Abstract
AbstractIntroduction: Since it was introduced in 2012, the Neuroid has been used to aid in understanding how functionally different neural populations contribute to sensory information processing. However, insights about whether this neuronmodel could perform better than others or about when its utilization should be considered have not been provided yet.
Methods
In an attempt to address this issue, a comparison between the Neuroid and the leakyintegrateandfire (LIF) model in terms of accuracy and computational cost was performed. Both models were tested for different stimulation amplitudes and stimulation periods, with time step sizes ranging from 10^{4} to 1 ms.
Results
It was found that, although the Neuroid was able to produce more accurate results than its original version, its accuracy was lower than the achieved with the LIF model solved by the forward Euler method. On the other hand, the Neuroid performed its calculations in an amount of time significantly lower (Mulfactorial ANOVA test, p < 0.05) than that required by the LIF model when it was solved by using the forward Euler method. Moreover, it was possible to use Neuroidbased networks to replicate biologically relevant firing patterns produced by lowscale networks composed of more detailed neuronmodels.
Conclusion
Results suggest that the Neuroid could be an interesting choice when computational resources are limited, although its use might be restricted to a narrow band of applications.
Keywords
Neuroid; Spiking neuronmodel; Frequencyintensity curve; Accuracy; Computational cost; Heuristic
Introduction
In spite of their simplicity, phenomenological models of spiking neurons have proved particularly useful in elucidating the dynamics of single neurons, as well as their role within largescale neural networks. For instance, it was found that integrateandfire models with adaptation could predict the response of cortical neurons to somatically injected currents with high accuracy in spike timing (Brette and Gerstner, 2005Brette R, Gerstner W. Adaptive exponential integrateandfire model as an effective description of neuronal activity. J Neurophysiol. 2005; 94(5):363742. PMid:16014787. https://doi.org/ 10.1152/jn.00686.2005.
https://doi.org/ 10.1152/jn.00686.2005...
; Jolivet et al., 2004Jolivet R, Lewis TJ, Gerstner W. Generalized integrateandfire models of neuronal activity approximate spike trains of a detailed model to a high degree of accuracy. J Neurophysiol. 2004; 92(2):95976. PMid:15277599. https://doi.org/10.1152/jn.00190.2004.
https://doi.org/10.1152/jn.00190.2004...
; Kobayashi et al., 2009Kobayashi R, Tsubo Y, Shinomoto S. Madetoorder spiking neuron model equipped with a multitimescale adaptive threshold. Front Comput Neurosci. 2009; 3:9. PMid: 19668702. https://doi.org/10.3389/neuro.10.009.2009.
https://doi.org/10.3389/neuro.10.009.200...
). An innovative alternative known as Neuroid (Prada et al., 2012Prada EJA, Bustillos RJS, Castillo C, Huerta M. The neuroid: a novel and simplified neuronmodel. In: Proceedings of the 34th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2012 Aug 28Sep 1; San Diego, CA. San Diego: IEEE; 2012. p. 12347. PMid:23366121. https://doi.org/10.1109/EMBC.2012.6346160.
https://doi.org/10.1109/EMBC.2012.634616...
) was introduced at the 34^{th} International Annual Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’12). Since then, this neuronmodel has been utilized to aid in understanding how functionally different neural populations (e.g., lowthreshold vs. highthreshold afferent fibers; normally silent vs. tonically active neurons) interact each other and how those differences affect the way that visual (Prada et al., 2013Prada EJA, Bustillos RJS, Castillo C, Huerta M. New trends in computational modeling: a neuroidbased retina model. In: Proceedings of the 35th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2013 Jul 37; Osaka, Japan. Osaka: IEEE; 2013. p. 45614. PMid: 24110749. https://doi.org/10.1109/EMBC.2013.6610562.
https://doi.org/10.1109/EMBC.2013.661056...
) and tactile (Prada and Bustillos, 2013Prada EJA, Bustillos RJS. The implementation of the Neuroid in the gate control system leads to new ideas about pain processing. Rev Bras Eng Bioméd. 2013; 29(3):25461. http://dx.doi.org/10.4322/rbeb.2013.025.
http://dx.doi.org/10.4322/rbeb.2013.025...
; Prada et al., 2015Prada EJA, Bustillos RJS, Huerta MK, Martínez ADA. Lamina specific loss of inhibition may lead to distinct neuropathic manifestations: a computational modeling approach. Res Biomed Eng. 2015; 31(2):13347. http://dx.doi.org/10.1590/24464740.0734.
http://dx.doi.org/10.1590/24464740.0734...
) information is processed.
The Neuroid is, indeed, one of the simplest neuronmodels that have ever been conceived. It was built under the assumption that some neurons, under certain conditions, fire at regular rates when stimulation amplitude is held constant. The similarities between the action potential generation process and pulse frequency modulation (PFM) that have been pointed out by several authors (Bayly, 1968Bayly EJ. Spectral analysis of pulse frequency modulation in the nervous systems. IEEE Trans Biomed Eng. 1968; 15(4):25765. PMid:5699902. http://dx.doi.org/10.1109/TBME.1968.4502576.
http://dx.doi.org/10.1109/TBME.1968.4502...
; Horch and Dhillon, 2004Horch KW, Dhillon GS. Neuroprosthetics: theory and practice. New York: World Scientific; 2004.; Rieke et al., 1997Rieke F, Warland D, van Steveninck RR, Bialek W. Spikes: exploring the neural code. Cambridge: MIT Press; 1997.) were also considered in building this neuronmodel. It relies on a pair of heuristics that make possible to generate a spike train whose frequency is modulated by the amplitude of the stimulus (even though is widely known that the neuron firing rate may be affected by other factors, like the subthreshold dynamics) and to demodulate the spike train in order to recover the modulating signal. But the real novelty of the Neuroid lies on what kind of experimental data is used to model different neural populations. Instead of ionic conductances, equilibrium potentials and/or electrical membrane properties, the firing rate as a function of the stimulus intensity is the only requirement to build a Neuroidbased replica of the neuron under study. Essentially, the goal is to adjust the Neuroid’s parameters such that its frequencyintensity (FI) curve resembles as much as possible the one that was built from experimental data. This novel approach, although simple in concept and application, may be little confusing for those who have already dealt with the
issues involved in using conductancebased neuronmodels. Likewise, insights about whether this neuronmodel could perform better than others or about when its utilization should be considered have not been provided so far.
Coordinated rhythmicity of neural populations may arise from the interaction of three aspects: the intrinsic properties of the cells composing the network, the synaptic properties of connections between neurons, and the topology of the network (Ermentrout and Terman, 2010Ermentrout GB, Terman DH. Mathematical foundations of neuroscience. Vol. 35. New York: Springer Science & Business Media; 2010.). Specifically, the rhythm with which vertebrates and invertebrates walk, fly or swim, as well as communication based in stereotypically repeated visual or sound signals (e.g., the cricket song), is mostly driven by oscillatory patterns produced by neural networks of the central nervous system (Delcomyn, 1980Delcomyn F. Neural basis of rhythmic behavior in animals. Science. 1980; 210(4469):4928. PMid:7423199. http://dx.doi.org/10.1126/science.7423199.
http://dx.doi.org/10.1126/science.742319...
). In order to study the mechanisms underlying this oscillatory activity, several authors (Friesen and Stent, 1977Friesen WO, Stent GS. Generation of a locomotory rythm by a Neural Network with Recurrent Cyclic Inhibition. Biol Cybern. 1977; 28(1):2740. PMid:597508. http://dx.doi.org/10.1007/BF00360911.
http://dx.doi.org/10.1007/BF00360911...
