Eye position dependency of nystagmus during constant vestibular stimulation

Alexander's law, the eye position dependency of nystagmus due to peripheral vestibular lesions, has been hypothesized to occur due to adaptive changes in the brainstem velocity-to-position neural integrator in response to non-reciprocal vestibular stimulation. We investigated whether it develops during passive head rotations that produce constant nystagmus for >35 s. The yaw rotation stimulus consisted of a 1-s acceleration (100°/s(2)), followed by a lower acceleration ramp (starting at 7.3°/s(2) and increasing at 0.04°/s(2)/s) until 400°/s was reached after 38 s. This stimulus was designed to offset the ~15 s vestibular ocular reflex time constant (and the 150 s adaptation time constant) and produce constant velocity slow phases. In contrast to peripheral lesions, this vestibular stimulation is the result of real head turns and has the push-pull characteristics of natural movements. The procedure was successful, as the average velocity of 31°/s was unchanged over the final 35 s of the acceleration period. In all 10 healthy human subjects, we found a large and stable Alexander's law, with an average velocity-versus-position slope of -0.366 in the first half that was not significantly different in the second half, -0.347. These slopes correspond to integrator time constants of <3 s, are much less than normal time constants (~25 s), and are similar to those observed in patients with peripheral vestibular lesions. Alexander's law also developed, on average, in 10 s. We conclude that Alexander's law is not simply a consequence of non-reciprocal vestibular stimulation.