\section{Results} The test procedure by which the numerical and analytical solutions of the model equations are compared will involve various levels of discretisation of the branched dendrite. The comparison of the behaviour of the traditional compartmental model, represented by the NEURON simulator (Hines and Carnevale, \cite{Hines97}), and the generalised compartmental model is based on simulations of large scale synaptic activity across the model dendrite illustrated in Figure \ref{TestNeuron}. Each simulation begins by distributing nodes across the test dendrite such that each dendritic section begins and ends on a node, and that within each dendritic section the nodes are uniformly spaced. For a given discretisation, 2000 simulations of the traditional and generalised models under identical conditions are carried out. Each simulation starts with the dendrite at rest and places a single exogenous input at a randomly chosen location on the dendrite. The potential at the soma is computed by solving the differential equations numerically for each model, and the magnitude of the relative error in this potential is recorded at $1$ms intervals up to and including $10$ms after the exogenous current is applied (see the Appendix for tables of complete results). The calculation of the relative error is made possible by the fact that an analytical solution is available for all distributions of exogenous input on the branched dendrite. At large (approximate) internodal distances, the discretisation of each section of the test dendrite may be very different, but as the maximum internodal distance decreases, the variation in internodal distances across different dendritic sections approaches zero. For example, the number of nodes used in the simulations here will vary from 21 ($166.8\mu\mbox{m}\le h \le 501.2\mu$m) to 992 ($h\approx7.7\mu$m) where $h$ is the internodal distance. Since the computational effort involved in the numerical problem is entirely determined by the number of nodes appearing in the numerical scheme, under all circumstances the same discretisation is used in the numerical solution of both models. Moreover, a temporal discretisation of $dt=0.001$ms was used in all integrations to ensure that errors due to integration were insignificant compared with those introduced by the spatial discretisation process. The results illustrate separately the effect of the two major assumptions made in the construction of the traditional compartmental model and relaxed in the construction of the generalised compartmental model. Recall that in the traditional model all compartments are assumed to be iso-potential and all input is assumed to act at the designated node of the compartment. We use the term \emph{modified compartmental model} to denote a compartmental model in which the compartments are iso-potential but the input is distributed in accordance with the scheme set out for the generalised model. In practice, this means that exogenous input is partitioned between the nodes either side of its point of application. The fraction falling on each of these nodes will depend on the geometry of the dendritic section and the location of the point of application of the input. The modified compartmental model in which the iso-potential assumption remains in place allows one to investigate the effect that placement alone has on the accuracy the numerical solution. The move to the generalised model now relaxes the iso-potential assumption of the modified model and allows the combined effect of both generalisations to come into play. Figure \ref{mean} shows the percentage mean value of the modulus of the relative error of the membrane potential of the soma at times 2ms and 8ms after the application of