; Kling and Székely, 1968Kling U, Székely G. Simulation of rhythmic nervous activities. I. Function of networks with cyclic inhibitions. Kybernetik. 1968; 5(3):89103. PMid:5728516. http://dx.doi.org/10.1007/BF00288899.
http://dx.doi.org/10.1007/BF00288899...
; Koch and Brunner, 1988Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920.
http://dx.doi.org/10.1007/BF00332920...
) have used artificial neurons, also known as “neuromimes”, built from elementary electronic components and able to provide a biologically plausible description of the neuron’s membrane. Nevertheless, it is unclear whether that activity is due to one of the above aspects, or to their combined action. Moreover, it is unknown whether oscillatory patterns produced by lowscale networks composed of highly detailed neuronmodels can be replicated by Neuroidbased replicas of those networks.
In this sense, the present study aims: 1) to study how different sizes of time step affect the accuracy of the Neuroid, 2) to compare its performance to the exhibited by the leakyintegrateandfire (LIF) model in terms of accuracy and computational cost, and 3) to assess the feasibility in using Neuroidbased networks to replicate biologically relevant firing patterns produced by lowscale networks composed of much more detailed neuronmodels.
Methods
Theoretical background
It is widely accepted that stimulus information (e.g., the intensity) is encoded not in the magnitude of a single spike but in the number of spikes fired per unit time (firing rate). With that in mind, we think it would be appropriate to provide a mathematical representation of neural spike trains rather than investing time and effort in describing the action potential as an isolated event, as brilliantly done by Hodgkin and Huxley (Hodgkin and Huxley, 1952Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952; 117(4):50044. PMid:12991237. http://dx.doi.org/10.1113/jphysiol.1952.sp004764.
http://dx.doi.org/10.1113/jphysiol.1952....
). Let us consider the triggering event s(t) given by:
where x_{1}, x_{2}, …, x_{M} are M normalized input signals and w_{1}, w_{2}, …, w_{M} are their respective synaptic weights. Then, based on the fact that, under specific conditions, some neurons can fire at a regular rate when the stimulus amplitude remains constant, the signal travelling along the neuron’s axon y(t) can be modeled as:
where δ(∙) represents a single spike, T denotes a constant with time units (necessary for dimensional consistency), ϑ is the relative threshold intensity and β is a proportionality constant that controls the slope of the Neuroid’s (FI) curve. The Neuroid is also able to yield an amplitudediscrete version of s(t), named nt_out(t), by adjusting two additional parameters: K_{r}, a dimensionless constant which controls the output’s amplitude, and maxcount, a temporal parameter which allows to extend the output signal by several milliseconds after the last spike (Prada et al., 2012Prada EJA, Bustillos RJS, Castillo C, Huerta M. The neuroid: a novel and simplified neuronmodel. In: Proceedings of the 34th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2012 Aug 28Sep 1; San Diego, CA. San Diego: IEEE; 2012. p. 12347. PMid:23366121. https://doi.org/10.1109/EMBC.2012.6346160.
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).
Even though it is not evident from the present study, each parameter of the Neuroid is inspired by a biological property of real neurons. For instance, the term ϑ represents the minimum stimulus intensity at which the neuron fires, at least, one action potential, and it has been defined in this way in order to be consistent with different stimulus types (thermal, mechanical, etc). The parameter β is associated to the potassium current flowing through the membrane, so the greater its value, the lower the slope of the FI curve (Alberts et al., 2002Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell. 4th ed. New York: Garland Science; 2002.; Koch and Brunner, 1988Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920.
http://dx.doi.org/10.1007/BF00332920...
). The term maxcount denotes the time during which the neurotransmitter concentration is such that it has a synaptic effect in the cleft (Scimemi and Beato, 2009Scimemi A, Beato M. Determining the neurotransmitter concentration profile at active synapses. Mol Neurobiol. 2009. 40(3):289306. https://doi.org/ 10.1007/s1203500980877.
https://doi.org/ 10.1007/s120350098087...
). Finally, although the parameter K_{r} does not have an obvious biological counterpart, its value depends on the firing frequency at the maximum amplitude of stimulation, which is calculated from the experimental FI curve.
To avoid the division by zero in Equation 1, it was arranged that spike trains were generated only if the amplitude of the triggering input signal s(t) exceeds the threshold intensity ϑ. However, this is not consistent with experimental observations, which underline that spikes are produced not only when neuron’s membrane potential exceeds threshold, but also when the former reaches the latter (Matzner and Devor, 1992Matzner O, Devor M. Na+ conductance and the threshold for repetitive neuronal firing. Brain Res. 1992; 597(1):928. PMid:1335824. http://dx.doi.org/10.1016/00068993(92)91509D.
http://dx.doi.org/10.1016/00068993(92)9...
). To address this issue, the heuristic able to produce the signal y(t) (the Pulse Frequency Modulator in (Prada et al., 2012Prada EJA, Bustillos RJS, Castillo C, Huerta M. The neuroid: a novel and simplified neuronmodel. In: Proceedings of the 34th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2012 Aug 28Sep 1; San Diego, CA. San Diego: IEEE; 2012. p. 12347. PMid:23366121. https://doi.org/10.1109/EMBC.2012.6346160.
https://doi.org/10.1109/EMBC.2012.634616...
) was modified such that the case in which the membrane potential reaches threshold was considered. Figure 1 shows a flowchart describing the new heuristic.
A novel heuristic, which, unlike the one originally proposed by Prada et al. (2012)Prada EJA, Bustillos RJS, Castillo C, Huerta M. The neuroid: a novel and simplified neuronmodel. In: Proceedings of the 34th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2012 Aug 28Sep 1; San Diego, CA. San Diego: IEEE; 2012. p. 12347. PMid:23366121. https://doi.org/10.1109/EMBC.2012.6346160.
https://doi.org/10.1109/EMBC.2012.634616... , considers the case in which membrane potential reaches threshold.
The accuracy of a neuronmodel describes how reliable is the model in representing the behavior of biological neurons, in terms of the temporal resolution with which neural spikes can be produced (from miliseconds to fractions of miliseconds). Since simulating spiking neuronmodels involves repeatedly solving the associated system of differential equations using analytical or numerical integration methods, the accuracy provided by such models may depends on, amongst other factors, the numerical method used to solve the system and the size of the time step Δt, an aspect that has not been explicitly mentioned and whose influence has not been studied in previous implementations of our neuronmodel.
Modeling approach
For each I
which represents one of the multiple inputs that may contribute to create the triggering event s(t), as expressed in Equation 1. As can be seen from Figure 1, if s(t) > ϑ, a spike is fired whenever the variable count1 reaches the smallest integer greater than or equal to the quantity
where the operator
where r is a real number.
From Equation 5, it is clear that for all real number r we have:
Therefore, from Equations 4 and 6, the value of the parameter β can be expressed as:
Typically, the firing rate (f) of a single neuron is calculated by using Equation 8:
where N_{spikes} is the total number of spikes fired within the observation period while t_{first} and t_{last} are, respectively, the instants at which the first and the last spike occur.
Interestingly, Equation 8 can be rewritten as:
where ISI_{avg} represents the average interspike interval, which can be approximated to ISI when the neuron fires at a regular rate.
