Non-invasive Electrical Stimulation Research Articles

Activation thresholds for electrical phrenic nerve stimulation at the neck: evaluation of stimulation pulse parameters in a simulation study

Abstract Objective. Phrenic nerve stimulation reduces ventilator-induced-diaphragmatic-dysfunction, which is a potential complication of mechanical ventilation. Electromagnetic simulations provide valuable information about the effects of the stimulation and are used to determine appropriate stimulation parameters and evaluate possible co-activation. Approach. Using a multiscale approach, we built a novel detailed anatomical model of the neck and the phrenic nerve. The model consisted of a macroscale volume conduction model of the neck with 13 tissues, a mesoscale volume conduction model of the phrenic nerve with three tissues, and a microscale biophysiological model of axons with diameters ranging from 5 to 14 µm based on the McIntyre–Richardson–Grill-model for myelinated axons. This multiscale model was used to quantify activation thresholds of phrenic nerve fibers using different stimulation pulse parameters (pulse width, interphase delay, asymmetry of biphasic pulses, pulse polarity, and rise time) during non-invasive electrical stimulation. Electric field strength was used to evaluate co-activation of the other nerves in the neck. Main results. For monophasic pulses with a pulse width of 150 µs, the activation threshold depended on the fiber diameter and ranged from 20 to 156 mA, with highest activation threshold for the smallest fiber diameter. The relationship was approximated using a power fit function x −3. Biphasic (symmetric) pulses increased the activation threshold by 25 to 30 %. The use of asymmetric biphasic pulses or an interphase delay lowered the threshold close to the monophasic threshold. Possible co-activated nerves were the more superficial nerves and included the transverse cervical nerve, the supraclavicular nerve, the great auricular nerve, the cervical plexus, the brachial plexus, and the long thoracic nerve. Significance. Our multiscale model and electromagnetic simulations provided insight into phrenic nerve activation and possible co-activation by non-invasive electrical stimulation and provided guidance on the use of stimulation pulse types with minimal activation threshold.

Sensory studies on the taste and flavor perception of food products by anodal transcutaneous electrical stimulation.

Electrical taste technologies designed to modify the taste of foods have recently garnered increasing recognition as a viable strategy to regulate excessive salt intake. Transcutaneous electrical stimulation (TES) is a method used in non-invasive electrical taste stimulation, which involves the placement of electrodes near the mouth (not inside the mouth) to avoid disruption of natural eating behavior. Previous studies have demonstrated the taste-enhancing effect of anodal TES (aTES) applied to the anterior part of the jaw. However, there has been no detailed examination of TES-mediated alteration of the taste characteristics of different types of food products with complex flavors. In this study involving 27 human participants, we used the Quantitative Descriptive Profile method to conduct a sensory evaluation investigation of aTES-mediated changes in taste characteristics of six processed food products: cold potato potage, chicken broth soup, rice porridge with pickled plums (umeboshi), Chinese pork stir fry, stir-fried pork and radish, and fried dumplings. The application of aTES significantly increased both the intensity of saltiness and overall taste in all six foods. Furthermore, aTES significantly enhanced and suppressed some of the flavor attributes of these foods. An aTES-mediated increase in palatability was only observed in fried dumplings, indicating that further investigation of the relationship between flavor characteristics and palatability is needed.

Transcutaneous Auricular Vagus Stimulation Attenuates LPS-Induced Depression-Like Behavior by Regulating Central α7nAChR/JAK2 Signaling.

Depression is a serious disabling disease worldwide. Accumulating evidence supports that there is a close relationship between depression and inflammation, and then inhibition of neuroinflammation may be another mechanism for the treatment of depression. Transcutaneous auricular vagus stimulation (taVNS), as a noninvasive transcutaneous electrical stimulation, could effectively treat depression, but its mechanism is unclear. In this study, rats with depression-like behavior were induced by intraperitoneal injection of lipopolysaccharide (LPS). The rats were randomly divided to control group, LPS group, taVNS + LPS group, and the same as the α7 nicotinic acetylcholine chloride receptor (α7nAChR) (- / -) gene knockout rats. The expressions of tumor necrosis factor alpha (TNF-ɑ) and phosphorylated-Janus kinase2 (p-JAK2), phosphorylated-signal transducer and activator of transcription3(p-STAT3) in the hypothalamus, amygdala, and hippocampus were detected by Western blot. We observed that LPS significantly decreased the sucrose preference, the time of into the open arms in the elevated plus maze, and the number of crossing and reaping in the open field test. TaVNS treatment improves these depression-like behaviors, but taVNS is not effective in α7nAChR (- / -) gene knockout rats. The expression of TNF-ɑ significantly increased, and the expression of p-Jak2 and p-STAT3 markedly decreased in the hypothalamus and amygdala induced by LPS. TaVNS could significantly reverse the abovementioned phenomena but had rare improvement effect for α7nAChR (- / -) rats. We conclude that the antidepressant effect of taVNS for LPS-induced depressive rats is related to α7nAchR/JAK2 signal pathway in the hypothalamus and amygdala.

