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Using the 10-20 system for TMS positioning is applicable at low cost and may reach desired cortex regions reliably on a larger scale level. For finer grained positioning, possible interindividual differences, and therefore the application of neuroimaging based methods, are to be considered.

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Evidence from magnetic resonance imaging (MRI) suggests early structural and functional brain changes in individuals with the Huntington's disease (HD) gene mutation who are presymptomatic for the motor symptoms of the disorder (pre-HD subjects). The objective of this study was to investigate the functional neuroanatomy of verbal working memory (WM) in pre-HD subjects. By means of event-related functional MRI, we studied healthy controls (n = 16) and pre-HD subjects (n = 16) with a parametric WM paradigm comprising three different WM load levels. Voxel-based morphometry (VBM) was used to control potentially confounding brain atrophy. Although WM performance did not significantly differ between pre-HD subjects and healthy controls, pre-HD subjects showed a significantly decreased activation of the left dorsolateral prefrontal cortex (DLPFC) at intermediate and high WM load levels only. This region was not affected by early cortical atrophy, as revealed by VBM. Pre-HD individuals close to the onset of motor symptoms showed an increased activation of the left inferior parietal lobule and the right superior frontal gyrus compared with both pre-HD subjects far from symptom onset and healthy controls. In addition, the activation level in the left DLPFC was positively correlated with the UHDRS cognitive subscore in pre-HD subjects. Our findings demonstrate that early functional brain changes in pre-HD subjects may occur in the DLPFC before manifest cortical atrophy, and support a role of this region in the expression of clinical symptoms. Compensatory brain responses in pre-HD individuals may occur with closer proximity to the onset of manifest clinical symptoms.

Theta-burst Stimulation (TBS) is a novel form of repetitive transcranial magnetic stimulation (rTMS). Applied over the primary motor cortex it has been successfully used to induce changes in cortical excitability. The advantage of this stimulation paradigm is that it is able to induce strong and long lasting effects using a lower stimulation intensity and a shorter time of stimulation compared to conventional rTMS protocols. Since its first description, TBS has been used in both basic and clinical research in the last years and more recently it has been expanded to other domains than the motor system. Its capacity to induce synaptic plasticity could lead to therapeutic implications for neuropsychiatric disorders. The neurobiological mechanisms of TBS are not fully understood at present; they may involve long-term potentiation (LTP)- and depression (LTD)-like processes, as well as inhibitory mechanisms modulated by GABAergic activity. This article highlights current hypotheses regarding the mechanisms of action of TBS and some central factors which may influence cortical responses to TBS. Furthermore, previous and ongoing research performed in the field of TBS on the motor cortex is summarized.