Monophasic Stimulation Research Articles

P26-S Left and right motor cortical excitability and relationship to motor functions in healthy adolescents

Background The interhemispheric difference in cortical excitability and its relationship to motor functions is unclear. Aim We examined the relationship between handedness, left and right motor cortex excitability and fine and gross motor functions in adolescence. Methods 28 healthy adolescents (age 16–19 years, 19 girls) were studied. Handedness was determined by the Waterloo Handedness Questionnaire. Motor threshold (MT) of the abductor pollicis brevis was measured on both hemispheres using biphasic stimulation, and on the left hemisphere also with monophasic stimulation. Box and block test (BBT) was used for manual dexterity, line run and standing long jump for gross motor tasks. Spearman correlations and paired samples t -test were used. Results All subjects were right-handed; handedness score varied between 16 and 40. MT of the left hemisphere assessed with monophasic stimulation correlated with handedness (−0.516, p = 0.006) and remained a trend with biphasic waveform (−0.353, p = 0.065). MT was not different between hemispheres (40.3 in the left vs. 41.3% in the right hemisphere). BBT result was better with right hand (76.7 vs 73.9, p = 0.008). MT of the right hemisphere correlated with the BBT of the right hand ( r = −0.383, p = 0.044). MTs and gross motor tasks did not correlate. Discussion On the right, non-dominant hemisphere, higher excitability was associated with better ipsilateral performance. Gross motor functions may be more strongly related to muscle force and therefore do not correlate with cortical excitability. Clearly established right-handedness is related to higher excitability in the dominant hemisphere. Interestingly, this seems to partly depend on the stimulation type.

Arrestin-β-1 Physically Scaffolds TSH and IGF1 Receptors to Enable Crosstalk.

Endogenously expressed TSH receptors (TSHRs) on orbital fibroblasts of patients with Graves ophthalmopathy (GO) use crosstalk with IGF1 receptors (IGF1R) to synergistically stimulate secretion of hyaluronan (HA), a major component of GO pathology. We previously showed crosstalk occurred upstream of mitogen-activated protein kinase (ERK) phosphorylation. Because other G protein-coupled receptors engage arrestin-β-1 (ARRB1) and ERK, we tested whether ARRB1 was a necessary component of TSHR/IGF1R crosstalk. HA secretion was stimulated by the TSHR-stimulating monoclonal antibodies M22 and KSAb1, or immunoglobulins from patients with GO (GO-Igs). Treatment with M22, as previously shown, resulted in biphasic dose-response stimulation of HA secretion. The high-potency phase was IGF1R dependent, and the low-potency phase was partly IGF1R independent. KSAb1 produced a monophasic dose-response stimulation of HA secretion, whose potency was lowered >20-fold after IGF1R knockdown. ARRB1 knockdown abolished M22's high-potency phase and lowered KSAb1's potency and efficacy. ARRB1 knockdown inhibited GO-Ig stimulation of HA secretion and of ERK phosphorylation. Last, ARRB1 was shown to be necessary for TSHR/IGF1R proximity. In contrast, ARRB2 knockdowns did not show these effects. Thus, TSHR must neighbor IGF1R for crosstalk in GO fibroblasts to occur, and this depends on ARRB1 acting as a scaffold. Similar scaffolding of TSHR and IGF1R by ARRB1 was found in human osteoblast-like cells and human thyrocytes. These findings support a model of TSHR/IGF1R crosstalk that may be a general mechanism for G-protein-coupled receptor/receptor tyrosine kinase crosstalk dependent on ARRB1.

