neuronavigated-focalized-transcranial-direct-current-stimulation

Neuronavigated Focalized Transcranial Direct Current Stimulation Administered During Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that allows the modulation of the excitability and plasticity ...

Technische Universität Ilmenau

Physical head phantoms allow the assessment of source reconstruction procedures in electroencephalography and electrical stimulation profiles during transcranial electric stimulation. Volume conduction in the head is strongly influenced by the skull, which represents the main conductivity barrier. Realistic modeling of its characteristics is thus important for phantom development. In the present study, we proposed plastic clay as a material for modeling the skull in phantoms. We analyzed five clay types varying in granularity and fractions of fire clay, each with firing temperatures from 550°C to 950°C. We investigated the conductivity of standardized clay samples when immersed in a 0.9% sodium chloride solution with time-resolved four-point impedance measurements. To test the reusability of the clay model, these measurements were repeated after cleaning the samples by rinsing in deionized water for 5 h. We found time-dependent impedance changes for approximately 5 min after immersion in the solution. Thereafter, the conductivities stabilized between 0.0716 S/m and 0.0224 S/m depending on clay type and firing temperatures. The reproducibility of the measurement results proved the effectiveness of the rinsing procedure. Clay provides formability, is permeable to ions, can be adjusted in conductivity value and is thus suitable for the skull modeling in phantoms.

Head phantoms for electroencephalography and transcranial electric stimulation: a skull material study.

Neuromodulation induced by transcranial electric stimulation (TES) exhibited promising potential for clinical practice. However, the underlying mechanisms remain subject of research. The combination of TES and electroencephalography (EEG) offers great potential for investigating these mechanisms and brain function in general, especially when performed simultaneously. In conventional applications, the combination of EEG and TES suffers from limitations on the electrode level (gel for electrode-skin interface) and the usability level (preparation time, reproducibility of positioning). To overcome these limitations, we designed a bifunctional cap for simultaneous TES-EEG applications. We used novel electrode materials, namely textile stimulation electrodes and dry EEG electrodes integrated in a flexible textile cap. We verified the functionality of this cap by analysing the effect of TES on visual evoked potentials (VEPs). In accordance with previous reports using standard TES, the amplitude of the N75 component was significantly decreased post-stimulation, indicating the feasibility of using this novel flexible cap for simultaneous TES and EEG. Further, we found a significant reduction of the P100 component only during TES, indicating a different brain modulation effect during and after TES. In conclusion, the novel bifunctional cap offers a novel tool for simultaneous TES-EEG applications in clinical research, therapy monitoring and closed-loop stimulation.

Novel bifunctional cap for simultaneous electroencephalography and transcranial electrical stimulation.

Recent studies indicate therapeutic benefits of electrical stimulation in cases of specific ophthalmic diseases that are associated with dysfunctional ocular microcirculation. This suggests effects of electrical stimulation on vascular functions. In the present study, we investigated the effects of electrical stimulation on retinal vessel reactions using dynamic vessel analysis (DVA). Eighty healthy subjects were randomly assigned to one of three groups receiving electrical stimulation with different current intensities: 400 μA ( = 26); 800 μA ( = 27); 1200 μA ( = 27). The electrode montage for electrical stimulation consisted of a ring-shaped active electrode surrounding one eye and a square return electrode at the occiput. Rectangular, monophasic, positive current pulses were applied at 10 Hz for a duration of 60 s per stimulation period. DVA was used to observe the stimulation-induced reactions of retinal vessel diameters in response to different provocations. In three DVA measurements, three stimulus conditions were investigated: flicker light stimulation (FLS); electrical stimulation (ES); simultaneous electrical and flicker light stimulation (ES+FLS). Retinal vasodilation caused by these stimuli was compared using paired -test. The subjects receiving electrical stimulation with 800 μA showed significantly increased retinal vasodilation for ES+FLS compared to FLS ( < 0.05). No significant differences in retinal vessel reactions were found between ES+FLS and FLS in the 400 and 1200 μA groups. No retinal vasodilation was observed for ES for all investigated current intensities. The results indicate that positive pulsed electrical stimulation of an adequate intensity enhances the flicker light-induced retinal vasodilation.