Preservation of vision by transpalpebral electrical stimulation in mice with inherited retinal degeneration.

The potential neuroprotective and regenerative properties of electrical stimulation (ES) were studied in rhodopsin knockout mice (Rho -/- ), a murine model of inherited retinal degeneration. The study focused on assessing the impact of varying ES frequencies on visual functions and photoreceptor cell survival in Rho -/- mice. To elucidate the impact of electrical stimulation on cone survival, Rho -/- mice received either sham or transpalpebral ES using biphasic ramp or rectangular waveforms at 100µA amplitude, starting at sixweeks of age. The treatment duration spanned from one to three weeks. The optimal treatment frequency of ES sessions was determined by applying ES every one, two, or three days in three separate groups of Rho -/- mice. The sham group received daily treatments without the application of ES. Our study revealed significant improvement of visual function in Rho -/- mice following daily or every-other-day noninvasive transpalpebral ES, as evidenced by electroretinogram and optomotor response-based visual behavior assays. Concurrently, assessment of outer nuclear thickness and immunohistochemistry for the cone photoreceptor cell marker PNA demonstrated pronounced increases in the survival of rods and cones and improvement in the morphology of the inner and outer segments. This study underscores the protective effect of non-invasive ES in rhodopsin knockout-induced retinal degenerative disorders, providing a foundation for developing targeted therapeutic interventions for retinitis pigmentosa.

Evaluating Commercial Electrical Neuromodulation Devices with Low-Cost Neural Phantoms

Non-invasive transcranial electrical stimulation is a category of neuromodulation techniques used for various disorders. Although medically approved devices exist, the variety of consumer electrical stimulation devices is increasing. Because clinical trials and animal tests are costly and risky, using a brain phantom can provide preliminary experimental validation. However, existing brain phantoms are often costly or require excessive preparation time, precluding their use for rapid, real-time optimization of stimulation settings. A limitation of direct electric fields in a phantom is the lack of 3D spatial resolution. Using well-researched modalities such as transcranial direct current stimulation (tDCS) and newer modalities such as amplitude-modulated transcranial pulsed-current stimulation (am-tPCS), a range of materials was tested for use as electrical phantoms. Based on cost, preparation time, and efficiency, ground beef and agar gel with a 10% salt mix were selected. The measured values for the total dosages were 0.55 W-s for am-tPCS and 0.91 W-s for tDCS. Due to a low gain on the recording electrodes, the signal efficiency measured against the power delivered was 4.2% for tDCS and 3.1% for am-tPCS. Issues included electrodes shifting in the soft material and the low sensitivity of the recording electrodes. Despite these issues, the effective combination of the phantom and recording methodologies can enable low costs and the rapid testing, experimentation, and verification of consumer neuromodulation devices in three dimensions. Additionally, the efficiency factors (EFs) between the observed dosage and the delivered dosage could streamline the comparison of experimental configurations. As demonstrated by comparing two types of electrical neuromodulation devices across the 3D space of a phantom, EFs can be used in conjunction with a cost-effective, time-expedient phantom to rapidly iterate and optimize stimulation parameters.

Thinking on the classification of non-invasive brain stimulation as neuromodulation technique

Neuromodulation techniques have gradually evolved from electrical or chemical methods to various physical stimulation techniques including electricity, magnetism, sound, light, heat, and more. However, the clinical efficacy and mechanisms of each stimulation technique or paradigm vary greatly. To facilitate the understanding of the therapeutic effects and mechanisms of different neuromodulation techniques, combined with current clinical practice, the author takes the classification of non-invasive transcranial electrical stimulation as an example and proposes the idea of using energy magnitude as the primary classification and different media/stimulation routes as the secondary classification. This classification emphasizes the energy essence of various physical stimuli, followed by the transmission carriers of physical stimuli. This classification method helps to guide and design neuromodulation paradigms for different target symptoms in various brain disorders, which is beneficial for better serving clinical diagnosis and treatment. The Expert Forum also discusses the advantages and disadvantages of various neuromodulation technologies and their clinical applications.

