BACKGROUND: Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD.
METHODS: We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups.
RESULTS: LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes.
CONCLUSIONS: The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.

With the ever-changing social environment, individual creativity is facing a severe challenge induced by stress. However, little is known regarding the underlying mechanisms by which acute stress affects creative cognitive processing. The current research explored the impacts of the neuroendocrine response on creativity under stress and its underlying cognitive flexibility mechanisms. The enzyme-linked immuno sorbent assay was employed to assess salivary cortisol, which acted as a marker of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis. Eye blink rate (EBR) and pupil diameter were measured as respective indicators of dopamine and noradrenaline released by the activation of the sympathetic-adrenal-medullary (SAM) axis. The Wisconsin card task (WCST) measured cognitive flexibility, while the alternative uses task (AUT) and the remote association task (RAT) measured separately divergent and convergent thinking in creativity. Results showed higher cortisol increments following acute stress induction in the stress group than control group. Ocular results showed that the stress manipulation significantly increased EBR and pupil diameter compared to controls, reflecting increased SAM activity. Further analysis revealed that stress-released cortisol impaired the originality component of the AUT, reducing cognitive flexibility as measured by perseverative errors on the WCST task. Serial mediation analyses showed that both EBR and pupil diameter were also associated with increased perseverative errors leading to poor originality on the AUT. These findings confirm that physiological arousal under stress can impair divergent thinking through the regulation of different neuroendocrine pathways, in which the deterioration of flexible switching plays an important mediating role.

Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer\'s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD).
The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline.
We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute.
MCI subjects had an increased BR (p <0.001), whereas AD subjects had a lower BR than HCs (p <0.05). Conversely, SCD subjects had a BR similar to HCs. No significant correlations emerged between neuropsychological scores and BR in SCD, MCI, and AD subjects.
Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

Previous evidence suggests that changes in spontaneous eye blink rate (EBR) in human adults might reflect the amount of attentional demand (i.e. cognitive load) during cognitive tasks. However, the actual direction of this relation is uncertain, since most studies investigated the role of cognitive load on EBR by employing visual tasks only. Here we aimed at elucidating the relationship between EBR and cognitive load in non-visual tasks. Sixteen healthy participants performed two auditory oddball tasks, i.e. passive listening to auditory tones versus active counting of target tones; each oddball task was immediately followed by a rest phase. Throughout the oddball tasks we assessed EBR and recorded the P300 on ERPs as an electrophysiological measure of attention. The results showed that participants\' EBR increased during the active task compared to the respective rest phase. Amplitude and latency of the P300 too differed between passive and active tasks, but changes in EBR and P300 features were not correlated with each other. Our findings demonstrated that an increase in cognitive load is associated with an increase in EBR in cognitive tasks not involving visual attention. These findings are consistent with previous evidence suggesting shared neurobiological bases between attention and EBR.

Adaptive behavioral control involves a balance between top-down persistence and flexible updating of goals under changing demands. According to the metacontrol state model (MSM), this balance emerges from the interaction between the frontal and the striatal dopaminergic system. The attentional blink (AB) task has been argued to tap into the interaction between persistence and flexibility, as it reflects overpersistence-the too-exclusive allocation of attentional resources to the processing of the first of two consecutive targets. Notably, previous studies are inconclusive about the association between the AB and noninvasive proxies of dopamine including the spontaneous eye blink rate (sEBR), which allegedly assesses striatal dopamine levels. We aimed to substantiate and extend previous attempts to predict individual sizes of the AB in two separate experiments with larger sample sizes (N = 71 & N = 65) by means of noninvasive behavioral and physiological proxies of dopamine (DA), such as sEBR and mood measures, which are likely to reflect striatal dopamine levels, and color discrimination, which has been argued to tap into the frontal dopamine levels. Our findings did not confirm the prediction that AB size covaries with sEBR, mood, or color discrimination. The implications of this inconsistency with previous observations are discussed.

Sleep-dependent memory processing is dependent on several factors at learning, including emotion, encoding strength, and knowledge of future relevance. Recent work documents the role of curiosity on learning, showing that memory associated with high-curiosity encoding states is retained better and that this effect may be driven by activity within the dopaminergic circuit. Here, we examined whether this curiosity effect was enhanced by or dependent on sleep-related consolidation. Participants learned the answers to trivia questions that they had previously rated on a curiosity scale, and they were shown faces between each question and answer presentation. Memory for these answers and faces was tested either immediately or after a 12-hour delay containing sleep or wakefulness, and polysomnography data was collected for a subset of the sleep participants. Although the curiosity effect for both the answers and incidentally-learned faces was replicated in immediate tests and after the 12-hour delay, the effect was not impacted by the presence of sleep in either case, nor did the effect show a relationship with total sleep time or time in slow-wave sleep. This study suggests that curiosity may be a learning factor that is not subsequently affected by sleep-dependent memory consolidation, but more work ought to examine the role of sleep on curiosity-driven memory in other contexts.