Monophasic transcranial constant-current versus constant-voltage stimulation of motor-evoked potentials during spinal surgery

Constant-voltage and constant-current stimulators may be used for transcranial electrical stimulation of motor evoked potentials (TES-MEP). However, no previous report has determined whether the two monophasic stimulation methods lead to similar responses during intra-operative monitoring. We studied differences in the lateralities of compound muscle action potentials (CMAPs) during intra-operative spinal cord monitoring via TES-MEP using monophasic constant-current and constant-voltage stimulations. CMAPs were bilaterally recorded from the upper and lower limb muscles in 95 patients who underwent elective spine and spinal cord surgery. We used two monophasic stimulation patterns: pattern 1, right anode and left cathode; pattern 2, right cathode and left anode. There were no statistically significant differences between the right and left sides with respect to success rates, wave amplitudes, and efficiencies, with constant-voltage stimulation, however, there were statistically significant differences between the right and left sides with constant-current stimulation. In case of our stimulation condition, there were no statistically significant differences between the right and left sides with respect to CMAPs with constant-voltage stimulation; constant-current stimulation was influenced by the type of monophasic stimulation, which necessitates the switch the polarity of the stimulation to bilaterally record CMAPs.

Effect of monophasic pulsed stimulation on live single cell de-adhesion on conducting polymers with adsorbed fibronectin as revealed by single cell force spectroscopy.

The force required to detach a single fibroblast cell in contact with the conducting polymer, polypyrrole doped with dodecylbenzene, was quantified using the Atomic Force Microscope-based technique, Single Cell Force Spectroscopy. The de-adhesion force for a single cell was 0.64 ± 0.03 nN and predominately due to unbinding of α5β1 integrin complexes with surface adsorbed fibronectin, as confirmed by blocking experiments using antibodies. Monophasic pulsed stimulation (50 μs pulse duration) superimposed on either an applied oxidation (+500) or reduction (-500 mV) constant voltage caused a significant decrease in the de-adhesion force by 30%-45% to values ranging from 0.34 to 0.43 nN (±0.02 nN). The electrical stimulation caused a reduction in the molecular-level jump and plateau interactions, while an opposing increase in nonspecific interactions was observed during the cell de-adhesion process. Due to the monophasic pulsed stimulation, there is an apparent change or weakening of the cell membrane properties, which is suggested to play a role in reducing the cell de-adhesion. Based on this study, pulsed stimulation with optimized threshold parameters represents a possible approach to tune cell interactions and adhesion on conducting polymers.

Stimulation Pattern Efficiency in Percutaneous Auricular Vagus Nerve Stimulation: Experimental Versus Numerical Data.

Percutaneous electrical stimulation of the auricular vagus nerve (pVNS) is an electroceutical technology. The selection of stimulation patterns is empirical, which may lead to under-stimulation or over-stimulation. The objective is to assess the efficiency of different stimulation patterns with respect to individual perception and to compare it with numerical data based on in-silico ear models. Monophasic (MS), biphasic (BS) and triphasic stimulation (TS) patterns were tested in volunteers. Different clinically-relevant perception levels were assessed. In-silico models of the human ear were created with embedded fibers and vessels to assess different excitation levels. TS indicates experimental superiority over BS which is superior to MS while reaching different perception levels. TS requires about 57% and 35% of BS and MS magnitude, respectively, to reach the comfortable perception. Experimental thresholds decrease from non-bursted to bursted stimulation. Numerical results indicate a slight superiority of BS and TS over MS while reaching different excitation levels, whereas the burst length has no influence. TS yields the highest number of asynchronous action impulses per stimulation symbol for the used tripolar electrode set-up. The comparison of experimental and numerical data favors the novel TS pattern. The analysis separates excitatory pVNS effects in the auricular periphery, as accounted by in-silico data, from the combination of peripheral and central pVNS effects in the brain, as accounted by experimental data. The proposed approach moves from an empirical selection of stimulation patterns towards efficient and optimized pVNS settings.

Effects of biphasic and monophasic electrical stimulation on mitochondrial dynamics, cell apoptosis, and cell proliferation.

