Guilherme B. Saturnino

Field modeling for transcranial magnetic stimulation: A useful tool to understand the physiological effects of TMS?

Electric field calculations based on numerical methods and increasingly realistic head models are more and more used in research on Transcranial Magnetic Stimulation (TMS). However, they are still far from being established as standard tools for the planning and analysis in practical applications of TMS. Here, we start by delineating three main challenges that need to be addressed to unravel their full potential. This comprises (i) identifying and dealing with the model uncertainties, (ii) establishing a clear link between the induced fields and the physiological stimulation effects, and (iii) improving the usability of the tools for field calculation to the level that they can be easily used by non-experts. We then introduce a new version of our pipeline for field calculations (www.simnibs.org) that substantially simplifies setting up and running TMS and tDCS simulations based on Finite-Element Methods (FEM). We conclude with a brief outlook on how the new version of SimNIBS can help to target the above identified challenges.

On the importance of electrode parameters for shaping electric field patterns generated by tDCS

Transcranial direct current stimulation (tDCS) uses electrode pads placed on the head to deliver weak direct current to the brain and modulate neuronal excitability. The effects depend on the intensity and spatial distribution of the electric field. This in turn depends on the geometry and electric properties of the head tissues and electrode pads. Previous numerical studies focused on providing a reasonable level of detail of the head anatomy, often using simplified electrode models. Here, we explore via finite element method (FEM) simulations based on a high-resolution head model how detailed electrode modeling influences the calculated electric field in the brain. We take into account electrode shape, size, connector position and conductivities of different electrode materials (including saline solutions and electrode gels). These factors are systematically characterized to demonstrate their impact on the field distribution in the brain. The goals are to assess the effect of simplified electrode models; and to develop practical rules-of-thumb to achieve a stronger stimulation of the targeted brain regions underneath the electrode pads. We show that for standard rectangular electrode pads, lower saline and gel conductivities result in more homogeneous fields in the region of interest (ROI). Placing the connector at the center of the electrode pad or farthest from the second electrode substantially increases the field strength in the ROI. Our results highlight the importance of detailed electrode modeling and of having an adequate selection of electrode pads/gels in experiments. We also advise for a more detailed reporting of the electrode montages when conducting tDCS experiments, as different configurations significantly affect the results.

How to target inter-regional phase synchronization with dual-site Transcranial Alternating Current Stimulation

&NA; Large‐scale synchronization of neural oscillations is a key mechanism for functional information exchange among brain areas. Dual‐site Transcranial Alternating Current Stimulation (ds‐TACS) has been recently introduced as non‐invasive technique to manipulate the temporal phase relationship of local oscillations in two connected cortical areas. While the frequency of ds‐TACS is matched, the phase of stimulation is either identical (in‐phase stimulation) or opposite (anti‐phase stimulation) in the two cortical target areas. In‐phase stimulation is thought to synchronize the endogenous oscillations and hereby to improve behavioral performance. Conversely, anti‐phase stimulation is thought to desynchronize neural oscillations in the two areas, which is expected to decrease performance. Critically, in‐ and anti‐phase ds‐TACS should only differ with respect to temporal phase, while all other stimulation parameters such as focality and stimulation intensity should be matched to enable an unambiguous interpretation of the behavioral effects. Using electric field simulations based on a realistic head geometry, we tested how well this goal has been met in studies, which have employed ds‐TACS up to now. Separating the induced electrical fields in their spatial and temporal components, we investigated how the chosen electrode montages determined the spatial field distribution and the generation of phase variations in the injected electric fields. Considering the basic physical mechanisms, we derived recommendations for an optimized stimulation montage. The latter allows for a principled design of in‐ and anti‐phase ds‐TACS conditions with matched spatial distributions of the electric field. This knowledge will help cognitive neuroscientists to design optimal ds‐TACS configurations, which are suited to probe unambiguously the causal contribution of phase coupling to specific cognitive processes in the human brain. HighlightsProviding a framework for selective in‐ and anti‐phase TACS of two cortical areas.Evaluation of previously published TACS montages using realistic simulations.They mostly failed to induce selective in‐ or anti‐phase TACS in the target areas.They rather produced complex differences in temporospatial stimulation patterns.Phase‐controlled TACS of two target areas is possible using focal ring montages.

Evaluation of a Modified High-Definition Electrode Montage for Transcranial Alternating Current Stimulation (tACS) of Pre-Central Areas

OBJECTIVE To evaluate a modified electrode montage with respect to its effect on tACS-dependent modulation of corticospinal excitability and discomfort caused by neurosensory side effects accompanying stimulation. METHODS In a double-blind cross-over design, the classical electrode montage for primary motor cortex (M1) stimulation (two patch electrodes over M1 and contralateral supraorbital area) was compared with an M1 centre-ring montage. Corticospinal excitability was evaluated before, during, immediately after and 15 minutes after tACS (10 min., 20 Hz vs. 30 s low-frequency transcranial random noise stimulation). RESULTS Corticospinal excitability increased significantly during and immediately after tACS with the centre-ring montage. This was not the case with the classical montage or tRNS stimulation. Level of discomfort was rated on average lower with the centre-ring montage. CONCLUSIONS In comparison to the classic montage, the M1 centre-ring montage enables a more focal stimulation of the target area and, at the same time, significantly reduces neurosensory side effects, essential for placebo-controlled study designs.

The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation.

