Do brainstem omnipause neurons terminate saccades?

Abstract

Saccade-generating burst neurons (BN) are inhibited by omnipause neurons (OPN), except during saccades. OPN activity pauses before saccade onset and resumes at the saccade end. Microstimulation of OPN stops saccades in mid-flight, which shows that OPN can end saccades. However, OPN pause duration does not correlate well with saccade duration, and saccades are normometric after OPN lesions. We tested whether OPN were responsible for stopping saccades both in late-onset Tay-Sachs, which causes premature saccadic termination, and in individuals with cerebellar hypermetria. We studied gaze shifts between two targets at different distances aligned on one eye, which consist of a disjunctive saccade followed by vergence. High-frequency conjugate oscillations during the vergence movements that followed saccades were present in all subjects studied, indicating OPN silence. Thus, mechanisms other than OPN discharge (e.g., cerebellar caudal fastigial nucleus-promoting inhibitory BN discharge) must contribute to saccade termination.

Figure 1

Sagittal monkey brainstem diagram showing ocular motor–related nuclei. The shaded region in the pons represents the paramedian pontine reticular formation (PPRF), containing premotor excitatory burst neurons (EBN) for horizontal saccades (black oval in lower PPRF). The shaded region in the medulla represents the medullary reticular formation (Med RF), containing premotor inhibitory burst neurons (IBN) (black oval in upper Med RF). The asterisk just caudal to the CN VI rootlets represents the location of the omnipause neurons in the raphe interpositus. PC, posterior commisure; riMLF, rostral interstitial medial longitudinal fasciculus; INC, interstitial nucleus of Cajal; CN III, oculomotor nerve fascicle; III, oculomotor nucleus; IV, trochlear nucleus; MLF, medial longitudinal fasciculus; VI, abducens nucleus; CN VI, abducens nerve rootlets; NRTP, nucleus reticularis tegmenti pontis. Courtesy of Jean Buttner-Ennever.

Figure 2

Representative examples of saccades between targets on a tangent screen at 1.2 m viewing distance. (A) Normal subject made a mildly hypometric saccade followed by a corrective saccade. (B) Patient with late-onset Tay–Sachs disease (LOTS), showing an interrupted saccade with premature saccadic termination. Note that eye velocity abruptly decreases (arrow) but the eye does not completely stop. (C) Saccadic hypermetria in a control patient with a midline cerebellar lesion bilaterally involving the caudal fastigial nuclei. Upward deflections indicate rightward eye movements; note that scales differ.

Figure 3

Representative responses during testing with the Müller paradigm. (A) Normal subject makes a gaze shift from far to near targets aligned on his right eye. Following the initial saccade, and during the vergence movement that follows, small conjugate oscillations are evident. (B) Patient with LOTS makes a gaze shift from far to near targets aligned on his right eye. Note that during and following the prematurely terminated, initial saccade, conjugate oscillations are occurring. (C) The patient with a lesion bilaterally affecting the caudal fastigial nuclei makes a gaze shift from far to near targets aligned on his left eye. The combined saccade–vergence movement is hypermetric, requiring a corrective saccade. Following the initial saccade, and during the subsequent vergence movement, conjugate oscillations are evident. In A–C, version velocity represents the velocity differentiation of version, which is equal to (right horizontal position + left horizontal position)/2.

Figure 4

(A) Midsagittal T1-weighted MRI without contrast in a LOTS patient demonstrating severe midline cerebellar atrophy. (B) Luxol stain through a cerebellar vermis lobule reveals nearly complete loss of Purkinje cells, with two residual Purkinje cells visible (arrow), and atrophy of the underlying granular cell layer. (C) High-powered photomicrograph of Luxol-stained putative OPN shows massive intraneuronal storage inclusions (arrows).