Systems biology and the virtual physiological human

The virtual physiological human (VPH) initiative is intended to support the development of patient‐specific computer models and their application in personalised and predictive healthcare. The VPH, a core target of the European Commission's 7th Framework Programme, will serve as a ‘methodological and technological framework that, once established, will enable collaborative investigation of the human body as a single complex system’ (http://www.europhysiome.org/roadmap/). As such, the VPH initiative constitutes an integral part of the international Physiome Project (http://www.physiome.org.nz/), a worldwide public domain effort to develop a computational framework for the quantitative description of biological processes in living systems across all relevant levels of structural and functional integration, from molecule to organism, including the human (Kohl et al, 2000; Bassingthwaighte et al, 2009). So, what is the connection between this grand challenge and systems biology? To explore this, we must first agree on what we take systems biology to mean

Dancing with physio: a mobile game with physiologically aware virtual humans

This study presents an evaluation of a mobile game with physiologically aware virtual humans as an approach to modulate the participant's affective and physiological state. We developed a mobile version of a virtual reality scenario where the participants were able to interact with virtual human characters through their psychophysiological activity. Music was played in the background of the scenario and, depending on the experimental condition, the virtual humans were initially either barely dancing or dancing very euphorically. The task of the participants was to encourage the apathetic virtual humans to dance or to calm down the frenetically dancing characters, through the modulation of their own mood and physiological activity. Results from our study show that by using this mobile game with the physiologically aware and affective virtual humans the participants were able to emotionally arouse themselves in the Activation condition and were able to relax themselves in the Relaxation condition, during the same session with only a brief break between conditions. The self-reported affective data was also corroborated by the physiological data (heart rate, respiration and skin conductance) which significantly differed between the Activation and Relaxation conditions

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters

EJS-Based Laboratory for Learning the Function of the Cardiovascular System

One of the career areas included in the field of Biomedical Engineering is the application of engineering system analysis: physiological modelling, simulation and control. This paper describes a Virtual Laboratory for the analysis and the study of Human circulatory system. The Virtual Laboratory is based on the compilation of several mathematical models described in the literature. Presented application has been build using MATLAB/Simulink and EJS, so it combines good computation capabilities and it is completely interactive. The Virtual Laboratory is designed in order to understand the operation of the circulatory system under normal conditions, and to predict circulatory variables at different levels of stimuli and conditions.Postprint (published version

Multimodal assessment of emotional responses by physiological monitoring: novel auditory and visual elicitation strategies in traditional and virtual reality environments

This doctoral thesis explores novel strategies to quantify emotions and listening effort through monitoring of physiological signals. Emotions are a complex aspect of the human experience, playing a crucial role in our survival and adaptation to the environment. The study of emotions fosters important applications, such as Human-Computer and Human-Robot interaction or clinical assessment and treatment of mental health conditions such as depression, anxiety, stress, chronic anger, and mood disorders. Listening effort is also an important area of study, as it provides insight into the listeners’ challenges that are usually not identified by traditional audiometric measures. The research is divided into three lines of work, each with a unique emphasis on the methods of emotion elicitation and the stimuli that are most effective in producing emotional responses, with a specific focus on auditory stimuli. The research fostered the creation of three experimental protocols, as well as the use of an available online protocol for studying emotional responses including monitoring of both peripheral and central physiological signals, such as skin conductance, respiration, pupil dilation, electrocardiogram, blood volume pulse, and electroencephalography. An emotional protocol was created for the study of listening effort using a speech-in-noise test designed to be short and not induce fatigue. The results revealed that the listening effort is a complex problem that cannot be studied with a univariate approach, thus necessitating the use of multiple physiological markers to study different physiological dimensions. Specifically, the findings demonstrate a strong association between the level of auditory exertion, the amount of attention and involvement directed towards stimuli that are readily comprehensible compared to those that demand greater exertion. Continuing with the auditory domain, peripheral physiological signals were studied in order to discriminate four emotions elicited in a subject who listened to music for 21 days, using a previously designed and publicly available protocol. Surprisingly, the processed physiological signals were able to clearly separate the four emotions at the physiological level, demonstrating that music, which is not typically studied extensively in the literature, can be an effective stimulus for eliciting emotions. Following these results, a flat-screen protocol was created to compare physiological responses to purely visual, purely auditory, and combined audiovisual emotional stimuli. The results show that auditory stimuli are more effective in separating emotions at the physiological level. The subjects were found to be much more attentive during the audio-only phase. In order to overcome the limitations of emotional protocols carried out in a laboratory environment, which may elicit fewer emotions due to being an unnatural setting for the subjects under study, a final emotional elicitation protocol was created using virtual reality. Scenes similar to reality were created to elicit four distinct emotions. At the physiological level, it was noted that this environment is more effective in eliciting emotions. To our knowledge, this is the first protocol specifically designed for virtual reality that elicits diverse emotions. Furthermore, even in terms of classification, the use of virtual reality has been shown to be superior to traditional flat-screen protocols, opening the doors to virtual reality for the study of conditions related to emotional control

Simulating the decentralized processes of the human immune system in a virtual anatomy model

BACKGROUND: Many physiological processes within the human body can be perceived and modeled as large systems of interacting particles or swarming agents. The complex processes of the human immune system prove to be challenging to capture and illustrate without proper reference to the spacial distribution of immune-related organs and systems. Our work focuses on physical aspects of immune system processes, which we implement through swarms of agents. This is our first prototype for integrating different immune processes into one comprehensive virtual physiology simulation. RESULTS: Using agent-based methodology and a 3-dimensional modeling and visualization environment (LINDSAY Composer), we present an agent-based simulation of the decentralized processes in the human immune system. The agents in our model - such as immune cells, viruses and cytokines - interact through simulated physics in two different, compartmentalized and decentralized 3-dimensional environments namely, (1) within the tissue and (2) inside a lymph node. While the two environments are separated and perform their computations asynchronously, an abstract form of communication is allowed in order to replicate the exchange, transportation and interaction of immune system agents between these sites. The distribution of simulated processes, that can communicate across multiple, local CPUs or through a network of machines, provides a starting point to build decentralized systems that replicate larger-scale processes within the human body, thus creating integrated simulations with other physiological systems, such as the circulatory, endocrine, or nervous system. Ultimately, this system integration across scales is our goal for the LINDSAY Virtual Human project. CONCLUSIONS: Our current immune system simulations extend our previous work on agent-based simulations by introducing advanced visualizations within the context of a virtual human anatomy model. We also demonstrate how to distribute a collection of connected simulations over a network of computers. As a future endeavour, we plan to use parameter tuning techniques on our model to further enhance its biological credibility. We consider these in silico experiments and their associated modeling and optimization techniques as essential components in further enhancing our capabilities of simulating a whole-body, decentralized immune system, to be used both for medical education and research as well as for virtual studies in immunoinformatics