BackgroundMeasurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the folded cortex results in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS.MethodsHere we test this idea by using Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP) to measure changes in corticospinal excitability following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus.ResultsCurrent flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces non-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is thought to select different afferent pathways to M1.ConclusionsOur results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.

Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society.

width range, current steering, and other programmable features of the device. It is not possible to test all settings in a single programming visit, and more studies are needed to define the optimal parameter space for target signs.Another limitation was the lack of data on efficacy of chronic stimulation at a short pulse width. The participants were only exposed to each stimulation setting for a short time during a single programming visit; it is possible that long-term stimulation would have revealed differences between short and conventional pulse widths that were not apparent during the acute visit. However, the blinded assessment of motor signs (UPDRS III) during an acute stimulation challenge has previously been used as the primary efficacy endpoint in DBS studies [8][9][10] and reflected the chronic benefit of DBS.Despite these limitations, few controlled studies are aimed at achieving optimization of DBS programming, and this is the first double-blind assessment of the effect of a shorter pulse width and 1 of only a handful of DBS programming studies that have ever been conducted in a double-blind condition.In conclusion, stimulation using a shorter than currently recommended pulse width may be more efficient at achieving therapeutic efficacy and less likely to reach a side effect threshold. This may translate into a fundamentally new basic parameter setting for patients with DBS in PD. Supporting DataAdditional Supporting Information may be found in the online version of this article at the publisher's website. Short Pulse Width in AbstractBackground: We investigated the acute effect of short pulse widths on the therapeutic window in subthalamic nucleus deep brain stimulation in Parkinson's disease. Methods: We assessed 10 PD patients with STN-DBS at a 60-ms pulse width. We randomly and doubleblindedly applied 10-to 50-ms pulse widths. The principal outcome was the therapeutic window (difference --

Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the cephalic cortex result in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. Here we test this idea by measuring changes in cortico-spinal excitability by Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP), following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus. Current flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces none-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is through to select different afferent pathways to M1. Our results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.