a sustained stimulus at a randomly chosen location on the dendrite. For a given level of discretisation, identical for each compartmental model, this mean value is based on 2000 simulations of the effect of the stimulus which is again placed randomly, but identically, in each model. Figure \ref{mean} illustrates that for any level of discretisation the error in the NEURON simulator (Fig. \ref{mean} dotted line) is significantly greater than that in either the modified model (Fig. \ref{mean} dashed line) or generalised model (Fig. \ref{mean} solid line). For example, to achieve a 1\% mean error, the NEURON simulator needs approximately 400 nodes, the modified model 65 nodes and the generalised model 50 nodes. In this example, it is the accurate placement of input that has greatest impact on reducing the error, although the benefit obtained by relaxing the iso-potential assumption is also significant. \begin{figure}[!h] \centering \begin{tabular}{cc} \begin{mfpic}[0.4][60]{-30}{400}{-0.2}{2.3} \headlen7pt \pen{1pt} \dotspace=4pt \dotsize=1.5pt % % x-axis \lines{(0,0),(400,0)} \lines{(0,0),(0,2)} \lines{(0,0),(0,-0.1)} \lines{(100,0),(100,-0.1)} \lines{(200,0),(200,-0.1)} \lines{(300,0),(300,-0.1)} \lines{(400,0),(400,-0.1)} \tlabel[tc](0,-0.2){\textsf{0}} \tlabel[tc](100,-0.2){\textsf{100}} \tlabel[tc](200,-0.2){\textsf{200}} \tlabel[tc](300,-0.2){\textsf{300}} \tlabel[tc](400,-0.2){\textsf{400}} % % y-axis \lines{(0,0.0),(-10,0.0)} \lines{(0,0.5),(-10,0.5)} \lines{(0,1.0),(-10,1.0)} \lines{(0,1.5),(-10,1.5)} \lines{(0,2.0),(-10,2.0)} \tlabel[cr](-15,0.0){\textsf{0.0}} \tlabel[cr](-15,0.5){\textsf{0.5}} \tlabel[cr](-15,1.0){\textsf{1.0}} \tlabel[cr](-15,1.5){\textsf{1.5}} \tlabel[cr](-15,2.0){\textsf{2.0}} \tlabel[cr](350,1.75){\textsf{t = 2ms}} % % Gen Mean error at t=2 \curve{ ( 34,1.807),( 43,1.114),( 54,0.632),( 61,0.514),( 75,0.338), ( 82,0.269),( 93,0.211),(119,0.132),(142,0.091),(169,0.060), (193,0.050),(244,0.029),(293,0.021),(391,0.011)} % % Mod Mean error at t=2 \dashed\curve{ ( 43, 2.226),( 54, 1.258),( 61, 1.049),( 75, 0.680),( 82, 0.550), ( 93, 0.447),(119, 0.273),(142, 0.181),(169, 0.128),(193, 0.101), (244, 0.063),(293, 0.043),(391, 0.023)} % % Old Mean error at t=2 \dotted\curve{ (193, 2.072),(244, 1.657),(293, 1.397),(391, 1.005)} \end{mfpic} &\qquad \begin{mfpic}[0.4][60]{-30}{400}{-0.2}{2.3} \headlen7pt \pen{1pt} \dotspace=4pt \dotsize=1.5pt % % x-axis \lines{(0,0),(400,0)} \lines{(0,0),(0,2)} \lines{(0,0),(0,-0.1)} \lines{(100,0),(100,-0.1)} \lines{(200,0),(200,-0.1)} \lines{(300,0),(300,-0.1)} \lines{(400,0),(400,-0.1)} \tlabel[tc](0,-0.2){\textsf{0}} \tlabel[tc](100,-0.2){\textsf{100}} \tlabel[tc](200,-0.2){\textsf{200}} \tlabel[tc](300,-0.2){\textsf{300}} \tlabel[tc](400,-0.2){\textsf{400}} % % y-axis \lines{(0,0.0),(-10,0.0)} \lines{(0,0.5),(-10,0.5)} \lines{(0,1.0),(-10,1.0)} \lines{(0,1.5),(-10,1.5)} \lines{(0,2.0),(-10,2.0)} \tlabel[cr](-15,0.0){\textsf{0.0}} \tlabel[cr](-15,0.5){\textsf{0.5}} \tlabel[cr](-15,1.0){\textsf{1.0}} \tlabel[cr](-15,1.5){\textsf{1.5}} \tlabel[cr](-15,2.0){\textsf{2.0}} \tlabel[cr](350,1.75){\textsf{t = 8ms}} % % Gen Mean error at t=8 \curve{ ( 21,1.732),( 34,0.412),( 43,0.252),( 54,0.140),( 61,0.119), ( 75,0.077),( 82,0.062),( 93,0.050),(119,0.031),(142,0.020), (169,0.014),(193,0.011),(244,0.007),(293,0.004),(391,0.002)} % % Mod Mean error at t=8 \dashed\curve{ ( 21,1.941),( 34,0.477),( 43,0.294),( 54,0.163),( 61,0.142), ( 75,0.090),( 82,0.073),( 93,0.059),(119,0.037),(142,0.024), (169,0.016),(193,0.013),(244,0.008),(293,0.005),(391,0.003)} % % Old Mean error at t=8 \dotted\curve{ ( 54,2.155),( 61,1.929),( 75,1.552),( 82,1.404),( 93,1.262), (119,1.000),(142,0.780),(169,0.665),(193,0.586),(244,0.469), (293,0.396),(391,0.286)} \end{mfpic} \end{tabular} \parbox{6in}{\caption{\label{mean} The percentage mean value of the modulus of the relative error of the membrane potential of the soma at 2ms and 8ms after the application of a randomly placed sustained stimulus is plotted against the number of nodes used to discretise the dendrite for the NEURON simulator (dotted line), the modified compartmental model (dashed line) and the generalised compartmental model (solid line).