The effect of transcranial electrical stimulation on the relief of mental fatigue.

The presence of mental fatigue seriously affects daily life and working conditions. Non-invasive transcranial electrical stimulation has become an increasingly popular tool for relieving mental fatigue. We investigated whether transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) could be used to alleviate the state of mental fatigue in a population of healthy young adults and compared their effects. We recruited 10 participants for a blank control, repeated measures study. Each participant received 15 min of anodal tDCS, α-tACS, and blank stimulation. Participants were required to fill in the scale, perform the test task and collect ECG signals in the baseline, fatigue and post-stimulus states. We then assessed participants' subjective fatigue scale scores, test task accuracy and HRV characteristics of ECG signals separately. We found that both anodal tDCS and α-tACS significantly (P < 0.05) reduced subjective fatigue and improved accuracy on the test task compared to the blank group, and the extent of change was greater with tACS. For the HRV features extracted from ECG signals. After tACS intervention, SDNN (t = -3.241, P = 0.002), LF (t = -3.511, P = 0.001), LFn (t = -3.122, P = 0.002), LFn/HFn (-2.928, P = 0.005), TP (t = -2.706, P = 0.008), VLF (t = -3.002, P = 0.004), SD2 (t = -3.594, P = 0.001) and VLI (t = -3.564, P = 0.001) showed a significant increasing trend, and HFn (t = 3.122, P = 0.002), SD1/SD2 (t = 3.158, P = 0.002) and CCM_1 (t = 3.106, P = 0.003) showed a significant decreasing trend. After tDCS intervention, only one feature, TINN, showed a significant upward trend (P < 0.05). The other features showed non-significant changes but roughly the same trend as the tACS group. Both tDCS and α-tACS can be effective in relieving mental fatigue, and α-tACS is more effective than tDCS. This study provides theoretical support for tDCS with α-tACS having a alleviating effect on mental fatigue and the use of ECG as a valid objective assessment tool.

A method for noninvasive electrical stimulation of the diaphragm

A method for noninvasive electrical stimulation of the diaphragm

Non-invasive electrical brain stimulation modulates human conscious perception of mental representation

Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation and functional magnetic resonance imaging to address this. During this process, participants perceived flickering red and green visual stimuli, discerning them either as distinct, non-fused colours or as a mentally generated, fused colour (orange). The application of transcranial alternating current stimulation to the medial prefrontal region (a key node of the default-mode network) suppressed haemodynamic activation in higher-order subthalamic and central executive networks associated with the perception of fused colours. This implies that higher-order thalamocortical and default-mode networks are crucial in humans’ conscious perception of mental representation.

Biomimetic-inspired piezoelectric ovalbumin/BaTiO3 scaffolds synergizing with anisotropic topology for modulating Schwann cell and DRG behavior

The treatment of peripheral nerve injury is a clinical challenge that tremendously affected the patients' health and life. Anisotropic topographies and electric cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, most studies just unilaterally emphasize the effect of sole topological- or electric- cue on nerve regeneration, while rarely considering the synergistic function of both cues simultaneously. In this study, a biomimetic-inspired piezoelectric topological ovalbumin/BaTiO3 scaffold that can provide non-invasive electrical stimulation in situ was constructed by combining piezoelectric BaTiO3 nanoparticles and surface microtopography. The results showed that the incorporation of piezoelectric nanoparticles could improve the mechanical properties of the scaffolds, and the piezoelectric output of the scaffolds after polarization was significantly increased. Biological evaluation revealed that the piezoelectric topological scaffolds could regulate the orientation growth of SCs, promote axon elongation of DRG, and upregulate the genes expression referring to myelination and axon growth, thus rapidly integrated chemical-mechanical signals and transmitted them for effectively promoting neuronal myelination, which was closely related to peripheral neurogenesis. The study suggests that the anisotropic surface topology combined with non-invasive electronic stimulation of the ovalbumin/BaTiO3 scaffolds possess a promising application prospect in the repair and regeneration of peripheral nerve injury.