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field “hot spots” in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared to the healthy control, both TBS methods are safe in patients with large brain lesions (in practice, however, additional factors such as potentially lowered thresholds for seizure-induction have to be considered). Focused stimulation by TMS seems to be possible, but standard tDCS protocols appear to be less efficient than they are in healthy subjects, strongly suggesting that tDCS studies in this population might benefit from individualized treatment planning based on realistic field calculations.

Enhancing Predicted Efficacy of Tumor Treating Fields Therapy of Glioblastoma Using Targeted Surgical Craniectomy: A Computer Modeling Study.

Objective The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios. Results For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60–70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30–50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50–70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect. Conclusions Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in healthy tissues. A clinical trial is being planned to validate safety and efficacy.

Automatic skull segmentation from MR images for realistic volume conductor models of the head: Assessment of the state-of-the-art

ABSTRACT Anatomically realistic volume conductor models of the human head are important for accurate forward modeling of the electric field during transcranial brain stimulation (TBS), electro‐ (EEG) and magnetoencephalography (MEG). In particular, the skull compartment exerts a strong influence on the field distribution due to its low conductivity, suggesting the need to represent its geometry accurately. However, automatic skull reconstruction from structural magnetic resonance (MR) images is difficult, as compact bone has a very low signal in magnetic resonance imaging (MRI). Here, we evaluate three methods for skull segmentation, namely FSL BET2, the unified segmentation routine of SPM12 with extended spatial tissue priors, and the skullfinder tool of BrainSuite. To our knowledge, this study is the first to rigorously assess the accuracy of these state‐of‐the‐art tools by comparison with CT‐based skull segmentations on a group of ten subjects. We demonstrate several key factors that improve the segmentation quality, including the use of multi‐contrast MRI data, the optimization of the MR sequences and the adaptation of the parameters of the segmentation methods. We conclude that FSL and SPM12 achieve better skull segmentations than BrainSuite. The former methods obtain reasonable results for the upper part of the skull when a combination of T1‐ and T2‐weighted images is used as input. The SPM12‐based results can be improved slightly further by means of simple morphological operations to fix local defects. In contrast to FSL BET2, the SPM12‐based segmentation with extended spatial tissue priors and the BrainSuite‐based segmentation provide coarse reconstructions of the vertebrae, enabling the construction of volume conductor models that include the neck. We exemplarily demonstrate that the extended models enable a more accurate estimation of the electric field distribution during transcranial direct current stimulation (tDCS) for montages that involve extraencephalic electrodes. The methods provided by FSL and SPM12 are integrated into pipelines for the automatic generation of realistic head models based on tetrahedral meshes, which are distributed as part of the open‐source software package SimNIBS for field calculations for transcranial brain stimulation. HIGHLIGHTSAssessment of three methods for the automatic skull segmentation from MR images.Rigorous test of their accuracy by comparison against CT data of the same subjects.FSL and SPM12 can achieve reasonable accuracy for the upper part of the head.A combination of T1‐ and T2‐weighted images, rather than a single T1, is suggested.Accuracy strongly benefits from optimization of the MRI sequence parameters.

The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies

&NA; Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud “click” sound, the TMS‐evoked EEG potentials (TEPs) reflect not only neural activity induced by transcranial neuronal excitation but also neural activity due to somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS‐compatible EEG system. Real TMS was delivered with a figure‐of‐eight coil over the left para‐median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by realistic sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state‐of‐the‐art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the design of TMS‐EEG studies to enable a dissociation between truly transcranial and non‐transcranial components of TEPs. HighlightsIndividually adjusted somato‐auditory sham stimulation can mimic real TMS.A realistic sham stimulation is capable to evoke complex EEG potentials.Real TMS and sham evoked responses strongly correlated at early and late latencies.Future TMS‐EEG studies need to control for the effect of multisensory stimulation.

P080 Fundamental limitations of focal transcranial weak current stimulation

Introduction Transcranial weak current stimulation (tCS) are a range of brain stimulation methods in which current is applied to the brain through surface electrodes mounted on the scalp, with the goal of promoting cortical excitability in a certain brain region. However, electric fields are governed by the Laplace equation, which result in physical constraints on how the electric field will be distributed in the tissue and to which extent its distribution can be controlled by manipulation of the external electrode configuration and applied current strengths. Methods In order to assess the inherent limits on tCS focality, we set up various constrained optimization problems to find electrode positions and current combinations which maximize either the field strength at a selected target or stimulation focality, while keeping the injected current within safe limits. Simulations were performed in both simple 3-layered spherical models as well as realistic head models, generated by the SimNIBS package ( www.simnibs.org ). Results The human head can be approximated as a piecewise-constant conductor, with constant conductivity in each tissue and boundaries between tissues. In such a conductor, it can be shown that due to the inherent properties of the Laplace equation, the maximal electrical field in any of the constant conductivity domains must be in its boundaries. This means that focal stimulation of deep cortical targets is not feasible under normal circumstances. Also, for limited amounts of current, our optimization results show that there is a natural trade-off between field focality and intensity at a target in tCS. That is, if we optimize the stimulation so that it is maximally focal, intensity at the target is lost, and vice versa. Conclusion While optimization procedures can substantially improve tCS targeting in terms of focality, the electric fields produced by those techniques are inherently subject to physical constraints, which fundamentally limit the focality and selectivity of stimulation, in particular for deeper targets. Download : Download high-res image (486KB) Download : Download full-size image