S162. Excessive tonic inhibition of superior colliculus in tourette syndrome suggested by saccade profiles

Abstract

Tourette syndrome (TS) is a common neurobehavioral disorder starting from childhood characterized by motor and vocal tics. Some suggest primary hypodopaminergic state followed by upward regulation of dopamine receptors for the cause of tics. The visually-guided saccade (VGS) task is a reflexive saccade task triggered by sudden extinction of a fixation spot and appearance of a target, while the memory-guided saccade (MGS) task is a voluntary saccade task to the memorized target. We previously reported slightly prolonged VGS latency and significantly prolonged MGS latency in Parkinson’s disease, presumably due to impaired function of the direct pathway of the basal ganglia (BG) and excessive inhibition of superior colliculus (SC) caused by the increased BG output. We investigated the performance of VGS and MGS to see whether the pathophysiology of TS represented the dopaminergic deficiency. We recruited 62 male drug-naïve participants with TS and 49 normal controls (NC) who were 5–16 years old. In VGS, after illumination of a central spot for 2.0–2.8 s, a target was presented at locations 5°, 10° or 20° to the right or left. The subjects moved their gaze from the spot to the target quickly. In MGS, a target stimulus flashed for 50 ms while they fixated the central spot. Once the spot disappeared, they moved their gaze to the remembered location, where the light re-appeared 600 ms later. Each subject performed at least 36 VGS and 36 MGS trials. Eye movements were recorded by electrooculography. The latency of the saccade from the extinction of the central spot and amplitude of the first saccade were measured in each trial. Age-matched analysis on 29 pairs was performed by Student’s t-test. [VGS] The median of latencies in TS was comparable at 5° (202.0 vs 203.3 ms), whereas it was longer at 20° (251.2 vs 236.0 ms). The difference between latencies towards peripheral (20°) and central (5°) targets was larger (49.1 vs 32.6 ms∗, 16.6 ± 15.5 ms). The median of amplitudes was smaller in TS (4.9 vs 5.4°∗ at 5°, 18.3 vs 19.0°∗ at 20°). [MGS] The median of latencies in TS was shorter at 5° (324.1 vs 338.5 ms), whereas it was longer at 20° (308.4 vs 290.3 ms). The difference between latencies towards central and peripheral targets was smaller (15.8 vs 48.1 ms, −32.4 ± 48.4 ms). The median of amplitudes was comparable (5.0 vs 4.6° at 5°, 16.2 vs 15.4° at 20°). Success rate of MGS was lower (61.5 vs 83.1%†). The occurrence of saccades to cue was comparable (30.2 vs 36.6%). ∗ p < 0.05, † p < 0.01, otherwise not statistically significant. In TS, latencies to peripheral targets in VGS and MGS were longer than in normal subjects. Dopaminergic deficiency may explain the prolonged MGS latency. The resultant excessive tonic inhibition of SC by the increased BG input may decrease the activity of fixation neurons, which may shorten the VGS latency to central targets, while leading to the prolonged latency to peripheral targets through the suppressed activity of saccade neurons.