}} \end{figure} The conclusion from Figure \ref{mean} is that the generalised compartmental model performs better than both the modified and traditional models at all levels of discretisation. Therefore the ratio of the errors in the modified and NEURON simulator models to the error in the generalised model is a sensible measure of relative performance. The Common logarithm of this ratio is most useful for representational purposes as it will always be positive since the generalised model is known \emph{a priori} to perform better than either of the other two models. Figure \ref{sdev} indicates that this ratio is relatively insensitive to time for all levels of discretisation. This observation suggests that although the relative error in all models decreases with time (Figure \ref{mean}), the rate at which this occurs is effectively the same for all three models. More importantly, Figure \ref{sdev} also shows that the accuracy of the NEURON simulator (dashed line) relative to that of the generalised model deteriorates as spatial resolution is refined. The inference one would draw from this observation is that the NEURON simulator and the generalised compartmental model have different orders of numerical accuracy with respect to spatial discretisation. On the other hand, the modified model (solid line) and the generalised model appear to enjoy the same level of numerical accuracy with respect to spatial discretisation. An examination of the standard deviations of the errors (not shown) in the three models leads to a similar set of conclusions as those described for the relative accuracy of the different models. The standard deviation of the error in the generalised model is again the smallest of the three models, and so the Common logarithm of the ratios of the standard deviations in the modified and NEURON simulator models to that in the generalised model is a good measure. The Common logarithm of the two ratios is again largely independent of time for both models. With respect to spatial discretisation, this ratio is independent of the level of spatial disctetisation for all practical purposes. On the other hand, the same ratio for the NEURON simulator grows in a similar way to that shown in Figure \ref{mean} (dashed lines) as the spatial discretisation is refined. So not only is the accuracy achieved by the NEURON simulator significantly less than that of the generalised model, it is also more erratic and therefore less precise. \begin{figure}[!h] \[ \begin{array}{c} $\begin{mfpic}[15][60]{-1}{12}{-0.3}{2.7} \headlen7pt \pen{1pt} \dotspace=4pt \dotsize=1.5pt % % x-axis \lines{(0,0),(0,2.5)} \lines{(0,0),(10,0)} \lines{(0,0),(0,-0.1)} \lines{(2,0),(2,-0.1)} \lines{(4,0),(4,-0.1)} \lines{(6,0),(6,-0.1)} \lines{(8,0),(8,-0.1)} \lines{(10,0),(10,-0.1)} \tlabel[tc](0,-0.2){\textsf{0.0}} \tlabel[tc](2,-0.2){\textsf{2.0}} \tlabel[tc](4,-0.2){\textsf{4.0}} \tlabel[tc](6,-0.2){\textsf{6.0}} \tlabel[tc](8,-0.2){\textsf{8.0}} \tlabel[tc](10,-0.2){\textsf{10.0}} % % y-axis \lines{(0,0.0),(-0.3,0.0)} \lines{(0,0.5),(-0.3,0.5)} \lines{(0,1.0),(-0.3,1.0)} \lines{(0,1.5),(-0.3,1.5)} \lines{(0,2.0),(-0.3,2.0)} \lines{(0,2.5),(-0.3,2.5)} \tlabel[cr](-0.5,0.0){\textsf{0.0}} \tlabel[cr](-0.5,0.5){\textsf{0.5}} \tlabel[cr](-0.5,1.0){\textsf{1.0}} \tlabel[cr](-0.5,1.5){\textsf{1.5}} \tlabel[cr](-0.5,2.0){\textsf{2.0}} \tlabel[cr](-0.5,2.5){\textsf{2.5}} % % Mod