Currently, electrical stimulation (ES) is used to induce changes in various tissues and cellular processes, but its effects on mitochondrial dynamics and mechanisms are unknown. The aim of this study was to compare the effects of monophasic and biphasic, anodal, and cathodal ES on apoptosis, proliferation, and mitochondrial dynamics in neuroblastoma SH-SY5Y cells. Cells were cultured and treated with ES. Alamar blue assay was performed to measure cell proliferation. The proteins expression of apoptotic-related proteins Bcl-2 associated X (Bax), B cell lymphoma 2 (Bcl-2), optic-atrophy-1 (OPA1), mitofusin2 (Mfn2), phosphorylated dynamin-related protein 1 at serine 616 (p-DRP1), and total dynamin-related protein 1 (Total-DRP1) were also determined. The results showed that monophasic anodal and biphasic anodal/cathodal (Bi Anod) ES for 1 hr at 125 pulses per minute (2.0 Hz) produced the most significant increase in cell proliferation. In addition, monophasic anodal and Bi Anod ES treated cells displayed a significant increase in the levels of anti-apoptotic protein Bcl-2, whereas the Bax levels were not changed. Moreover, the levels of Mfn2 were increased in the cells treated by Bi Anod, and OPA1 was increased by monophasic anodal and Bi Anod ES, indicating increased mitochondrial fusion in these ES-treated cells. However, the levels of mitochondrial fission indicated by DRP1 remained unchanged compared with non-stimulated cells. These findings were confirmed through visualization of mitochondria using Mitotracker Deep Red, demonstrating that monophasic anodal and Bi Anod ES could induce pro-survival effects in SH-SY5Y cells through increasing cell proliferation and mitochondrial fusion. Future research is needed to validate these findings for the clinical application of monophasic anodal and Bi Anod ES.

Electrode placement on the forearm for selective stimulation of finger extension/flexion.

It is still challenging to achieve a complex grasp or fine finger control by using surface functional electrical stimulation (FES), which usually requires a precise electrode configuration under laboratory or clinical settings. The goals of this study are as follows: 1) to study the possibility of selectively activating individual fingers; 2) to investigate whether the current activation threshold and selective range of individual fingers are affected by two factors: changes in the electrode position and forearm rotation (pronation, neutral and supination); and 3) to explore a theoretical model for guidance of the electrode placement used for selective activation of individual fingers. A coordinate system with more than 400 grid points was established over the forearm skin surface. A searching procedure was used to traverse all grid points to identify the stimulation points for finger extension/flexion by applying monophasic stimulation pulses. Some of the stimulation points for finger extension and flexion were selected and tested in their respective two different forearm postures according to the number and the type of the activated fingers and the strength of finger action response to the electrical stimulation at the stimulation point. The activation thresholds and current ranges of the selectively activated finger at each stimulation point were determined by visual analysis. The stimulation points were divided into three groups (“Low”, “Medium” and “High”) according to the thresholds of the 1st activated fingers. The angles produced by the selectively activated finger within selective current ranges were measured and analyzed. Selective stimulation of extension/flexion is possible for most fingers. Small changes in electrode position and forearm rotation have no significant effect on the threshold amplitude and the current range for the selective activation of most fingers (p > 0.05). The current range is the largest (more than 2 mA) for selective activation of the thumb, followed by those for the index, ring, middle and little fingers. The stimulation points in the “Low” group for all five fingers lead to noticeable finger angles at low current intensity, especially for the index, middle, and ring fingers. The slopes of the finger angle variation in the “Low” group for digits 2~4 are inversely proportional to the current intensity, whereas the slopes of the finger angle variation in other groups and in all groups for the thumb and little finger are proportional to the current intensity. It is possible to selectively activate the extension/flexion of most fingers by stimulating the forearm muscles. The physiological characteristics of each finger should be considered when placing the negative electrode for selective stimulation of individual fingers. The electrode placement used for the selective activation of individual fingers should not be confined to the location with the lowest activation threshold.

Comparison of Monophasic and Biphasic Electrical Stimulation by Using Temporal Analysis for Different Inter-electrode Spacings in the Hexagonal Arrays

