New Paper: Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects


Brain Stimulation 2016 May 24. pii: S1935-861X(16)30104-8. doi: 10.1016/j.brs.2016.05.008. [Epub ahead of print]

Abstract: The safety and tolerability of limited output tES in clinical populations support a non-significant risk designation. The tolerability of long-term use in a healthy population had remained untested. We tested the tolerability and compliance of two tES waveforms, tDCS and modulated high frequency transcranial pulsed current stimulation (MHF-tPCS) compared to sham-tDCS, applied to healthy subjects for three to five days (17–20 minutes per day) per week for up to six weeks in a communal setting. MHF-tPCS consisted of asymmetric high-frequency pulses (7–11 kHz) having a peak amplitude of 10–20 mA peak, adjusted by subject, resulting in an average current of 5–7 mA. A total of 100 treatment blind healthy subjects were randomly assigned to one of three treatment groups: tDCS (n = 33), MHF-tPCS (n = 30), or sham-tDCS (n = 37). In order to test the role of waveform, electrode type and montage were fixed across tES and sham-tDCS arms: high-capacity self-adhering electrodes on the right lateral forehead and back of the neck. We conducted 1905 sessions (636 sham-tDCS, 623 tDCS, and 646 MHF-tPCS sessions) on study volunteers over a period of six weeks. Common adverse events were primarily restricted to influences upon the skin and included skin tingling, itching, and mild burning sensations. The incidence of these events in the active tES treatment arms (MHF-tPCS, tDCS) was equivalent or significantly lower than their incidence in the sham-tDCS treatment arm. Other adverse events had a rarity (<5% incidence) that could not be significantly distinguished across the treatment groups. Some subjects were withdrawn from the study due to atypical headache (sham-tDCS n = 2, tDCS n = 2, and MHF-tPCS n = 3), atypical discomfort (sham-tDCS n = 0, tDCS n = 1, and MHF-tPCS n = 1), or atypical skin irritation (sham-tDCS n = 2, tDCS n = 8, and MHF-tPCS n = 1). The rate of compliance, elected sessions completed, for the MHF-tPCS group was significantly greater than the sham-tDCS group’s compliance (p = 0.007). There were no serious adverse events in any treatment condition. We conclude that repeated application of limited output tES across extended periods, limited to the hardware, electrodes, and protocols tested here, is well tolerated in healthy subjects, as previously observed in clinical populations.

Electrode configurations and montages. Identical electrodes and montages were ...

marsEqCurrently available automated segmentation tools only provide results for brain tissues (gray matter, white matter, cerebrospinal fluid (CSF)), have a limited FOV, and do not guarantee continuity and smoothness of tissues, which is crucially important for accurate modeling of transcranial electrical or magnetic stimulation. MARS is a tool that addresses these needs.

MARS is an extended toolbox for SPM software. It is developed based on the SPM8 toolbox “New Segment”, which is an implementation of the Unified Segmentation algorithm (Ashburner & Friston 2005), where the image intensity model and anatomical prior (atlas) are combined into a Bayesian inference framework. MARS further added the morphological constraints on neighboring tissue voxels to the framework, which is encoded by Markov Random Field (MRF). This MRF information is added into the updating equation of the E-step of the algorithm, not just as a post-processing step. Compared to the New Segment, the resulting segmentation is shown to be more smooth and with less discontinuities, while at the same time the accuracy is not significantly changed. For more details on the algorithm, see Yu Huang, Lucas C. Parra, Fully Automated Whole-Head Segmentation with Improved Smoothness and Continuity, with Theory Reviewed. PLoS ONE 10(5): e0125477.

MARS is always initialized by the New Segment. In other words, this toolbox will run New Segment in the first step to get the optimal estimates on the bias field, the registration parameters between atlas and the image(s) to be segmented, and the initial estimates of segmentation posteriors and parameters of Gaussian mixture model. MARS will then continues to update the segmentation posteriors and Gaussian mixture model by using both atlas (tissue probability map, TPM) and tissue correlation map (TCM), while keep the bias field and registration parameters untouched. The toolbox is backwards compatible with the New Segment toolbox, as users can disable the MARS update so that only New Segment will be run.

The TCM is a way of representing MRF constraint. It indicates the probability of co-occurrence of specific two tissues in two neighboring voxels. For example, white matter cannot be adjacent to the air, and thus the probability of observing white matter as a neighbor of air voxel is 0, and this is encoded in the TCM. We developed three categories of TCM: the local, global and regional. The local TCM gives different co-occurrence probabilities depending on the location of the voxels, while the global version uses the same value for all the voxels in the image. The local TCM has nice theoretical properties, but not practical for implementation, as it needs too much memory to store and compute; while the global one is too rough to include any local information. The regional TCM is a trade-off between the two: it encodes locality information such as the interior of white matter and the boundary between grey and white matters, while at the same time uses the same co-occurrence value for one specific locality. Therefore, the regional TCM is highly recommended, and local TCM is not recommended unless you have a 64-bit computer with at least 50 GB memory.

Download the Matlab code and TPM/TCM here.

The “Non-invasive neuromodulation technology and regulation meeting” is a national meeting covering topics on the commercialization and regulation of non-invasive neuromodulation technology intended for medical and wellness use. This intensive one-day event is in direct response to the proliferation of clinical trials, popular press coverage, and now consumer-directed devices. The meeting is focused on transcranial Direct Current Stimulation (tDCS) but spans any investigational techniques or marketed technologies that apply electrical energy to the head. Ample time will be allowed for discussion with speakers.

Date: August 28, 2016
Location Center for Discovery and Innovation (CDI) Room Number – 4352

For more information visit the links below:
About this Meeting
Registration and Tickets

Neural Engineering Lab members can ask for free registraton code from Dr. Marom Bikson or Bhaskar Paneri