The effects of anisotropy and inhomogeneity of the electrical conductivity
of extracellular tissue on excitation of nerve fibers by an extracellular p
oint source electrode were determined by computer simulation. Analytical so
lutions to Poisson's equation were used to calculate potentials in anisotro
pic infinite homogeneous media and isotropic semi-infinite inhomogeneous me
dia, and the net driving function was used to calculate excitation threshol
ds for nerve fibers. The slope and intercept of the current-distance curve
in anisotropic media were power functions of the ratio and product of the o
rthogonal conductivities, respectively. Excitation thresholds in anisotropi
c media were also dependent on the orientation of the fibers, and in strong
ly anisotropic media (sigma(z)/sigma(xy) > 4) there were reversals in the r
ecruitment order between different diameter fibers and between fibers at di
fferent distances from the electrode. In source-free regions of inhomogeneo
us media (two regions of differing conductivity separated by a plane bounda
ry). the current-distance relationship of fibers parallel to the interface
was dependent only on the average conductivity, whereas in regions containi
ng the source the current-distance relationship was dependent on the indivi
dual, values of conductivity. Reversals in recruitment order between fibers
at different distances from the electrode and between fibers of differing
diameter were found in inhomogeneous media. The results of this simulation
study demonstrate that the electrical properties of the extracellular mediu
m can have a strong influence on the pattern of neuronal excitation generat
ed by extracellular electric fields, and indicate the importance of tissue
electrical properties in interpreting results of studies employing electric
al stimulation applied in complex biological volume conductors.