Novel surface electrode design for preferential activation of cutaneous nociceptors

Objective Small area electrodes enable preferential activation of nociceptive fibers. It is debated, however, whether co-activation of large fibers still occurs for the existing electrode designs. Moreover, existing electrodes are limited to low stimulation intensities, for which behavioral and physiological responses may be considered less reliable. A recent optimization study showed that there is a potential for improving electrode performance and increase the range of possible stimulation intensities. Based on those results, the present study introduces and tests a novel planar concentric array electrode design for small fiber activation in healthy volunteers. Approach Volunteers received electrical stimulation with the planar concentric array electrode and a regular patch electrode. Perception thresholds were estimated at the beginning and the end of the experiment. Evoked cortical potentials were recorded in blocks of 30 stimuli. For the patch, stimulation intensity was set to two times perception threshold (PT), while three intensities, 2, 5, and 10 times PT, were applied with the planar concentric array electrode. Sensation quality, numerical-rating scores, and reaction times were obtained for each PT estimation and during each block of evoked potential recordings. Main results Stimulation with the patch electrode was characterized as dull, while stimulation with the planar concentric array electrode was characterized as sharp, with increased sharpness for increasing stimulus intensity. Likewise, NRS scores were higher for the planar concentric array electrode compared to the patch and increased with increasing stimulation intensity. Reaction times and ERP latencies were longer for the planar concentric array electrode compared to the patch. Significance The presented novel planar concentric array electrode is a small, non-invasive, and single-use electrode that has the potential to investigate small fiber neuropathy and pain mechanisms, as it is small fiber preferential for a wide range of stimulation intensities.

Comparison of Threshold and Tolerance Nociceptive Withdrawal Reflexes in Horses

The nociceptive withdrawal reflex (NWR) is used to investigate nociception in horses. The NWR threshold is a classical model endpoint. The aims of this study were to determine NWR tolerance and to compare threshold and tolerance reflexes in horses. In 12 horses, the NWR was evoked through electrical stimulation of the digital nerve and recorded via electromyography from the deltoid. Behavioral reactions were scored from 0 to 5 (tolerance). First, the individual NWR threshold was defined, then stimulation intensity was increased to tolerance. The median NWR threshold was 7.0 mA, whereas NWR tolerance was 10.7 mA. Upon visual inspection of the records, two main reflex components R1 (median latency 44 ms) and R2 (median latency 81 ms) were identified at threshold. Increasing stimulation intensity to tolerance led to a significant increase in the amplitude and duration of R1 and R2, whereas their latency decreased. At tolerance, a single burst of early, high-amplitude reflex activity, with a median latency of 39 ms, was detected in 15 out of 23 stimulations (65%). The results of this study suggest that (1) it is feasible to determine NWR tolerance in horses and (2) high-intensity stimuli initiate ultrafast bursts of reflex activity, which is well known in practice and has now been quantified using the NWR model.

Optimizing transcranial direct current stimulation (tDCS) electrode position, size, and distance doubles the on-target cortical electric field: Evidence from 3000 Human Connectome Project models

Transcranial direct current stimulation (tDCS) is a widely used noninvasive brain stimulation technique with mixed results and no FDA-approved therapeutic indication to date. So far, thousands of published tDCS studies have placed large scalp electrodes directly over the intended brain target and delivered the same stimulation intensity to each person. Inconsistent therapeutic results may be due to insufficient cortical activation in some individuals and the inability to determine an optimal dose. Here, we computed 3000 MRI-based electric field models in 200 Human Connectome Project (HCP) participants, finding that the largely unexamined variables of electrode position, size, and between-electrode distance significantly impact the delivered cortical electric field magnitude. At the same scalp stimulation intensity, smaller electrodes surrounding the neural target deliver more than double the on-target cortical electric field while stimulating only a fraction of the off-target brain regions. This new optimized tDCS method can ensure sufficient cortical activation in each person and could produce larger and more consistent behavioral effects in every prospective research and transdiagnostic clinical application of tDCS.