Decreasing the blood flow of non-compressible intra-abdominal organs with non-invasive transcutaneous electrical stimulation

Non-invasive neuromodulation of non-compressible internal organs has significant potential for internal organ bleeding and blood-shift in aero/space medicine. The present study aims to investigate the potential influences of the non-invasive transcutaneous electrical nerve stimulation (TENS) on multiple non-compressible internal organs’ blood flow. Porcine animal model (n = 8) was randomized for a total of 48 neuromodulation sessions with two different TENS stimulation frequencies (80 Hz, 10 Hz) and a placebo stimulation. A combination of two different electrode configurations (Abdominal-only or Abdominal and hind limb) were also performed. Intraarterial blood flow measurements were taken during pre and post-stimulation periods at the left renal artery, common hepatic artery, and left coronary artery. Intracranial, and extracranial arterial blood flows were also assessed with digital subtraction angiography. TENS with abdominal-only electrode configurations at 10 Hz demonstrated significant reductions in average peak blood flow velocity (APV) of the common hepatic artery (p = 0.0233) and renal arteries (p = 0.0493). Arterial pressures (p = 0.0221) were also significantly lower when renal APV was reduced. The outcome of the present study emphasises the potential use of TENS in decreasing the blood flow of non-compressible internal organs when the correct combination of electrodes configuration and frequency is used.

Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472.

Electrical Ear Canal Stimulation as a Therapeutic Approach for Tinnitus-A Proof of Concept Study.

Background: Tinnitus-the perception of sound despite the absence of an external source-can be a debilitating condition for which there are currently no pharmacological remedies. Our proof of concept study focused on the immediate effects of non-invasive electrical stimulation through the ear canal on loudness and tinnitus-induced distress. In addition, we aimed to identify variables that may affect the simulation outcomes. Methods: Sixty-six patients (29 women and 37 men, mean age 54.4 ± 10.4) with chronic tinnitus were recruited to the tertiary referral hospital between December 2019 and December 2021. They underwent 10 min of electrical stimulation through the ear canal for three consecutive days. Visual analog scales measured loudness and tinnitus-induced distress immediately before and after stimulation. Results: After three days of electrical stimulation, tinnitus loudness decreased in 47% of patients, 45.5% reported no change, and 7.6% reported worsening. Tinnitus severity decreased in 36.4% of cases, 59.1% of patients reported no change, and 4.5% reported worsening. Women responded positively to therapy earlier than men. In addition, tinnitus distress decreased in patients with compensated tinnitus but not in those with uncompensated tinnitus. Finally, patients with bilateral tinnitus improved earlier than those with unilateral tinnitus, and the age of the patients did not influence the stimulation results. Conclusions: Our proof of concept study confirms the potential of non-invasive electrical stimulation of the ear as a promising screening approach to identifying patients for more advanced electrostimulation treatment, such as an extracochlear anti-tinnitus implant. These findings have practical implications for tinnitus management, offering hope for improved patient care.

A modified neural circuit framework for semantic memory retrieval with implications for circuit modulation to treat verbal retrieval deficits.

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart etal., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto-polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co-activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre-SMA (e.g., frontal aslant tract and fronto-striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits.

Effects of tDCS and tRNS in two electrode placement methods on the excitability of basal ganglia cells in Parkinson's disease compared to DBS

Despite advances in the drug therapy of neurological disorders in recent decades, it has faced limitations such as resistance to specific drugs or subsequent complications. Nowadays, the studies on cortical stimulations to improve motor function in Parkinson's disease (PD) are increasing. Given the side effects of invasive stimulations to enhance motor function in the disease (e.g., deep brain stimulation (DBS)), non-invasive methods like transcranial direct current (tDCS) and transcranial random noise (tRNS) stimulations have attracted researchers' attention. Treatments are currently applied despite the non-well understood mechanism behind the techniques. The present study aimed to evaluate the effects of tDCS and tRNS on globus pallidus (GP) and subthalamic nucleus (STN) areas in PD patients. Thus, 3D head models were first created using MRI images, and the two stimulations were simulated based on two electrode placements of primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) anodal stimulation. The stimulations were compared using the current distributed in the two regions. Additionally, the effect of basal ganglia (BG) model on the excitation current distributed in the target areas was examined. Considering the membrane potential of each excitation in the two areas of all subjects, each electrode method was compared with tDCS, tRNS, and DBS in order for effectiveness. The results represented more appropriate effectiveness of the tDCS with M1 than the tRNS in the target region. Further, the method results were acceptable compared to the DBS results. The tDCS and non-invasive electrical stimulation were useful in improving the motor function of PD patients.

A device for non-invasive electrical stimulation of the phrenic nerve

A device for non-invasive electrical stimulation of the phrenic nerve

An Exploratory Study of Bimodal Electro-Aural Stimulation Through the Ear Canals for Tinnitus.

