Porcine Model of Cerebral Ischemic Stroke Utilizing Intracortical Recordings for the Continuous Monitoring of the Ischemic Area.

PURPOSE: Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation. METHODS: Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability. RESULTS: Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO2, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment. CONCLUSIONS: The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.

Morphology and morphometry of the ulnar nerve in the forelimb of pigs.

The knowledge of the morphology and morphometry of peripheral nerves is essential for developing neural interfaces and understanding nerve regeneration in basic and applied research. Currently, the most adopted animal model is the rat, even though recent studies have suggested that the neuroanatomy of large animal models is more comparable to humans. The present knowledge of the morphological structure of large animal models is limited; therefore, the present study aims to describe the morphological characteristics of the Ulnar Nerve (UN) in pigs. UN cross-sections were taken from seven Danish landrace pigs at three distinct locations: distal UN, proximal UN and at the dorsal cutaneous branch of the UN (DCBUN). The nerve diameter, fascicle diameter and number, number of fibres and fibre size were quantified. The UN diameter was larger in the proximal section compared to the distal segment and the DCBUN. The proximal branch also had a more significant number of fascicles (median: 15) than the distal (median: 10) and the DCBUN (median: 11) segments. Additionally, the mean fascicle diameter was smaller at the DCBUN (mean: 165 µm) than at the distal (mean: 197 µm) and proximal (mean: 199 µm) segments of the UN. Detailed knowledge of the microscopical structure of the UN in pigs is critical for further studies investigating neural interface designs and computational models of the peripheral nervous system.

The effect of peripheral high-frequency electrical stimulation on the primary somatosensory cortex in pigs.

This study implements the use of Danish Landrace pigs as subjects for the long-term potentiation (LTP)-like pain model. This is accomplished by analyzing changes in the primary somatosensory cortex (S1) in response to electrical stimulation on the ulnar nerve after applying high-frequency electrical stimulation (HFS) on the ulnar nerve. In this study, eight Danish Landrace pigs were electrically stimulated, through the ulnar nerve, to record the cortically evoked response in S1 by a 16-channel microelectrode array (MEA). Six of these pigs were subjected to HFS (four consecutive, 15 mA, 100 Hz, 1000 µs pulse duration) 45 min after the start of the experiment. Two pigs were used as control subjects to compare the cortical response to peripheral electrical stimulation without applying HFS. Low-frequency components of the intracortical signals (0.3-300 Hz) were analyzed using event-related potential (ERP) analysis, where the minimum peak during the first 30-50 ms (N1 component) in each channel was detected. The change in N1 was compared over time across the intervention and control groups. Spectral analysis was used to demonstrate the effect of the intervention on the evoked cortical oscillations computed between 75 ms and 200 ms after stimulus. ERP analysis showed an immediate increase in N1 amplitude that became statistically significant 45 mins after HFS (p < 0.01) for the intervention group. The normalized change in power in frequency oscillations showed a similar trend. The results show that the LTP-like pain model can be effectively implemented in pigs using HFS since the cortical responses are comparable to those described in humans.

Induction of Neural Plasticity Using a Low-Cost Open Source Brain-Computer Interface and a 3D-Printed Wrist Exoskeleton.

Brain-computer interfaces (BCIs) have been proven to be useful for stroke rehabilitation, but there are a number of factors that impede the use of this technology in rehabilitation clinics and in home-use, the major factors including the usability and costs of the BCI system. The aims of this study were to develop a cheap 3D-printed wrist exoskeleton that can be controlled by a cheap open source BCI (OpenViBE), and to determine if training with such a setup could induce neural plasticity. Eleven healthy volunteers imagined wrist extensions, which were detected from single-trial electroencephalography (EEG), and in response to this, the wrist exoskeleton replicated the intended movement. Motor-evoked potentials (MEPs) elicited using transcranial magnetic stimulation were measured before, immediately after, and 30 min after BCI training with the exoskeleton. The BCI system had a true positive rate of 86 ± 12% with 1.20 ± 0.57 false detections per minute. Compared to the measurement before the BCI training, the MEPs increased by 35 ± 60% immediately after and 67 ± 60% 30 min after the BCI training. There was no association between the BCI performance and the induction of plasticity. In conclusion, it is possible to detect imaginary movements using an open-source BCI setup and control a cheap 3D-printed exoskeleton that when combined with the BCI can induce neural plasticity. These findings may promote the availability of BCI technology for rehabilitation clinics and home-use. However, the usability must be improved, and further tests are needed with stroke patients.

The Use of the Velocity Selective Recording Technique to Reveal the Excitation Properties of the Ulnar Nerve in Pigs.

Decoding information from the peripheral nervous system via implantable neural interfaces remains a significant challenge, considerably limiting the advancement of neuromodulation and neuroprosthetic devices. The velocity selective recording (VSR) technique has been proposed to improve the classification of neural traffic by combining temporal and spatial information through a multi-electrode cuff (MEC). Therefore, this study investigates the feasibility of using the VSR technique to characterise fibre type based on the electrically evoked compound action potentials (eCAP) propagating along the ulnar nerve of pigs in vivo. A range of electrical stimulation parameters (amplitudes of 50 µA-10 mA and pulse durations of 100 µs, 500 µs, 1000 µs, and 5000 µs) was applied on a cutaneous and a motor branch of the ulnar nerve in nine Danish landrace pigs. Recordings were made with a 14 ring MEC and a delay-and-add algorithm was used to convert the eCAPs into the velocity domain. The results revealed two fibre populations propagating along the cutaneous branch of the ulnar nerve, with mean velocities of 55 m/s and 21 m/s, while only one dominant fibre population was found for the motor branch, with a mean velocity of 63 m/s. Because of its simplicity to provide information on the fibre selectivity and direction of propagation of nerve fibres, VSR can be implemented to advance the performance of the bidirectional control of neural prostheses and bioelectronic medicine applications.

The Effect of Spinal Manipulation on the Electrophysiological and Metabolic Properties of the Tibialis Anterior Muscle.

There is growing evidence showing that spinal manipulation increases muscle strength in healthy individuals as well as in people with some musculoskeletal and neurological disorders. However, the underlying mechanism by which spinal manipulation changes muscle strength is less clear. This study aimed to assess the effects of a single spinal manipulation session on the electrophysiological and metabolic properties of the tibialis anterior (TA) muscle. Maximum voluntary contractions (MVC) of the ankle dorsiflexors, high-density electromyography (HDsEMG), intramuscular EMG, and near-infrared spectroscopy (NIRS) were recorded from the TA muscle in 25 participants with low level recurring spinal dysfunction using a randomized controlled crossover design. The following outcomes: motor unit discharge rate (MUDR), strength (force at MVC), muscle conduction velocity (CV), relative changes in oxy- and deoxyhemoglobin were assessed pre and post a spinal manipulation intervention and passive movement control. Repeated measures ANOVA was used to assess within and between-group differences. Following the spinal manipulation intervention, there was a significant increase in MVC (p = 0.02; avg 18.87 ± 28.35%) and a significant increase in CV in both the isometric steady-state (10% of MVC) contractions (p < 0.01; avg 22.11 ± 11.69%) and during the isometric ramp (10% of MVC) contractions (p < 0.01; avg 4.52 ± 4.58%) compared to the control intervention. There were no other significant findings. The observed TA strength and CV increase, without changes in MUDR, suggests that the strength changes observed following spinal manipulation are, in part, due to increased recruitment of larger, higher threshold motor units. Further research needs to investigate the longer term and potential functional effects of spinal manipulation in various patients who may benefit from improved muscle function and greater motor unit recruitment.