The Impact of Stimulation Intensity on Spatial Discrimination with Multi-Pad Finger Electrode

Multi-pad electrotactile stimulation can be used to provide tactile feedback in different applications. The electrotactile interface needs to be calibrated before each use, which entails adjusting the intensity to obtain clear sensations while allowing the subjects to differentiate between active pads. The present study investigated how the stimulation intensity affects the localization of sensations using a multi-pad electrode placed on a fingertip and proximal phalange. First, the sensation, localization, smearing and discomfort thresholds were determined in 11 subjects. Then, the same subjects performed a spatial discrimination test across a range of stimulation intensities. The results have shown that all thresholds were significantly different, while there was no difference in the threshold values between the pads and phalanges. Despite the subjective feeling of spreading of sensations, the success rates in spatial discrimination were not significantly different across the tested stimulation intensities. However, the performance was better for distal compared to proximal phalange. Presented results indicate that spatial discrimination is robust to changes in the stimulation intensity. Considering the lack of significant difference in the thresholds between the pads, these results imply that more coarse adjustment of stimulation amplitude (faster calibration) might be enough for practical applications of a multi-pad electrotactile interface.

Stoney vs. Histed: Quantifying the Spatial Effects of Intracortical Microstimulation

Background: Intracortical microstimulation (ICMS) is used to map neural circuits and restore lost sensory modalities such as vision, hearing, and somatosensation. The spatial effects of ICMS remain controversial: Stoney and colleagues proposed that the volume of somatic activation increased with stimulation intensity, while Histed et al. suggested activation density, but not somatic activation volume, increases with stimulation intensity. Objective: We used computational modeling to quantify the spatial effects of ICMS intensity and unify the apparently paradoxical findings of Histed and Stoney. Methods: We implemented a biophysically-based computational model of a cortical column comprising neurons with realistic morphology and representative synapses. We quantified the spatial effects of single pulse ICMS, including the radial distance to activated neurons and the density of activated neurons as a function of stimulation intensity. Results: At all amplitudes, the dominant mode of somatic activation was by antidromic propagation to the soma following axonal activation, rather than via trans-synaptic activation. There were no occurrences of direct activation of somata or dendrites. The volume over which antidromic action potentials were initiated grew with stimulation amplitude, while the volume of somatic activations did not. However, the density of somatic activation within the activated volume increased with stimulation amplitude. Conclusions: The results resolve the apparent paradox between Stoney and Histed's results by demonstrating that the volume over which action potentials are initiated grows with ICMS amplitude, consistent with Stoney. However, the volume occupied by the activated somata remains approximately constant, while the density of activated neurons within that volume increase, consistent with Histed.

Vagus Nerve Stimulation Amplifies Task-Induced Cerebral Blood Flow Increase

BackgroundVagus nerve stimulation (VNS) is an established palliative surgical treatment for refractory epilepsy. Recently, pairing VNS with rehabilitation received growing attention for their joint effect on neural plasticity. However, objective biological measurements proving the interaction between VNS effects and cortical recruitment are lacking. Studies reported that VNS induced little blood flow increase in the cerebral cortex.ObjectiveThis study tested the hypothesis that pairing VNS with a cognitive task amplifies task-induced cerebral blood flow (CBF).MethodsThis study included 21 patients implanted with vagus nerve stimulator to treat refractory epilepsy. Near-infrared spectroscopy (NIRS) with sensors on the forehead measured CBF changes in the frontal cortices in response to VNS. Cerebral blood flow was measured when VNS was delivered during a resting state or a verbal fluency task. We analyzed the VNS effect on CBF in relation to stimulation intensity and clinical responsiveness.ResultsWe observed no CBF change when VNS was delivered during rest, irrespective of stimulation intensity or responsiveness. Cerebral blood flow changed significantly when a verbal fluency task was paired with VNS in a stimulation intensity-dependent manner. Cerebral blood flow changes in the non-responders showed no intensity-dependency.ConclusionOur results could be an important biological proof of the interaction between VNS effects and cortical recruitment, supporting the validity of pairing VNS with rehabilitation.

Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson’s Disease Model Rats

Background: The major surgical treatment for Parkinson’s disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats. Methods: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA). Results: VNS with 0.25–0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy. Conclusions: VNS with 0.25–0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device.