DEFICITS IN VERTICAL AND TORSIONAL EYE-MOVEMENTS AFTER UNILATERAL ANDBILATERAL MUSCIMOL INACTIVATION OF THE INTERSTITIAL NUCLEUS OF CAJAL OF THE ALERT MONKEY

The mesencephalic interstitial nucleus of Cajal (iC) is considered the neural integrator for vertical and torsional eye movements and has al so been proposed to be involved in saccade generation. The aim of this study was to elucidate the function of iC in neural integration of di fferent types of eye movements and to distinguish eye movement deficit s due to iC impairment from that of the immediately adjacent rostral i nterstitial nucleus of the medial longitudinal fasciculus (riMLF). We addressed the following questions: (1) According to the neural integra tor hypothesis, all eye movements including the saccadic system and th e vestibulo-ocular reflex (VOR) share a common neural integrator. Do i C lesions impair gaze-holding function for vertical and torsional eye positions and the torsional and vertical VOR gain to a similar degree? (2) What are the dynamic properties of vertical and torsional eye mov ements deficits after iC lesions, e.g., the specificity of torsional a nd vertical nystagmus? (3) Is iC involved in saccade generation? We pe rformed 13 uni- and three bilateral iC inactivations by muscimol micro injections in four alert monkeys. Three-dimensional eye movements were studied under head-stationary conditions during vertical and torsiona l VOR. Under static conditions, unilateral iC injections evoked a shif t of Listing's plane to the contralesional side (up to 20 degrees), wh ich increased (ipsilesional ear down) or decreased (ipsilesional ear u p) by additional static vestibular stimulation in the roll plane, i.e. , ocular counterroll was preserved. The monkeys showed a spontaneous t orsional nystagmus with a profound downbeat component. The fast phases of torsional nystagmus always beat toward the lesion side (ipsilesion al). Pronounced gaze-holding deficit for torsional and vertical eye po sitions (neural integrator failure) was reflected by the reduction of time constants of the exponential decay of the slow phase to 330-370 m s. Whereas the vertical oculomotor range was profoundly decreased (up to 50%) and vertical saccades were reduced in amplitude, saccade veloc ity remained normal and horizontal eye movements were not affected. Bi lateral iC injections reduced the shift of Listing's plane caused by u nilateral injections, i.e., back toward the plane of zero torsion. Tor sional nystagmus reversed its direction and ceased, whereas vertical n ystagmus persisted. In contrast to unilateral injection, there was add itional upbeating nystagmus. Time constants of the position integrator of the gaze-holding system did not differ between unilateral and bila teral injections. The range of stable vertical eye positions and sacca de amplitude was smaller when compared with unilateral injections, but the main sequence remained normal. Dynamic vestibular stimulation aft er unilateral iC injections had virtually no effect on torsional and v ertical VOR gain and phase at the same time when time constants alread y indicated severe integrator failure. Torsional VOR elicited a consta nt slow-phase velocity offset up to 30 degrees toward the contralesion al side, i.e., in the opposite direction to spontaneous torsional nyst agmus. Likewise, vertical VOR showed a velocity offset in an upward di rection? i.e., opposite to the spontaneous downbeat nystagmus. Contral esional torsional and upward vertical quick phases were missing or sev erely reduced in amplitude but showed normal velocity. In contrast, bi lateral iC injections reduced the gain of the torsional and vertical V OR by 50% and caused a phase lead of 10-20 degrees (eye compared with head velocity). We propose that the slow-phase velocity offset during torsional and vertical VOR reflects a vestibular imbalance. It therefo re appears likely that the vertical and torsional nystagmus after iC l esions is not only caused by a neural integrator failure but also by a vestibular imbalance. Unilateral iC injections have clearly different ial effects on the VOR and the gaze-holding function. These results ar e not compatible with a single common neural integrator model, which w ould predict a much stronger VOR gain reduction and phase advance, as found in our data. Our data support the existence of multiple integrat ors in iC with parallel processing.