The aim of this study was to explore the potential for bimodal auditory and noninvasive electrical stimulation at the ears to alleviate tonal, somatic tinnitus that was investigated in a small preliminary trial (11 participants). Auditory stimulation took the form of short "notched noise" bursts customized to each participant's tinnitus percept. Simultaneous pulsed electrical stimulation, intended to facilitate neuroplasticity, was delivered via hydrogel electrodes placed in opposite ears. After a 6-week intervention period, average Tinnitus Functional Index (TFI) and Tinnitus Primary Function Questionnaire (TPFQ) scores were consistent with clinically meaningful improvements in the study population. Magnitudes and effect sizes of improvements in TFI and TPFQ are comparable to those reported in other recent bimodal therapy studies using different auditory and electrical stimulation parameters. Our results should be considered preliminary given the small sample size, lack of crossover data, and small subject pool. When considered alongside other recent bimodal therapy results, we do believe that there are therapeutic benefits of bimodal stimulation for tinnitus sufferers that have the potential to help some with tinnitus, with a variety of stimulation parameters and electrode placements. https://doi.org/10.23641/asha.25444546.

No Frequency-Specific Effect of Transcranial Random Noise Stimulation on Resting EEG.

Transcranial random noise stimulation (tRNS) is a form of noninvasive transcranial electrical stimulation that applies alternating current in various randomized frequencies to the cortex, thereby improving cognitive functioning in multiple domains. However, the precise mechanism of tRNS, as well as its impact on human electroencephalography (EEG), remains unclear. This is partly because most studies have used tRNS in conjunction with a cognitive task, making it difficult to tease apart whether the observed changes in EEG are a result of tRNS, the cognitive task, or their interaction. Forty-nine healthy individuals participated in this study and were randomly assigned to active tRNS (n = 24) and sham (n = 25) groups. tRNS was delivered for 20 minutes over Fp1/Fp2 and Oz. Resting-state EEG data were collected before and after either tRNS or sham stimulation. Cluster-based permutation tests using FieldTrip revealed no frequency-specific effect of tRNS on resting-state EEG data across four frequency bands (theta, alpha, beta, gamma). These observations suggest that tRNS itself does not target or alter specific EEG frequencies. Rather, tRNS most likely interacts with the cognitive task/activity at hand to produce an observable difference in post-tRNS EEG. Positive tRNS-EEG findings from previous studies are also likely to have resulted from the interactive and cognitive activity-dependent nature of tRNS.

Insights from a model based study on optimizing non invasive brain electrical stimulation for Parkinson’s disease

Parkinson’s Disease (PD) is a disorder in the central nervous system which includes symptoms such as tremor, rigidity, and Bradykinesia. Deep brain stimulation (DBS) is the most effective method to treat PD motor symptoms especially when the patient is not responsive to other treatments. However, its invasiveness and high risk, involving electrode implantation in the Basal Ganglia (BG), prompt recent research to emphasize non-invasive Transcranial Electrical Stimulation (TES). TES proves to be effective in treating some PD symptoms with inherent safety and no associated risks. This study explores the potential of using TES, to modify the firing pattern of cells in BG that are responsible for motor symptoms in PD. The research employs a mathematical model of the BG to examine the impact of applying TES to the brain. This is conducted using a realistic head model incorporating the Finite Element Method (FEM). According to our findings, the firing pattern associated with Parkinson’s disease shifted towards a healthier firing pattern through the use of tACS. Employing an adaptive algorithm that continually monitored the behavior of BG cells (specifically, Globus Pallidus Pars externa (GPe)), we determined the optimal electrode number and placement to concentrate the current within the intended region. This resulted in a peak induced electric field of 1.9 v/m at the BG area. Our mathematical modeling together with precise finite element simulation of the brain and BG suggests that proposed method effectively mitigates Parkinsonian behavior in the BG cells. Furthermore, this approach ensures an improvement in the condition while adhering to all safety constraints associated with the current injection into the brain.

Currents of Change: Galvanic Vestibular Stimulation

Galvanic vestibular stimulation (GVS) is an electrode-mediated method of non-invasive electrical stimulation. Its ability to modulate vestibular neuronal activity through electrical currents makes it a coveted diagnostic and therapeutic tool for vestibular and neurodegenerative disorders. Although more robust clinical research is needed before wide-spread implementation, GVS shows promise as a safe, cost-effective, and accessible therapeutic tool for neurological rehabilitation.