Finally, by identifying the firing rate of the neuron under study at the maximum amplitude of stimulation (f_{I_max}), the interspike interval at that amplitude (ISI_{I_max}) is given by:
which in turn allows us to rewrite Equation 7 to calculate the value of β required to model that neuron (note that s(t) = 1 at the maximum amplitude of stimulation):
Evaluating the Neuroid’s performance: firing pattern and FI curve
To evaluate the performance of a neuronmodel, a benchmark solution (i.e., another model capable of providing a fairly good representation of neuronal behavior) is required. In our case, the benchmark solution was built by implementing the LIF model (Jolivet et al., 2004Jolivet R, Lewis TJ, Gerstner W. Generalized integrateandfire models of neuronal activity approximate spike trains of a detailed model to a high degree of accuracy. J Neurophysiol. 2004; 92(2):95976. PMid:15277599. https://doi.org/10.1152/jn.00190.2004.
https://doi.org/10.1152/jn.00190.2004...
), which is commonly described by Equation 12:
where V(t) is the membrane potential, I(t) is the input current, E_{rest} is the resting membrane potential, V_{th} is the firing threshold, V_{r} is the afterspike membrane potential, R_{m} is the membrane resistance and τ_{m} is the membrane time constant. The LIF model was chosen as the benchmark solution because it has only a small number of parameters and it is one of the most computationally efficient spiking neuronmodels, as reported in previous work (Long and Fang, 2010Long L, Fang G. A review of biologically plausible neuron models for spiking neural networks. In: Proceedings of the AIAA InfoTech@ Aerosp Conference; 2010 Apr 2022; Atlanta, GA. Atlanta: AIAA; 2010. http://dx.doi.org/10.2514/6.20103540.
http://dx.doi.org/10.2514/6.20103540...
; Skocik and Long, 2014Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
). In order to compute the parameters required to build a Neuroidbased replica of this “neuron”, Equation 12 was numerically solved by adopting the fourthorder RungeKutta method (RK4) with a time step Δt = 10^{4} ms. The benchmark solution was implemented under MatLab 2013a using E_{rest} = 0 mV, V_{th} = 30 mV, V_{r} = 50 mV, V_{spike} = 70 mV, R_{m} = 8.22 MΩ, τ_{m} = 23.5 ms, and its FI curve was built by increasing the amplitude of a rectangular current pulse I(t) applied during 1000 ms (the total time of run of each trial, denoted as t_{span}), from 0 to 20 nA (increments of 0.1 nA). The frequency was calculated by using Equation 8.
Once the FI curve of the benchmark solution was built, the threshold intensity (I_{th} = 3.7 nA) and the firing rate at the maximum amplitude of stimulation (f_{I_max} = 92.11 Hz) were identified. Then, to build a Neuroidbased replica of that “neuron”, we found β from Equation 11 whereas ϑ was calculated by using Equation 13:
where I_{th} is the threshold intensity.
Both the Neuroid (Δt = 10^{4} ms) and the benchmark solution were run in MatLab 2013a for I = 3.7 nA (the threshold intensity) and I = 6 nA to compare their firing patterns at this two stimulation amplitudes. The same method used to calculate the firing rate of the LIF model, was used to calculate the firing rate achieved by the Neuroid. With time steps ranging from 10^{4} to 1 ms, the FI curve of the Neuroid was compared to the one previously built for the benchmark solution.
Accuracy and computational cost
Several methods have been used recently to evaluate the accuracy of a neuronmodel. Wang and coworkers (Wang et al., 2014Wang Z, Guo L, Adjouadi M. A generalized Leaky IntegrateandFire neuron model with fast implementation method. Int J Neural Syst. 2014; 24(5):1440004. PMid:24875788. http://dx.doi.org/10.1142/S0129065714400048.
http://dx.doi.org/10.1142/S0129065714400...
) totalized the number of false negatives (missed spikes) and false positives (additional or accidental spikes) with respect to the spike train generated by the HH neuronmodel solved by the RK4 method, and then they divided each total by the number of matched spikes pairs to obtain two different indicators of accuracy. Skocik and Long (2014)Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
estimated the accuracy of the LIF model, the HH model and the Izhikevich’s model (Izhikevich, 2003Izhikevich EM. Simple model of spiking neuron. IEEE Trans Neural Netw. 2003; 14(6):156972. PMid:18244602. https://doi.org/10.1109/TNN.2003.820440.
https://doi.org/10.1109/TNN.2003.820440...
) by quantifying the absolute difference between the frequency of the model being tested (f_{model}) and the frequency of its respective benchmark solution (f_{BM}), which was taken to be the solution provided by the RK4 method with a time step of 10^{4} ms, and then dividing the difference by the latter, as expressed in Equation 14:
Such estimation was performed for three different frequency values (70, 90 and 120 Hz), which were considered as falling into the low, medium, and highfrequency range. Since these ranges may vary between different neuronal populations, we estimated the accuracy of the Neuroid by calculating the frequency error defined by Skocik and Long (2014)Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
, except that this time the estimation was performed for three different stimulation amplitudes, taking into account the relative location of these amplitudes with respect to the dynamic range of the benchmark solution (i.e., the range of amplitudes for which it is able to fire, from I_{th} to I_{max}). Thus, three values were chosen: one slightly greater than the threshold intensity (I = 5 nA), one at the middle of the dynamic range (I = 12 nA), and one close to the maximum stimulation amplitude (I = 19 nA). For each, with a total time of run t_{span} = 1000 ms and with time steps ranging from 10^{4} to 1 ms, we quantified the frequency error produced by both the Neuroid and the LIF model solved by the Forward Euler (FE) method.
The interest in calculating the computational cost of a neuronmodel arises from the assumption that the less computational power is required to simulate a single neuron, the easier it is to implement it into a largescale neural network. According to several authors (Izhikevich, 2004Izhikevich EM. Which model to use for cortical spiking neurons? IEEE Trans Neural Netw. 2004; 15(5):106370. PMid:15484883. https://doi.org/10.1109/TNN.2004.832719.
https://doi.org/10.1109/TNN.2004.832719...
; Long and Fang, 2010Long L, Fang G. A review of biologically plausible neuron models for spiking neural networks. In: Proceedings of the AIAA InfoTech@ Aerosp Conference; 2010 Apr 2022; Atlanta, GA. Atlanta: AIAA; 2010. http://dx.doi.org/10.2514/6.20103540.
http://dx.doi.org/10.2514/6.20103540...
; Skocik and Long, 2014Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
), a good indicator of how fast a neuronmodel will perform its calculations is the number of floating point operations (FLOPs) required by the model. For a given time of run (t_{span}), the total of FLOPs required by a neuronmodel can be estimated as follows:
where #FLOPs denotes the number of FLOPs per iteration and #iterations represents the total number of iterations for the given time of run:
The number of FLOPs per iteration depends mostly on the method used to determine if a spike can or cannot be fired. For instance, when the FE method is used to solve the LIF model (see Equation 12), the membrane potential is updated as follows:
which takes only 5 FLOPs by assuming that addition, multiplication, subtraction and division costs only one FLOP each, as done in previous studies (Izhikevich, 2004Izhikevich EM. Which model to use for cortical spiking neurons? IEEE Trans Neural Netw. 2004; 15(5):106370. PMid:15484883. https://doi.org/10.1109/TNN.2004.832719.
https://doi.org/10.1109/TNN.2004.832719...
; Long and Fang, 2010Long L, Fang G. A review of biologically plausible neuron models for spiking neural networks. In: Proceedings of the AIAA InfoTech@ Aerosp Conference; 2010 Apr 2022; Atlanta, GA. Atlanta: AIAA; 2010. http://dx.doi.org/10.2514/6.20103540.
http://dx.doi.org/10.2514/6.20103540...
