Misdirected horizontal saccades in pan-cerebellar atrophy

• Misdirected saccades are described in siblings with pan-cerebellar atrophy.
• Intended horizontal saccades were associated with vertical cross-coupled saccades.
• Cross-coupled vertical saccades were followed by corrective drifts.
• Normally, orthogonal signals generated at burst neurons are actively canceled.
• Active cancellation of orthogonal signals is under cerebellar supervision.

Saccadic dysmetria is a sensitive marker of cerebellar dysfunction. We discovered misdirected horizontal saccades due to cross-coupled orthogonal (vertical) saccades in siblings with pan-cerebellar atrophy. There was an upward drift in vertical eye position after each cross-coupled downward saccade. Such drifts brought the eyes back to the desired target. Due to strong upward bias, downward compensatory slow movements did not follow cross-coupled upward saccades. There was minimal horizontal cross-coupling associated with vertical saccades. There was a reduced gain of horizontal pursuit causing lag in the horizontal eye movement and subsequent catch-up horizontal saccades. The horizontal catch-up saccades were also associated with vertical cross-coupled eye movements and subsequent drifts. There was no cross-coupling of pursuit eye movements. Our results support the hypothesis emphasizing adaptive cerebellar control of saccade direction. Commands for horizontal saccades trigger not only the activity of the horizontal burst generators, but also the vertical burst neurons. The activity of orthogonal (vertical) burst neurons is canceled by opposing signals under cerebellar supervision. Cerebellar lesions could disrupt such balance between opposing orthogonal signals leading to vertical cross-coupling during horizontal saccade. We speculate that upward drift might result from an imbalance in opposing orthogonal signals at the level of neural integrators.