Journal articles

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Iszak, Krisztián; Gronemann, Simon Mathies; Meyer, Stefanie; Hunold, Alexander; Zschüntzsch, Jana; Bähr, Mathias; Paulus, Walter; Antal, Andrea
Why temporal inference stimulation may fail in the human brain: a pilot research study. - In: Biomedicines, ISSN 2227-9059, Bd. 11 (2023), 7, 1813, S. 1-25

Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal.



https://doi.org/10.3390/biomedicines11071813
Schier, Peter; Jaufenthaler, Aaron; Liebl, Maik; Arsalani, Soudabeh; Wiekhorst, Frank; Baumgarten, Daniel
Human-sized quantitative imaging of magnetic nanoparticles with nonlinear magnetorelaxometry. - In: Physics in medicine and biology, ISSN 1361-6560, Bd. 68 (2023), 15, 155002, S. 1-10

Objective. Magnetorelaxomety imaging (MRXI) is a noninvasive imaging technique for quantitative detection of magnetic nanoparticles (MNPs). The qualitative and quantitative knowledge of the MNP distribution inside the body is a prerequisite for a number of arising biomedical applications, such as magnetic drug targeting and magnetic hyperthermia therapy. It was shown throughout numerous studies that MRXI is able to successfully localize and quantify MNP ensembles in volumes up to the size of a human head. However, deeper regions that lie far from the excitation coils and the magnetic sensors are harder to reconstruct due to the weaker signals from the MNPs in these areas. On the one hand, stronger magnetic fields need to be applied to produce measurable signals from such MNP distributions to further upscale MRXI, on the other hand, this invalidates the assumption of a linear relation between applied magnetic field and particle magnetization in the current MRXI forward model which is required for the imaging procedure. Approach. We tackle this problem by introducing a nonlinear MRXI forward model that is also valid for strong magnetic excitation fields. Main results. We demonstrate in our experimental feasibility study that scaling up the imaging region to the size of a human torso using nonlinear MRXI is possible. Despite the extreme simplicity of the imaging setup applied in this study, an immobilized MNP sample with 6.3 cm3 and 12 mg Fe could be localized and quantified with an acceptable quality. Significance. A well-engineered MRXI setup could provide much better imaging qualities in shorter data acquisition times, making nonlinear MRXI a viable option for the supervision of MNP related therapies in all regions of the human body, specifically magnetic hyperthermia.



https://doi.org/10.1088/1361-6560/ace304
Ramon, Ceon; Graichen, Uwe; Gargiulo, Paolo; Zanow, Frank; Knösche, Thomas R.; Haueisen, Jens
Spatiotemporal phase slip patterns for visual evoked potentials, covert object naming tasks, and insight moments extracted from 256 channel EEG recordings. - In: Frontiers in integrative neuroscience, ISSN 1662-5145, Bd. 17 (2023), 1087976, S. 01-20

Phase slips arise from state transitions of the coordinated activity of cortical neurons which can be extracted from the EEG data. The phase slip rates (PSRs) were studied from the high-density (256 channel) EEG data, sampled at 16.384 kHz, of five adult subjects during covert visual object naming tasks. Artifact-free data from 29 trials were averaged for each subject. The analysis was performed to look for phase slips in the theta (4-7 Hz), alpha (7-12 Hz), beta (12-30 Hz), and low gamma (30-49 Hz) bands. The phase was calculated with the Hilbert transform, then unwrapped and detrended to look for phase slip rates in a 1.0 ms wide stepping window with a step size of 0.06 ms. The spatiotemporal plots of the PSRs were made by using a montage layout of 256 equidistant electrode positions. The spatiotemporal profiles of EEG and PSRs during the stimulus and the first second of the post-stimulus period were examined in detail to study the visual evoked potentials and different stages of visual object recognition in the visual, language, and memory areas. It was found that the activity areas of PSRs were different as compared with EEG activity areas during the stimulus and post-stimulus periods. Different stages of the insight moments during the covert object naming tasks were examined from PSRs and it was found to be about 512 ± 21 ms for the ‘Eureka’ moment. Overall, these results indicate that information about the cortical phase transitions can be derived from the measured EEG data and can be used in a complementary fashion to study the cognitive behavior of the brain.



