The importance of precision: a model for movement and movement disorders.

Parkinson's disease is the second most common neurodegenerative disorder in the world, affecting ~7 million people, with ~130,000 patients in the UK. Parkinson's patients have pronounced movement tremor and are hypokinetic in their movements, they are slower both to initiate their movements and in the time it takes them to make movements. The aim of the work proposed here is to test a new theoretical account of movement and movement disorders, investigating whether this account can explain some of the hypokinetic symptoms observed in Parkinson's disease.

Every movement we make stimulates receptors in the skin and the muscles of the limbs we move that provide the brain with information about the nature of the movement we have made and the current position and state of where our limbs are in space. It has been known for a long time that when we move we attenuate the size of these sensory signals from the limbs we move. This is known as sensory attenuation or sensory gating. Why this occurs is not known. According to a recent theory of movement generation, active inference, sensory attenuation is required in order to initiate a movement. Within this framework the brain is constantly trying to generate a prediction of the sensory information the brain receives. The brain then compares the prediction to the actual sensory input. Any difference between the two is called a prediction error. Within this framework the brain works to minimise prediction error. When we plan a movement we start to generate a prediction of the sensory consequences of that new movement. This creates a prediction error between the prediction of the future sensory information and the current sensory information. To minimise this prediction error we could either (1) stop planning the new movement or (2) move so as the sensory information matches our prediction. The factor that determines which of these two things we do is how much weight we give to the current sensory information. In order to move it has been proposed that we give less weight to the current sensory information and this explains why we observe sensory attenuation during movements.

This framework also provides a new way in which we can explain why Parkinson's disease patients are slower both to initiate their movements and in the time it takes them to make movements. These symptoms would occur if Parkinson's disease patients failed to reduce the weight of the current sensory information. This suggests that Parkinson's disease patients might have a pathology in their ability to correctly estimate the correct weight to give to the current sensory information, always over weighting this information. The aim of the research proposed in this application is to test this theory. We propose to test firstly, if sensory attenuation is impoverished in Parkinson's disease patients compared to healthy subjects, secondly, to determine how the brain modulates the weight given to the current sensory information, and finally to test new non-invasive interventions that could ameliorate some of the motor symptoms of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative disorder in the world, affecting ~7 million people, with ~130,000 patients in the UK. Parkinson's patients have pronounced movement tremor and are hypokinetic in their movements, presenting with akinesia, bradykinesia, freezing and rigidity. The aim of the work proposed here is to test a novel theoretical account of movement and movement disorders, investigating whether this account can explain some of the hypokinetic symptoms observed in Parkinson's disease. In particular, this research will test a theory of the functional role of sensorimotor beta oscillations that could explain beta power modulations in healthy subjects and the increase in beta power observed in Parkinson's disease patients. Finally, based on this theoretical framework we propose to test a new non-invasive intervention that could ameliorate some of the hypokinetic symptoms of Parkinson's disease.
It has been known for over 50 years that power in the beta frequency range (~15-30 Hz), originating in the sensorimotor cortices in healthy human subjects, is modulated during action execution. However, despite extensive research into these neuronal oscillations their functional role, if any, remains unknown. The importance of understanding their functional role is highlighted by the observation that Parkinson's disease patients have a pathologically higher amplitude of beta oscillations, both in the cortex and sub-cortically in the subthalamic nucleus. In Parkinson's disease patients it has been proposed that this pathologically high amplitude of beta oscillations can lead to some of the motor symptoms of Parkinson's disease. Here, we propose to test a novel theory of the functional role sensorimotor beta oscillations, namely that they are causally linked to the imprecision or demodulation of proprioceptive predictions.

Beneficiaries

i) Long term the key beneficiaries to this work are Parkinson's disease patients. One of the aims of this work is to test a novel non-invasive intervention that might ameliorate some of the motor symptoms of Parkinson's disease. Clearly, if this was achieved this would be of enormous benefit to those people who suffer from this disorder. Progress on this intervention will be reviewed after 24 months and every 3 months there after.

ii) The results of the proposed work have potential important implications for the field of motor control and movements. The main aim of the research is to test a novel functional role for a well known neurophysiological phenomenon, sensorimotor beta oscillations. It has been known for over 50 years that power in the beta frequency range (~15-30 Hz), originating in the sensorimotor cortices in healthy human subjects, is modulated during action execution. However, despite extensive research into these neuronal oscillations their functional role, if any, remains unknown. If successful this research will provide an account of their function role and this would open up new research areas in other movement and cognitive disorders where there have been reported pathological differences in sensorimotor beta power, e.g. Tourettes and schizophrenia patients.

iii) The proposed research involves, in part, a novel analysis of EEG data and development of new models to this end. All these new methodologies will be made publically available through the existing SPM software package.