Dopamine is central to a number of cognitive functions and brain disorders. Given the cost of neurochemical imaging in humans, behavioural proxy measures of dopamine have gained in popularity in the past decade, such as spontaneous eye blink rate (sEBR). Increased sEBR is commonly associated with increased dopamine function based on pharmacological evidence and patient studies. Yet, this hypothesis has not been validated using in vivo measures of dopamine function in humans. To fill this gap, we measured sEBR and striatal dopamine synthesis capacity using [18 F]DOPA PET in 20 participants (nine healthy individuals and 11 pathological gamblers). Our results, based on frequentist and Bayesian statistics, as well as region-of-interest and voxel-wise analyses, argue against a positive relationship between sEBR and striatal dopamine synthesis capacity. They show that, if anything, the evidence is in favour of a negative relationship. These results, which complement findings from a recent study that failed to observe a relationship between sEBR and dopamine D2 receptor availability, suggest that caution and nuance are warranted when interpreting sEBR in terms of a proxy measure of striatal dopamine.

Spontaneous eye blink rate (EBR) has been proposed as a noninvasive, inexpensive marker of dopamine functioning. Support for a relation between EBR and dopamine function comes from observations that EBR is altered in populations with dopamine dysfunction and EBR changes under a dopaminergic manipulation. However, the evidence across the literature is inconsistent and incomplete. A direct correlation between EBR and dopamine function has so far been observed only in nonhuman animals. Given significant interest in using EBR as a proxy for dopamine function, this study aimed to verify a direct association in healthy, human adults. Here we measured EBR in healthy human subjects whose dopamine D2 receptor (DRD2) availability was assessed with positron emission tomography (PET)-[18F]fallypride to examine the predictive power of EBR for DRD2 availability. Effects of the dopamine agonist bromocriptine on EBR also were examined to determine the responsiveness of EBR to dopaminergic stimulation and, in light of the hypothesized inverted-U profile of dopamine effects, the role of DRD2 availability in EBR responsivity to bromocriptine. Results from 20 subjects (age 33.6 ± 7.6 years, 9F) showed no relation between EBR and DRD2 availability. EBR also was not responsive to dopaminergic stimulation by bromocriptine, and individual differences in DRD2 availability did not modulate EBR responsivity to bromocriptine. Given that EBR is hypothesized to be particularly sensitive to DRD2 function, these findings suggest caution in using EBR as a proxy for dopamine function in healthy humans.

Estradiol and progesterone levels vary along the menstrual cycle and have multiple neuroactive effects, including on the dopaminergic system. Dopamine relates to executive functions in an \"inverted U-shaped\" manner and its levels are increased by estradiol. Accordingly, dopamine dependent changes in executive functions along the menstrual cycle have been previously studied in the pre-ovulatory phase, when estradiol levels peak. Specifically it has been demonstrated that working memory is enhanced during the pre-ovulatory phase in women with low dopamine baseline levels, but impaired in women with high dopamine baseline levels. However, the role of progesterone, which peaks in the luteal cycle phase, has not been taken into account previously. Therefore, the main goals of the present study were to extend these findings (i) to the luteal cycle phase and (ii) to other executive functions. Furthermore, the usefulness of the eye blink rate (EBR) as an indicator of dopamine baseline levels in menstrual cycle research was explored. 36 naturally cycling women were tested during three cycle phases (menses-low sex hormones; pre-ovulatory-high estradiol; luteal-high progesterone and estradiol). During each session, women performed a verbal N-back task, as measure of working memory, and a single trial version of the Stroop task, as measure of response inhibition and cognitive flexibility. Hormone levels were assessed from saliva samples and spontaneous eye blink rate was recorded during menses. In the N-back task, women were faster during the luteal phase the higher their progesterone levels, irrespective of their dopamine baseline levels. In the Stroop task, we found a dopamine-cycle interaction, which was also driven by the luteal phase and progesterone levels. For women with higher EBR performance decreased during the luteal phase, whereas for women with lower EBR performance improved during the luteal phase. These findings suggest an important role of progesterone in modulating dopamine-cycle interactions. Additionally, we identified the eye blink rate as a non-invasive indicator of baseline dopamine function in menstrual cycle research.

We investigated task switching among four tasks by means of a modified cuing procedure with two types of cues. One type of cue consisted of a standard task cue indicating the next task. In half of the trials, this task cue was preceded by another type of cue that reduced the set of candidate tasks from four to two tasks. In addition, we measured participants\' spontaneous eye blink rates (EBRs) at the beginning, in the middle, and at the end of the experiment. Whereas interindividual differences in mean EBR had no pronounced effect on task switching performance, changes in EBRs during the first half of the experiment significantly modulated the interaction of the effects of the two types of cues. We suggest that changes in EBRs in the early phase of the experiment reflect adaptations of dopaminergic projections serving to integrate advance information about a forthcoming task switch.