Modular Current Stimulation System for Pre-clinical Studies.

Electric stimulators with precise and reliable outputs are an indispensable part of electrophysiological research. From single cells to deep brain or neuromuscular tissue, there are diverse targets for electrical stimulation. Even though commercial systems are available, we state the need for a low-cost, high precision, functional, and modular (hardware, firmware, and software) current stimulation system with the capacity to generate stable and complex waveforms for pre-clinical research. The system presented in this study is a USB controlled 4-channel modular current stimulator that can be expanded and generate biphasic arbitrary waveforms with 16-bit resolution, high temporal precision (μs), and passive charge balancing: the NES STiM (Neuro Electronic Systems Stimulator). We present a detailed description of the system's structural design, the controlling software, reliability test, and the pre-clinical studies [deep brain stimulation (DBS) in hemi-PD rat model] in which it was utilized. The NES STiM has been tested with MacOS and Windows operating systems. Interfaces to MATLAB source codes are provided. The system is inexpensive, relatively easy to build and can be assembled quickly. We hope that the NES STiM will be used in a wide variety of neurological applications such as Functional Electrical Stimulation (FES), DBS and closed loop neurophysiological research

Effects of radioiodine therapy on fertility indicators among men with differentiated thyroid cancer: A cohort study

Background: Following thyroidectomy, radioiodine therapy is the standard management of differentiated thyroid cancer. The effects of such treatment on testicular function remained a concern for cases and clinicians. Objective: We aimed to observe changes in fertility indicators in men treated with ablation. Materials and Methods: In this prospective cohort study, 18 men with differentiated thyroid cancer from June to December 2020 underwent thyroidectomy plus radioiodine therapy. Participants were grouped based on iodine dose (8 men with 30 mCi vs. 10 men with ≥ 150 mCi). Baseline values (VB) of the follicular stimulating hormone, luteinizing hormone, testosterone, and sperm analyses were measured 3 wk before iodine ablation and repeated 3 (V3) and 12 (V12) months later. They were analyzed once as a whole and once based on their groups via ANOVA and Friedman’s tests where appropriate. Results: The mean age of participants was 35.61 ± 9.74 yr. Follicular stimulating hormone levels showed a significant trend among all participants (VB: 12.51 ± 1.72, V3: 13.54 ± 1.41, and V12: 13.10 ± 1.67 IU/mL; p < 0.001). Luteinizing hormone showed a similar pattern (VB: 4.98 ± 1.27, V3: 5.65 ± 1.29, and V12: 5.21 ± 0.95 IU/mL; p < 0.001). Testosterone levels did not differ significantly from baseline. Sperm count decreased at the first checkpoint and returned to normal after 12 months (VB: 38.22 ± 19.40, V3: 32.05 ± 17.96, and V12: 36.66 ± 18.81 million/mL; p < 0.001). Sperm motility and morphology did not change significantly. Conclusion: Our research showed that even less than 5 GBq irradiation could induce a transient testicular dysfunction in the first 3 months of therapy, but it was mostly reversible after 12 months. Key words: Follicle-stimulating hormone, Iodine-131, Male infertility, Semen analyses

Bilateral intracranial beta activity during forced and spontaneous movements in a 6-OHDA hemi-PD rat model

Cortico-basal ganglia beta oscillations (13–30 Hz) are assumed to be involved in motor impairments in Parkinson’s Disease (PD), especially in bradykinesia and rigidity. Various studies have utilized the unilateral 6-hydroxydopamine (6-OHDA) rat PD model to further investigate PD and test novel treatments. However, a detailed behavioral and electrophysiological characterization of the model, including analyses of popular PD treatments such as DBS, has not been documented in the literature. We hence challenged the 6-OHDA rat hemi-PD model with a series of experiments (i.e., cylinder test, open field test, and rotarod test) aimed at assessing the motor impairments, analyzing the effects of Deep Brain Stimulation (DBS), and identifying under which conditions excessive beta oscillations occur. We found that 6-OHDA hemi-PD rats presented an impaired performance in all experiments compared to the sham group, and DBS could improve their overall performance. Across all the experiments and behaviors, the power in the high beta band was observed to be an important biomarker for PD as it showed differences between healthy and lesioned hemispheres and between 6-OHDA-lesioned and sham rats. This all shows that the 6-OHDA hemi-PD model accurately represents many of the motor and electrophysiological symptoms of PD and makes it a useful tool for the pre-clinical testing of new treatments when low β (13–21 Hz) and high β (21–30 Hz) frequency bands are considered separately

