The importance of precision
Research type
Research Study
Full title
The importance of precision: a model for movement and movement disorders
IRAS ID
184013
Contact name
James Morvan Kilner
Contact email
Sponsor organisation
University College London Sponsor Rep
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
The aim of this research work 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. 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. Beta power is reduced just prior to and during the period of movement and is transiently increased subsequent to the end of the movement. The importance of understanding their functional role is highlighted by the observation that Parkinson’s disease patients have a pathologically higher power of beta oscillations, both in the cortex and sub-cortically in the subthalamic nucleus. Successful treatment of Parkinson’s disease with levodopa or with subthalamic deep brain stimulation is associated with an decrease in beta power. Conversely, stimulation of the subthalamic nucleus at the beta frequency causes a slowing of movement in patients with Parkinson’s disease. It has therefore been proposed that in Parkinson’s disease patients pathologically high amplitude of beta oscillations causes bradykinesia and other motor symptoms, but the mechanism of this effect and proof of the causal relationship between pathological beta activity and motor symptoms of Parkinson’s disease is lacking.
Every movement we make stimulates peripheral sensory receptors that activate neurons in the cortex via ascending sensory pathways. However, not all of these afferent signals generated during voluntary movement influence the cortical neuronal activity in the same way and they are known to be heavily modulated by top-down signals.This sensory attenuation, also called sensory gating, is well documented and is most commonly believed to reflect an active suppression or cancelation of the predicted sensory consequences of an action so as to make the system more sensitive to unexpected sensations.
More recently an alternative theoretical account, active inference, has been proposed where sensory attenuation prior to and during active movement is a thought to be an essential step in actually being able to move. Within this framework sensory attenuation is a necessary consequence of reducing the precision (synaptic gain) of sensory evidence during movement to allow the expression of the prior beliefs that incite movement. One consequence of this framework is that in order to be able to move the prediction errors about the hidden states must be greater than the prediction errors about the somatosensory expectations. Of particular interest here is that within the active inference framework a failure to move can be modeled by a failure to sufficiently attenuate precision on the somatosensory expectations. Indeed, it has been proposed that some of the hypokinetic symptoms of Parkinson’s disease, specifically akinesia and bradykinesia, can be recast as a result of a pathology in reducing the precision of the somatosensory expectations. Furthermore, the attenuation of the precision has been proposed to be mediated by changes in neuromodulators such as dopamine.This results in a totally novel and exciting hypothesis to explain the hypokinetic motor symptoms of Parkinson’s disease that we propose to test with the combination of experimental and modeling work outlined in this proposal.REC name
East of Scotland Research Ethics Service REC 1
REC reference
15/ES/0144
Date of REC Opinion
29 Oct 2015
REC opinion
Further Information Favourable Opinion