To curve fit a model to a set of data, you run the model with different sets of parameters to find the the output that best matches the data. For each parameter set, the model output is compared to the existing data with a comparison function, which is the difference between the model's output and the data. This function is minimized through a process of testing different parameter sets for the model. The difficulty in this process is finding an algorithm that finds the parameter set that produces the best match. It is difficult because in a nonlinear model the output (given a set of parameters) is not always easy to predict.

There are many methods for fitting parameter sets to a nonlinear model. One method is the "downhill simplex" method. This is often useful when a simulation function can be evaluated but no first or second derivative is directly available. Since the simplex method does not rely on the derivatives of the function, it is not as computationally efficient, but it can work with a wider variety of nonlinear functions. Both of these methods work well only to find "local minima" and may get stuck in a minima which is not the global minimum for a function.

The Levenberg-Marquardt least-squares fitting method is implemented in NeuronC. You can use the "lmfit()" procedure in either the interpreted or compiled versions, and a 2D compiled version is also available. A test program, "gaussfit.cc" is provided for the 2D version.

To fit a model such as "retsim" to a set of real data, you compile "modelfit" and run it like this:

modelfit --data_file R2_111201_03_prefnull.txt --template_file R2_111201_03_prefnull_template_s9.data --template_file2 fdsgc_chans28_template_s9.data --expt_string "mosrun -l -b -g retsim --expt dsgc_chans --n_dsgc 1 --n_sbac 0 --sbarr -1 --dsgc_file morph_ds1e --dsgc_densfile dens_dsgc_chans.n --nvalfile nval_dsgc_sbac_chans.n --sbac_file morph_sbac3c --minten -0.058 --econtrast 0.017 --eincr 0 --icontrast 0.017 --iincr 0.00417 --velocity 2000 --prestimdur 0.05 --poststimdur 0.05 --vstart -0.115 --vstop 0.045 --dvst -0.06 --dvrev -0.051 --drm 41.3e3 --dendrm 60e3 --dri 95 --elec_rs 5e6 --elnode 5000 --light_inhib 1 --ampa_cond 4e-09 --nmda_cond 1.0177e-09 --gaba_cond 4.60799e-09 --movein -1 --set_vclamp 1 --ttxbath 1 --tea 0.9937 --kdr_voff 0.02714 --kexp 2.7438 --fourap 1 --ioffset 0 --use_ghki 1 --ninfo 2 -s 18 --stimscale 0.45 --skipv 9" --p1 --ampa_cond --c1 1e-9 --p2 --gaba_cond --c2 0.5e-9 --p3 --iincr --c3 0.001 --p4 --nmda_cond --c4 1e-9 --c4_min 0 >& modelfit_run91 &The modelfit program takes arguments describing the data file, either 1 or 2 template files, and the parameters for the fit. The data file is a 2D matrix, typically with rows and columns, where each row represents one time point, and each column is a separate trace from the data set. The template file is a copy of the data file, with the same number of rows and columns, except that it contains numbers from zero to 1. The modelfit program reads in the data file and the template and multiplies them. For each non-zero value in the template (typically 1.0), the resulting value is selected from the original data file. This allows the modelfit program to use a subset of the points from the original data file. Then when the model runs, its output is also multiplied by the template, and the values into the Levenberg-Marquard "lmfit()" procedure.

The "mosrun" command is from the "mosix" job management system (http://www.mosix.cs.huji.ac.il). This allows jobs to be run in parallel in a cluster of computers connected on a fast local net. Although it is easy to install on a 64-bit Linux system, "mosrun" is not necessary to run modelfit or retsim, because you can run jobs in parallel in the shell using "&" after each command.

If a second template file is defined, the modelfit program uses it to select the points from the model data output, which allows a different set of points to be passed to the Levenberg-Marquardt procedure. This is useful when you want to run the model faster by omitting some of the unnecessary data points found in the original data file.

