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7Tel: +45 3862 6541; Email: hartwig.siebner@drcmr.dk; http://www.drcmr.dk/siebner 2 8All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/337782 doi: bioRxiv preprint first posted online Jun. 4, 2018; 2 Abstract (246 words) 2 9Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the 3 0 resulting activation may spread to connected brain regions. The distributed cortical response can be 3 1 recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor 3 2 axons and generates a loud "click" sound, the TMS-evoked EEG potential (TEP) not only reflects neural 3 3 activity induced by transcranial neuronal excitation but also neural activity reflecting somatosensory and 3 4 auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of 3 5 multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was 3 6 delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal 3 7 gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the 3 8 EEG responses evoked by sham stimulation over the posterior parietal and superior frontal cortex, 3 9 mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art 4 0 procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement 4 1 of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal 4 2 and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely 4 3 resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. 4Our findings stress the need to include a peripheral multisensory control stimulation in the study design to 4 5 enable a dissociation between truly transcranial and non-transcranial components of TEPs. 4 6 4 7All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique capable of modulating cortical excitability and thereby influencing behavior and learning. Recent evidence suggests that bilateral tDCS over both primary sensorimotor cortices (SM1) yields more prominent effects on motor performance in both healthy subjects and chronic stroke patients than unilateral tDCS over SM1. To better characterize the underlying neural mechanisms of this effect, we aimed to explore changes in resting-state functional connectivity during both stimulation types. In a randomized single-blind crossover design, 12 healthy subjects underwent functional magnetic resonance imaging at rest before, during, and after 20 min of unilateral, bilateral, and sham tDCS stimulation over SM1. Eigenvector centrality mapping (ECM) was used to investigate tDCS-induced changes in functional connectivity patterns across the whole brain. Uni- and bilateral tDCS over SM1 resulted in functional connectivity changes in widespread brain areas compared with sham stimulation both during and after stimulation. Whereas bilateral tDCS predominantly modulated changes in primary and secondary motor as well as prefrontal regions, unilateral tDCS affected prefrontal, parietal, and cerebellar areas. No direct effect was seen under the stimulating electrode in the unilateral condition. The time course of changes in functional connectivity in the respective brain areas was nonlinear and temporally dispersed. These findings provide evidence toward a network-based understanding regarding the underpinnings of specific tDCS interventions.

Long-term motor skill learning has been consistently shown to result in functional as well as structural changes in the adult human brain. However, the effect of short learning periods on brain structure is not well understood. In the present study, subjects performed a sequential pinch force task (SPFT) for 20 min on 5 consecutive days. Changes in brain structure were evaluated with anatomical magnetic resonance imaging (MRI) scans acquired on the first and last day of motor skill learning. Behaviorally, the SPFT resulted in sequence-specific learning with the trained (right) hand. Structural gray matter (GM) alterations in left M1, right ventral premotor cortex (PMC) and right dorsolateral prefrontal cortex (DLPFC) correlated with performance improvements in the SPFT. More specifically we found that subjects with strong sequence-specific performance improvements in the SPFT also had larger increases in GM volume in the respective brain areas. On the other hand, subjects with small behavioral gains either showed no change or even a decrease in GM volume during the time course of learning. Furthermore, cerebellar GM volume before motor skill learning predicted (A) individual learning-related changes in the SPFT and (B) the amount of structural changes in left M1, right ventral PMC and DLPFC. In summary, we provide novel evidence that short-term motor skill learning is associated with learning-related structural brain alterations. Additionally, we showed that practicing a motor skill is not exclusively accompanied by increased GM volume. Instead, bidirectional structural alterations explained the variability of the individual learning success.

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