Comparing realistic subthalamic nucleus neuron models

The mechanism of action of clinically effective electrical high frequency stimulation is still under debate. However, recent evidence points at the specific activation of GABA-ergic ion channels. Using a computational approach, we analyze temporal properties of the spike trains emitted by biologically realistic neurons of the subthalamic nucleus (STN) as a function of GABA-ergic synaptic input conductances. Our contribution is based on a model proposed by Rubin and Terman and exhibits a wide variety of different firing patterns, silent, low spiking, moderate spiking and intense spiking activity. We observed that most of the cells in our network turn to silent mode when we increase the GABAA input conductance above the threshold of 3.75 mS/cm2. On the other hand, insignificant changes in firing activity are observed when the input conductance is low or close to zero. We thus reproduce Rubin's model with vanishing synaptic conductances. To quantitatively compare spike trains from the original model with the modified model at different conductance levels, we apply four different (dis)similarity measures between them. We observe that Mahalanobis distance, Victor-Purpura metric, and Interspike Interval distribution are sensitive to different firing regimes, whereas Mutual Information seems undiscriminative for these functional changes

A Newcomer\u27s Guide to Functional Near Infrared Spectroscopy Experiments

This review presents a practical primer for functional near-infrared spectroscopy (fNIRS) with respect to technology, experimentation, and analysis software. Its purpose is to jump-start interested practitioners considering utilizing a non-invasive, versatile, nevertheless challenging window into the brain using optical methods. We briefly recapitulate relevant anatomical and optical foundations and give a short historical overview. We describe competing types of illumination (trans-illumination, reflectance, and differential reflectance) and data collection methods (continuous wave, time domain and frequency domain). Basic components (light sources, detection, and recording components) of fNIRS systems are presented. Advantages and limitations of fNIRS techniques are offered, followed by a list of very practical recommendations for its use. A variety of experimental and clinical studies with fNIRS are sampled, shedding light on many brain-related ailments. Finally, we describe and discuss a number of freely available analysis and presentation packages suited for data analysis. In conclusion, we recommend fNIRS due to its ever-growing body of clinical applications, state-of-the-art neuroimaging technique and manageable hardware requirements. It can be safely concluded that fNIRS adds a new arrow to the quiver of neuro-medical examinations due to both its great versatility and limited costs

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

Cellular Modulation of Polymeric Device Surfaces: Promise of Adult Stem Cells for Neuro-Prosthetics

Minimizing the foreign body response is seen as one critical research strategy for implants especially when designed for immune-privileged organs like the brain. The context of this work is to improve deep brain stimulating devices used in a consistently growing spectrum of psychomotor and psychiatric diseases mainly in form of stiff electrodes. Based on the compliance match hypothesis of biocompatibility we present another step forward using flexible implant materials covered with brain cell-mimicking layers. We covered two types of flexible polyimide films with glandular stem cells derived from pancreatic acini. Using real time-PCR and fluorescent immunocytochemistry we analyzed markers representing various cell types of all three germ layers and stemness. The results demonstrate an unchanged differentiation potential of the polyimide fixated cells as measured by mRNA and protein level. Additionally we developed a fibrinous hydrogel coating to protect them against shear forces upon eventual implantation. By repeating previous analysis and additional metabolism tests for all stages we corroborate the validity of this improvement. Consequently we assume that a stem cell-containing cover may provide a native, fully and actively integrating brain-mimicking interface to the neuropil

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

Initial severity of depression and efficacy of cognitive-behavioural therapy: individual-participant data meta-analysis of pill-placebo-controlled trials

BACKGROUND: The influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive-behavioural therapy (CBT) in comparison with pill placebo. AIMS: To synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression. METHOD: A systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data. RESULTS: We identified five RCTs, and we were given access to individual-level data (n = 509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interaction P = 0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of -0.22 (95% CI -0.42 to -0.02, P = 0.03, I2 = 0%). CONCLUSIONS: Patients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.R01 MH060998 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R01 AT007257 - NCCIH NIH HHS; R21 MH101567 - NIMH NIH HHS; K02 MH001697 - NIMH NIH HHS; R01 MH060713 - NIMH NIH HHS; R34 MH099311 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; K23 MH100259 - NIMH NIH HHS; R01 MH099021 - NIMH NIH HH