The parameters for the modelfit program are set up on the command line:

--p1 --ampa_cond (the label for the first parameter to be used as the variable name on the command line ) --c1 1e-9 (the starting value) --c1_max 10e-9 (the max value) --c1_min 1e-12 (the min value) --p2 --gaba_cond (the label for the second parameter) --c2 0.5e-9 (the starting value for the second parameter) . . .You can set up to 10 free parameters to be fit. They are all given default values of zero for their minimum value, so if you want to allow them to go negative, you must set their minimum values explicitly. (Or you can comment out the code in modelfit.cc that sets their minimum to zero.) Although several parameters can be run in parallel on a multiprocessor CPU or in the Mosix multiprocessing envirnoment, a modelfit running with many free parameters will generally take longer than with just a few.

The Levenberg-Marquart algorithm determines the gradient in N-space for each big step it takes to find and test a new point. If you have set many parameters, you will find that this slows down the L-M curve fitting because the gradient of the model must be tested for each parameter at each point. If you have several processors or cores, you can speed up the L-M procedure by turning on multi-processing. You do this by setting "--lm_multi_proc 1", either in the command line for modelfit or in the source code (set to 1 by default). This directs the modelfit program to send the test of each different parameter to a different job, which speeds up the L-M algorithm by the number of processors (up to the number of parameters).

To work correctly, the lm_multi_proc option requires that the output from the model contain a line that includes "done". Typically, you set up the model so that at the end after all the data has been output to the model data file you print out a final line similar to: printf ("# done\n"); The "#" at the beginning of the line allows the "plotmod" plotting program to ignore the line when plotting the data. Once each job is run, the modelfit program checks to see if it is done by reading the file using "tail". If "done" is found, modelfit then proceeds to direct the L-M algorithm to read and test the completed model data.

The filename for the model data file is defined by the modelfit program as "modelfit0xxxxx_y", where xxxxx = the modelfit process number, and y = the number of the parameter that is being tested in parallel jobs. For some L-M tests of the model fitting, there is no test of the gradient for all the parameters and only one job is run at a time, with y = 0. A negative value for y means this is a multi-processing job running in parallel with others.

You can see the progress of the model fitting by looking at the modelfit_runxx file (xx=the run number, defined by the command that runs modelfit). For each model run, the command line that was run along with the parameters, including their values that are being tested, are placed into the run file. To find the model output files for each modelfit run, you can look in the run file to find the process number that is included in the model output file name. You can then plot this file using the "plotmod filename | vid" data plotting command.

data_split = "plotmod -t -s 18 %s_%%d | plotsplit --plotn 18 --info 0 > %s_%%d.data\n";The %s is replaced with the model output filename, and the %%d is replaced by the parameter number.

To make the template file, you create one with all zeros and the same number of rows and columns as the data file:

make_template --ntraces 5 --tracelen 10000 > file_template.dataThen you edit this template file to add 1's wherever you want to define a point to be used in the fitting process. You can use the same template file for original data and model data, or you can use different template files that define different points, as long as the number of points for each template file is the same.

There are several methods for fitting nonlinear functions that use a random search method. These methods don't get stuck in local minima, and don't require knowing the derivatives of the simulated function, and in many cases can be faster than the simplex method. The reason is that an N-dimensional landscape in a typical neural circuit simulation can be very rugged, e.g. the voltage in a neuron is nearly linear with input for some combinations of parameters but for other combinations it fires action potentials which are very nonlinear. If the search includes a random component to it, the nonlinearities prevent the search from getting stuck in a local minimum and can find a global minimum faster than a purely directed search method.

One method is *simulated annealing* which finds a local minimum
but has random noise added to the comparison function which
allows it to jump out of a local minimum to be more efficient at
finding a global minimum. One variation of this method adapts
the "downhill simplex" method with different levels of noise
depending on how close it gets to the minimum. Another method is
*stochastic search*. This method is very general and does not use
a directed search procedure. Instead it relies on random
sampling to find the minima.

Both *simulated annealing* and *stochastic search* are
implemented in NeuronC. To use these fitting methods: