Arno M. Janssen

Simulating Transcranial Direct Current Stimulation With a Detailed Anisotropic Human Head Model

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce long-lasting changes in cortical excitability that can benefit cognitive functioning and clinical treatment. In order to both better understand the mechanisms behind tDCS and possibly improve the technique, finite element models are used to simulate tDCS of the human brain. With the detailed anisotropic head model presented in this study, we provide accurate predictions of tDCS in the human brain for six of the practically most-used setups in clinical and cognitive research, targeting the primary motor cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, occipital cortex, and cerebellum. We present the resulting electric field strengths in the complete brain and introduce new methods to evaluate the effectivity in the target area specifically, where we have analyzed both the strength and direction of the field. For all cerebral targets studied, the currently accepted configurations produced sub-optimal field strengths. The configuration for cerebellum stimulation produced relatively high field strengths in its target area, but it needs higher input currents than cerebral stimulation does. This study suggests that improvements in the effects of transcranial direct current stimulation are achievable.

The coil orientation dependency of the electric field induced by TMS for M1 and other brain areas

BackgroundThe effectiveness of transcranial magnetic stimulation (TMS) depends highly on the coil orientation relative to the subject’s head. This implies that the direction of the induced electric field has a large effect on the efficiency of TMS. To improve future protocols, knowledge about the relationship between the coil orientation and the direction of the induced electric field on the one hand, and the head and brain anatomy on the other hand, seems crucial. Therefore, the induced electric field in the cortex as a function of the coil orientation has been examined in this study.MethodsThe effect of changing the coil orientation on the induced electric field was evaluated for fourteen cortical targets. We used a finite element model to calculate the induced electric fields for thirty-six coil orientations (10 degrees resolution) per target location. The effects on the electric field due to coil rotation, in combination with target site anatomy, have been quantified.ResultsThe results confirm that the electric field perpendicular to the anterior sulcal wall of the central sulcus is highly susceptible to coil orientation changes and has to be maximized for an optimal stimulation effect of the motor cortex. In order to obtain maximum stimulation effect in areas other than the motor cortex, the electric field perpendicular to the cortical surface in those areas has to be maximized as well. Small orientation changes (10 degrees) do not alter the induced electric field drastically.ConclusionsThe results suggest that for all cortical targets, maximizing the strength of the electric field perpendicular to the targeted cortical surface area (and inward directed) optimizes the effect of TMS. Orienting the TMS coil based on anatomical information (anatomical magnetic resonance imaging data) about the targeted brain area can improve future results. The standard coil orientations, used in cognitive and clinical neuroscience, induce (near) optimal electric fields in the subject-specific head model in most cases.

The effect of local anatomy on the electric field induced by TMS: evaluation at 14 different target sites

Many human cortical regions are targeted with transcranial magnetic stimulation (TMS). The stimulus intensity used for a certain region is generally based on the motor threshold stimulation intensity determined over the motor cortex (M1). However, it is well known that differences exist in coil-target distance and target site anatomy between cortical regions. These differences may well make the stimulation intensity derived from M1 sub-optimal for other regions. Our goal was to determine in what way the induced electric fields differ between cortical target regions. We used finite element method modeling to calculate the induced electric field for multiple target sites in a realistic head model. The effects on the electric field due to coil-target distance and target site anatomy have been quantified. The results show that a correction based on the distance alone does not correctly adjust the induced electric field for regions other than M1. In addition, a correction based solely on the TMS-induced electric field (primary field) does not suffice. A precise adjustment should include coil-target distance, the secondary field caused by charge accumulation at conductivity discontinuities and the direction of the field relative to the local cerebrospinal fluid–grey matter boundary.

Cerebellar theta burst stimulation does not improve freezing of gait in patients with Parkinson’s disease

Freezing of gait (FOG) in Parkinson’s disease (PD) likely results from dysfunction within a complex neural gait circuitry involving multiple brain regions. Herein, cerebellar activity is increased in patients compared to healthy subjects. This cerebellar involvement has been proposed to be compensatory. We hypothesized that patients with FOG would have a reduced ability to recruit the cerebellum to compensate for dysfunction in other brain areas. In this study cerebellar activity was modified unilaterally by either excitatory or inhibitory theta burst stimulation (TBS), applied during two separate sessions. The ipsilateral cerebellar hemisphere, corresponding to the body side most affected by PD, was stimulated. Seventeen patients with PD showing ‘off’ state FOG participated. The presence of FOG was verified objectively upon inclusion. We monitored gait and bimanual rhythmic upper limb movements before and directly after TBS. Gait was evaluated with a FOG-provoking protocol, including rapid 360° turns and a 10-m walking test with small fast steps. Upper limb movement performance was evaluated with a repetitive finger flexion–extension task. TBS did not affect the amount of freezing during walking or finger tapping. However, TBS did increase gait speed when walking with small steps, and decreased gait speed when walking as fast as possible with a normal step size. The changes in gait speed were not accompanied by changes in corticospinal excitability of M1. Unilateral cerebellar TBS did not improve FOG. However, changes in gait speed were found which suggests a role of the cerebellum in PD.

