DE102021106334A1 - Method and system for generating and applying stimulation configurations on humans and associated computer program - Google Patents

Abstract

The present invention relates to a method and a system for generating and applying stimulation configurations to humans, in particular to the human head, for multi-channel transcranial electrical stimulation (tES), transcranial magnetic field stimulation (tMS) or transcranial focused ultrasound stimulation (tFUS) and an associated computer program, with which an optimal distribution of the stimulation current can be determined in order to address dedicated target areas in the brain. According to the invention, the optimal intensity distribution for the multi-channel tES, tMS or tFUS is calculated with a spatially harmonic analysis of the field topographies and an applicator configuration is determined.

Description

The present invention relates to a method and a system for generating and applying stimulation configurations to humans, in particular to the human head, for multi-channel transcranial electrical stimulation (tES), transcranial magnetic field stimulation (tMS) or transcranial focused ultrasound stimulation (tFUS) and an associated computer program.

Electrical stimulation (ES) (Kempe et al., 2015), magnetic stimulation (MS) (Rad et al., 2019) or ultrasonic stimulation (US) (Bouakaz & Beizung, 2020) in humans is used in the eye to improve visual performance ( Tano et al., 2007) and on the muscle in physiotherapeutic therapy approaches (Wollenzien et al., 2013).

As a non-invasive transcranial stimulation of target areas in the brain, ES (Shakour et al., 2017) is of interest for the therapy of depression and neurorehabilitation after stroke (Arle & Shils, 2013), for which controlled stimulation paradigms must be observed (Priori et al ., 2009). Traditional transcranial ES (tES) uses two electrodes that are attached to the scalp manually (Bikson et al., 2012) or using holding devices (Mansson & Rehn, 2020).

Recent, multi-channel tES approaches suggest cap-based electrode attachment (Bikson et al., 2011). Multi-channel stimulation configurations have the advantage that target areas can be addressed more specifically (Berenyi & Buzsaki, 2018; Ge et al., 2012).

Conventional tES applications are based on rubber electrodes inserted into saline-soaked sponge pockets and attached to the head with rubber bands to ensure low impedance of the electrode-skin junction (Antal et al., 2007). This complicated and time-consuming procedure requires specially trained personnel and is prone to error in the positioning and application of electrodes, which can lead to a lack of reproducibility in repeated applications, group and multi-center studies (Padberg et al., 2017). Furthermore, the attachment of the flat electrodes with rubber bands limits the number of available electrodes and the positions that can be approached (Klein et al., 2013).

In addition, the problem of ensuring a reproducible stimulation dosage arises with repeated applications of the tES (Peterchev et al., 2012). In repeated applications, studies with several participants and across several centers, the electrode attachment and positioning must be reproducible on the one hand and dedicated stimulation of a target area with predefined intensity and orientation and simultaneous protection of non-target areas as well as individualized electrode configurations and distributions of the stimulation currents on the other the available electrodes are ensured. The optimization of the distribution of stimulation currents via electrodes for addressing target areas in the brain represents an ill-posed problem, since the number of possible target areas in the brain clearly exceeds the number of electrodes available.

Methods are known from the prior art with which the intensity distributions of stimulation currents for predefined electrode configurations can be calculated. However, the stimulation configurations generated using these methods have a number of weaknesses, as they provide Pareto-optimal solutions in terms of intensity, direction and focus in the target area (Dmochowski et al., 2011; Sadleir et al., 2012; Wagner et al., 2016 ) represent. The electrode configurations used are based on small electrodes with diameters of up to 2 cm (Minhas et al., 2010), electrode arrays (Park et al., 2011) or surface electrodes (Sadleir et al., 2012) at predefined positions (Klem et al ., 1999). These systems can cause current density problems at the scalp, raising safety concerns. In addition, the electrode configurations, designed as pre-assembled semi-rigid or rigid caps, limit individual fits.

To overcome these limitations, Hunold et al. (2020) proposed a system of flexible caps with integrated textile electrodes based on light and flexible fabric and silver-coated fibers.

Approaches for current distribution and stimulation electrodes based on EEG recordings (Cancelli et al., 2016) and reciprocity (Fernandez-Corazza et al., 2016) have already been presented. However, these approaches only take into account the current electrode configuration and the currently measured field topography, without providing information about the stimulation achieved in the target area.

