Exploring the physiology and behavioural relevance of circuits in the human motor cortex with a novel transcranial magnetic stimulation device

点击翻译按钮获取中文摘要

Transcranial magnetic stimulation is a non-invasive and painless way of stimulating the brain in conscious healthy individuals. In the 30 years since its introduction it has become a mainstay tool in cognitive neuroscience as well as a potential therapeutic tool to treat a variety of neurological conditions such as depression and to enhance recovery after stroke. However, it is still a relatively blunt tool. It activates a mixture of neurones in an excited area. Some of these are inhibitory, some excitatory; some are interneurons and some are projection neurones. Thus the effect we observe physiologically (on EEG or fMRI) and behaviourally (e.g. reaction times or response accuracy) represents a net effect of multiple interacting circuits. Variations in the proportions of neural types activated can vary between people and contribute to the large inter-individual differences that are common in TMS experiments. The aim of this project is to increase selectivity of TMS by employing an advanced TMS device to manipulate the shape and directionality of the stimulus waveform. We will use it to explore the role of selected populations of neurones in motor cortex during movement preparation and learning in a way that previously has not been possible. We will also show that the same principles may also apply to frontal areas of the cortex.We have some pilot data which has identified important pulse parameters that we focus on in the present proposal. In the motor cortex we expect that with one set of parameters we will be able to target a population of inputs to motor cortex from premotor areas that are also modulated by information from cerebellum. These inputs will be most important in choosing the right action from a known set of alternative actions. They will also participate in tasks involving adaptation to new movement parameters, such as modulation of visual input gain. This data will be complemented by detailed neurophysiological investigations that will help us to understand the actions of targeted stimulation on identified neural circuits (GABAa-, GABAb- and cholinergic connections). We will in parallel collect data about the form of EEG evoked activity and the interaction of stimulus types with ongoing EEG rhythms. This will allow us to extend our work to other cortical areas and compare their effects with that on motor cortex. Finally we will examine effects of targeted stimulation on repetitive TMS protocols. These are often referred to as "plasticity" protocols since they are thought to change the excitability of synaptic connections in the stimulated area for an hour or so after rTMS. They are important because they are used in therapeutic setting, for example to treat depression or rehabilitation after stroke. By targeting specific populations of neurones we expect to change the effects of rTMS, making it potentially more reliable and better focussed to the disorders it may be used to treat.