https://doi.org/10.3389/fnint.2023.1087976
Heitmar, Rebekka; Link, Dietmar; Kotliar, Konstantin; Schmidl Doreen Silvia; Klee, Sascha
Editorial: Functional assessments of the ocular circulation. - In: Frontiers in medicine, ISSN 2296-858X, Bd. 10 (2023), 1222022, S. 01-04

https://doi.org/10.3389/fmed.2023.1222022
Warsito, Indhika Fauzhan; Komosar, Milana; Bernhard, Maria Anne; Fiedler, Patrique; Haueisen, Jens
Flower electrodes for comfortable dry electroencephalography. - In: Scientific reports, ISSN 2045-2322, Bd. 13 (2023), 16589, S. 1-15

Dry electroencephalography (EEG) electrodes provide rapid, gel-free, and easy EEG preparation, but with limited wearing comfort. We propose a novel dry electrode comprising multiple tilted pins in a flower-like arrangement. The novel Flower electrode increases wearing comfort and contact area while maintaining ease of use. In a study with 20 volunteers, we compare the performance of a novel 64-channel dry Flower electrode cap to a commercial dry Multipin electrode cap in sitting and supine positions. The wearing comfort of the Flower cap was rated as significantly improved both in sitting and supine positions. The channel reliability and average impedances of both electrode systems were comparable. Averaged VEP components showed no considerable differences in global field power amplitude and latency, as well as in signal-to-noise ratio and topography. No considerable differences were found in the power spectral density of the resting state EEGs between 1 and 40 Hz. Overall, our findings provide evidence for equivalent channel reliability and signal characteristics of the compared cap systems in the sitting and supine positions. The reliability, signal quality, and significantly improved wearing comfort of the Flower electrode allow new fields of applications for dry EEG in long-term monitoring, sensitive populations, and recording in supine position.



https://doi.org/10.1038/s41598-023-42732-8
Esmaeilzadeh Kiabani, Negin; Kazemi, Reza; Hadipour, Abed L.; Khomami, Sanaz; Kalloch, Benjamin; Hlawitschka, Mario
Targeting the insula with transcranial direct current stimulation: a simulation study. - In: Psychiatry research, ISSN 1872-7506, Bd. 335 (2023), 111718

Insula is considered an important region of the brain in the generation and maintenance of a wide range of psychiatric symptoms, possibly due to being key in fundamental functions such as interoception and cognition in general. Investigating the possibility of targeting this area using non-invasive brain stimulation techniques can open new possibilities to probe the normal and abnormal functioning of the brain and potentially new treatment protocols to alleviate symptoms of different psychiatric disorders. In the current study, COMETS2, a MATLAB based toolbox was used to simulate the magnitude of the current density and electric field in the brain caused by different transcranial direct current stimulation (tDCS) protocols to find an optimum montage to target the insula and its 6 subregions for three different current intensities, namely 2, 3, and 4 mA. Frontal and occipital regions were found to be optimal candidate regions. The results of the current study showed that it is viable to reach the insula and its individual subregions using tDCS.



https://doi.org/10.1016/j.pscychresns.2023.111718
Chamaani, Somayyeh; Sachs, Jürgen; Prokhorova, Alexandra; Smeenk, Carsten; Wegner, Tim Erich; Helbig, Marko
Microwave angiography by ultra-wideband sounding: a preliminary investigation. - In: Diagnostics, ISSN 2075-4418, Bd. 13 (2023), 18, 2950, S. 1-17

Angiography is a very informative method for physicians such as cardiologists, neurologists and neuroscientists. The current modalities experience some shortages, e.g., ultrasound is very operator dependent. The computerized tomography (CT) and magnetic resonance (MR) angiography are very expensive and near infrared spectroscopy cannot capture the deep arteries. Microwave technology has the potential to address some of these issues while compromising between operator dependency, cost, speed, penetration depth and resolution. This paper studies the feasibility of microwave signals for monitoring of arteries. To this aim, a homogenous phantom mimicking body tissue is built. Four elastic tubes simulate arteries and a mechanical system creates pulsations in these arteries. A multiple input multiple output (MIMO) array of ultra-wideband (UWB) transmitters and receivers illuminates the phantom and captures the reflected signals over the desired observation time period. Since we are only interested in the imaging of dynamic parts, i.e., arteries, the static clutters can be suppressed easily by background subtraction method. To obtain a fast image of arteries, which are pulsating with the heartbeat rate, we calculate the Fourier transform of each channel of the MIMO system over the observation time and apply delay and sum (DAS) beamforming method on the heartbeat rate aligned spectral component. The results show that the lateral and longitudinal images and motion mode (M-mode) time series of different points of phantom have the potential to be used for diagnosis.



