%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \chapter{Simulations} \label{simulationschapter} \exercisechapter{Simulations} The real power of computers for data analysis is the possibility to run simulations. Experimental data of almost unlimited sample sizes can be simulated in no time. This allows to explore basic concepts, the ones we introduce in the following chapters and many more, with well controlled data sets that are free of confounding pecularities of real data sets. With simulated data we can also test our own analysis functions. More importantly, by means of simulations we can explore possible outcomes of our experiments before we even started the experiment. We could even explore possible results for regimes that we cannot test experimentally. How dynamical systems, like for example predator-prey interactions or the activity of neurons or whole brains, evolve in time is a central application for simulations. The advent of computers at the second half of the twentieth century pushed the exciting field of nonlinear dynamical systems forward. Conceptually, many kinds of simulations are very simple and are implemented in a few lines of code. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \section{Random numbers} At the heart of many simulations are random numbers that we get from \enterm[random number generator]{random number generators}. These are numerical algorithms that return sequences of numbers that appear to be as random as possible. If we draw random numbers using, for example, the \code{rand()} function, then these numbers are indeed uniformly distributed and have a mean of one half. Subsequent numbers are independent of each other, i.e. the autocorrelation function is zero everywhere except at lag zero. However, numerical random number generators have a period, after which they repeat the exact same sequence of numbers. This differentiates them from truely random numbers and hence they are called \enterm[random number generator!pseudo]{pseudo random number generators}. In rare cases this periodicity can induce problems in simulations whenever more random numbers than the period of the random number generator are used. Luckily, nowadays the periods of random nunmber generators are very large. Periods are at least in the range of $2^{64}$, that is about $10^{18}$, or even larger. The pseudo randomness of numerical random number generators also has an advantage. They allow to repeat exactly the same sequence of random numbers. After defining the state of the generator or setting a \enterm{seed} with the \code{rng()} function, a particular sequence of random numbers is generated by subsequent calls of the random number generator. This way we can not only precisly define the statistics of noise in our simulated data, but we can repeat an experiment with exactly the same sequence of noise values. This is useful for plots that involve some random numbers but should look the same whenever the script is run. \begin{exercise}{randomnumbers.m}{randomnumbers.out} First, read the documentation of the \varcode{rand()} function and check its output for some (small) input arguments. Generate three times the same sequence of 10 uniformly distributed numbers using the \code{rand()} and \code{rng()} functions. Generate 10\,000 uniformly distributed random numbers and compute the correlation coefficient between each number and the next one in the sequence. This is the serial correlation at lag one. \end{exercise} \begin{figure}[t] \includegraphics[width=1\textwidth]{randomnumbers} \titlecaption{\label{randomnumbersfig} Random numbers.} {Numerical random number generators return sequences of numbers that are as random as possible. The returned values approximate a given probability distribution. Here, for example, a uniform distribution between zero and one (top left). The serial correlation (auto-correlation) of the returned sequences is zero at any lag except for zero (bottom left). However, by setting a seed, defining the state, or spawning the random number generator, the exact same sequence can be generated (right).} \end{figure} %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \section{Univariate data} A basic type of stochastic simulations is to draw random numbers from a given distribution like, for example, the normal distribution. This simulates repeated measurements of some quantity (weight of tigers, firing rate of neurons). Doing so we must specify from which probability distribution the data should originate from and what are the parameters of that distribution (mean, standard deviation, shape parameters). How to illustrate and quantify univariate data, no matter whether they have been actually measured or whether they have been simulated as described in the following, is described in chapter~\ref{descriptivestatisticschapter}. \subsection{Normally distributed data} For drawing numbers from a normal distribution \begin{equation} p_{norm}(x) = \frac{1}{\sqrt{2\pi}}e^{-\frac{1}{2}x^2} \end{equation} with zero mean and unit standard deviation we use the \code{randn()} function. This function returns normally distributed numbers $\xi_i$ with zero mean and unit standard deviation. For changing the standard deviation we need to multiply the returned data values with the required standard deviation $\sigma$. For changing the mean we just add the desired mean $\mu$ to the random numbers: \begin{equation} x_i = \sigma \xi_i + \mu \end{equation} \begin{figure}[t] \includegraphics[width=1\textwidth]{normaldata} \titlecaption{\label{normaldatafig} Generating normally distributed data.}{With the help of a computer the weight of 300 tigers can be measured in no time using the \code{randn()} function (left). By construction we then even know the population distribution (red line, right), its mean (here 220\,kg) and standard deviation (40\,kg) from which the simulated data values were drawn (yellow histogram).