; Skocik and Long, 2014Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
). However, from Figure 1, it can be seen that, depending on whether the triggering input signal s(t) is less than, equal to or greater than the relative threshold intensity ϑ, the number of FLOPs per iteration may vary, as expressed in Equation 18:
This suggests that the total of FLOPs required by the Neuroid for a given time of run may decrease 1) when no stimulus is present, and 2) when firing rate increases. To test this hypothesis, we run both the Neuroid and the LIF model solved by the FE method under DevC++ 4.9.9.2, an integrated development environment for the C/C++ programming language, with time steps ranging from 10^{4} to 1 ms. We used the FE method instead of the RK4 method because, even though the former is not the most accurate, it is one of the simplest numerical methods (Skocik and Long, 2014Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
), which allowed us to perform a much more fair comparison. Wang et al. (2014)Wang Z, Guo L, Adjouadi M. A generalized Leaky IntegrateandFire neuron model with fast implementation method. Int J Neural Syst. 2014; 24(5):1440004. PMid:24875788. http://dx.doi.org/10.1142/S0129065714400048.
http://dx.doi.org/10.1142/S0129065714400...
introduced a generalized exponential moving average method to solve a modified version of the LIF model. Such method required a computation time lower than the required by the original LIF model and the HH model when they were solved by adopting the RK4 method. On the other hand, the utilization of the RK4 method for benchmarking clearly favored the method proposed by the group of Wang because the former is computationally expensive. Instead, we used a numerical method more affordable from a computational point of view in order to make a more fair comparison. The C++ programming language was used in calculating the computation time required by the Neuroid and the LIF model because it is possible to speedup simulations up to several hundreds of times compared to MatLab (Andrews, 2012Andrews T. Computation time comparison between Matlab snd C++ using Launch Windows. Aerosp Eng. 2012; 78:16.).
With time steps ranging from 10^{4} to 1 ms, the LIF model and the Neuroid were run for three different simulation amplitudes (I = 5, 12 and 19 nA) and for three different stimulation periods (T = 200, 500 and 800 ms). The computation time required by each model was measured by using the QueryPerformanceCounter() function, and measurements were averaged over 10 repetitions. A factorial design was adopted by considering the neuronmodel (LIF and Neuroid), the time step size, the stimulus amplitude and the stimulation duration as factors, each with 2, 5, 3 and 3 possible values or levels, respectively. Even though the analysis of the effects of interactions between factors on the computation time achieved by each model is beyond the scope of the present study, a multifactor analysis of variance (ANOVA) was used to identify significant effects of each factor on the computation time (Montgomery, 2017Montgomery DC. Design and analysis of experiments. Hoboken: John Wiley & Sons; 2017.
Hoboken...
). Values of p < 0.05 were considered statistically significant. Microsoft Excel 2010 (Microsoft Corporation, USA) and STATGRAPHICS Centurion XVI.I (version 16.1.18, Statistical Graphics Corporation) and Minitab 18 (ver 18.1, Minitab, Inc.) were used to perform the analysis.
Lowscale neural networks
To assess whether Neuroidbased networks are able to preserve oscillatory patterns produced by networks composed of those artificial units, we replicated the topology of the threeneuron oscillator and the “cricket song generator”, previously built by Koch and Brunner (1988)Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920.
http://dx.doi.org/10.1007/BF00332920...
to test the neuronmodel they developed. Neuroidbased replicas of the neurons modeled by Koch and Brunner were implemented under MatLab 2013a using ϑ = 0.2, β = 2.5, K_{r} = 3, maxcount = 24 and Δt = 0.1 ms for the threeneuron oscillator, and ϑ = 0.2, β = 2.5, K_{r} = 3, maxcount = 24 and Δt = 0.1 ms for the “cricket song generator”. As done in previous studies (Prada and Bustillos, 2013Prada EJA, Bustillos RJS. The implementation of the Neuroid in the gate control system leads to new ideas about pain processing. Rev Bras Eng Bioméd. 2013; 29(3):25461. http://dx.doi.org/10.4322/rbeb.2013.025.
http://dx.doi.org/10.4322/rbeb.2013.025...
; Prada et al., 2012Prada EJA, Bustillos RJS, Castillo C, Huerta M. The neuroid: a novel and simplified neuronmodel. In: Proceedings of the 34th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2012 Aug 28Sep 1; San Diego, CA. San Diego: IEEE; 2012. p. 12347. PMid:23366121. https://doi.org/10.1109/EMBC.2012.6346160.
https://doi.org/10.1109/EMBC.2012.634616...
; 2013; 2015), synaptic coupling factors were taken to be equal to 1 or 1 in order to simulate, respectively, postsynaptic facilitation or inhibition. However, in the “cricket song generator”, neuron 4 strongly activates neuron 5, which in turn strongly inhibits neuron 1 (see section 3.2.4 in (Koch and Brunner, 1988Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920.
http://dx.doi.org/10.1007/BF00332920...
)), so we empirically increased the coupling factors between these two pairs of neurons until the firing patterns of our Neuroidbased replica were as similar as possible to those obtained by Koch and Brunner. An Acer TravelMate B113, with an Intel Core i33217U and 4 GB of memory, was used to perform all simulations.
Results
The Neuroid can now fire at the threshold intensity
As shown in Figure 2, the Neuroid fired one single spike when the stimulation amplitude reached the threshold intensity (I = 3.7 nA), while the benchmark solution fired several spikes for the same stimulus. Both neuronmodels showed a tonic response for I = 6 nA and the total number of spikes produced by them were very similar.
The firing pattern of the Neuroid (Δt = 10^{4} ms) and the benchmark solution (the LIF model solved by the fourth order RungeKutta method with Δt = 10^{4} ms) for two different stimulation amplitudes: 3.7 nA (threshold intensity) and 6 nA. (a) When the stimulation amplitude reached threshold, the Neuroid (blue dotted line) fired only one spike, while the benchmark solution (red solid line) fired several spikes. (b) For I = 6 nA both models showed a tonic response, although the Neuroid added one more spike to the total produced by the benchmark solution.
The accuracy of the Neuroid improved when a time step of 10^{2} ms or lower was used
A comparison of the FI curves for the Neuroid and the benchmark solution is shown in Figure 3. With a time step of 1 ms, discrepancies were observed between the responses produced by the Neuroid and the benchmark solution over the whole range of stimulation amplitudes. On the other hand, with a time step of 10^{2} ms, the response of the Neuroid was in good agreement with that provided by the benchmark solution, except for a short range of amplitudes slightly greater than the threshold intensity (from 3.7 to 7 nA). It is worth noting that, as with many neuronmodels, the firing frequency calculated by the Neuroid “jumped” to a nonzero value instead of increasing continuously at the threshold intensity. In fact, at this value, the Neuroid yielded f = 0 Hz and only for stimulation amplitudes greater than threshold our neuronmodel yielded nonzero frequency values. This is because, to calculate the firing frequency, at least two spikes were required (see Methods). Since at the threshold intensity, only one spike was fired, the condition was not fulfilled and the frequency was taken to be zero.
A comparison between the FI curve of the Neuroid (blue dotted line) for two different time steps and the FI curve of the benchmark solution (red solid line). (a) When a time step of 1 ms was used, the Neuroid showed a poor agreement with the benchmark solution. (b) When a time step of 10^{2} ms (or lower) was used, the Neuroid showed a good agreement with the benchmark solution, except for a short range of amplitudes slightly greater than the threshold intensity.
As it can be seen from Table 1, the Neuroid produced a firing frequency that approximates the one produced by the benchmark solution with an error less than 1%, using a time step less than or equal to 10^{2} ms, except for I = 5 nA. Better results were obtained for the whole range of stimulation amplitudes by using the LIF model solved by adopting the FE method with a time step less than or equal to 10^{1} ms.
