Integrative Systems Biology

Whiplash injury is a type of indirect injury that can occur when the neck is subjected to sudden acceleration or deceleration forces where the head is thrown forward and backward, for example in a car accident. Muscles, joints, tendons, discs, vertebrae and nerves in the neck can then be damaged. Common symptoms include neck pain, dizziness, fatigue, headache, shooting arm pain, and pain in the jaw. In Sweden, 30 000 persons per year are subjected to whiplash injury and in approximately half of the cases the symptoms become chronic, making it hard to live a normal life and causing economic and social losses. When a person is in pain their pattern of movement may change to protect the injured body part. Prof. Peolsson (Linköping University) is a physiotherapist and one of Sweden’s leading researchers in rehabilitation of whiplash injuries. Her group has recently shown that inpatients with chronic whiplash injury, the neck muscles do not cooperated in the same way that they do in healthy controls. Instead, their pattern of movement is more stereotypical, more fat infiltration in the muscles increases and the stamina of the muscles decreases. However, the pattern of movement is not generated solely on the level of the muscles, but also in the brain, and several levels of control cooperate to generate movement. This cooperation makes it hard to understand how the functioning of the neck changes in a whiplash injury without also studying the activity of the brain.

In a series of experiments, Prof. Peolssons group is going to collect ultrasound data showing the movement of the neck muscles during everyday activities, as well as MRI data measuring muscle volume, cross-sectional area, fat infiltration and inflammation in addition to fMRI data measuring the brain activity in individuals with whiplash injury before and 3 months after rehabilitation. Healthy individuals matched in age and gender will also be measured. Data such as this is extensive and complex, and the relations between the measurements are hard to interpret. Therefore, a new type of analysis tool that can analyze all data at the same time and also take the interactions between the neck muscles and the brain into account is needed. Computer models is such a tool: models where the biological mechanisms of both the brain and the neck muscles are represented. In other words, the next step to understand the mechanisms of whiplash injuries is to combine existing models of brain and neck muscles. In this manner, the interaction between these two organs would be investigated on an individual basis, our understanding of how whiplash injuries affect the pattern of movement would increase and training programs to strengthen each individual's healthy pattern of movements could be constructed.

The aim of this project is to use computer modeling of the brain and the neck musculature in order to develop better understanding of how pattern of movement develops and changes, which will be used to develop tools for diagnosis and treatment of whiplash injured patients. This multidisciplinary project is a collaboration with the group of Prof. Peter Hunter in Auckland, New Zealand, in order to construct multi-level whole-body models of the interaction between the brain and the neck to increase our understanding of how patterns of movement is generated and changes in response to pain. A rich set of multimodal data from both patients with chronic whiplash associated disorder (WAD) and from healthy controls will be collected at Linköping university hospital, which will be analyzed using these models.

Apart from understanding the cardiovascular mechanisms of hypertension, it is important to understand the mechanisms of lowering blood pressure. Lowering the blood pressure in hypertension is crucial to reduce morbidity and mortality. To lower blood pressure, there is a large range of anti-hypertensive drugs along with lifestyle advice for the health professionals to choose from, acting on different parts of the cardiovascular system. Despite this increasing number of treatment options together with increased knowledge of the mechanisms of hypertension, the proportion of controlled hypertension is only around 20% and a trial- and error approach is used when initiating a blood-pressure lowering treatment. To better understand the patient-specific effects of anti-hypertensive drugs, we want to further develop our cardiovascular models to include drug effects. We have developed a few initial models that accurately can describe the blood pressure decrease due to anti-hypertensive drugs both on a simple long-term scale and the more detailed effect son the renin-angiotensin system over a few weeks. The next step is to create detailed models of the patient-specific change in beat-to-beat regulation of blood pressure before and after starting to take anti-hypertensive drugs.

• • Peter Hunter, New Zealand University.
  • Anneli Peolsson, Linköping University.