Recent multidisciplinary studies in the field of visual prosthesis rely on electrically stimulating retinal tissue by placing electrode array into different part of it, bypassing the nerve cells of the visual pathway which have lost their functionality due to various degenerative diseases. The visual prosthesis systems could be more efficient by mimicking physiologically natural electrical signals. In this study, the responses of the retina to biphasic and monophasic electrical stimulations were compared temporally using in-vitro rabbit retina. The retinal tissue was electrically stimulated with charge-balanced biphasic and monophasic pulses. When temporal diversity was comparatively analyzed, spike activity was observed to intensify in the first 20 ms after the moment of stimulation for biphasic stimulation. On the other hand, the spike activity was observed to form in a way that it can be classified into two categories, the primary one forming in the first 20 ms and the secondary delayed one forming between 80 and 100 ms for monophasic stimulation. Moreover, the effect of retina stimulation amplitude was also analyzed. The spike distribution was observed to cumulate mostly in the post-stimulation time interval of the first 20 ms as the stimulation amplitude for biphasic stimulation increased. In monophasic stimulation, secondary delayed spike activity was observed over 80 \({\upmu }\hbox {A}\). The obtained experimental findings suggested that lower amplitude charge-balanced short biphasic waveforms could better elicit the precise and proper stimulation patterns necessary to mimic the neural activity of retinal circuitry that resembles the natural ones when it was compared with monophasic stimulation.

Correspondence between visual and electrical input filters of ON and OFF mouse retinal ganglion cells

Objective. Over the past two decades retinal prostheses have made major strides in restoring functional vision to patients blinded by diseases such as retinitis pigmentosa. Presently, implants use single pulses to activate the retina. Though this stimulation paradigm has proved beneficial to patients, an unresolved problem is the inability to selectively stimulate the on and off visual pathways. To this end our goal was to test, using white noise, voltage-controlled, cathodic, monophasic pulse stimulation, whether different retinal ganglion cell (RGC) types in the wild type retina have different electrical input filters. This is an important precursor to addressing pathway-selective stimulation. Approach. Using full-field visual flash and electrical and visual Gaussian noise stimulation, combined with the technique of spike-triggered averaging (STA), we calculate the electrical and visual input filters for different types of RGCs (classified as on, off or on–off based on their response to the flash stimuli). Main results. Examining the STAs, we found that the spiking activity of on cells during electrical stimulation correlates with a decrease in the voltage magnitude preceding a spike, while the spiking activity of off cells correlates with an increase in the voltage preceding a spike. No electrical preference was found for on–off cells. Comparing STAs of wild type and rd10 mice revealed narrower electrical STA deflections with shorter latencies in rd10. Significance. This study is the first comparison of visual cell types and their corresponding temporal electrical input filters in the retina. The altered input filters in degenerated rd10 retinas are consistent with photoreceptor stimulation underlying visual type-specific electrical STA shapes in wild type retina. It is therefore conceivable that existing implants could target partially degenerated photoreceptors that have only lost their outer segments, but not somas, to selectively activate the on and off visual pathways.

Optimization of Interphase Intervals to Enhance the Evoked Muscular Responses of Transcutaneous Neuromuscular Electrical Stimulation.

Neuromuscular electrical stimulation (NMES) is a widely used technique for clinical diagnostic, treatment, and research. Normally, it applies charge-balanced biphasic pulses, which several publications have reported to be less efficient than monophasic pulses. A good alternative is the use of interphase intervals (IPI) on biphasic pulses that allows to achieve similar responses than those evoked by monophasic stimulation. This study analyzes the enhancing mechanism of the IPI and provides guidelines on how to optimize the IPI in order to reduce secondary effects such as the electrode corrosion. The tibial nerve was excited by NMES biphasic pulses with different IPI durations and polarities. Then, the elicited responses were recorded on the soleus muscle via electromyography. When cathodic-first pulses were applied, the responses increased proportionally to the IPI until the duration of 250 µs, where the increase saturated at 30% of the original amplitude. The responses evoked during anodic-first were 6% to 30% smaller than those evoked during cathodic-first pulses and continuously increased until the IPI duration of 2500 µs, where the responses reached an increase of around 30%. The results suggest that when a cathodic-first pulse is used, the IPI could be optimized (based on the setup geometry) to allow the action potentials to travel out of the hyperpolarization zone induced by the anodic phase. When anodic-first stimuli are applied, the IPI duration allows the fiber to recover from an apparent insensitive state induced by the anodic phase. The use of IPI is a viable option to improve the efficiency of actual stimulation systems, since only small modifications are required to significantly reduce the electrical charge required and boost the stimulation efficiency.