Frequency errors for the LIF model (solved by the Forward Euler method) and the Neuroid at three different stimulation amplitudes (I = 5, 12 and 19 nA) with time steps ranging from 10^{4} to 1 ms. Values are expressed in percentages.
The neuroid is significantly faster than the LIF model solved by the FE method
From Figure 4 and Table 2, it can be seen that the mean computation time required by the Neuroid was significantly lower (Multifactorial ANOVA, p < 0.05) than the required by the LIF model when it was solved by using one of the simplest methods for approximating solutions to differential equations (i.e., the FE method). On the other hand, no significant differences were found in the computation time achieved by each model when different stimulation amplitudes and different stimulation periods were used (see Table 3).
LeastSquares means of the computation times achieved by the LIF model (FE method) and the Neuroid. Both models were run for three different simulation amplitudes (I = 5, 12 and 19 nA) and for three different stimulation periods (T = 200, 500 and 800 ms), with time steps ranging from 10^{4} to 1 ms.
Summary of multiple range tests for computation time (the response variable) by model. A multiple comparison procedure (the Fisher's least significant difference (LSD) procedure) was applied to determine which means are significantly different from which others. The bottom half of the table shows the estimated difference between means. An asterisk has been placed next to the pair showing a statistically significant difference at the 95% confidence level (LIF: leakyintegrateandfire; NEU: Neuroid).
LeastSquares Means for computation time with 95% confidence interval. Means, standard errors, lower and upper limits are expressed in milliseconds. An asterisk has been placed next to the factor showing a statistically significant difference between means at the 95% confidence level (LIF: leakyintegrateandfire; NEU: Neuroid).
Figure 5 shows, in the form of a Pareto chart, the absolute values of the standardized effects of each factor and all their possible combinations on the computation time required to calculate several hundreds of milliseconds of neural response. As can be seen, only the model (A) has a significantly and markedly effect on the computation time.
Absolute values of the standardized effects of each factor and all their possible combinations on the computation time. Only the model (A) has a significative and markedly effect on the computation time required to calculate several hundreds of milliseconds of neural response.
Neuroidbased networks can replicate the firing patterns produced by shortscale networks composed of more detailed units
Figures 6 and 7 show, respectively, the firing patterns produced by Neuroidbased replicas of both a threeneuron oscillator and the “cricket song generator”. In general, results are in good agreement with those obtained by earlier studies, in which more detailed neuronmodels were used (Friesen and Stent, 1977Friesen WO, Stent GS. Generation of a locomotory rythm by a Neural Network with Recurrent Cyclic Inhibition. Biol Cybern. 1977; 28(1):2740. PMid:597508. http://dx.doi.org/10.1007/BF00360911.
http://dx.doi.org/10.1007/BF00360911...
; Kling and Székely, 1968Kling U, Székely G. Simulation of rhythmic nervous activities. I. Function of networks with cyclic inhibitions. Kybernetik. 1968; 5(3):89103. PMid:5728516. http://dx.doi.org/10.1007/BF00288899.
http://dx.doi.org/10.1007/BF00288899...
; Koch and Brunner, 1988Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920.
http://dx.doi.org/10.1007/BF00332920...
). Different oscillation frequencies can be achieved by the Neuroidbased replica of the three neuron oscillator by varying the stimulation amplitude (see Figure 6b), and the order in which neurons start firing is also preserved (N3 → N2 → N1 → N3). Although the Neuroidbased replica of the “cricket song generator” required a transition period of more than 400 ms in order to produce a firing pattern consistent with previous results (see Figure 7b), Neuroids 2, 3 and 4 start firing shortly after the second spike of the previous unit occurs, and the burst of spikes generated by N5 produces a longterm pause in N1, in consistency with previous results (see Figure 10 in Koch and Brunner, 1988Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920.
http://dx.doi.org/10.1007/BF00332920...
).
A threeNeuroid oscillator. (a) The oscillator consists of three neurons simultaneously receiving a constant excitatory input (●), while they are cyclically connected through inhibitory synapses (○). (b) Firing patterns obtained by the authors for three different simulation intensities (Input = 5, 3 and 2.7 μA) after implementing a Neuroidbased replica of the threeneuron oscillator.
Using the Neuroid to build the “cricket song generator”. (a) Neuron 1 receives a constant excitatory input, which is transmitted to neurons 2, 3, 4 and 5 through excitatory synapses (●), while neuron 5 provides neuron 1 with strong inhibition (○). (b) Firing patterns obtained by the authors after implementing a Neuroidbased replica of the “cricket song generator”.
Discussion
Figure 2a shows that, unlike the benchmark solution, the Neuroid was able to fire a single spike when the stimulus amplitude reached the threshold intensity (I = 3.7 nA), which is consistent with the differences between the conditions required for the propagation of single spikes and those required for spike train generation (when sustained depolarizing pulses are applied at progressive increasing intensities, a “threshold intensity” is reached at which one single spike is fired... only when the stimulus intensity becomes higher, a spike train is produced) (Matzner and Devor, 1992Matzner O, Devor M. Na+ conductance and the threshold for repetitive neuronal firing. Brain Res. 1992; 597(1):928. PMid:1335824. http://dx.doi.org/10.1016/00068993(92)91509D.
http://dx.doi.org/10.1016/00068993(92)9...
). However, the response shown in Figure 2a cannot be assumed to be a phasic response, which include not only those exhibiting one single spike at the onset of the stimulus, but also those showing brief spike trains starting during the beginning of the stimulation period (Madrid et al., 2003Madrid R, Sanhueza M, Alvarez O, Bacigalupo J. Tonic and phasic receptor neurons in the vertebrate olfactory epithelium. Biophys J. 2003; 84(6):416781. PMid:12770919. https://doi.org/10.1016/S00063495(03)751418.
https://doi.org/10.1016/S00063495(03)75...
; Mitra and Miller, 2007Mitra P, Miller RF. Normal and rebound impulse firing in retinal ganglion cells. Vis Neurosci. 2007; 24(1):7990. PMid:17430611. https://doi.org/10.1017/S0952523807070101.
https://doi.org/10.1017/S095252380707010...
; Ruscheweyh and Sandkühler, 2002Ruscheweyh R, Sandkühler J. Laminaspecific membrane and discharge properties of rat spinal dorsal horn neurones in vitro. J Physiol. 2002; 541(1):23144. PMid:12015432. http://dx.doi.org/10.1113/jphysiol.2002.017756.
http://dx.doi.org/10.1113/jphysiol.2002....
). In fact, the absence of a delay in spike firing at different stimulus intensities shows a fundamental limitation of our neuronmodel and the assumption on which the model relies is, indeed, an oversimplification of the neural behavior because only some neurons fire at a regular frequency when stimulation amplitude is held constant and they do only under certain conditions. The Neuroid does not account for the dynamics of the voltagedependent membrane conductances that are responsible for the generation of action potentials, which is why spike trains show no clear threshold dependence or temporal behavior consistent with the latencies of ionic channels (see Figure 2b). Small differences in the membrane voltage are a great concern for several neural phenomena, such as spiketimingdependent plasticity (STDP) (Dan and Muming, 2004Dan Y, Muming P. Spike timingdependent plasticity of neural circuits. Neuron. 2004; 4(1):2330. https://doi.org/10.1016/j.neuron.2004.09.007.
https://doi.org/10.1016/j.neuron.2004.09...