Pulsed Electrical Stimulation of the Human Eye Enhances Retinal Vessel Reaction to Flickering Light.

The visual system has one of the most complex structures of all sensory systems and is perhaps the most important sense for everyday life. Its functional organization was extensively studied for decades in animal and humans, for example by correlating circumscribed anatomical lesions in patients with the resulting visual dysfunction. During the past two decades, significant achievements were accomplished in characterizing and modulating visual information processing using non-invasive stimulation techniques of the normal and damaged human eye and brain. Techniques include transcranial magnetic stimulation (TMS) and low intensity electric stimulation using either direct or alternating currents applied transcranially (tDCS or tACS) near or above the visual cortex, or alternating currents applied transorbitally (trACS). In the case of transorbital stimulation of the visual system the electrodes are attached near the eye, to the eyelids (transpalpebral electrical stimulation - TPES) or the cornea (tanscorneal electrical stimulation TcES). Here, we summarize the state-of-the-art of visual system magnetic and electric stimulation as a method to modulate normal vision, induce brain plasticity, and to restore visual functions in patients. We review this field's history, models of current flow paths in the eye and brain, neurophysiological principles (e.g. entrainment and after-effects), the effects on vision in normal subjects and the clinical impact on plasticity and vision restoration in patients with low vision, with a particular focus on "off-line" or "after-effects". With regard to the therapeutic possibilities, ACS was demonstrated to be effective in patients affected by glaucoma and optic neuropathy, while tDCS and random noise stimulation (tRNS) are most promising for the treatment of amblyopia, hemianopia and myopia. In addition, rTMS applied above the occipital area is a promising approach to treat migraine, neglect and hemianopia. Although the response to these treatment options is better than to sham stimulation in double blinded clinical studies, the clinical efficacy is still rather variable and a proportion of patients do not respond. It is therefore imperative to better understand the mechanisms of action to be able to optimize treatment protocols possibly through personalization of brain stimulation protocols. By identifying the current opportunities and challenges in the field, we hope to provide insights to help improve neuromodulation protocols to restore visual function in patients with visual system damage.

Vision modulation, plasticity and restoration using non-invasive brain stimulation - An IFCN-sponsored review.

[This corrects the article DOI: 10.3389/fnhum.2019.00371.].

Corrigendum: Pulsed Electrical Stimulation of the Human Eye Enhances Retinal Vessel Reaction to Flickering Light.

Advances in transcranial electrical stimulation (tES) are hampered by the conventional rubber electrodes manually attached to the head with rubber bands. This procedure limits montages to a few electrodes, is error prone with respect to electrode configurations and is burdensome for participants and operators. A newly developed flexible cap with integrated textile stimulation electrodes was compared to the conventional setup of rubber electrodes inserted into sponges fixated by rubber bands, with respect to usability and reliability. Two operators applied both setups to 20 healthy volunteers participating in the study. Electrode position and impedance measures as well as subjective evaluations from participants and operators were obtained throughout the stimulation sessions.

Novel flexible cap for application of transcranial electrical stimulation: a usability study.