A 2.048 Mb/s Full-Duplex Free-Space Optical Transceiver IC for a Real-Time <italic>In Vivo</italic> Brain–Computer Interface Mouse Experiment Under Social Interaction

This paper presents the first free-space optical transceiver IC for social, psychological brain–computer interface experiments with multiple mice. The proposed IC embedded in a head-mounted module (HMM) includes 8-channel neural recorder and a neural stimulator in order to record extracellular action potentials and local field potentials while injecting diverse waveforms of monophasic intracranial stimulation current into the medial forebrain bundle for the activation of the nervous system. The HMM implanted on a mouse transmits the neural recording data to an optical base station by using a mandatory 591/624-nm (amber/red) visible behavior tracking LED as an optical transmitter to save power. The HMM is controlled simultaneously via a 940 nm infrared optical downlink to reduce interference to the visible optical uplink. The proposed IC fabricated in a 0.18- $\mu \text{m}$ HV BCDMOS process consumes 90 $\mu \text{W}$ while achieving a 2.048-Mb/s transmission rate.

Electrical neurostimulation with imbalanced waveform mitigates dissolution of platinum electrodes

Objective. Electrical neurostimulation has traditionally been limited to the use of charge-balanced waveforms. Charge-imbalanced and monophasic waveforms are not used to deliver clinical therapy, because it is believed that these stimulation paradigms may generate noxious electrochemical species that cause tissue damage. Approach. In this study, we investigated the dissolution of platinum as one of such irreversible reactions over a range of charge densities up to 160 μC cm−2 with current-controlled first phase, capacitive discharge second phase waveforms of both cathodic-first and anodic-first polarity. We monitored the concentration of platinum in solution under different stimulation delivery conditions including charge-balanced, charge-imbalanced, and monophasic pulses. Main results. We observed that platinum dissolution decreased during charge-imbalanced and monophasic stimulation when compared to charge-balanced waveforms. Significance. This observation provides an opportunity to re-evaluate the charge-balanced waveform as the primary option for sustainable neural stimulation.

Probing Corticospinal Recruitment Patterns and Functional Synergies with Transcranial Magnetic Stimulation.

Background: On the one hand, stimulating the motor cortex at different spots may activate the same muscle and result in a muscle-specific cortical map. Maps of different muscles, which are functionally coupled, may present with a large overlap but may also show a relevant variability. On the other hand, stimulation of the motor cortex at one spot with different stimulation intensities results in a characteristic input–output (IO) curve for one specific muscle but may simultaneously also activate different, functionally coupled muscles. A comparison of the cortical map overlap of synergistic muscles and their IO curves has not yet been carried out.Objective: The aim of this study was to probe functional synergies of forearm muscles with transcranial magnetic stimulation by harnessing the convergence and divergence of the corticospinal output.Methods: We acquired bihemispheric cortical maps and IO curves of the extensor carpi ulnaris, extensor carpi radialis, and extensor digitorum communis muscles by subjecting 11 healthy subjects to both monophasic and biphasic pulse waveforms.Results: The degree of synergy between pairs of forearm muscles was captured by the overlap of the cortical motor maps and the respective IO curves which were influenced by the pulse waveform. Monophasic and biphasic stimulation were particularly suitable for disentangling synergistic muscles in the right and left hemisphere, respectively.Conclusion: Combining IO curves and different pulse waveforms may provide complementary information on neural circuit dynamics and corticospinal recruitment patterns of synergistic muscles and their neuroplastic modulation.

Tonic Investigation Concept of Cervico-vestibular Muscle Afferents.