; Shulz and Feldman, 2013Shulz DE, Feldman DE. Spike timingdependent plasticity. In: Rubenstein JLR, Rakic P. Comprehensive developmental neuroscience: neural circuit development and function in the healthy and diseased brain. San Diego, CA: Elsevier; 2013. p. 15581.), so the use and value of our neuronmodel might be limited to a narrow band of applications.
While the Neuroid is now able to produce more accurate results when a time step of 10^{2} ms or lower is used, its accuracy is considerably lower than the achieved with the LIF model solved by the FE method (see Table 1). The latter is consistent with the result obtained during a previous study (Skocik and Long, 2014Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
), in which it was shown that the LIF model provides fairly accurate results when the FE method with a time step of 0.1 ms or lower is used. On the other hand, that comparison was carried out not between models but between numerical methods because, by definition, the firing frequency produced by one model is different from the firing frequency produced by the others. More reliable results could be obtained if the firing rate of the model is compared to the firing rate of a biological neuron. Still, this comparison would be a bit more complicated since the neural response varies between different populations. A previous study (Prada et al., 2015Prada EJA, Bustillos RJS, Huerta MK, Martínez ADA. Lamina specific loss of inhibition may lead to distinct neuropathic manifestations: a computational modeling approach. Res Biomed Eng. 2015; 31(2):13347. http://dx.doi.org/10.1590/24464740.0734.
http://dx.doi.org/10.1590/24464740.0734...
) found that the Neuroid might be used to predict the firing frequency of nociceptive primary afferent A and Cfibers, but it could be insufficient to model spinal dorsal horn neurons. All this suggests that, in the absence of a quantitative index for the evaluation of the accuracy achieved by several neuronmodels, the results obtained by previous (Izhikevich, 2004Izhikevich EM. Which model to use for cortical spiking neurons? IEEE Trans Neural Netw. 2004; 15(5):106370. PMid:15484883. https://doi.org/10.1109/TNN.2004.832719.
https://doi.org/10.1109/TNN.2004.832719...
; Long and Fang, 2010Long L, Fang G. A review of biologically plausible neuron models for spiking neural networks. In: Proceedings of the AIAA InfoTech@ Aerosp Conference; 2010 Apr 2022; Atlanta, GA. Atlanta: AIAA; 2010. http://dx.doi.org/10.2514/6.20103540.
http://dx.doi.org/10.2514/6.20103540...
; Skocik and Long, 2014Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
; Wang et al., 2014Wang Z, Guo L, Adjouadi M. A generalized Leaky IntegrateandFire neuron model with fast implementation method. Int J Neural Syst. 2014; 24(5):1440004. PMid:24875788. http://dx.doi.org/10.1142/S0129065714400048.
http://dx.doi.org/10.1142/S0129065714400...
) and the current study may not be absolutely conclusive.
From Figures 4 and 5, and Tables 2 and 3, it is clear that the computation time required by the Neuroid is significantly lower (Multifactorial ANOVA, p < 0.05) than the required by the LIF model when it is solved by using the FE method, which is one of the simplest methods for approximating solutions to differential equations (Izhikevich, 2004Izhikevich EM. Which model to use for cortical spiking neurons? IEEE Trans Neural Netw. 2004; 15(5):106370. PMid:15484883. https://doi.org/10.1109/TNN.2004.832719.
https://doi.org/10.1109/TNN.2004.832719...
; Skocik and Long, 2014Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016.
https://doi.org/10.1109/TNNLS.2013.22940...
). In general, the Neuroid performs its calculations in an amount of time significantly lower than the required by the LIF model, under the same conditions. Surprisingly, such differences do not increase significantly either when the stimulation amplitude increases or the stimulation period decreases (see Table 3). Even so, it is worth noting that the FLOPs per iteration required by the Neuroid decreases by one whenever a spike is fired, since the variable count1 is reset instead of increasing by one when its value reaches or exceeds the quantity
Effects of the stimulus amplitude and duration on the estimated computational cost of the Neuroid and the LIF model solved by the FE method. The band between dashed lines denotes the stimulation period and an encircled number indicates that a spike was fired. It was assumed that both models fire synchronously. (a) The total of FLOPs required by the Neuroid to perform its calculations is, in general, less than that for the LIF model when it is solved by using the FE method because no operations are executed by the Neuroid in the absence of stimulus; (b) As the stimulus amplitude increases, the FLOPs per iteration required by the Neuroid decreases by one per each “elicited” spike and the FLOPs required for the given total of iterations decreases slightly; (c) As the stimulus duration decreases, the FLOPs required by the Neuroid for the given total of iterations decreases considerably because the FLOPs per iteration drops to zero in the absence of stimulus. On the contrary, the LIF model (like other classic neuronmodels) is constantly performing calculations regardless the amplitude and duration of the stimulus, so the FLOPs per iteration required by the model and the FLOPs for the given total of iterations remains unaffected, even in the absence of stimulus.
This “compare first, calculate later” feature makes the Neuroid an attractive option for those who want to model the behavior of largescale neural networks through which the information is transmitted in the form of shortduration pulses (e.g., Spiking Neural Networks), especially when computational resources are limited, since its computational cost is significantly lower than the one required by the legendary LIF model. For instance, about one third to 40% of the cortical neuron population is composed by neurons capable of firing extremely narrow spikes at a very high frequency (300400 Hz) with a very low adaptation rate (Wang et al., 2016Wang B, Ke W, Guang J, Chen G, Yin L, Deng S, et al. Firing frequency maxima of fastspiking neurons in human, monkey, and mouse neocortex. Front Cell Neurosci. 2016; 10:239. http://dx.doi.org/10.3389%2Ffncel.2016.00239.
http://dx.doi.org/10.3389%2Ffncel.2016.0...
), precisely the kind of behavior that the Neuroid is able to reproduce. However, it must be taken into account that the computational cost of a neuronmodel tends to increase with its accuracy, which in turn depends on, among other factors, the size of the time step. Nowadays, it is possible to implement some alternatives, like the one proposed by Wang et al. (2014)Wang Z, Guo L, Adjouadi M. A generalized Leaky IntegrateandFire neuron model with fast implementation method. Int J Neural Syst. 2014; 24(5):1440004. PMid:24875788. http://dx.doi.org/10.1142/S0129065714400048.
http://dx.doi.org/10.1142/S0129065714400...
, whose accuracy is not significantly affected by the time step size. Yet, and as we previously pointed out, results reported by that and other studies should be analyzed in the light of a common quantitative index of a neuronmodel’s accuracy, which may lead to a more objective comparison.
Figures 6 and 7 show that it is feasible to use Neuroidbased networks to replicate biologically relevant firing patterns produced by lowscale networks composed of much more detailed units, as those used in earlier studies (Friesen and Stent, 1977Friesen WO, Stent GS. Generation of a locomotory rythm by a Neural Network with Recurrent Cyclic Inhibition. Biol Cybern. 1977; 28(1):2740. PMid:597508. http://dx.doi.org/10.1007/BF00360911.
http://dx.doi.org/10.1007/BF00360911...
; Kling and Székely, 1968Kling U, Székely G. Simulation of rhythmic nervous activities. I. Function of networks with cyclic inhibitions. Kybernetik. 1968; 5(3):89103. PMid:5728516. http://dx.doi.org/10.1007/BF00288899.
http://dx.doi.org/10.1007/BF00288899...
; Koch and Brunner, 1988Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920.
http://dx.doi.org/10.1007/BF00332920...
). Moreover, it was possible to generate periodic bursts of spikes by using a heuristic that was originally conceived to respond tonically. No matter which values are chosen for the parameters of the Neuroid, it is not able to produce by itself bursts of spikes, unlike other spiking neuronmodels (e.g., the Izhikevich’s model). This suggests that, even though spike bursts are known to be caused by intrinsic mechanisms of cells (Izhikevich, 2007Izhikevich EM. Dynamical systems in neuroscience: the geometry of excitability and bursting. Cambridge: MIT Press; 2007.; Krahe and Gabbiani, 2004Krahe R, Gabbiani F. Burst firing in sensory systems. Nat Rev Neurosci. 2004; 5(1):1323. PMid:14661065. http://dx.doi.org/10.1038/nrn1296.
http://dx.doi.org/10.1038/nrn1296...
), they can also be attributed to the synaptic properties of neuron connectivity and/or the topology of the network. Therefore, it would be possible to use Neuroids in analyzing to what extent emergent properties derived from mutual connectivity between neurons contribute to the generation of bursting oscillatory patterns. Neuroidbased replicas of some biological neural networks, whose architecture is well known, might be built and studied before using much more detailed simulation tools or packages. This, in turn, demands an accurate identification of the cells composing those networks as well as a wiring diagram describing how they are connected, which may lead to new research opportunities. Lastly, a result like this could be viewed as a small extension of the Hopfield’s work (Hopfield, 1984Hopfield JJ. Neurons with graded response have collective computational properties like those of twostate neurons. Proc Natl Acad Sci USA. 1984; 81(10):308892. PMid:6587342. http://dx.doi.org/10.1073/pnas.81.10.3088.
http://dx.doi.org/10.1073/pnas.81.10.308...
; ^{1982}Hopfield JJ. Neural networks and physical systems with emergent collective computational abilities. Proc Natl Acad Sci USA. 1982; 79(8):25548. PMid:6953413. http://dx.doi.org/10.1073/pnas.79.8.2554.
http://dx.doi.org/10.1073/pnas.79.8.2554...
), in which it was found that the computational properties of networks composed of binary unrealistic units, like the McCulloch and Pitts model (McCulloch and Pitts, 1943McCulloch WS, Pitts WH. A logical calculus of the ideas immanent in nervous activity. Bull Math Biol. 1943; 5(4):11533. https://doi.org/ 10.1007/BF02478259.
https://doi.org/ 10.1007/BF02478259...
), are often preserved in networks composed of units having continuous inputoutput relationships and integrative time delays.
Like any heuristic, the Neuroid does not guarantee an optimal solution for a wide range of problems. Our neuronmodel is, indeed, far from being a biologically meaningful model, since the conditions and assumptions upon which the model was formulated are very specific. It is widely known that the firing rate of real neurons depends not only on the stimulation intensity, but also on several other factors like subthreshold dynamics, a feature which our neuronmodel fails to exhibit. On the other hand, and according with results presented before, the Neuroid requires a smaller amount of computational resources than those required by the LIF model to simulate several hundreds of milliseconds of neuronal response under the same conditions. This suggests that the Neuroid may be an interesting option for the implementation of networks through which the information is transmitted in the form of shortduration pulses (e.g., Spiking Neural Networks), especially when computational resources are limited. Furthermore, the low computational cost required by the Neuroid, as well as its flexibility to be adapted to any type of programming language (C ++, MATLAB, HPVEE, LabVIEW) make it suitable for the development of free and open computational tools based on Neuroids, as the one developed in the University of Guayaquil (Silva Muñoz, 2015Silva Muñoz AM. Desarrollo de un software para la construcción de redes neuroidales [thesis]. GuayaquilEcuador: Universidad de Guayaquil; 2015.). Future work may include considering the noise influence by adding a probabilistic component to the Neuroid without altering its low computational requirement.
The fact that our neuronmodel is able to reproduce only a few neurocomputational properties could make it a useful tool for determining if the firing patterns exhibited by neurons composing certain networks are due to the intrinsic properties of these cells, or to the topology of the network. In other words, if a Neuroidbased replica is able to reproduce the firing patterns observed in a biological network, then these patterns are likely to be produced by the interactions between different cells or nodes. This indeed underlines the importance of neural connection for the generation of specific firing patterns, and also demands an accurate identification of the cells composing those networks as well as a wiring diagram describing how they are connected, which may lead to new research opportunities.
As a concluding remark, beyond a simple comparison between different average firing rates or coincident spikes, researchers and modelers still lack a standardized set of tests to quantify and compare the accuracy of distinct neuronmodels, so further work is needed to provide these communities with a common framework that can be used as a reference for this purpose.
Acknowledgements
The authors thank Prof. Minaya Villasana for her valuable ideas and useful observations during the realization of this article.

How to cite this article: Prada EJA, Arteaga IAB, Martínez AJD. The Neuroid revisited: a heuristic approach to model neural spike trains. Res Biomed Eng. 2017; 33(4):pppp. DOI: 10.1590/24464740.02617.
References
 Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell. 4th ed. New York: Garland Science; 2002.
 Andrews T. Computation time comparison between Matlab snd C++ using Launch Windows. Aerosp Eng. 2012; 78:16.
 Bayly EJ. Spectral analysis of pulse frequency modulation in the nervous systems. IEEE Trans Biomed Eng. 1968; 15(4):25765. PMid:5699902. http://dx.doi.org/10.1109/TBME.1968.4502576
» http://dx.doi.org/10.1109/TBME.1968.4502576  Brette R, Gerstner W. Adaptive exponential integrateandfire model as an effective description of neuronal activity. J Neurophysiol. 2005; 94(5):363742. PMid:16014787. https://doi.org/ 10.1152/jn.00686.2005
» https://doi.org/ 10.1152/jn.00686.2005  Dan Y, Muming P. Spike timingdependent plasticity of neural circuits. Neuron. 2004; 4(1):2330. https://doi.org/10.1016/j.neuron.2004.09.007
» https://doi.org/10.1016/j.neuron.2004.09.007  Delcomyn F. Neural basis of rhythmic behavior in animals. Science. 1980; 210(4469):4928. PMid:7423199. http://dx.doi.org/10.1126/science.7423199
» http://dx.doi.org/10.1126/science.7423199  Ermentrout GB, Terman DH. Mathematical foundations of neuroscience. Vol. 35. New York: Springer Science & Business Media; 2010.
 Friesen WO, Stent GS. Generation of a locomotory rythm by a Neural Network with Recurrent Cyclic Inhibition. Biol Cybern. 1977; 28(1):2740. PMid:597508. http://dx.doi.org/10.1007/BF00360911
» http://dx.doi.org/10.1007/BF00360911  Gerstner W, Kistler WM, Naud R, Paninsky L. Neuronal dynamics: from single neurons to networks and models of cognition. Cambridge: University Press; 2014.
 Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952; 117(4):50044. PMid:12991237. http://dx.doi.org/10.1113/jphysiol.1952.sp004764
» http://dx.doi.org/10.1113/jphysiol.1952.sp004764  Hopfield JJ. Neural networks and physical systems with emergent collective computational abilities. Proc Natl Acad Sci USA. 1982; 79(8):25548. PMid:6953413. http://dx.doi.org/10.1073/pnas.79.8.2554
» http://dx.doi.org/10.1073/pnas.79.8.2554  Hopfield JJ. Neurons with graded response have collective computational properties like those of twostate neurons. Proc Natl Acad Sci USA. 1984; 81(10):308892. PMid:6587342. http://dx.doi.org/10.1073/pnas.81.10.3088
» http://dx.doi.org/10.1073/pnas.81.10.3088  Horch KW, Dhillon GS. Neuroprosthetics: theory and practice. New York: World Scientific; 2004.
