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Title: The use of functional neuroimaging to study reorganisation of the motor system during task performance following altered corticospinal excitability caused by repetitive transcranial magnetic stimulation
Author: Rounis, Elisabeth
ISNI:       0000 0001 3538 3396
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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Repetitive transcranial magnetic stimulation (rTMS) in motor areas has been shown to induce transient and reversible changes in the corticospinal excitability of healthy individuals' brains. Furthermore, a number of studies have shown that this reorganisation can occur not only at the site of stimulation but also in other areas which might be anatomically or functionally connected to it. These effects are thought to depend on various parameters such as the protocol of stimulation, the site of stimulation and the behavioural paradigm chosen to study the effects. The aim of this thesis was to use functional neuroimaging in order to explore how the effects of long-lasting rTMS protocols (30-60min stimulation) on the motor system depend on specific conditioning parameters such as the frequency, the site and the pattern of stimulation. We examined how the pattern of activity in the brain reorganises depending on the anatomical and effective connectivity of the stimulated area, and on the behavioural task. Initial studies presented in this thesis used Positron Emission Tomography to compare the effects of high (5Hz) versus low (1Hz) frequency of rTMS on activity and motor network connectivity of the primary motor cortex (M1) during performance of a simple finger movement task or at rest. I found that task-related activity of motor area 4p within M1 and its connectivity with non-primary motor areas, such as the ipsilesional dorsal premotor (PMd) cortex could be modulated bidirectionally with low or high frequency rTMS over M1: compared to sham stimulation, 5Hz rTMS reduced task-related activity and network connectivity of that area. The opposite was true for 1Hz rTMS. A further study using the same task examined whether such reorganisation would be observed with 5Hz rTMS over the PMd. The effect of 5Hz rTMS on this site of stimulation revealed a different pattern of regional cerebral blood flow than rTMS over M1. However, a similar reorganisation in task-related activity and network connectivity was observed, particularly within the PMd area caudal to the stimulated site, which increased in activity after 5Hz rTMS. These two studies demonstrated that rTMS leads to widespread activity changes. However, changes in task-related activity and motor network connectivity occur in motor areas adjacent to the stimulated site. Given the lack of any behavioural effects in these studies, it can be hypothesised that these changes occur as compensatory mechanisms to the "virtual lesion" caused by rTMS. A functional magnetic resonance imaging (fMRI) study of the effects of rTMS over the lateral prefrontal cortex showed task-related changes in activity during performance of a cued choice reaction time task. Targeting the dorsolateral prefrontal cortex (DLPFC) with 5Hz rTMS led to task-related decreases in activity in the adjacent ventrolateral prefrontal cortex. This is reminiscent of the task-related decreases in activity of area 4p observed following 5Hz rTMS over M1 (described above). The side of lateral prefrontal conditioning affected behavioural performance in a further study which distinguished motor from spatial attention in the same behavioural paradigm. Left DLPFC stimulation led to a more prominent switch cost in the motor attention version of this task, confirming a left-lateralised dominance for switching motor responses, described in previous studies. These results provide new evidence that reorganisation in the brain observed following rTMS conditioning is very similar to reorganisation observed following lesions in patients. This reorganisation seems to depend on the task that is required to be performed and determines the pattern of activity obtained in functional neuroimaging studies. In addition, whether this will lead to a behavioural effect depends on the role of that particular area during task performance which is a function of its effective connectivity. These factors seem to determine whether the brain can compensate for the "virtual lesion" induced by rTMS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available