Model at 21 nodes \lines{ ( 1.0,0.319),( 2.0,0.214),( 3.0,0.140),( 4.0,0.098), ( 5.0,0.075),( 6.0,0.061),( 7.0,0.054),( 8.0,0.049), ( 9.0,0.047),(10.0,0.045)} \tlabel[cr](0.8,0.319){\textsf{21}} % % Old Model at 21 nodes \dashed\lines{ ( 1.0,0.285),( 2.0,0.430),( 3.0,0.492),( 4.0,0.523), ( 5.0,0.537),( 6.0,0.544),( 7.0,0.549),( 8.0,0.551), ( 9.0,0.554),(10.0,0.555)} \tlabel[cl](10.5,0.555){\textsf{21}} % % Mod Model at 54 nodes \lines{ ( 1.0,0.487),( 2.0,0.299),( 3.0,0.188),( 4.0,0.128),( 5.0,0.097), ( 6.0,0.080),( 7.0,0.071),( 8.0,0.067),( 9.0,0.064),(10.0,0.064)} % % Old Model at 54 nodes \dashed\lines{ ( 1.0,0.898),( 2.0,1.071),( 3.0,1.127),( 4.0,1.151), ( 5.0,1.165),( 6.0,1.175),( 7.0,1.181),( 8.0,1.186), ( 9.0,1.190),(10.0,1.191)} \tlabel[cl](10.5,1.191){\textsf{54}} % % Mod Model at 119 nodes \lines{ ( 1.0,0.529),( 2.0,0.315),( 3.0,0.195),( 4.0,0.136), ( 5.0,0.104),( 6.0,0.087),( 7.0,0.078),( 8.0,0.072), ( 9.0,0.069),(10.0,0.069)} % % Old Model at 119 nodes \dashed\lines{ ( 1.0,1.268),( 2.0,1.422),( 3.0,1.459),( 4.0,1.477), ( 5.0,1.487),( 6.0,1.494),( 7.0,1.499),( 8.0,1.503), ( 9.0,1.506),(10.0,1.503)} \tlabel[cl](10.5,1.503){\textsf{119}} % % Mod Model at 244 nodes \lines{ ( 1.0,0.536),( 2.0,0.326),( 3.0,0.205),( 4.0,0.142), ( 5.0,0.108),( 6.0,0.090),( 7.0,0.080),( 8.0,0.074), ( 9.0,0.071),(10.0,0.074)} % % Old Model at 244 nodes \dashed\lines{ ( 1.0,1.581),( 2.0,1.744),( 3.0,1.782),( 4.0,1.798), ( 5.0,1.807),( 6.0,1.814),( 7.0,1.818),( 8.0,1.822), ( 9.0,1.826),(10.0,1.821)} \tlabel[cl](10.5,1.821){\textsf{244}} % % Mod Model at 495 nodes \lines{ ( 1.0,0.514),( 2.0,0.309),( 3.0,0.194),( 4.0,0.135), ( 5.0,0.103),( 6.0,0.086),( 7.0,0.077),( 8.0,0.072), ( 9.0,0.069),(10.0,0.071)} % % Old Model at 495 nodes \dashed\lines{ ( 1.0,1.873),( 2.0,2.045),( 3.0,2.091),( 4.0,2.111), ( 5.0,2.122), ( 6.0,2.130),( 7.0,2.136),( 8.0,2.140), ( 9.0,2.144),(10.0,2.138)} \tlabel[cl](10.5,2.138){\textsf{495}} % % Mod Model at 992 nodes \lines{ ( 1.0,0.510),( 2.0,0.312),( 3.0,0.197),( 4.0,0.136), ( 5.0,0.106),( 6.0,0.089),( 7.0,0.079),( 8.0,0.073), ( 9.0,0.072),(10.0,0.062)} % % Old Model at 992 nodes \dashed\lines{ ( 1.0,2.168),( 2.0,2.352),( 3.0,2.399),( 4.0,2.418), ( 5.0,2.430),( 6.0,2.439),( 7.0,2.444),( 8.0,2.447), ( 9.0,2.453),(10.0,2.414)} \tlabel[cl](10.5,2.414){\textsf{992}} \end{mfpic}$ \end{array}\qquad \begin{tabular}{p{2.5in}} \caption{\label{sdev} The Common logarithm of the ratio of the mean value of the modulus of the relative error in the NEURON simulator to that of the generalised compartmental model (dashed line) and the modified compartmental model to that of the generalised compartmental model (solid line) are plotted against time for various levels of spatial discretisation.} \end{tabular} \] \end{figure} \section{Concluding remarks} This investigation has demonstrated that it is possible to achieve a cost free increase in the accuracy and precision of compartmental models once the assumption of iso-potential compartments is relaxed and the actual placement of input taken into account. In the case of large scale exogenous input, it was clear that placement was the major determinant of accuracy but that the relaxation of the iso-potential assumption produced a further significant reduction in overall error. One would anticipate that the physiological manifestations of these differences in accuracy would appear as errors in the measurement of the time constant of the somal membrane in response to a sustained input on a dendrite. \section*{Acknowledgement} Alan E Lindsay would like to thank the Wellcome Trust for the award of Vacation Scholarship (VS/03/GLA/8/SL/TH/FH) which was used to fund this work.