The object of the present invention is to overcome the disadvantages known from the prior art and to provide a method and a system for generating and applying stimulation configurations to humans, in particular to the human head, for a multi-channel transcranial elec rostimulation (tES), transcranial magnetic field stimulation (tMS) or transcranial focused ultrasound stimulation (tFUS) as well as an associated computer program, with which it is possible to optimally distribute current intensities to stimulation electrodes, so that a dedicated stimulation intensity and orientation is achieved in the target area, with individualized Electrode configurations based on textile electrodes in flexible caps are used.

The subtasks are, on the one hand, to carry out a spatial analysis of the forward-calculated potential distribution for a dedicated target configuration and, on the other hand, the classified potential distribution in current intensities must be transmitted to the stimulation electrodes.

According to the invention, this object is achieved with the features of the first, seventh and ninth patent claims. Advantageous refinements of the method according to the invention can be found in dependent claims 2 to 7, while a preferred embodiment of the system according to the invention is specified in dependent claim 8.

With the present invention it is proposed to use a spatially harmonic analysis of the field topographies to calculate an optimal current distribution for a multi-channel tES, tMS or tFUS and to determine the electrode configuration from this.

In 1 the individual process steps are shown schematically. According to this, volume conductor models (here an example of the human head) are created based on individual magnetic resonance imaging (MRI) data. From this, binary masks are generated from identifiable tissue classes such as white and gray matter, cerebrospinal fluid, skull and scalp (Bikson et al., 2010). These voxel-based binary masks of the segmented tissue classes are additively combined into an overall model. Based on the dimension of the voxel, a finite element (FE) model is created by meshing the hexahedron elements while preserving the resolution (Berti, 2004). Each FE is assigned a conductivity value according to tissue class affiliation based on literature references. This provides an individual volume conductor model for use in forward simulations.

Subsequently, target areas are modeled using a method that maps neuronal centers based on their localization and spatial orientation based on anatomical or functional properties. The layered and parallel aligned pyramidal cells of a functional unit are modeled as a current dipole. Positions according to functional localizations based on electroencephalography (EEG) or magnetoencephalography (MEG) data, or according to areas in anatomical atlases such as the Destrieux atlas (Destrieux et al., 2010) serve as reference points for the dipole models, with anatomical areas being based on surface representations of the gray or white mass are defined. The orientation of the dipole models represents the orientation of the localized activity from EEG or MEG data and is carried out according to the spatial directions of the model or according to the orientation of the anatomical area tangential or normal to the local surface. Forward simulation of source activation in the volume conductor model produces a scalar electric potential field topography on the surface of the volume conductor on which the applicators are defined.

Furthermore, the Euclidean centers of each applicator of a given setup are calculated and used to derive a triangulated network representation of the given applicator positions. The basis functions (sC) of the generalized spatial Fourier analysis SPHARA (Graichen et al., 2016) were calculated for the resulting triangular network.

in die die Koeffizienten der zweiten sC_d,2 und dritten SC_d,3 SPHARA-Komponenten einfließen. Hiervon ausgehend erzeugt eine ideal dipolare Verteilung einen Radius r_d= 1.With the present invention, a method is presented which evaluates the scalar electrical potential from the forward simulation for the activation of a target area, represented by a dipole model, at the support points of the triangular network for the present applicator positions. Based on the SPHARA decomposition of the scalar electrical potential distribution, which was simulated for the dipole model d for the current target area, a classification into predominantly dipolar or monopolar distributions is made. The classification is carried out using a Euclidean metric, $${\mathrm{right}}_{\mathrm{i.e}}=\sqrt{s{C}_{\mathrm{i.e}\mathrm{,2}}{}^2+s{C}_{\mathrm{i.e}\mathrm{,3}}{}^2},$$

into which the coefficients of the second sC _d,2 and third SC _d,3 SPHARA components flow. Based on this, an ideal dipolar distribution produces a radius r _d = 1.

r _d = 0.8 is suggested as the classification limit between predominantly dipolar and monopolar potential distributions, so that a deviation of 20% from the ideal radius is permitted.

$$u_n=\frac{u_{i,n}}{{\displaystyle \sum {}_n{u}_{i,n}}}$$

(3), wobei p für Elektroden mit positivem und n für Elektroden mit negativem elektrischen Potentialwert u stehen.In the case of a predominantly dipolar electrical potential distribution, the electrical potential at each electrode i is standardized according to equations (2) and (3) depending on the sign: $${\mathrm{and}}_p=\frac{{\mathrm{and}}_{i,p}}{{\displaystyle \sum {}_p{\mathrm{and}}_{i,p}}}$$

$${\mathrm{and}}_n=\frac{{\mathrm{and}}_{i,n}}{{\displaystyle \sum {}_n{\mathrm{and}}_{i,n}}}$$

(3), where p stands for electrodes with a positive and n for electrodes with a negative electric potential value u.

