8th International Conference on
Functional Mapping of the Human Brain
June 2 - 6,2002, Sendai, JAPAN
Symposium Wednesday 5th June
Contributions of transcranial magnetic stimulation to human brain mapping
1. Background
Transcranial magnetic stimulation (TMS) is a well-established tool to stimulate the human cortex through the intact scalp. By contrast to any other brain mapping technique, TMS actively interacts with neuronal activity in the cortex. In recent years, TMS has mainly been applied in four different areas of research. (i.) TMS has been widely used to probe distinct changes in excitability within the (motor) cortex caused by a given intervention (i.e. drug administration) or pathology. (ii.) TMS has become a well-established neuropsychological tool to induce a temporary functional dysfunction (often referred to as å×irtual lesionÒ) in the stimulated cortex and thus to interfere with task performance when being applied over a key cortical area. (iii.) Since the effects of TMS on neuronal activity is not limited to the stimulated cortex, but does spread to other brain regions which are functionally interconnected with the stimulated cortex, TMS has proved to be suitable to study functional inter-regional interactions in the brain (iv.) By applying regular trains of magnetic pulses, repetitive TMS (rTMS) has been shown to induce lasting changes in cortical excitability and function. This virtue of repetitive TMS has prompted numerous studies that employed rTMS to study the mechanisms underlying cortical reorganization. 2. Aim of the symposium
The aim of the symposium is to highlight how TMS can be used to extend the current scope of human brain mapping. 3. Concept of the symposium
At the last OHBM meeting in Brighton, a teaching course focussed on the combined use of TMS and functional neuroimaging. In the teaching course, each talk addressed specific questions related to the combination of TMS with a distinct imaging modality (ie. TMS and PET, TMS and fMRI). In this proposal, rather than focussing on a specific imaging modality, we intend to adopt a somewhat different concept by concentrating on the scientific questions that can be addressed using TMS in combination with a variety of other imaging methods. Therefore, each talk will deal with a specific technical advantage of TMS (i.e. interfering with ongoing cortical processing, assessing connectivity, or inducing plastic changes) and put this feature in the context of human brain mapping. This concept will help to bring together and foster interactions between the most prominent research approaches that exploit TMS in the field of human brain mapping.
The symposium will be coordinated by H. Siebner (Sobell Department of Neurophysiology, Institute of Neurology, UCL) and will consist of three talks. The speakers and the titles of each presentation, including a summary of each talk, are given below in chronological order. The time allotted for each talk is 30 minutes including 10 minutes of discussion. All speakers have already agreed to participate.
T. Paus will start off with a short introduction regarding the principles of TMS. Then, he will point out how TMS in combination with PET and EEG can be used to map connectivity of the human brain and its modulation by repetitive TMS. The second talk will be given by M. Rushworth who will concentrate on the issue of how TMS can be employed to interfere with normal brain function. Based on his work, he will show that TMS as a tool to induce a temporary cortical lesion can be used to bridge the gap between an observed focus of activation during a given task and the functional relevance of the activation focus to accomplish the task. In the last talk, H. Siebner will go on to demonstrate how TMS can be used to image the time course and regional pattern of functional plasticity in the intact human brain. In addition, he will address the question as to how basic and clinical research derive benefit from combined TMS / imaging studies on functional reorganization. Effective connectivity of the human frontal cortex and its modulation by repetitive transcranial magnetic stimulation.
Tomas Paus Montreal Neurological Institute, McGill University
3801 University St., Montreal, Quebec H3A 2B4
tomas@bic.mni.mcgill.ca
Three principal reasons have motivated recent advances in combining transcranial magnetic stimulation (TMS) with brain mapping and its use to study brain-behaviour relationships in health and disease. First, TMS allows the investigator to manipulate neural activity in space and time and, as such, provides a tool for testing the causality of structure-function correlations revealed by functional imaging techniques. Second, TMS combined with a concurrent measurement of neural activity with PET, fMRI or EEG serves as a behaviour-independent assay of cortical excitability and connectivity. Third, the measurement of TMS-induced changes in neural activity in general, and specific neurotransmitter systems in particular, furthers our understanding of the potential treatment effects of brain stimulation and the pathophysiology of certain brain disorders. This talk will illustrate some of the ways in which TMS can be combined with brain imaging to achieve the above goals, focusing in particular on studies of cortical connectivity of the human frontal cortex and its modulation by repetitive TMS.
Using TMS to test the importance of functional activations.
