Comments on the Studies of Pupil Metrics: Ways to Separate Physiology and Psychology

The article is a review of the publication, which explores the joint dynamics of heart rate and pupillary reflex. The focus of the article is on the metrics of the state of the autonomic nervous system. Understanding of the nature of the relationship between heart rate and pupillary reflex can help develop methods for normalizing the dynamics of pupil diameter to the dynamics of the state of the autonomic nervous system, which will make it possible to more accurately understand what exactly caused change in pupil diameter.

Introduction

Pupil diameter is one of the frequently used metrics in both psychological studies, where this indicator is most often used as an assessment of the level of cognitive load in a particular task, and in physiological ones – in such works, the dynamics of pupil opening is regarded as one of the characteristics of the state of the autonomic nervous system. Most researchers agree that the pupil diameter is affected by the level of illumination and the brightness of the scene a person is looking at, the state of the autonomic nervous system, affective processes, and the level of cognitive load. Such a number of heterogeneous factors affecting the pupil diameter significantly complicate the interpretation of this indicator in a particular study, since all of the above factors affect the pupil diameter at the same time. It is impossible to distinguish for what reason the narrowing of the pupil occurred – the cognitive load increased or the state of the autonomic nervous system changed.

One of the solutions to this problem – a large number of influencing factors – can be the normalization of the pupil diameter, for example, to the dynamics of the state of the autonomic nervous system known from other metrics. The state of the autonomic nervous system (ANS) is reflected not only in the dynamics of pupil opening, but also in indicators of the activity of the cardiovascular system, galvanic skin response, etc. Is it possible in one way or another to remove the well-measurable dynamics of the state of the autonomic nervous system from the dynamics of the pupil? Outdoor illumination is easy to control during the experiment. In this case, we will be able to significantly “clear” the reactions of the pupil from the physiological and environmental components. If successful, the pupil diameter will be a much more accurate representation of the remaining characteristics – mainly cognitive load.

 One of the first steps in this direction may be to study the joint dynamics of pupil opening and other physiological parameters that also reflect the dynamics of the state of the autonomic nervous system. The results of such a study were published in 2020 in the article: Ishikawa, Masaaki. (2020). Effective combination of pupil light reflex and heart rate variability to assess foot bath effects on autonomic function in healthy adults. Biomedical Physics & Engineering Express. 6. doi:10.1088/2057-1976/ab6e1c. In this work, the modulation of the state of the subjects was carried out using a foot bath. The foot bath has been used in the field of nursing and is regarded as a simple technique to induce comfort and relaxation. Previous studies have examined the effects of foot bathing on the autonomic nervous system (ANS) by measuring heart rate variability (HRV) (Saeki, 2000; Yamamoto et al., 2008; Miyazato & Matsukawa, 2010). HRV is the fluctuation of the length of heartbeat intervals, representing the involvement of the ANS in cardiac regulation. Two studies have reported enhanced activity of the parasympathetic nervous system (PNS) following a foot bath in healthy adult subjects (Saeki, 2000; Yamamoto et al., 2008), while one study demonstrated decreased activity of the PNS in non-pregnant and pregnant women (Miyazato & Matsukawa, 2010).

One in-vivo study revealed that oral application of G-hesperidin excited the sympathetic nervous system (SNS) activity of brown adipose tissue but inhibited that of the cutaneous artery (Shen et al., 2009). These findings indicate that ANS innervation of organs and tissues does not change in the same way under altered external and internal environments, highlighting the importance of evaluating ANS alteration in several organs and tissues. Clinical studies have indicated a possible association between pupil light reflex (PLR) and HRV in adults during exercise (Kaltsatou et al., 2011; Okutucu et al., 2016), healthy children (Daluwatte et al., 2012), healthy adults (Bar et al., 2009), and patients with acute schizophrenia (Bar et al., 2008). Indeed, a correlation between PLR and HRV was found in adults during exercise (Kaltsatou et al., 2011), but there were no, or limited, correlations among healthy children (Daluwatte et al., 2012) and adults (Bar et al., 2009).