Assessment of the equivalent dipole layer source model in the reconstruction of cardiac activation times on the basis of BSPMs produced by an anisotropic model of the heart

Promising results have been reported in noninvasive estimation of cardiac activation times (AT) using the equivalent dipole layer (EDL) source model in combination with the boundary element method (BEM). However, the assumption of equal anisotropy ratios in the heart that underlies the EDL model does not reflect reality. In the present study, we quantify the errors of the nonlinear AT imaging based on the EDL approximation. Nine different excitation patterns (sinus rhythm and eight ectopic beats) were simulated with the monodomain model. Based on the bidomain theory, the body surface potential maps (BSPMs) were calculated for a realistic finite element volume conductor with an anisotropic heart model. For the forward calculations, three cases of bidomain conductivity tensors in the heart were considered: isotropic, equal, and unequal anisotropy ratios in the intra- and extracellular spaces. In all inverse reconstructions, the EDL model with BEM was employed: AT were estimated by solving the nonlinear optimization problem with the initial guess provided by the fastest route algorithm. Expectedly, the case of unequal anisotropy ratios resulted in larger localization errors for almost all considered activation patterns. For the sinus rhythm, all sites of early activation were correctly estimated with an optimal regularization parameter being used. For the ectopic beats, all but one foci were correctly classified to have either endo- or epicardial origin with an average localization error of 20.4 mm for unequal anisotropy ratio. The obtained results confirm validation studies and suggest that cardiac anisotropy might be neglected in clinical applications of the considered EDL-based inverse procedure.

Visual cueing using laser shoes reduces freezing of gait in Parkinson's patients at home: Laser Shoes For Freezing at Home

Freezing of gait (FOG) in Parkinson’s disease (PD) is common and debilitating. Although the evidence for cueing efficacy is encouraging, it remains difficult to translate cueing strategies into an efficient visual cueing device for use in patients’ home environments, allowing them to benefit from a safer gait in everyday life and prevent falls and related injuries. Laser shoes might offer such a home-based cueing device, and a recent laboratory study showed reduced FOG severity. Here we assess the effectiveness of laser shoes at home in a pilot study. A total of 21 PD patients with severe FOG completed 3 consecutive conditions: week 1 = wearing laser shoes, but without cueing (“without cueing”); week 2 = wearing laser shoes, with cueing (“with cueing”); week 3 = without laser shoes (“follow-up”). Outcomes were assessed at the end of each week. The primary outcome was FOG severity (New FOG Questionnaire [NFOGQ]). The relation with cognitive status was explored by correlating the NFOGQ results with the Frontal Assessment Battery. Exploratory secondary outcomes included quality of life (Parkinson’s Disease Questionnaire-39), self-reported falls and near falls, number of self-reported FOG episodes, and perceived efficacy. An activity monitor objectively measured relative locomotion duration. FOG severity improved significantly (NFOGQ: 20.35 ± 5.00 without cueing vs 18.12 ± 5.44 with cueing, P = .036; Fig. 1A). There was no correlation with the Frontal Assessment Battery. Furthermore, the NFOGQ did not differ between with cueing and follow-up (P = .235), perhaps suggesting a possible carryover, although the difference between without cueing and followup was nonsignificant (P = .156). Secondary outcomes show a reduction of self-reported falls (41%), near falls (58%; Fig. 1B), and FOG episodes (31%) with cueing. The reduction in near falls continued during the follow-up week. Although the overall number of falls decreased with cueing, the number of individuals who fell actually increased, from 3 at baseline to 5 with cueing, and similarly in the follow-up week. These results were paralleled by positive subjective experiences on the efficacy of laser shoes. The Parkinson’s Disease Questionnaire-39 and relative locomotion duration did not differ across conditions. The findings from this pilot study, although preliminary, suggest that laser shoes have potential as a mobile visual cueing device to reduce FOG and risk of falls in PD patients within their home situations and that improvements may last beyond their punctual use. Using laser shoes for 1 week perhaps boosted the participants’ confidence, but the carry-over might also represent a training effect. However, a significant difference between without cueing and follow-up is missing, hence we cannot make any firm statements about the possible existence of carry-over effects. The reduction in FOG severity did not lead to an increase in net locomotion time, perhaps because physical performance and physical activity represent associated but separate domains of physical function. It is also possible that longer lasting use of laser shoes is needed to change the a patient’s walking habits, and future studies should evaluate this. Finally, laser shoes induced falls in some individuals, possibly because the patients gained too much confidence or were too distracted and ended up falling. We acknowledge that placebo effects might partially explain the effects seen in the present open-label study, and further work should include passive or active control interventions. Moreover, new studies should investigate the added value of laser shoes relative to other cueing techniques. Finally, longer training periods and prolonged follow-ups are needed to better document the long-term efficacy and to further study possible learning and retention effects.