Introduction Interdisciplinary research has contributed greatly to an improved understanding of the vestibular system. To date, however, very little research has focused on the vestibular system's somatosensory afferents. To ensure the diagnostic quality of vestibular somatosensory afferent data, especially the extra cranial afferents, stimulation of the vestibular balance system has to be precluded. Objective Sophisticated movements require intra- and extra cranial vestibular receptors. The study's objective is to evaluate an investigation concept for cervico-vestibular afferents with respect to clinical feasibility. Methods A dedicated chair was constructed, permitting three-dimensional trunk excursions, during which the volunteer's head remains fixed. Whether or not a cervicotonic provocation nystagmus (c-PN) can be induced with static trunk excursion is to be evaluated and if this can be influenced by cervical monophasic transcutaneous electrical nerve stimulation (c-TENS) with a randomized test group. 3D-video-oculography (VOG) was used to record any change in cervico-ocular examination parameters. The occurring nystagmuses were evaluated visually due to the small caliber of nystagmus amplitudes in healthy volunteers. Results The results demonstrate: no influence of placebo-controlled c-TENS on the spontaneous nystagmus; a significant increase of the vertical nystagmus on the 3D-trunk-excursion chair in static trunk flexion with cervical provocation in all young healthy volunteers (n = 49); and a significant difference between vertical and horizontal nystagmuses during static trunk excursion after placebo-controlled c-TENS, except for the horizontal nystagmus during trunk torsion. Conclusion We hope this cervicotonic investigation concept on the 3D trunk-excursion chair will contribute to new diagnostic and therapeutic perspectives on cervical pathologies in vestibular head-to-trunk alignment.

A Phenomenological Model of the Electrically Stimulated Auditory Nerve Fiber: Temporal and Biphasic Response Properties.

We present a phenomenological model of electrically stimulated auditory nerve fibers (ANFs). The model reproduces the probabilistic and temporal properties of the ANF response to both monophasic and biphasic stimuli, in isolation. The main contribution of the model lies in its ability to reproduce statistics of the ANF response (mean latency, jitter, and firing probability) under both monophasic and cathodic-anodic biphasic stimulation, without changing the model's parameters. The response statistics of the model depend on stimulus level and duration of the stimulating pulse, reproducing trends observed in the ANF. In the case of biphasic stimulation, the model reproduces the effects of pseudomonophasic pulse shapes and also the dependence on the interphase gap (IPG) of the stimulus pulse, an effect that is quantitatively reproduced. The model is fitted to ANF data using a procedure that uniquely determines each model parameter. It is thus possible to rapidly parameterize a large population of neurons to reproduce a given set of response statistic distributions. Our work extends the stochastic leaky integrate and fire (SLIF) neuron, a well-studied phenomenological model of the electrically stimulated neuron. We extend the SLIF neuron so as to produce a realistic latency distribution by delaying the moment of spiking. During this delay, spiking may be abolished by anodic current. By this means, the probability of the model neuron responding to a stimulus is reduced when a trailing phase of opposite polarity is introduced. By introducing a minimum wait period that must elapse before a spike may be emitted, the model is able to reproduce the differences in the threshold level observed in the ANF for monophasic and biphasic stimuli. Thus, the ANF response to a large variety of pulse shapes are reproduced correctly by this model.

Monophasic Pulsed Microcurrent of 1-8 Hz Increases the Number of Human Dermal Fibroblasts.

Pressure injuries seriously impact the quality of life of patients and increase public and private healthcare costs. Electrical stimulation therapy is recommended for wound contraction, and some clinical studies have shown that the application of a monophasic pulsed microcurrent can help to reduce the treatment period. However, the optimal stimulus conditions are unclear. The purpose of this study was to investigate the effect of different frequencies of monophasic pulsed microcurrent stimulation on the number and viability of human dermal fibroblasts. Human dermal fibroblasts were electrically stimulated in vitro (intensity: 200 μA; frequency: 1, 2, 4, 8, 16, 32, and 64 Hz; duty factor: 50%) for 1 h three times every 24 h. Controls were unstimulated. Cell numbers and cell viability were assessed after each electrical stimulation session. In the 1-, 2-, 4-, and 8-Hz groups, cell numbers were significantly higher than those in the control group, whereas electrical stimulation at 64 Hz resulted in a decrease in cell numbers at 24 h after the third treatment (p < 0.05). Cell viability was high in both the control and low-frequency stimulation groups, with no significant differences between groups. Application of 1-8 Hz monophasic pulsed microcurrent stimulation increased the number of human dermal fibroblasts in vitro, and is proposed as the optimal condition for accelerating the healing of pressure injuries.

