rattay, F. (1990). Electrical Nerve Stimulation: Theory, Experiments and Applications. Wien, New York: Springer. p. 264. ISBN 3-211-82247-X.
5. ^ Rattay, F. (1998). "Analysis of the electrical excitation of CNS neurons". IEEE Transactions on Biomedical Engineering. 45 (6): 766–772. doi:10.1109/10.678611. PMID 9609941.
6. ^ Rattay, F. (1999). "The basic mechanism for the electrical stimulation of the nervous system". Neuroscience. 89 (2): 335–346. doi:10.1016/S0306-4522(98)00330-3. PMID 10077317.
7. ^ Danner, S.M.; Wenger, C.; Rattay, F. (2011). Electrical stimulation of myelinated axons. Saarbrücken: VDM. p. 92. ISBN 978-3-639-37082-9.
8. ^ Rattay, F.; Greenberg, R.J.; Resatz, S. (2003). "Neuron modeling". Handbook of Neuroprosthetic Methods,. CRC Press. ISBN 978-0-8493-1100-0.
9. ^ McNeal, D. R. (1976). "Analysis of a Model for Excitation of Myelinated Nerve". IEEE Transactions on Biomedical Engineering (4): 329–337. doi:10.1109/TBME.1976.324593.