Matthew Rushworth Department of Experimental Psychology, University of Oxford
South Parks Road, Oxford, OX 3UD, United Kingdom
matthew.rushworth@psy.ox.ac.uk
Neuroimaging techniques, such as fMRI, have revolutionised our understanding of human brain function. fMRI reveals regions of activity change that are correlated with cognitive processes. Two issues remain unclear. First it is not always easy to ascertain if an activation is causally essential for the cognitive process in question. Because it interferes with the normal pattern of activity in a brain area, TMS can be used to test whether an area is essential for a cognitive process. Second, it is not always clear when a region of activation is making its critical contribution to a cognitive process. Because of the limited duration of the interference it induces, TMS can be used to investigate when a brain area is making its critical contribution to behaviour. These principles will emerge during the discussion of the following experiments: 1) Investigations of the correspondences between the positions of areas of activation and of areas susceptible to TMS-induced interference; 2) TMS has been used to establish when activated areas make their critical contribution in investigations of movement, attention, and language; 3) In an fMRI investigation of attentional switching we found an area of medial frontal activation associated with switching in different paradigms. TMS of the same region suggested that it only played an essential role in attentional switching in some situations; 4) Changes in brain activation have been measured as patients recover from neurological illness. It has been controversial whether such changes play a causal role in recovery or whether they are epiphenomena. This can be tested with TMS.
Combining transcranial magnetic stimulation and human brain mapping: applications in basic neuroscience and clinical research
Hartwig Siebner Sobell Department of Neurophysiology, Institute of Neurology, University College of London
8-11 Queen Square, London WC1N 3BG, United Kingdom
h.siebner@ion.ucl.ac.uk
The talk will provide three illustrative examples as to how basic and clinical research can benefit from combining TMS with neuroimaging techniques.
(i.) By systematically manipulating a specific variable of stimulation such as frequency or intensity, concurrent functional brain imaging can assess the regional excitability profile of a distinct cortical area. This opens up clinical applications such as the in-vivo assessment of disease-related or drug-induced changes in cortical excitability in a cortical target area.
(ii.) Concurrent electrophysiological assessment of cortical excitability and cortico-cortical coherence allows to relate TMS-induced changes in intracortical excitability and inter-regional coupling to TMS-associated changes in rCBF or BOLD response. This multimodal approach provides revealing insights into the neural mechanisms underlying neurometabolic coupling and cortico-cortical interactions.
(iii.) By applying regular trains of magnetic pulses, repetitive TMS (rTMS) is capable of inducing enduring functional changes in a distributed functional network. The time course and the regional pattern of rTMS-induced functional plasticity, can be readily assessed with various neuroimaging techniques. In addition, one can directly compare rTMS-induced changes in task performance with changes in the task-related activation pattern. It will be demonstrated that this approach is suitable to investigate both, the pathophysiology and functional reorganization in patients with neuropsychiatric disorders.
Therapeutic Uses of TMS
Alvaro Pasqual-Leone Laboratory for Magnetic Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School
330 Brookline Avenue, Boston, MA,USA
Transcranial magnetic stimulation (TMS) is the only non-invasive technique available that allows us to interfere actively with brain function, and thus investigate the relationship between focal cortical activity and behavior, trace the timing at which a cortical region contributes to a given task, and map the functional connectivity between brain regions. However, TMS, applied in trains of repetitive stimuli (rTMS) to a given cortical area can be used to modulate the level of cortical excitability and induce changes in excitability that outlast the duration of the TMS train itself. Depending on stimulation frequency and intensity, cortex excitability can either be enhanced or reduced and the resulting behavioral changes explored systematically. Therapeutic applications of TMS and behavioral enhancement can be entertained thanks to this lasting rTMS effects. However the large inter-individual differences in the physiologic effects of rTMS need to be considered.
Fundamentally, such gtherapeutic applications of rTMSh are examples of neuromodulation and can be classified as (1) attempts to enhance cortical excitability and increase function of the targeted brain region; (2) attempts to suppress activity in the targeted brain region and induce paradoxical behavioral facilitations; (3) attempts to induce network effects resulting in distant modulations of brain activity or releases of neurotransmitters; and (4) attempts to induce release of neurochemical agents with generalized neuromodulatory effects.
Examples of these different ways to attempt induction of behaviorally desirable effects of TMS will be reviewed. However, to date, there is really no definite evidence that any of these approaches has a definite, clinically significant therapeutic effect.
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