A case for hybrid BCIs: combining optical and electrical modalities improves accuracy

Near-infrared spectroscopy (NIRS) is a promising research tool that found its way into the field of brain-computer interfacing (BCI). BCI is crucially dependent on maximized usability thus demanding lightweight, compact, and low-cost hardware. We designed, built, and validated a hybrid BCI system incorporating one optical and two electrical modalities ameliorating usability issues. The novel hardware consisted of a NIRS device integrated with an electroencephalography (EEG) system that used two different types of electrodes: Regular gelled gold disk electrodes and tri-polar concentric ring electrodes (TCRE). BCI experiments with 16 volunteers implemented a two-dimensional motor imagery paradigm in off- and online sessions. Various non-canonical signal processing methods were used to extract and classify useful features from EEG, tEEG (EEG through TCRE electrodes), and NIRS. Our analysis demonstrated evidence of improvement in classification accuracy when using the TCRE electrodes compared to disk electrodes and the NIRS system. Based on our synchronous hybrid recording system, we could show that the combination of NIRS-EEG-tEEG performed significantly better than either single modality only

Bilateral Intracranial Beta Activity During Forced and Spontaneous Movements in a 6-OHDA Hemi-PD Rat Model.

Cortico-basal ganglia beta oscillations (13-30 Hz) are assumed to be involved in motor impairments in Parkinson's Disease (PD), especially in bradykinesia and rigidity. Various studies have utilized the unilateral 6-hydroxydopamine (6-OHDA) rat PD model to further investigate PD and test novel treatments. However, a detailed behavioral and electrophysiological characterization of the model, including analyses of popular PD treatments such as DBS, has not been documented in the literature. We hence challenged the 6-OHDA rat hemi-PD model with a series of experiments (i.e., cylinder test, open field test, and rotarod test) aimed at assessing the motor impairments, analyzing the effects of Deep Brain Stimulation (DBS), and identifying under which conditions excessive beta oscillations occur. We found that 6-OHDA hemi-PD rats presented an impaired performance in all experiments compared to the sham group, and DBS could improve their overall performance. Across all the experiments and behaviors, the power in the high beta band was observed to be an important biomarker for PD as it showed differences between healthy and lesioned hemispheres and between 6-OHDA-lesioned and sham rats. This all shows that the 6-OHDA hemi-PD model accurately represents many of the motor and electrophysiological symptoms of PD and makes it a useful tool for the pre-clinical testing of new treatments when low β (13-21 Hz) and high β (21-30 Hz) frequency bands are considered separately

First Steps towards Localized Opening of the Blood-Brain-Barrier by IR Laser Illumination Through the Rodent Skull

Glioblastoma, an aggressive malign tumor of the brain, is one of the most shattering diagnoses due to its very poor prognosis and limited treatment options. These options mainly consist of surgical or radiation therapeutic removal of as much tumor mass as possible, which unfortunately is almost always incomplete. Even worse, chemotherapy is of little use, as the special setup of the brain′s vessels severely limits the transit into the parenchyma of elsewhere efficient cytostatica. This Blood-Brain-Barrier (BBB) is for quite some time the target of sophisticated and nano-particle based transport mechanisms, however it is reported, that a boost of permeability for most of the brain can be achieved based on moderate temperature increase. One means to locally and reversibly increase the brain′s temperature and thus potentially opening the BBB may be achieved by illuminating the skull with infrared laser light, thus causing punctual heating and heat diffusion into the cortex. In extension of the common laser light guiding by glass fibres, we use a micro-positioned simple optics to focus a 1470 nm laser beam of approximately 500 µm in diameter on the skull. The apparent opening of the BBB is evidenced by the localized spread of Evans Blue injected into the tail vein of said rat, binding to Albumin (64,6 kDa) in the body. This marker molecule is usually blocked from passing through the intact BBB, but under IR illumination for half a minute, it appeared in post mortem visible blobs. Temperature profiles and potential tissue damage are now under investigation by high speed thermal camera and post mortem histology

