New biomarkers for the assessment of fatigue evoked by long-term sleep deprivation based on pupillary light reflex using rheological models

Abstract

BackgroundThe pupillary reflex (PLR) can be used to describe the function of individual segments of the visual pathway. It is modulated by the autonomic nervous system (ANS) and clinical disorders. The results of the research on the PLR parameterization methods presented in the article show that it is possible to use the phenomenon of pupil contraction as a result of light stimulation to assess the level of sleepiness. Currently, the PLR reflex is mainly used as the primary tool to study the integrity of the sensory and motor functions of the eye. Emergency medicine physicians routinely test the pupil light reflex to assess brainstem function. MethodsThe study utilized a method for estimating the fatigue level caused by 48-hour sleep deprivation under standardized and controlled conditions through the development and implementation of the Kelvin-Voigt rheology model (KV), explaining the dynamics of the pupillary light reflex. The baseline parameters for the model were as follows: parasympathetic force (fp), sympathetic force (fs), pupil radius in rest conditions (r0), onset time: parasympathetic system (tp), onset time: sympathetic system (ts), product fp × tp and product fs × ts. These parameters were subject to a statistical analysis of variance and compared with the parameters determined by the pupillographic assessment system by AmTech, such as contraction velocity (CV), relative amplitude (RA), pupil diameter (DDil1-fast), pupil diameter (DDil2-slow), latency (Lat), time of minimum diameter (TMD), contraction time (CT), redilation time (RT). ResultsThe statistical analysis involved the data obtained in the research experiment on a group of 18 healthy volunteers enrolled in our study (range 26–32 years, fifty percent of the study group were female). Based on the parameters from the KV model developed, the statistical significance for the model indicators was determined, i.e, fp, r0, tp, ts and fp × ts, compared at different levels of sleep deprivation of 48 h. In addition, analysis of the determined indicators, via the AmTech pupillographic system, demonstrated that an increased level of sleep deprivation does not only result in a change in the slope and amplitude of the curve of the pupil diameter in the contraction phase, which is visualized by the CV, RA, CT parameters, but also in the pupil dilation curve shape (Dil1-fast, Dil2-slow, RT). Sleep deprivation was observed to cause an increase of TMD and Lat. Correlation analysis presented the strongest correlations between fp and the contraction velocity r = 0.73 (p < 0.05) and the minimum pupil diameters as expressed by the RA values: 0.66 (p < 0.05). The force fp, originating from the parasympathetic system, was correlated with redilation time – i.e., the larger the force, the shorter the time: −0.52 (p < 0.05). It also affected the value of the pupil diameter at the end of dilatation (DDil2-slow) r = 0.49 (p < 0.05).The delay in the force tp, originating from the parasympathetic nervous system (PNS), increased the duration of pupil contraction time. In this case, the correlation coefficient was r = 0.73 (p < 0.05). This was also facilitated by a delay (ts) on the part of the sympathetic nervous system (SNS), leading to a delay in dilatation and thus facilitating unrestrained pupil constriction. The correlation coefficient was r = 0.7 (p < 0.05).The controlled level of sleepiness, assessed via the Stanford Sleepiness Scale (SSS) test, had increased by about 150% by the end of the experiment. ConclusionThe results of the studies indicate that the fatigue biomarkers, as determined during the pupil dilation phase (DDil1-fast, DDil2-Slow), as well as the new method for describing the dynamics of the PLR, can provide an effective and specific indicator of sleepiness levels. These results are also confirmed by an analysis of the Stanford Sleepiness Scale assessment results.In addition, the use of the KV rheological model to describe the curve of the pupillary reflex makes it possible, through the designated parameters of the model, to independently assess the sympathetic (fs, ts) and parasympathetic (tp, tp) activation of the autonomic nervous system.