Studies on transcranial current stimulation have shown that a direct current stimulation of the occipital cortex can influence the amplitude size of a visual evoked potential (VEP). The current direction (cathodal or anodal) determines whether the VEP amplitudes increase or decrease. The aim of this study was to design a new experimental setup that will enable a simultaneous ocular direct current stimulation and electroretinogram (ERG) recording which will broaden our understanding of current stimulation effects on the visual system. Furthermore, we examined whether a direct current stimulation on the eye has a similar effect on an ERG as on a VEP. The pattern-reversal ERG was measured with sintered Ag/AgCl skin-electrodes, positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). Direct current was applied through a ring rubber electrode placed around the eye and a 5 cm × 5 cm rubber electrode placed at the ipsilateral temple with a current strength of 500 μA and a duration time of 5 min. Fifty-seven healthy volunteers were divided into three groups depending on the current direction (cathodal, anodal, and sham stimulation,  = 19 each). One ERG measurement (ERG 1) was performed before and another (ERG 2) during the direct current stimulation. The difference between ERG 1 and ERG 2 measurements for the characteristic P50, N95 and N95' (N95 minimum measured from zero line) amplitudes were evaluated by both confidence interval analysis and -test for related samples (α = 0.05, after Bonferroni correction   = 0.0055). The P50 amplitude was significantly decreased for ERG 2 measurement in the cathodal and anodal stimulation group (cathodal  = 0.001, anodal  = 0.000). No significant changes could be found in the N95 and N95' amplitudes as well as in the sham-stimulation group. Additionally, the latencies did not undergo any significant changes. In conclusion, the newly designed experimental setup enables simultaneous current stimulation and ERG recording. The current influenced P50 amplitude although not the N95 and N95' amplitudes. Furthermore, the amplitude size decreased for both current directions and did not lead to contrary effects as expected.

The Effects of an Ocular Direct Electrical Stimulation on Pattern-Reversal Electroretinogram.

Assessments of source reconstruction procedures in electroencephalography and computations of transcranial electrical stimulation profiles require verification and validation with the help of ground truth configurations as implemented by physical head phantoms. For these phantoms, synthetic materials are needed, which are mechanically and electrochemically stable and possess conductivity values similar to the modeled human head tissues. Three-compartment head models comprise a scalp layer with a conductivity range of 0.137 S/m to 2.1 S/m, a skull layer with conductivity values between 0.066 S/m and 0.00275 S/m, and an intracranial volume with an often-used average conductivity value of 0.33 S/m. To establish a realistically shaped physical head phantom with a well-defined volume conduction configuration, we here characterize the electrical conductivity of synthetic materials for modeling head compartments. We analyzed agarose hydrogel, gypsum, and sodium chloride (NaCl) solution as surrogate materials for scalp, skull, and intracranial volume. We measured the impedance of all materials when immersed in NaCl solution using a four-electrode setup. The measured impedance values were used to calculate the electrical conductivity values of each material. Further, the conductivities in the longitudinal and transverse directions of reed sticks immersed in NaCl solution were measured to test their suitability for mimicking the anisotropic conductivity of white matter tracts.

Head phantoms for bioelectromagnetic applications: a material study.

Studies on weak current stimulation (1-2 mA) examine effects on neuronal cells for the treatment of neurological diseases, like depression. Ocular current stimulation showed positive effects on retinal nerve cells which indicate that neurodegenerative ocular diseases, e.g., glaucoma, can be treated with current stimulation of the eye. However, up to now it remains unclear which exact retinal cells can be influenced. During an ocular direct current stimulation, a significant reduction of the characteristic P50 amplitude of a pattern-reversal electroretinogram (PERG) was found for an anodal and a cathodal stimulation. This current stimulation effect could originate from the modulation of pre-ganglion cell activity or by changes in local ON and OFF responses of ganglion cells. For clarification, we investigate acute direct current stimulation effects on a full field electroretinogram (ERG), which represents the activity of pre-ganglion cells (specifically cones and bipolar cells). The ERG from 15 subjects was evaluated before (ERG 1) and during (ERG 2) an ocular direct current stimulation with 800 μA over 5 min. The current was applied through a ring rubber electrode placed around the eye and a 25 cm rubber electrode placed at the ipsilateral temple. For ERG measurements, sintered Ag/AgCl skin-electrodes were positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). The volunteers were stimulated in three independent sessions, each with a different current application (randomized order): cathodal polarity, anodal polarity (referred to the electrode around the eye), or sham stimulation. The changes between the two ERG measurements of the characteristic full field ERG amplitudes, a-wave, b-wave, and b'-wave (b-wave measured from zero line) were tested with the Wilcoxon signed-rank test (α = 0.05). Comparing before to during the current stimulation for all applications, the ERG waves showed no effects on amplitudes or latencies. Furthermore, no significant difference between the cathodal, anodal, and sham stimulation could be found by a Friedman test. These results indicate an unlikely contribution of pre-ganglion cells to the previously reported stimulation effect on PERG signals.