 Izhikevich EM. Simple model of spiking neuron. IEEE Trans Neural Netw. 2003; 14(6):156972. PMid:18244602. https://doi.org/10.1109/TNN.2003.820440
» https://doi.org/10.1109/TNN.2003.820440  Izhikevich EM. Which model to use for cortical spiking neurons? IEEE Trans Neural Netw. 2004; 15(5):106370. PMid:15484883. https://doi.org/10.1109/TNN.2004.832719
» https://doi.org/10.1109/TNN.2004.832719  Izhikevich EM. Dynamical systems in neuroscience: the geometry of excitability and bursting. Cambridge: MIT Press; 2007.
 Jolivet R, Lewis TJ, Gerstner W. Generalized integrateandfire models of neuronal activity approximate spike trains of a detailed model to a high degree of accuracy. J Neurophysiol. 2004; 92(2):95976. PMid:15277599. https://doi.org/10.1152/jn.00190.2004
» https://doi.org/10.1152/jn.00190.2004  Kling U, Székely G. Simulation of rhythmic nervous activities. I. Function of networks with cyclic inhibitions. Kybernetik. 1968; 5(3):89103. PMid:5728516. http://dx.doi.org/10.1007/BF00288899
» http://dx.doi.org/10.1007/BF00288899  Kobayashi R, Tsubo Y, Shinomoto S. Madetoorder spiking neuron model equipped with a multitimescale adaptive threshold. Front Comput Neurosci. 2009; 3:9. PMid: 19668702. https://doi.org/10.3389/neuro.10.009.2009
» https://doi.org/10.3389/neuro.10.009.2009  Koch UT, Brunner M. A modular analog neuronmodel for research and teaching. Biol Cybern. 1988; 59(45):30312. PMid:3196775. http://dx.doi.org/10.1007/BF00332920
» http://dx.doi.org/10.1007/BF00332920  Krahe R, Gabbiani F. Burst firing in sensory systems. Nat Rev Neurosci. 2004; 5(1):1323. PMid:14661065. http://dx.doi.org/10.1038/nrn1296
» http://dx.doi.org/10.1038/nrn1296  Long L, Fang G. A review of biologically plausible neuron models for spiking neural networks. In: Proceedings of the AIAA InfoTech@ Aerosp Conference; 2010 Apr 2022; Atlanta, GA. Atlanta: AIAA; 2010. http://dx.doi.org/10.2514/6.20103540
» http://dx.doi.org/10.2514/6.20103540  Madrid R, Sanhueza M, Alvarez O, Bacigalupo J. Tonic and phasic receptor neurons in the vertebrate olfactory epithelium. Biophys J. 2003; 84(6):416781. PMid:12770919. https://doi.org/10.1016/S00063495(03)751418
» https://doi.org/10.1016/S00063495(03)751418  Matzner O, Devor M. Na+ conductance and the threshold for repetitive neuronal firing. Brain Res. 1992; 597(1):928. PMid:1335824. http://dx.doi.org/10.1016/00068993(92)91509D
» http://dx.doi.org/10.1016/00068993(92)91509D  McCulloch WS, Pitts WH. A logical calculus of the ideas immanent in nervous activity. Bull Math Biol. 1943; 5(4):11533. https://doi.org/ 10.1007/BF02478259
» https://doi.org/ 10.1007/BF02478259  Mitra P, Miller RF. Normal and rebound impulse firing in retinal ganglion cells. Vis Neurosci. 2007; 24(1):7990. PMid:17430611. https://doi.org/10.1017/S0952523807070101
» https://doi.org/10.1017/S0952523807070101  Montgomery DC. Design and analysis of experiments. Hoboken: John Wiley & Sons; 2017.
» Hoboken  Prada EJA, Bustillos RJS, Huerta MK, Martínez ADA. Lamina specific loss of inhibition may lead to distinct neuropathic manifestations: a computational modeling approach. Res Biomed Eng. 2015; 31(2):13347. http://dx.doi.org/10.1590/24464740.0734
» http://dx.doi.org/10.1590/24464740.0734  Prada EJA, Bustillos RJS, Castillo C, Huerta M. New trends in computational modeling: a neuroidbased retina model. In: Proceedings of the 35th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2013 Jul 37; Osaka, Japan. Osaka: IEEE; 2013. p. 45614. PMid: 24110749. https://doi.org/10.1109/EMBC.2013.6610562
» https://doi.org/10.1109/EMBC.2013.6610562  Prada EJA, Bustillos RJS, Castillo C, Huerta M. The neuroid: a novel and simplified neuronmodel. In: Proceedings of the 34th Annual International Conference IEEE Engineering in Medicine and Biology Society; 2012 Aug 28Sep 1; San Diego, CA. San Diego: IEEE; 2012. p. 12347. PMid:23366121. https://doi.org/10.1109/EMBC.2012.6346160
» https://doi.org/10.1109/EMBC.2012.6346160  Prada EJA, Bustillos RJS. The implementation of the Neuroid in the gate control system leads to new ideas about pain processing. Rev Bras Eng Bioméd. 2013; 29(3):25461. http://dx.doi.org/10.4322/rbeb.2013.025
» http://dx.doi.org/10.4322/rbeb.2013.025  Rieke F, Warland D, van Steveninck RR, Bialek W. Spikes: exploring the neural code. Cambridge: MIT Press; 1997.
 Ruscheweyh R, Sandkühler J. Laminaspecific membrane and discharge properties of rat spinal dorsal horn neurones in vitro. J Physiol. 2002; 541(1):23144. PMid:12015432. http://dx.doi.org/10.1113/jphysiol.2002.017756
» http://dx.doi.org/10.1113/jphysiol.2002.017756  Silva Muñoz AM. Desarrollo de un software para la construcción de redes neuroidales [thesis]. GuayaquilEcuador: Universidad de Guayaquil; 2015.
 Scimemi A, Beato M. Determining the neurotransmitter concentration profile at active synapses. Mol Neurobiol. 2009. 40(3):289306. https://doi.org/ 10.1007/s1203500980877
» https://doi.org/ 10.1007/s1203500980877  Shulz DE, Feldman DE. Spike timingdependent plasticity. In: Rubenstein JLR, Rakic P. Comprehensive developmental neuroscience: neural circuit development and function in the healthy and diseased brain. San Diego, CA: Elsevier; 2013. p. 15581.
 Skocik MJ, Long LN. On the capabilities and computational costs of neuron models. IEEE Trans Neural Netw Learn Syst. 2014; 25(8):147483. PMid: 25050945. https://doi.org/10.1109/TNNLS.2013.2294016
» https://doi.org/10.1109/TNNLS.2013.2294016  Wang Z, Guo L, Adjouadi M. A generalized Leaky IntegrateandFire neuron model with fast implementation method. Int J Neural Syst. 2014; 24(5):1440004. PMid:24875788. http://dx.doi.org/10.1142/S0129065714400048
» http://dx.doi.org/10.1142/S0129065714400048  Wang B, Ke W, Guang J, Chen G, Yin L, Deng S, et al. Firing frequency maxima of fastspiking neurons in human, monkey, and mouse neocortex. Front Cell Neurosci. 2016; 10:239. http://dx.doi.org/10.3389%2Ffncel.2016.00239
» http://dx.doi.org/10.3389%2Ffncel.2016.00239
Publication Dates

Publication in this collection
18 Dec 2017 
Date of issue
OctDec 2017
History

Received
27 May 2017 
Accepted
23 Nov 2017