Disrupted microsaccade responses in late-life depression

Abstract

Late-life depression (LLD) is a psychiatric disorder in older adults, characterized by high prevalence and significant mortality rates. Thus, it is imperative to develop objective and cost-effective methods for detecting LLD. Individuals with depression often exhibit disrupted levels of arousal, and microsaccades, as a type of fixational eye movement that can be measured non-invasively, are known to be modulated by arousal. This makes microsaccades a promising candidate as biomarkers for LLD. In this study, we used a high-resolution, video-based eye-tracker to examine microsaccade behavior in a visual fixation task between LLD patients and age-matched healthy controls (CTRL). Our goal was to determine whether microsaccade responses are disrupted in LLD compared to CTRL. LLD patients exhibited significantly higher microsaccade peak velocities and larger amplitudes compared to CTRL. Although microsaccade rates were lower in LLD than in CTRL, these differences were not statistically significant. Additionally, while both groups displayed microsaccadic inhibition and rebound in response to changes in background luminance, this modulation was significantly blunted in LLD patients, suggesting dysfunction in the neural circuits responsible for microsaccade generation. Together, these findings, for the first time, demonstrate significant alterations in microsaccade behavior in LLD patients compared to CTRL, highlighting the potential of these disrupted responses as behavioral biomarkers for identifying individuals at risk for LLD.

Keywords: Fixational eye movements; Geriatric psychiatrics; Microsaccade rate and metrics; Microsaccadic inhibition and rebound.

Fig. 1

Microsaccade dynamics between LLD and CTRL. (A) Dynamics of microsaccade rates following background luminance changes between LLD and CTRL, and mean rates (− 700 to 1700 ms) for each group. (B) Microsaccade main sequence, intercept, and slope between LLD and CTRL. (C) Dynamics of microsaccade peak velocity following background luminance changes between LLD and CTRL, and mean peak velocities (− 700 to 1700 ms) for each group. (D) Dynamics of microsaccade amplitude following background luminance changes between LLD and CTRL, and mean amplitudes (− 700 to 1700 ms) for each group. (E) Microsaccade direction density between LLD and CTRL. In (A), (C) and (D), the shaded colored regions surrounding microsaccadic dynamics curves represent the ± standard error range (across participants) for different groups. In (A–D), the color-filled squares and error-bars represent mean value ± standard error (across participants) for each group, and the small circles represent mean value for each subject. Circle color dots represent each subject data point. In (E), the colored-bars represent ± standard error (across participants) for each angle condition. CTRL: healthy age-matched older adults, LLD: late-life depression patients, Bkgd: background. *Indicates differences are statistically significant.

Fig. 2

Microsaccadic inhibition and rebound after background luminance decreases between LLD and CTRL. (A) Dynamics of microsaccade rates following background luminance changes in different conditions in CTRL. (B) Dynamics of microsaccade rates following background luminance changes in different conditions in LLD. (C) Mean microsaccade rates in the inhibition epoch (60–330 ms) in the NoChange (no background luminance change) and Change (background luminance changes: Dark and Black) condition between LLD and CTRL. (D) Mean microsaccade rates in the rebound epoch (350 to 550 ms) in the NoChange and Change condition between LLD and CTRL. (E) Normalized microsaccade rate (Change minus NoChange condition) between LLD and CTRL. (F) Mean normalized microsaccade rates in the inhibition epoch in different conditions between LLD and CTRL. (G) Mean normalized microsaccade rates in the rebound epoch in different conditions between LLD and CTRL. In (A), (B) and (E), the shaded colored regions surrounding microsaccade dynamics curves represent the ± standard error range (across participants) for different groups. The gray area represents the epoch selected for analyses. In (C), (D), (F) and (G), the color-filled squares and error-bars represent mean value ± standard error (across participants) for each group, and the small circles represent mean value for each subject. Circle color dots represent each subject data point. CTRL: healthy age-matched older adults. LLD: late-life depression patients. Dark: 50% decrease in contrast relative to the gray background. Black: 100% decrease in contrast relative to the gray background. Bkgd: background. *Indicates differences are statistically significant.

Fig. 3

Microsaccadic inhibition and rebound after background luminance increases between LLD and CTRL. (A) Dynamics of microsaccade rates following background luminance changes in different conditions in CTRL. (B) Dynamics of microsaccade rates following background luminance changes in different conditions in LLD. (C) Mean microsaccade rates in the inhibition epoch (60–330 ms) in the NoChange (no background luminance change) and Change (background luminance changes: Light and White) condition between LLD and CTRL. (D) Mean microsaccade rates in the rebound epoch (350–550 ms) in the NoChange and Change condition between LLD and CTRL. (E) Normalized microsaccade rate (Change minus NoChange condition) between LLD and CTRL. (F) Mean normalized microsaccade rates in the inhibition epoch in different conditions between LLD and CTRL. (G) Mean normalized microsaccade rates in the rebound epoch in different conditions between LLD and CTRL. In (A), (B) and (E), the shaded colored regions surrounding microsaccadic dynamics curves represent the ± standard error range (across participants) for different groups. The gray area represents the epoch selected for analyses. In (C), (D), (F) and (G), the color-filled squares and error-bars represent mean value ± standard error (across participants) for each group, and the small circles represent mean value for each subject. Circle color dots represent each subject data point. CTRL: healthy age-matched older adults, LLD: late-life depression patients. Light: 50% increase in contrast relative to the gray background. White: 100% increase in contrast relative to the gray background. Bkgd: background. *Indicates differences are statistically significant.

Fig. 4

Microsaccadic inhibition and rebound in different polarity conditions between LLD and CTRL. (A) Normalized dynamics of microsaccade rates following background luminance decreases and increases between LLD and CTRL. (B) Mean normalized microsaccade rates in the inhibition epoch in different polarity conditions between LLD and CTRL. (C) Mean normalized microsaccade rates in the rebound epoch in different polarity conditions between LLD and CTRL. In A, the shaded colored regions surrounding microsaccadic dynamics curves represent the ± standard error range (across participants) for different groups. The gray area represents the epoch selected for analyses. In (B) and (C), the color-filled squares and error-bars represent mean value ± standard error (across participants) for each group, and the small circles represent mean value for each subject. Circle color dots represent each subject data point. CTRL: healthy age-matched older adults, LLD: late-life depression patients, Neg: background luminance decrease conditions, Pos: background luminance increase conditions, Bkgd: background.