Effects of Ocular Direct Current Stimulation on Full Field Electroretinogram.

Most magneto- and electroencephalography (M/EEG) based source estimation techniques derive their estimates sample wise, independently across time. However, neuronal assemblies are intricately interconnected, constraining the temporal evolution of neural activity that is detected by MEG and EEG; the observed neural currents must thus be highly context dependent. Here, we use a network of Long Short-Term Memory (LSTM) cells where the input is a sequence of past source estimates and the output is a prediction of the following estimate. This prediction is then used to correct the estimate. In this study, we applied this technique on noise-normalized minimum norm estimates (MNE). Because the correction is found by using past activity (context), we call this implementation Contextual MNE (CMNE), although this technique can be used in conjunction with any source estimation method. We test CMNE on simulated epileptiform activity and recorded auditory steady state response (ASSR) data, showing that the CMNE estimates exhibit a higher degree of spatial fidelity than the unfiltered estimates in the tested cases.

Contextual MEG and EEG Source Estimates Using Spatiotemporal LSTM Networks.

Transcranial direct current stimulation protocols are often applied with a fixed parameter set to all subjects participating in an interventional study. This might lead to considerable effect variation in inhomogeneous subject groups or when transferring stimulation protocols to different age groups. The aim of this study was to evaluate magnitude differences of the electric current density distribution on the gray matter surface in children, adolescent and adults in correlation with the individual volume conductor geometry. We generated individual six compartment finite element models from structural magnetic resonance images of four children (age: 10.95 a±1.32 a), eight adolescents (age: 15.10 a±1.16 a) and eight young adults (age: 21.62 a±2.45 a). We determined the skull thickness in the models as Euclidean distance between the surface of the cerebrospinal fluid compartment and outer skull boundary. For tDCS simulations, we modeled 5×7cm patch electrodes impressing 1mA current intensity as anode and cathode over the left M1 and the right fronto-polar orbit, respectively. The resulting current density was analyzed on the gray matter surface. Our results demonstrate higher cortical current density magnitudes in children compared to adults for a given tDCS current strength. Above the evaluated cortex, the skull thickness increased with age. In conclusion, we underline the importance of age-dependent and individual models in tDCS simulations.

Cortical current density magnitudes during transcranial direct current stimulation correlate with skull thickness in children, adolescent and young adults.

Ocular current stimulation (oCS) with weak current intensities (a few mA) has shown positive effects on retinal nerve cells, which indicates that neurodegenerative ocular diseases could be treated with current stimulation of the eye. During oCS, a significant polarity-independent reduction in the characteristic P50 amplitude of a pattern-reversal electroretinogram was found, while no current stimulation effect was found for a full field electroretinogram (ffERG). The ffERG data indicated a trend for a polarity-dependent influence during oCS on the photopic negative response (PhNR) wave, which represents the sum activity of the retinal ganglion cells. Therefore, an ffERG with adjusted parameters for the standardized measurement of the PhNR wave was combined with simultaneous oCS to study the potential effects of direct oCS on cumulative ganglion cell activity. Compared with that measured before oCS, the PhNR amplitude in the cathodal group increased significantly during current stimulation, while in the anodal and sham groups, no effect was visible (α = 0.05, p = 0.006*). Furthermore, repeated-measures ANOVA revealed a significant difference in PhNR amplitude between the anodal and cathodal groups as well as between the cathodal and sham groups (p* ≤ 0.0167, p = 0.002*, p = 0.011*).

Ocular direct current stimulation affects retinal ganglion cells.

There is evidence that humans can survive a direct lightning strike to the head. Our question is: could water (rain) on the skin contribute to an increase in the survival rate? We measure the influence of rain during high-energy direct lightning strikes on a realistic three-compartment human head phantom. We find a lower number of perforations and eroded areas near the lightning strike impact points on the head phantom when rain was applied compared to no rain. Current amplitudes in the brain were lower with rain compared to no rain before a fully formed flashover. We conclude that rain on the scalp potentially contributes to the survival rate of 70-90% due to: (1) lower current exposition in the brain before a fully formed flashover, and (2) reduced mechanical and thermal damage.

