Harnessing sensorimotor cortical plasticity to improve outcomes in children with dystonia and dystonic cerebral palsy

Dystonia is a severely disabling movement disorder with no cure, in which people suffer painful muscle spasms causing twisting movements and abnormal postures. There are many causes, including genetic conditions and brain injury. The latter includes dystonic cerebral palsy (CP) in which the injury occurs around birth and which affects around 2.5 million people worldwide. Whilst adult-onset dystonia tends to involve a single body region, childhood-onset dystonia often affects the whole body. These children find it impossible to control their bodies, have difficulties accessing education or activities, and require costly life-long care. Dystonia is often unresponsive to drugs. Symptoms can be improved by Deep Brain Stimulation (DBS), in which fine wires are implanted into nerve cells deep in the brain. The wires deliver electrical pulses to modulate brain activity and reduce unwanted movements. DBS is very effective in some types of dystonia but less so in others. Predicting benefit is difficult, as the mechanisms that produce the abnormal movements are not fully understood. There is growing evidence that one mechanism involves abnormal brain processing of sensory information (eg signals to the brain from our senses of touch and body position): the distorted perception of these signals in turn disrupts the way the brain produces instructions for planning and performing movements. Most research in this field involves adults with dystonias affecting a single part of the body. Research in childhood dystonia, especially dystonic CP is sparse, despite these patients having the greatest clinical need: their dystonia affects the whole body, is very severe, and less responsive to therapy. Understanding the mechanisms that lead to different types of dystonia and how they affect the developing brain is critical if we are to improve outcomes and time interventions to exploit developmental time-windows when the brain is most able to respond. My own work shows that sensory pathways to the brain are abnormal in over 40% of children with dystonia (especially dystonic CP). I have also shown that the way the brain processes sensory information related to movement is abnormal in children with dystonia and dystonic CP, by using methods that record the EEG (electroencephalogram - brain wave signals) and/or EMG (electromyogram - electrical signal from muscles). Our brain waves show characteristic patterns in relation to our activities. For example, a particular brain rhythm known as "mu", which is seen over sensorimotor cortex (the outer layer of the brain responsible for processing sensory and movement information), is typically reduced in response to sensory stimulation or movement. This change in mu activity reflects the brain's processing of sensory information and is important in the development of motor skills in children. My research in children with dystonia/dystonic CP, shows that this movement-related change in mu activity is impaired, and that sensory stimuli related to movement trigger many cells across the brain to fire in synchrony with each other at a low frequency. It is possible that these two abnormal patterns of brain activity are linked and that they also relate to abnormal muscle activity. This project will 1. test these links and the effect of DBS on these abnormal brain patterns, thereby advancing knowledge of the mechanisms underlying dystonia/dystonic CP; 2. investigate whether movement-related changes in mu activity can be enhanced in children with dystonia/dystonic CP by using EEG feedback in the form of a computer game; and whether enhanced mu activity is associated with improved movement control. These findings will tell us whether biofeedback of mu activity could have a therapeutic role; 3. study the early development of movement-related changes in mu activity in healthy infants and those at risk of developing dystonic CP, thus demonstrating likely optimal time windows for therapeutic intervention.