In the case of a predominantly monopolar electrical potential distribution, as specified in equation (4), an electrical reference potential u _ref is determined as the maximum absolute electrical potential, integrated over a signed subset of the electrodes: $${\mathrm{and}}_{\mathrm{right}ef}=\text{Max}\left({\displaystyle \sum {}_p{\mathrm{and}}_{i,p}|\left|{\displaystyle \sum {}_n{\mathrm{and}}_{i,n}}\right|}\right)$$

The electric potential at each electrode i was normalized with respect to u _ref as given in equation (5): $$n_i=\frac{{\mathrm{and}}_i}{{\mathrm{and}}_{\mathrm{right}ef}}$$

The electrode with the maximum absolute normalized electrical potential serves as the feed-in electrode src according to equation (6): $$s\mathrm{right}c=\text{Max}\left(\left[\left|n\right|\right]\right)$$

The remaining electrodes according to equation (7) were used to determine the current sink configuration es: $$cs=\left[\left|\text{n}\right|\right]\backslash s\mathrm{right}c$$

According to a further aspect of the invention, the electrodes are used with a current intensity corresponding to the normalized electric potential value and according to the Helmholtz reciprocity (Helmholtz, 1853) with the opposite sign, as a current source and current sink of the form that all available electrodes or a subset of the available ones Electrodes are used for current stimulation.

The present invention differs from previously known methods in that a spatial approach is pursued here that can be generalized to individual electrode configurations and can take into account predefined target areas, so that physiologically effective stimulation intensities can be ensured in the target area.

The forward simulations take into account the dedicated alignment of the target configurations. The spatial analysis receives this directional information and it is transferred to the stimulation configuration. The present invention thus implements a method that intrinsically takes into account the orientation of the target configuration.

The stimulation intensity in the target area can be adjusted via a scaling factor when transferring the normalized electrical potential values into current intensities. The present method thus allows individual adjustments for subthreshold and suprathreshold stimulations.

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QUOTES INCLUDED IN DESCRIPTION

This list of documents cited by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Patent Literature Cited

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Claims (9)

Method for generating and applying stimulation configurations for multi-channel transcranial electrical stimulation (tES), transcranial magnetic field stimulation (tMS) or transcranial focused ultrasound stimulation (tFUS), with the stimulation signals with corresponding intensities starting from a multi-channel generator (G) being applied to a large number of applicators (A ) on humans, in particular on the human head, are divided, characterized in that the field topography emanating from a target area is classified based on a spatially harmonic decomposition and converted into a distribution of the stimulation intensity. procedure after claim 1 comprising the following steps: • acquisition of geometry data of the applicator setup, • triangulation between the applicator positions, • calculation of spatially harmonic basis functions, • calculation of the field topography for the target area, • discretization of the field topography at the applicator positions, • classification of the field topography based on contributions from spatially harmonic operators and • translation of the field topography into stimulation intensities at the applicator positions. Method according to one of the preceding claims, characterized in that the target area is approximated by a model for generating the field topography. Method according to one of the preceding claims, characterized in that the field topography for the target area is calculated using a volume conductor model. Method according to one of the preceding claims, characterized in that defined spatial frequencies are used to classify the field topography. Stimulation configurations based on a system of applicator positions, characterized in that intensities are generated for all available or for a subset of the available applicators of electrical, magnetic field or ultrasonic stimulation. System for generating and applying stimulation configurations for multi-channel transcranial electrical stimulation (tES), transcranial magnetic field stimulation (tMS) and/or transcranial focused ultrasound stimulation (tFUS), the system having a multi-channel generator (G) and a number of applicators (A), which are configured to couple the stimulation signals from the generator (G) into the human being, the stimulation signals being signals of constant amplitude, alternating signals with exactly one temporal frequency, alternating signals with several temporal components and pulses or pulse sequences. System according to one of the preceding claims, characterized in that the number of applicators is variable and can be optimized. Computer program with program code for performing the following steps when the computer program is run on a computer: generating intensity distributions on the applicators (A) and outputting stimulation signals for each applicator (A) to the generator (G), the stimulation signals being can be signals of constant amplitude, alternating signals with exactly one temporal frequency or alternating signals with several temporal components.

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