Rain may improve survival from direct lightning strikes to the human head.

Electrical stimulation (ES) techniques, such as deep brain and transcranial electrical stimulation, have shown promise in alleviating the symptoms of depression and other neurological disorders . A new noninvasive ES method called temporal interference stimulation (TIS), possesses great potential as it can be used to steer the stimulation and possibly selectively modulate different brain regions. To study TIS in a controlled environment, we successfully established an  'TIS on a chip' setup using rat cortical neurons on microelectrode arrays (MEAs) in combination with a current stimulator. We validated the developed TIS system and demonstrated the spatial steerability of the stimulation by direct electric field measurements in the chip setup. We stimulated cultures of rat cortical neurons at 28 days  (DIV) by two-channel stimulation delivering 1) TIS at 653 Hz and 643 Hz, resulting in a 10 Hz frequency envelope, 2) low-frequency stimulation (LFS) at 10 Hz and 3) high-frequency stimulation (HFS) at 653 Hz. Unstimulated cultures were used as control/sham. We observed the differences in the electric field strengths during TIS, HFS, and LFS. Moreover, HFS and LFS had the smallest effects on neuronal activity. Instead, TIS elicited neuronal electrophysiological responses, especially 24 hours after stimulation. Our 'TIS on a chip' approach eludicates the applicability of TIS as a method to modulate neuronal electrophysiological activity. The TIS on a chip approach provides spatially steerable stimuli while mitigating the effects of high stimulus fields near the stimulation electrodes. Thus, the approach opens new avenues for stimulation on a chip applications, allowing the study of neuronal responses to gain insights into the potential clinical applications of TIS in treating various brain disorders.

Article	Year
Head phantoms for electroencephalography and transcranial electric stimulation: a skull material study. Biomedizinische Technik. Biomedical engineering\| PubMed ID: 28820729	2018
Novel bifunctional cap for simultaneous electroencephalography and transcranial electrical stimulation. Scientific reports\| PubMed ID: 29740054	2018
Pulsed Electrical Stimulation of the Human Eye Enhances Retinal Vessel Reaction to Flickering Light. Frontiers in human neuroscience\| PubMed ID: 31695600	2019
Vision modulation, plasticity and restoration using non-invasive brain stimulation - An IFCN-sponsored review. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 32078919	2020
Corrigendum: Pulsed Electrical Stimulation of the Human Eye Enhances Retinal Vessel Reaction to Flickering Light. Frontiers in human neuroscience\| PubMed ID: 32477085	2020
Novel flexible cap for application of transcranial electrical stimulation: a usability study. Biomedical engineering online\| PubMed ID: 32552720	2020
The Effects of an Ocular Direct Electrical Stimulation on Pattern-Reversal Electroretinogram. Frontiers in neuroscience\| PubMed ID: 32587502	2020
Head phantoms for bioelectromagnetic applications: a material study. Biomedical engineering online\| PubMed ID: 33228687	2020
Effects of Ocular Direct Current Stimulation on Full Field Electroretinogram. Frontiers in neuroscience\| PubMed ID: 33679299	2021
Contextual MEG and EEG Source Estimates Using Spatiotemporal LSTM Networks. Frontiers in neuroscience\| PubMed ID: 33767606	2021
Cortical current density magnitudes during transcranial direct current stimulation correlate with skull thickness in children, adolescent and young adults. Progress in brain research\| PubMed ID: 34167664	2021
Ocular direct current stimulation affects retinal ganglion cells. Scientific reports\| PubMed ID: 34475417	2021
Rain may improve survival from direct lightning strikes to the human head. Scientific reports\| PubMed ID: 38336797	2024
Electric field temporal interference stimulation of neurons . Lab on a chip\| PubMed ID: 38994783	2024

Alexander Hunold

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