} \end{figure} \begin{exercise}{normaldata.m}{normaldata.out} Write a little script that generates $n=100$ normally distributed data simulating the weight of Bengal tiger males with mean 220\,kg and standard deviation 40\,kg. Check the actual mean and standard deviation of the generated data. Do this, let's say, five times using a for-loop. Then increase $n$ to 10\,000 and run the code again. It is so simple to measure the weight of 10\,000 tigers for getting a really good estimate of their mean weight, isn't it? Finally plot from the last generated data set of tiger weights the first 1000 values as a function of their index. \end{exercise} \subsection{Other probability densities} We can draw random numbers not only from normal distributions. Functions are provided that let you draw random numbers of almost any probability distribution. They differ in their shape and in the number of parameters they have. Most probability distributions are parameterized by a location parameter that usually coincides with their mean, and a scale parameter that often coincides with their standard deviation. Some distributions have additional shape parameters. For example, the time intervals $t$ between randomly generated action potentials (a so called Poisson spike train, see chapter~\ref{pointprocesseschapter}) are exponentially distributed --- as are the intervals between state transitions of ion channels, or the intervals between radioactive decays. The exponential distribution is only defined for positive time intervals: \begin{equation} \label{expdistribution} p_{exp}(t) = \lambda e^{-\lambda t} \; , \quad t \ge 0, \; \lambda > 0 \end{equation} A single rate parameter $\lambda$ measured in Hertz parameterizes the exponential distribution. It defines how often per time unit the event happens. Both the mean interval between the events and the corresponding standard deviation equal the inverse rate. \begin{exercise}{exprandom.m}{exprandom.out} Draw $n=200$ random time intervals from an exponential distribution with rate $\lambda=50$\,Hz. Calculate the mean and the standard deviation of the random numbers and compare them with the expected values. \end{exercise} \subsection{Uniformly distributed random numbers} \begin{figure}[t] Exponential distribution of ISIs. \end{figure} The \code{rand()} function returns uniformly distributed random numbers between zero and one \begin{equation} p_{uni}(x) = \left\{\begin{array}{rcl} 1 & ; & 0 \le x < 1 \\ 0 & ; & \text{else} \end{array}\right. \end{equation} For random numbers $x_i$ uniformly distributed between $x_{\rm min}$ and $x_{\rm max}$ we multiply by the desired range $x_{\rm max} - x_{\rm min}$ and add $x_{\rm min}$ to the numbers $u_i$ returned by \code{rand()}: \begin{equation} x_i = (x_{\rm max} - x_{\rm min}) u_i + x_{\rm min} \end{equation} \begin{exercise}{unirandom.m}{unirandom.out} Simulate the times of $n=10\,000$ action potentials occuring randomly within a time interval of 100\,s using the \code{rand()} function. Sort the times using \code{sort()}, compute the time intervals between the action potentials (interspike intervals, ISIs) using the \code{diff()} function, plot a histogram of the interspike intervals in milliseconds, and compute the mean and standard deviation of the interspike intervals, also in milliseconds. Compare the mean ISI with the firing rate (number of action potentials per time). \end{exercise} \subsection{Simulating probabilities} Simulating events that happen with some probability $P$ is also possible. That could be the probability of head showing up when flipping a coin, getting an action potential within some time, a ion channel to open, ... For this draw a random number $u_i$ from a uniform distribution between zero and one (\code{rand()}). If the random number is lower than $P$, the event happens, if it is larger the event does not occur. \begin{exercise}{probability.m}{probability.out} Let's flip a coin 20 times. The coin is biased and shows head with a probability of $P=0.6$. Count the number of heads. \end{exercise} \subsection{Random walks} A basic concept for stochastic models is the random walk. A walker starts at some initial position $x_0$. It then takes steps to the right, $x_n = x_{n-1} + 1$, with some probability $P_r$ or to the left, $x_n = x_{n-1} - 1$, with probability $P_l = 1-P_r$. For a symmetric random walk, the probabilities to step to the left or to the right are the same, $P_r = P_l = \frac{1}{2}$. The average position of many walkers is then independent of the iteration step and equals the initial position $x_0$. The standard deviation of the walker positions, however, grows with the square root of the number of iteration steps $n$: $\sigma_{x_n} = \sqrt{n}$. \begin{figure}[tb] Have a figure with a few 1D random walks and the increasing standard deviation as a shaded area behind. And with absorbing boundary. \end{figure} The sub-threshold membrane potential of a neuron can be modeled as a one-dimensional random walk. The thousands of excitatory and inhibitory synaptic inputs of a principal neuron in the brain make the membrane potential to randomly step upwards or downwards. Once the membrane potential hits a firing threshold an action potential is generated and the membrane potential is reset to the resting potential. The firing threshold in this context is often called an ``absorbing boundary''. The time it takes from the initial position to cross the threshold is the ``first-passage time''. For neurons this is the interspike interval. For symmetric random walks the first-passage times are again exponentially distributed. ??? Is that so ??? % Gerstein and Mandelbrot 1964 Higher dimensions, Brownian motion. The gamma distribution (\code{gamrnd()}) phenomenologically describes various types of interspike interval dsitributions (chapter~\ref{pointprocesseschapter}). scale and shape. exercise. \subsection{Random integers} \code{randi()} %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \section{Bivariate data} \subsection{Static nonlinearities} \begin{figure}[t] \includegraphics[width=1\textwidth]{staticnonlinearity} \titlecaption{\label{staticnonlinearityfig} Generating data fluctuating around a function.}{The conductance of the mechontransducer channels in hair cells of the inner ear is a saturating function of the deflection of their hairs (left, red line). Measured data will fluctuate around this function (blue dots). Ideally the residuals (yellow histogram) are normally distributed (right, red line).} \end{figure} Example: mechanotransduciton! draw (and plot) random functions. %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \section{Dynamical systems} \begin{itemize} \item iterated maps \item euler forward, odeint \item introduce derivatives which are also needed for fitting (move box from there here) \item Passive membrane \item Add passive membrane to mechanotransduction! \item Integrate and fire \item Fitzugh-Nagumo \item Two coupled neurons? Predator-prey? \end{itemize} %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \section{Summary} with outook to other simulations (cellular automata, monte carlo, etc.) %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% \printsolutions