https://doi.org/10.3390/diagnostics13182950
Jochmann, Thomas; Seibel, Marc S.; Jochmann, Elisabeth; Khan, Sheraz; Hämäläinen, Matti; Haueisen, Jens
Sex-related patterns in the electroencephalogram and their relevance in machine learning classifiers. - In: Human brain mapping, ISSN 1097-0193, Bd. 44 (2023), 14, S. 4848-4858

Deep learning is increasingly being proposed for detecting neurological and psychiatric diseases from electroencephalogram (EEG) data but the method is prone to inadvertently incorporate biases from training data and exploit illegitimate patterns. The recent demonstration that deep learning can detect the sex from EEG implies potential sex-related biases in deep learning-based disease detectors for the many diseases with unequal prevalence between males and females. In this work, we present the male- and female-typical patterns used by a convolutional neural network that detects the sex from clinical EEG (81% accuracy in a separate test set with 142 patients). We considered neural sources, anatomical differences, and non-neural artifacts as sources of differences in the EEG curves. Using EEGs from 1140 patients, we found electrocardiac artifacts to be leaking into the supposedly brain activity-based classifiers. Nevertheless, the sex remained detectable after rejecting heart-related and other artifacts. In the cleaned data, EEG topographies were critical to detect the sex, but waveforms and frequencies were not. None of the traditional frequency bands was particularly important for sex detection. We were able to determine the sex even from EEGs with shuffled time points and therewith completely destroyed waveforms. Researchers should consider neural and non-neural sources as potential origins of sex differences in their data, they should maintain best practices of artifact rejection, even when datasets are large, and they should test their classifiers for sex biases.



https://doi.org/10.1002/hbm.26417
Lei, Xiong-Xin; Hu, Juan-Juan; Zou, Chen-Yu; Jiang, Yan-Lin; Zhao, Long-Mei; Zhang, Xiu-Zhen; Li, Ya-Xing; Peng, An-Ni; Song, Yu-Ting; Huang, Li-Ping; Li-Ling, Jesse; Xie, Hui-Qi
Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing. - In: Bioactive materials, ISSN 2452-199X, Bd. 27 (2023), S. 461-473

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.



https://doi.org/10.1016/j.bioactmat.2023.04.015
Wegert, Laureen; Schramm, Stefan; Dietzel, Alexander; Link, Dietmar; Klee, Sascha
Three-dimensional light field fundus imaging: automatic determination of diagnostically relevant optic nerve head parameters. - In: Translational Vision Science & Technology, ISSN 2164-2591, Bd. 12 (2023), 7, 21, S. 1-16

Purpose: Morphological changes to the optic nerve head (ONH) can be detected at the early stages of glaucoma. Three-dimensional imaging and analysis may aid in the diagnosis. Light field (LF) fundus cameras can generate three-dimensional (3D) images of optic disc topography from a single shot and are less susceptible to motion artifacts. Here, we introduce a processing method to determine diagnostically relevant ONH parameters automatically and present the results of a subject study performed to validate this method. Methods: The ONHs of 17 healthy subjects were examined and images were acquired with both an LF fundus camera and by optical coherence tomography (OCT). The LF data were analyzed with a novel algorithm and compared with the results of the OCT study. Depth information was reconstructed, and a model with radial basis functions was used for processing of the 3D point cloud and to provide a finite surface. The peripapillary rising and falling edges were evaluated to determine optic disc and cup contours and finally calculate the parameters. Results: Nine of the 17 subjects exhibited prominent optic cups. The contours and ONH parameters determined by an analysis of LF 3D imaging largely agreed with the data obtained from OCT. The median disc areas, cup areas, and cup depths differed by 0.17 mm^2, -0.04 mm^2, and -0.07 mm, respectively. Conclusions: The findings presented here suggest the possibility of using LF data to evaluate the ONH. Translational Relevance: LF data can be used to determine geometric parameters of the ONH and thus may be suitable for future use in glaucoma diagnostics.



https://doi.org/10.1167/tvst.12.7.21