High frequency switched-mode stimulation can evoke post synaptic responses in cerebellar principal neurons.

This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100 kHz) duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation. These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency.

A comparative study of the effects of pulse parameters for intracranial direct electrical stimulation in epilepsy

ObjectivesIntracranial direct electrical stimulation (iDES) uses different parameters for mapping the epileptogenic and functional areas in patients with drug-resistant epilepsy. We aim at finding the common factor driving the electrographic responses to various iDES protocols reported in the literature. MethodsWe recorded early responses to single-pulse iDES in 11 subjects undergoing stereoelectroencephalographic presurgical evaluation. We systematically explored the role of several pulse parameters in evoking responses: monophasic versus biphasic pulses, current intensity, and pulse duration. We performed a correlation and regression analysis between responses to different protocols by amplitude, duration, and charge per phase. ResultsRegression analysis revealed that the responses were similar for the same charge per phase, regardless of their pulse duration and amplitude. Over eighty percent (82.8%) of the responses to variable pulse duration biphasic stimulation and between 58.6% and 81.9% of the responses to monophasic stimulation, depending on pulse polarity, were correlated to the responses evoked by the variable amplitude biphasic protocol, when expressing stimulus strength in terms of charge per phase. ConclusionsRegardless of the combination of different stimulation currents, it is the underlying charge per phase parameter that determines the magnitude of the responses to single-pulse electrical stimulation. SignificanceOur results provide a unifying method for comparing iDES protocols.

Modifying excitability of trigemino-facial reflex circuits with transcranial direct current stimulation

s / Brain Stimulation 8 (2015) 378e394 384 Background: Responses to a number of different plasticityinducing brain stimulation protocols are highly variable. However there is little data available on the variability of response to 1 Hertz repetitive transcranial magnetic stimulation (1Hz rTMS). Objective: We tested the effects of 1Hz rTMS over the motor cortex on corticospinal excitability. We also examined whether an individual’s response could be predicted frommeasurements of onset latency of motor evoked potential (MEP) following stimulationwith different orientations of monophasic transcranial magnetic stimulation (TMS). Methods: Thirty-two healthy subjects (mean age 30.3 years, SD 11.0; 13 females) participated in a crossover-design. Baseline latency measurements with different coil orientations and MEPs were recorded from the first dorsal interosseous muscle prior to the application of 900 pulses of 1Hz rTMS with two different stimulus intensities, i.e. 90% resting motor threshold (RMT) and 115%RMT. Thirty MEPs were measured every 5 min for up to half an hour after the intervention to assess after-effects on corticospinal excitability. Results: At the group level, there were no significant aftereffects of 1Hz rTMS for both stimulus intensities: about 50% individuals had only a minor or no response to 1Hz rTMS whereas the remainders had a facilitatory effect to both forms of stimulation. There was no significant correlation between the latency difference of MEPs (anterior-posterior stimulation minus latero-medial stimulation) and the response to 1Hz rTMS. Conclusions: The large variability in response to 1Hz rTMS is in line with similar studies using other forms of non-invasive brain stimulation. These results highlight the importance of individual factors influencing the responsiveness to these protocols.

Skin receptors and intradermal nerves do not generate the sensory double peak.

The cause of the double peak observed at submaximal stimulation of sensory nerves is unknown. The first peak is generated under the cathode and the second under the anode. The double peak is thought to arise from intradermal nerves or skin receptors, and in this study we tested this assumption. We studied the effect of different stimulus durations on anodal peak latency in volunteers. Biphasic anodal stimulation was used to investigate the latent additive effect of the trailing negative phase on the partial depolarization induced by the initial positive phase. We further tested the maximal amplitude of anode-generated potentials to estimate the number of neural structures involved in their generation. Increased stimulus duration caused anode-generated potential delay. Biphasic stimulation increased anode-generated amplitude 4-fold compared with monophasic stimulation. The anode-generated potential produced up to 85% of the supramaximal cathode-generated amplitude. The results suggest that the double peak arises from anodal break excitation and not from intradermal nerves or receptors.