Zsolt TOKAJI
Principal Investigator
HUMAN BIOPHYSICS AND MOVEMENT ANALYTICS
Movement is a fundamental feature of living organisms and systems, and the same is true for man, the most developed living system. The importance of the information content of these movements (frequently representing deeper, e.g. molecular or even intramolecular processes as well) have long been known intuitively. (Think about e.g. the effects of ethanol contained in alcoholic drinks). However, methods that are really suitable for the quantitative study of these motions have either been developed only recently, or are now in the process of being developed.
Presently the two main (methodological) focuses of our research activities are to study human body movements also affected voluntarily by actigraphy, and an internal movement that is practically uncontrollable voluntarily, the continuous changes in pupil size by video-pupillography.
The actigraph usually is a wrist-wearable watch-sized device that is capable of recording movement activities for a relatively long period of time (for several days or weeks), and the collected time-activity data can be transferred into a computer for the purpose of analysis. Actograms carry a lot of information about the biological clock, daily routine, jet lag and various psychiatric disorders. Some of their characteristics are already routinely used in medical therapy, but the complex structure of actograms is still mostly unexplored. The reason for this paradox is that while Fourier analysis, the main tool used for the evaluation of actograms, is effective in revealing periodic components, it fails to analyse stochastic events - resulting in fluctuations - that seem to be prevalent on the ultradian scale (Fig. 1a ).
Figure 1: A) Activity recording of a typical day. B) Integral function of the curve in A)
It is a key question in life sciences whether the stochastic dynamics of physiological rhythms are an essential feature for their function, or they are either simple consequences of environmental fluctuations or associated with certain malfunctions. Our aim is to find and characterize some new, general features in human physical activity patterns that are expected to shed more light on the nature of complex physiological processes underlying activity signals.
In the case of video-pupillography, the movements of the subject’s pupil(s) are recorded for a relatively short or long period of time (usually for 1-15 minutes) by a video-camera system, and analyzed by computer programs.
Figure 2: Probabilities of the appearance of different pupil diameters as a function of time during an 11-minute pupillographic sleepiness test in the case of an alert and a sleepy subject.
Both of these main methods were able to find and show differences between healthy state and the one accompanying affective disorder (depression). Both of these methods are extremely suitable for the measurement of alertness, which is presently hardly measurable by other objective methods. In these alertness measurements, the strength of video-pupillography is the ability to measure the actual/short term level of alertness as well, whereas actigraphy is excellent for measuring average alertness and its periodicity.
Using actigraphy, we have proved and characterized the appearance of a higher order structure of human daily activity. Figure 3 shows the result of a statistical analysis of the spikes in Fig. 1A.
Figure 3: Probability density functions (PDFs) of activity spikes recorded under conditions described in Fig.1. The time scale of the daily recordings was divided into equal intervals (“boxes”), and activity values were averaged within each box. PDFs were calculated from these averaged values. Data are shown for some characteristic box lengths between 1 and 720 minutes distinguished by different colours. Curves in (A) and (B) are obtained from the original recordings and the scrambled control, respectively.
Note that an explicit depression is built up in the middle of the curve by increasing box size, persisting for box lengths of several hours. The meaning of this feature becomes obvious when we take a look at the integral function of the daytime activity trace of an average day (Fig.1b). It is apparent that there are two characteristic slopes of this function, corresponding to the two peaks in the pdf. During the active periods average activities are similar, and centered to a higher value (right peak in Fig. 2a, or the bigger slope in Fig. 1b), while it is easy to distinguish resting periods with activities close to zero (left peak in Fig. 2a, or plateaus in Fig. 1b). In other words, on this time scale the human physical activity is quasi-binary: it is distributed such that well-defined bursts are followed by passive periods. This novel finding, generally characteristic of all cases studied, is expected to inspire new mathematical models of human physical activity.
Although video-pupillography is a relatively rapidly performable experimental method, we have used it successfully in darkness for the detection of changes of alertness due to natural reasons (for e.g. in the case of children with attention-deficit hyperactivity disorder) or drug effects (for e.g. nicotine). Under room light conditions video-pupillography can provide information about changes in the equilibrium of the sympathetic/parasympathetic nervous activities originating either in natural causes, or resulting from drug use (for e.g. methylphenidate) or a treatment (e.g. bright light exposure).
In our laboratories, unconventional methods (e.g., distribution function or wavelet analysis) for the evaluation of actigraphic and video-pupillographic data are also applied. Several new methods are under development or are being currently introduced into practice.
Further research plans, possible utilization of the results
Our methods are suitable for achieving a better understanding and characterization of human behaviour, with respect to its temporal organization and pathological alterations. The effects of drugs on the brain can be studied, the transport into and the elimination from the brain can be monitored by these methods. By using drug/chemical interactions, conclusions can also be drawn even for intramolecular alterations concerning e.g. receptor-mediated processes.
Selected publications
Szabó, Z., Tokaji, Z., Kálmán, J., Oroszi, L., Pestenácz, A. and Janka, Z. (2004). The effect of bright light exposure on pupillary fluctuations in healthy subjects. J. Affect. Disord. 78: 153-156.
Szabó, Z., Antal, A., Tokaji, Z., Kálmán, J., Kéri, S., Benedek, G. and Janka, Z. (2004). Light therapy increases visual contrast sensitivity in seasonal affective disorder. Psychiatry Res. 126: 15-21.
Dancshazy, Z., Der, A., Groma, G.I., Janka, Z., Jardanhazy, T., Makai, A., Szentistvanyi, I. and Vasadi, A. (2004). Phase-synchronization of daily motor activities can reveal differential circadian patterns. Chronobiol. Int. 21: 309-314.
Tokaji, Z., Szabó, K., Nagyova, K. and Vetró, Á. (2006). Darkness-induced alertness-increase in children with attention deficit hyperactivity disorder and its diminution by methylphenidate. Eur. Neuropsychopharmacol. 16: S532-S532.
Tokaji, Z., Szabó, Z., Kovács, Z. and Nagyova, K. (2007). Lack of the large aftereffect of bright light on pupillary fluctuations in patients with non-seasonal depression. Eur. Neuropsychopharmacol. 17: S322-S322.
Nagyova, K., Szabó, K., Vetró, Á. and Tokaji, Z. (2007). Methylphenidate-induced stabilization of the sympathetic/parasympathetic tone in children with ADHD. Eur. Neuropsychopharmacol. 17: S574-S575.



