Elsevier

Psychiatry Research

Volume 93, Issue 2, 6 March 2000, Pages 145-151
Psychiatry Research

Diurnal variation in spontaneous eye-blink rate

https://doi.org/10.1016/S0165-1781(00)00108-6Get rights and content

Abstract

The daily pattern of spontaneous eye-blink rate (BR), a non-invasive peripheral measure of central dopamine activity, was investigated in 24 healthy subjects. The spontaneous eye-blink rate showed a stable pattern in morning, midday and afternoon hours. A significant increase was found at the evening time point (20.30 h). The finding is suggestive of a late evening increase of central dopamine activity. An increased level of subjective sleepiness was also found at the same evening point, at a time corresponding to the ‘evening wake maintenance zone’ or the ‘forbidden zone for sleep’. A possible hypothesis is that the ‘forbidden zone for sleep’ may reflect a dopamine-mediated activation that counteracts a rising sleep drive. The role of diurnal variation of dopamine function should be considered both in the choice of the drug treatment regimen, and in the evaluation of biological and neuropsychological parameters.

Introduction

Clinical studies on patients with dopamine-related illnesses suggest a diurnal variation of dopamine activity. Patients with hereditary progressive dystonia (Segawa syndrome) show a remarkable diurnal fluctuation of symptoms, which become more severe towards the evening (Wang et al., 1994). An afternoon worsening of tardive dyskinetic symptomatology has been described in neuroleptic-treated patients (Hyde et al., 1995). The number of acute dystonic reactions following neuroleptic administration shows a significant distribution across the day: 80% of the episodes occurring between 12.00 and 23.00 h (Mazurek and Rosebush, 1996).

Previous studies on daily variations of dopaminergic activity in humans have mainly relied on plasma levels of the major dopamine metabolite, homovanillic acid (HVA). Doran et al. (1985) reported the highest levels of plasma HVA at night. In contrast to control subjects, schizophrenic patients did not show such a significant variation. Sack et al. (1988) found a diurnal rhythm of plasma HVA in depressed patients and normal subjects. They reported that HVA levels were highest in the morning and early afternoon and at nighttime. However, the rise in the morning and afternoon hours was not confirmed when the subjects were analyzed in a constant routine day protocol, suggesting that these increases were possibly due to a masking effect of diurnal activities. A number of confounding factors may account for these discrepancies in HVA data. Studies in rodents (Sternberg et al., 1983) and in humans (Swann et al., 1982) found that only 25–40% of total free levels of plasma HVA are derived from the central nervous system. Furthermore, plasma HVA levels appear strongly influenced by diet and motor activity (Kendler et al., 1983).

The spontaneous eye-blink rate (BR) provides a non-invasive peripheral measure of central dopamine activity (Karson et al., 1990). The eye-blink rate is reduced in Parkinson’s disease (Karson, 1983), whereas it is increased in schizophrenia (Stevens, 1978, Karson et al., 1990). Because of this relationship with dopamine activity, eye-blink frequency has been used as a parameter to monitor the effects of neuroleptic treatment (Bartko et al., 1990, Mackert et al., 1991, Adamson, 1995). The eye-blink rate is reduced by neuroleptics, and a decreased variability in blink rate after neuroleptic treatment has been suggested as a possible marker of the development of neuroleptic tolerance (Mackert et al., 1991).

The eye-blink rate has also been used to test dopamine activity in patients with seasonal affective disorder (SAD). Depue et al., 1989, Depue et al., 1990 found an increased blink rate in SAD patients that was normalized by light therapy. Although Barbato et al. (1993) failed to replicate the finding of increased blink rate in SAD, they also found a decreased blink rate following light therapy in premenopausal SAD patients, suggesting that light therapy might stimulate the activity of structures which inhibit the blink rate.

Individual blink rate appears to be influenced by psychophysiological factors. In their seminal study, Ponder and Kennedy (1927) implicated higher nervous processes as the major determinant of blink enhancement and inhibition. Higher levels of activation or arousal are associated with elevated blink rate (Stern et al., 1984). Blinks occur more frequently when subjects perform tests involving higher levels of attention (Gille et al., 1977, Tanaka and Yamaoka, 1993). A higher level of electroencephalographic (EEG) activation has also been associated with an increased eye-blink rate (Gille et al., 1977).

Karson et al. (1990) have hypothesized a functional linkage between eye-blink rate and alpha EEG activity. In their view, the eye-blink rate is regulated through a blink alpha neurocircuit (BANC) which begins in rostral pons and involves subcortical structures (midbrain tectum, substantia nigra, lateral geniculate bodies) and the occipital cortex. An increased blink rate may be related to a reduced inhibitory activity of the occipital cortex.

Previous studies have found that blink rate changes as a function of time on task (Wilson and Fisher, 1991, McGregor and Stern, 1996, Brookings et al., 1996). Morris and Miller (1996) found that variation in blink rate was one of the best predictors of changes in error rates during simulated flight between 13.00 and 17.30 h (Morris and Miller, 1996). Increased blink rates parallel the decline in task performance, suggesting that blink rate could reflect an increased level of fatigue (Stern, 1994).

Although some studies have addressed blink rates across time intervals, to the best of our knowledge, no study has systematically investigated a spontaneous diurnal variation of blink rate. Thus, the aim of the present study was to assess blink rates at different times of the day. To investigate the role of vigilance factors, possibly implicated in blink-rate regulation, subjective and objective measures of sleepiness were also assessed.

Section snippets

Methods

Twenty-four young subjects (16 females, 8 males), aged 18–23 years, were recruited for the experiment. All provided their informed consent. The subjects had no history of Axis I psychiatric illnesses, had normal physical examinations before the study and were not affected by any significant medical, neurological or ophthalmological illness. To exclude subjects with sleep impairments or substance abuse, a questionnaire assessing life and sleep habits was administered to all subjects.

To accustom

Results

All but one subject, who was not available for the 13.30 h session, completed the four experimental sessions. For another subject, blink suppression time was not recorded at the 17.00 h session.

Blink rate increased significantly across the day (Fig. 1) (n=23; F3,66=5.8, P=0.005); as shown by post-hoc contrasts, the point that contributed most to the overall result was that at 20.30 h, where blink rate was significantly higher than at the other three points (20.30 vs. 10.00, F1=12.3,

Discussion

In the present study, the spontaneous eye-blink rate showed a stable pattern in morning, midday and afternoon sessions, whereas a significant increase was present in the evening session. Using a constant routine protocol, Cajochen et al. (1998) also recently demonstrated that the blink rate reached peak levels after 16 h of sustained wakefulness and declined thereafter.

The findings are compatible with an evening increase in central dopamine activity and suggest an increased level of arousal

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