Experimental tests of a neural-network model for ocular oscillations caused by disease of central myelin

Spontaneous sinusoidal oscillations of the eyes are a feature of disorders affecting central myelin, including multiple sclerosis. The mechanism respo nsible for these oscillations (pendular nystagmus) is unknown. We tested th e hypothesis that pendular nystagmus is due to instability of the neural in tegrator, a network of neurons that normally guarantees steady gaze by math ematically integrating premotor signals. It was possible to make a model of the neural integrator unstable, and abnormal feedback then produced sustai ned oscillations so that it simulated pendular nystagmus. One prediction of the model is that a large premotor signal, such as is required to generate a rapid (saccadic) eye movement, will transiently suppress the activity of some neurons in the network, and that this will "reset" the oscillations, i.e., produce a phase shift: larger saccades will produce greater phase shi fts. Alternatively, if the source of pendular nystagmus is outside the neur al integrator (i.e., is present on velocity inputs to the stable integrator ), then it may not be possible to reset the oscillations with a saccadic ey e movement. We compared the phase relationships of pendular nystagmus prior to and following saccades in six patients with multiple sclerosis (MS). Al l patients showed phase shifts (median 64 degrees) of their ocular oscillat ions following large (more than 10 degrees) saccades; smaller saccades (les s than 5 degrees) caused smaller phase shifts (median 17 degrees). Our find ings suggest that, in MS, pendular nystagmus arises from an instability in the feedback control of the neural integrator for eye movements, which depe nds on a distributed network of neurons in the brainstem and cerebellum.