P 32. A comparison of TMS induced electric fields over multiple cortical areas using the finite element method

Introduction Transcranial magnetic stimulation (TMS) has proven to be a powerful non-invasive technique in the field of neuroscience and in clinical studies. The first applications were developed for stimulation of the motor cortex (M1), but nowadays many cortical areas have been studied with TMS. Although this widespread usage over all possible cortical areas, most of the protocols are still based on the standards developed for M1. In the specific case of M1 stimulation a motor evoked potential (MEP) can be measured with the use of electromyography (EMG). The minimal intensity needed to evoke such an MEP is called the motor threshold (MT) and it varies between individuals. This threshold is used to adapt the stimulation intensity in single pulse, paired pulse or repetitive stimulation protocols per individual. Because most of the cortical areas outside M1 do not have a similar outcome measure like the MEP, the MT found over M1 is commonly used. There are, however, next to intra-individual differences also inter-individual differences in anatomy and physiology between cortical areas. These differences are for example the distance to the cortex, the thickness of the several tissue layers or the local cortical folding. Therefore, the intensity found over M1 can be sub-optimal for the cortical areas outside M1. By including the inter-individual differences between M1 and other cortical areas for the determination of the stimulation intensity, the induced TMS effects could possibly be optimized. However, before TMS protocols can be adapted, a verification of these inter-individual differences is advisable. A way to perform this verification is by TMS simulations. Objectives Compare the TMS induced electric field for multiple cortical areas with the induced electric field found for M1 stimulation. Materials and methods To simulate the TMS induced electric field a bioelectric problem has to be solved for a volume that represents a human head. We constructed a highly realistic head model based on Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. This model includes 8 tissue types and brain anisotropy. To solve the bioelectric problem the finite element method (FEM) was used. The electric field was calculated for multiple cortical locations, including cerebellum and frontal areas. The locations were based on experimental studies. The strength of these induced fields were then compared with the strength of the field over M1. Results The results show that the magnitude of the induced electric field differs largely between cortical locations, as expected ( Fig. 1 ). The distance between the cortical location and the coil has the most prominent effect on the electric field magnitude, but also the local anatomy and conductivity has an influence that cannot be ignored. Especially, the cerebellar locations ( Fig. 1 B) and the locations along the sagittal midline ( Fig. 1 C) display a field strength that is influenced by the surrounding tissue distribution. Conclusion The results indicate that an increase in intensity for cortical areas more distant from the coil is needed to induce a similar electric field magnitude as for M1. However, a correction in stimulation intensity solely based on the distance between the TMS coil and the cortex will probably not suffice. However, at this moment in time the optimal stimulation intensity per individual for locations outside M1 can only be determined with TMS simulations.

PTMS56 Volume conductor modeling of the effects of transcranial magnetic stimulation

the frontal lobe and Rolandic region. We applied interstimulus intervals of 4 and 7 ms. The whole experiment was conducted at rest and during visually-guided manipulation of an object. Results: The PMv spots that exerted a short-latency effect on M1 were distributed mainly along the precentral sulcus. At rest the effects of PMv stimulation were mainly inhibitory. During manipulation we observed clear inversion of the effect, with M1 facilitation in some spots. The location of facilitatory spots varied greatly between subjects, from a dorsal position bordering with the inferior frontal sulcus to more ventral positions. Conclusion: These results show that within the lateral portion of the frontal lobe only a portion of cortex actually communicates with shortlatency connections with M1. Within this region the functional aspects are consistent and predictable between subjects (i.e. inhibitory connections turning facilitatory during active tasks) however its topographical organization seems highly variable between individuals.

P19.8 Determining the optimal electrode configuration for transcranial direct current stimulation: a model study

Introduction: The effects of Direct Current Stimulation (DCS) delivered in man with surface electrodes on basic bio-electrical parameters (membrane excitability, synaptic transmission) are largely unknown. Objectives: Myasthenia Gravis provides a unique opportunity as a “magnifying glass” to see the effects of membrane polarization on synaptic function since the degree of M response decrement during repetitive 3 Hz stimulation reflects a fraction of functionally instable neuromuscular junctions. Methods: Experiments have been carried out on anconeus muscle of 10 myastenic patients showing, in basal conditions, a clear cut M response decrement (30 40 %) on repetitive stimulation (8 stim, 3 Hz) on both sides. Anodal DCS (1 mA in 6 subjects and 2 mA in the other 4 subjects, 10 min) was delivered by means of saline-soaked sponge patches (6×8 cm) entirely covering the muscle. The same procedure was repeated on the opposite side by delivering anodal DCS. Repetitive trains were delivered at 2 minute intervals before (6 min), during (10 min) and after (10 min) DCS. Results: No significant change in M response decrement was observed in any subjects during and after application of both anodal and cathodal DCS with both current intensities. Conclusions: Within the limits of the technical settings and of the dosage and duration of DCS employed in our study, DCS does not seem to exert significant effects on neuromuscular synapses in man