Deep brain stimulation: increasing efficiency by alternative waveforms

Deep brain stimulation (DBS) is based on the effect of high frequency stimulation (HFS) in neuronal tissue. As a therapy option for patients suffering from e.g. Parkinson’s disease, DBS has been used for decades. Despite the widespread use, the effect of HFS on neurons is not fully investigated. Improving the stimulation efficiency und specificity could increase the efficiency of the INS (internal neuronal stimulator) as well as potentially reduce unwanted side effects. The effect of HFS on the GABAergic system was quantified using whole cell patch clamp electrophysiology during HFS stimulation in cortical human brain slices in vitro. Rectangular, sine, sawtooth and triangular waveforms were applied extracellularly. Since HFS has been hypothesized to increase the activity of the axons of GABAergic interneurons, a decrease in activity can be observed in the pyramidal cells that the interneurons project to. By isolating the incoming non- GABAergic events, we can filter out only the GABAA currents which can be verified using a GABAA antagonist. The results show that all the waveforms effectively increase the GABAA currents. The triangle waveform causes the highest significant increase in the activity which further increases over time after the stimulation was turned off

When the Ostrich-Algorithm Fails: Blanking Method Affects Spike Train Statistics

Modern electroceuticals are bound to employ the usage of electrical high frequency (130–180 Hz) stimulation carried out under closed loop control, most prominent in the case of movement disorders. However, particular challenges are faced when electrical recordings of neuronal tissue are carried out during high frequency electrical stimulation, both in-vivo and in-vitro. This stimulation produces undesired artifacts and can render the recorded signal only partially useful. The extent of these artifacts is often reduced by temporarily grounding the recording input during stimulation pulses. In the following study, we quantify the effects of this method, “blanking,” on the spike count and spike train statistics. Starting from a theoretical standpoint, we calculate a loss in the absolute number of action potentials, depending on: width of the blanking window, frequency of stimulation, and intrinsic neuronal activity. These calculations were then corroborated by actual high signal to noise ratio (SNR) single cell recordings. We state that, for clinically relevant frequencies of 130 Hz (used for movement disorders) and realistic blanking windows of 2 ms, up to 27% of actual existing spikes are lost. We strongly advice cautioned use of the blanking method when spike rate quantification is attempted.Impact statementBlanking (artifact removal by temporarily grounding input), depending on recording parameters, can lead to significant spike loss. Very careful use of blanking circuits is advised

Machine learning approaches to classify anatomical regions in rodent brain from high density recordings

Identifying different functional regions during a brain surgery is a challenging task usually performed by highly specialized neurophysiologists. Progress in this field may be used to improve in situ brain navigation and will serve as an important building block to minimize the number of animals in preclinical brain research required by properly positioning implants intraoperatively. The study at hand aims to correlate recorded extracellular signals with the volume of origin by deep learning methods. Our work establishes connections between the position in the brain and recorded high-density neural signals. This was achieved by evaluating the performance of BLSTM, BGRU, QRNN and CNN neural network architectures on multisite electrophysiological data sets. All networks were able to successfully distinguish cortical and thalamic brain regions according to their respective neural signals. The BGRU provides the best results with an accuracy of 88.6 % and demonstrates that this classification task might be solved in higher detail while minimizing complex preprocessing steps