The pupil is under control of the ANS (as is HRV), specifically the iris dilator and iris sphincter. The iris dilator is mediated by the post-ganglionic fibers of the SNS: the superior cervical ganglion receives the input from preganglionic neurons in the cilospinal center of the intermedio-lateral nuclear column of the cervicothoracic spinal cord. The iris sphincter is influenced by the projecting fibers of the ganglion ciliare which receives input from the parasympathetic preganglionic neurons in the Edinger-Westphal nucleus of the midbrain (Hall & Chilcott, 2018; Szabadi, 2018). Thus far, no studies have focused on either PLR or the combination of PLR and HRV to investigate the potential effects of foot bathing on the ANS.

Several factors such as age, sex, body mass index (BMI), and hormonal cycle can affect the activity of PLR and HRV via the ANS (Bitsios et al 1996, Fotiou et al 2007, Laeng and Falkenberg, 2007, Koenig and Thayer, 2016, Sharma et al 2016, von Holzen et al 2016, Shaffer and Ginsberg, 2017). In addition, the stimulus intensity of PLR can be a crucial factor affecting the parameter values such as amplitude, latency, constriction velocity and dilation velocity (Ellis, 1981, Gavriysky, 1991, Bitsios et al 1996). When analyzing the potential effects of foot bathing on ANS activity, these factors should be accounted and adjusted for when possible.

The aim of the current study was to compare PLR and HRV parameters before and during foot bathing in healthy adult subjects, and to evaluate the potential effects of foot bathing on ANS activity.

Discussion

Foot bath effects on PLR

There was a failure to collect over 62% of the T75 data because of an insufficient test duration to recover 75% of INIT; therefore, these data were excluded from the analysis. The main effects of the intervention and stimulus intensity were evaluated using a two-way repeated-measures ANOVA with Bonferroni’s correction (n = 220 eyes). All parameters showed significant effects with the intervention and stimulus intensity (supplementary table 1 is available online at stacks.iop.org/BPEX/6/015034/mmedia). Five out of seven parameters showed significant interactions (minimum pupil size at the end of light stimulus – END, averaged constriction velocity – ACV, constriction ratio defined as the difference between the initial and minimum size divided by the initial pupil size – DELTA, and averaged dilation velocity – ADV; p < 0.001, MCV; p = 0.002).

In the LME models with hierarchical stepwise regression analysis, the better-fit model for all parameters was Model 4 which included a random slope effect. An increased stimulus intensity and foot bath intervention resulted in significant parameter shifts: (1) decreased INIT, END, and ADV, (2) shortened LAT, and (3) increased ACV, MCV, and DELTA. Significant interactions were observed in all parameters except INIT and LAT. In Model 4, aging significantly decreased INIT and END, and females showed significantly lower values of MCV.

Foot bath effects on HRV

In the time domain, the Wilcoxon signedrank test found a significant increase in SDNN (p < 0.001) with the intervention, but no alteration of rMSSD (p = 0.3) or pNN50 (p = 0.07). In the frequency domain, LF norm, HF norm, and LF/HF showed no significant effects due to the intervention (LF norm, p = 0.3; HF norm, p = 0.3; LF/HF, p = 0.5). LF power and HF power showed significant differences (p < 0.001).

Conclusions

The current study demonstrated an increase in PNS activity as assessed by PLR, and few alterations in PNS activity as assessed by HRV, highlighting that the combination of PLR and HRV can be an effective method to evaluate ANS activity under altered external and internal environments. In PLR, light stimulus intensity can be a crucial factor in evaluating the effects of foot bathing.

As we can see from the results of this work, a number of indicators of cardiac activity and pupil dilation dynamics responded synchronously to the same physiological impact. Probably, this work could be supplemented by a study of the nature of the relationship between these two characteristics, and not only their separate study in connection with the use of a foot bath and light stimulation.

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