Age- and sex-related oculomotor manifestation of dopamine deficiency in Segawa disease

Yasuo Terao; Hideki Fukuda; Okihide Hikosaka; Akihiro Yugeta; Shun-Ichi Matsuda; Francesco Fisicaro; Yoshikazu Ugawa; Kyoko Hoshino; Yoshiko Nomura

doi:10.1016/j.clinph.2023.11.010

Age- and sex-related oculomotor manifestation of dopamine deficiency in Segawa disease

Clin Neurophysiol. 2024 Jan:157:73-87. doi: 10.1016/j.clinph.2023.11.010. Epub 2023 Nov 23.

Authors

Yasuo Terao¹, Hideki Fukuda², Okihide Hikosaka³, Akihiro Yugeta⁴, Shun-Ichi Matsuda⁴, Francesco Fisicaro⁵, Yoshikazu Ugawa⁶, Kyoko Hoshino², Yoshiko Nomura⁷

Affiliations

¹ Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Medical Physiology, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. Electronic address: yterao@ks.kyorin-u.ac.jp.
² Segawa Memorial Neurological Clinic for Children, 2-8 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
³ Section of Neuronal Networks, Laboratory of Sensorimotor Research, National Eye Institute, 49 Convent Drive, Bethesda 20892-4435, MD, USA.
⁴ Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
⁵ Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Piazza Università, 2, 95131 Catalina, Italy.
⁶ Department of Human Neurophysiology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
⁷ Yoshiko Nomura Neurological Clinic for Children, Tokyo 113-0034, Japan.

PMID: 38064930
DOI: 10.1016/j.clinph.2023.11.010

Abstract

Objective: To investigate the oculomotor manifestations of Segawa disease (SD), considered to represent mild dopamine deficiency and discuss their pathophysiological basis.

Methods: We recorded visually- (VGS) and memory-guided saccade (MGS) tasks in 31 SD patients and 153 age-matched control subjects to study how basal ganglia (BG) dysfunction in SD evolves with age for male and female subjects.

Results: SD patients were impaired in initiating MGS, showing longer latencies with occasional failure. Patients showed impaired ability to suppress reflexive saccades; saccades to cues presented in MGS were more frequent and showed a shorter latency than in control subjects. These findings were more prominent in male patients, particularly between 13 and 25 years. Additionally, male patients showed larger delay in MGS latency in trials preceded by saccades to cue than those unpreceded.

Conclusions: The findings can be explained by a dysfunction of the BG-direct pathway impinging on superior colliculus (SC) due to dopamine deficiency. The disturbed inhibitory control of saccades may be explained by increased SC responsivity to visual stimuli.

Significance: Oculomotor abnormalities in SD can be explained by dysfunction of the BG inhibitory pathways reaching SC, with a delayed maturation in male SD patients, consistent with previous pathological/physiological studies.

Keywords: Basal ganglia; Development; Dopamine deficiency; Inhibition; Saccade.

MeSH terms

Cues*
Dopamine*
Female
Humans
Male
Reaction Time / physiology
Saccades

Substances

Dopamine