TMS and brain function
Dr Hadwen Trust Research Fellowship 1998 — 2001
Using Transcranial Magnetic Stimulation (TMS) to model brain damage in human subjects
V Walsh, M Rushworth and A Ellison, then at the Department of Experimental Psychology, University of Oxford
This Dr Hadwen Trust research grant to develop transcranial magnetic stimulation (TMS) has had wide-reaching applications, as the technique is now used internationally in neuroscience research, often in place of non-human primates.
TMS uses magnetic fields to temporarily disrupt the firing of neurons in selected areas of the brain in volunteers. Subjects are then asked to perform tasks to establish the functions of the damaged brain areas. This enables researchers to learn more about human neural processing by studying a model of brain damage safely in volunteers.
Dr Hadwen Trust funding enabled Professor Walsh and colleagues to use TMS to study brain damage and function in humans: work that had previously been conducted in non-human primates. The research studied the role of the parietal cortex in visual and motor attention and in learning.
The studies demonstrated that both stimulus and response are important in neural plasticity. Following training, certain brain areas cease to be used in a task, but if either the stimulus or response is varied, the novel processing carried out by the brain after training is no longer applicable. The research further demonstrated that the parietal lobe is involved in attentional search tasks [1]. These were novel findings that could not have been achieved in monkeys, and they had important implications for understanding perceptual learning.
The three researchers involved have since published a total of 73 papers on the applications of TMS, one of which by late 2007 had already been cited 185 times [2]. Using TMS, studies of human learning, perception, awareness, attention [3], language and memory are now advancing rapidly because the technique can be used to explore many areas of cognitive neuroscience.
Previously, work like this would have been carried out on non-human primates, as Britain’s Royal Society has acknowledged [4]. Apart from the ethical advantages, one particular scientific benefit of TMS over non-human primate studies of brain damage is that the impairment is reversible. This enables researchers to study learning in healthy volunteers with momentary ‘virtual’ damage, thereby preventing the brain creating new strategies to cope with the removed or damaged area. In invasive primate experiments or studies of brain-damaged patients, the brain may reorganise, and in so doing may mask the normal situation.
A further advantage of TMS is that unlike other brain imaging techniques which provide only correlative data, TMS actually creates ‘virtual lesions’ in subjects, providing scientists with optimal stimulus and response information. Previously stimulus and response work was often done in monkeys, where researchers implanted electrodes into the monkey’s brain and monitored the output whilst the animal performed a task.
TMS also relates to specific sites of activation of just a few millimetres, which is far more precise than the spatial resolution of many other methods of studying the functioning human brain [5]. TMS does not allow for single cell studies, as can invasive animal experiments, but does allow for a systems level analysis, which has led to rapid developments in understanding of neural function [6].
Following their Dr Hadwen Trust-funded work, Professor Walsh and Drs Rushworth and Ellison have become experts in the field. They have given lectures and seminars internationally and the department in Oxford became a training centre for other scientists on the use of TMS, including how it can be used to replace animals in research.
In exciting new developments, TMS is now being combined with other brain imaging techniques, thereby widening its applications still further. Combining TMS with positron emission tomography (PET) enables researchers to explore more fully the connectivity of the human brain [7], while TMS combined with functional magnetic resonance imaging (fMRI) enables study of the function of temporarily damaged areas of the brain [8]. Complex cognitive processes such as memory and learning are likely to involve multiple brain areas, so the ability to study these in combination is vital.
TMS, especially used multi-modally with other techniques, is already fulfilling its promise to advance knowledge and understanding of the human brain.
References
1. Stewart L, Ellison A, Walsh V et al (2001). The role of transcranial magnetic stimulation (TMS) in studies of vision, attention and cognition. Acta Psychol (Amst) 107:275-291.
2. Pascual-Leone A & Walsh V (2001). Fast backprojections from the motion to the primary visual area necessary for visual awareness. Science 292:510-512.
3. Rushworth MF & Taylor PC (2006). TMS in the parietal cortex: updating representations for attention and action. Neuropsychologia 44:2700-2716.
4. Royal Society (2004). The use of non-human animals in research: a guide for scientists. London: Royal Society.
5. Walsh V & Cowey A (2000). Transcranial magnetic stimulation and cognitive neuroscience Nature Reviews Neurosci 1:73-79.
6. Rushworth MF, Ellison A & Walsh V (2001). Complementary localization and lateralization of orienting and motor attention. Nature Neurosci 4:656-661.
7. Winhuisen L, Thiel A, Schumacher B et al (2007). The right inferior frontal gyrus and poststroke aphasia: a follow-up investigation. Stroke 38:1286-1292.
8. O’Shea J, Johansen-Berg H, Trief D et al (2007). Functionally specific reorganization in human premotor cortex. Neuron 54:479-490.
Professor Vincent Walsh is now based at the Institute of Cognitive Neuroscience, University College London. His research interests include visual cognition, plasticity in visual and motor systems and all aspects of human brain stimulation.