SummaryChildren with neurological disorders may follow unique developmental trajectories whereby they undergo compensatory neuroplastic changes in brain structure and function that help them gain control over their symptoms [1–6]. We used behavioral and brain imaging techniques to investigate this conjecture in children with Tourette syndrome (TS). Using a behavioral task that induces high levels of intermanual conflict, we show that individuals with TS exhibit enhanced control of motor output. Then, using structural (diffusion-weighted imaging) brain imaging techniques, we demonstrate widespread differences in the white matter (WM) microstructure of the TS brain that include alterations in the corpus callosum and forceps minor (FM) WM that significantly predict tic severity in TS. Most importantly, we show that task performance for the TS group (but not for controls) is strongly predicted by the WM microstructure of the FM pathways that lead to the prefrontal cortex and by the functional magnetic resonance imaging blood oxygen level-dependent response in prefrontal areas connected by these tracts. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.

Transcranial magnetic stimulation (TMS) is a popular technique that can be used to investigate the functional role of specific cortical areas with reference to a particular behavioural task. Single-cell recording studies performed in non-human primates have demonstrated that a region of the parietal lobe known as the lateral intraparietal area is specialized in the planning and control of saccadic eye movements. The homologue of this area in humans is termed the parietal eye fields (PEF) and its role in relation to saccades has previously been examined using TMS. In this paper individual variability in the functional effect of parietal TMS on the latency, amplitude and angular direction of visually-guided saccades has been assessed. By examining individual variability in the spatial distribution of scalp-based localization and brain surface anatomy and stereotaxic localizations of the PEF it was shown that the distances between the sites determined by these three methods were not negligible, which raises problems regarding the most reliable anatomical localization technique to use. An assessment of the effect of TMS on saccade metrics (latency, amplitude error and angular error) at a grid of locations over parietal cortex demonstrated a large amount of intra-individual variability in the site where TMS had most affected saccades, leading to the conclusion that there is individual variability in the functional effects of parietal TMS on saccade planning and execution. This study confirms the idea that it may be problematic to use a fixed scalp location for every participant in a study. It may in fact be more appropriate to determine TMS sites functionally on an individual basis if possible. This finding may guide further studies using TMS and saccade planning in order to optimize their capability to investigate this area and to draw meaningful biological conclusions.

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