Non-invasive Electrical Stimulation Research Articles

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.

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.

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.

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.

Changes in sensitivity and hedonic rating to transcutaneous electrical nerve stimulation following COVID-19

COVID-19 affects not only the respiratory system but also other biological systems such as the nervous system. Usually, these changes are reported based on the patient's subjective description. The aim of our study, therefore, was to objectively determine the effect that the SARS-CoV-2 virus and COVID-19 disease has on sensory threshold and the hedonic and subjective perception of an electrical stimulus. The sensory threshold was tested on the inner forearm by applying non-invasive transcutaneous electrical nerve stimulation (TENS) with 100 Hz and 100 µs parameters and a biphasic current waveform. The study involved 211 participants, aged 22–79 years, with a mean age of 56.9 ± 12.1 years. There were 131 subjects in the COVID group, while the NON-COVID group, the control group, was matched to the COVID group in terms of gender, age, body mass index and presence of chronic diseases. The research was carried out in 2022. Sensory sensitivity was highest in the group that had suffered with COVID-19. The median sensory sensitivity was 11 mA in the COVID group and 14 mA (p < 0.001) in the NON-COVID group, however, the current sensitivity threshold decreased over time (R = 0.52, p < 0.001). Post COVID-19, the electrical stimulus was more often perceived as unpleasant: COVID versus NON-COVID (23% vs. 3%, p < 0.001) and as a different sensation to tingling (27% vs. 2%, p < 0.001). Post-COVID-19 patients have a lower sensory threshold, the electrical stimulus is more often described as unpleasant and in subjective feelings it is more often described as pinching. The differences between COVID and NON-COVID decrease with time since the onset of COVID symptoms.

Acute suppression of lower limb spasm by sacral afferent stimulation for people with spinal cord injury: A pilot study.

Lower limb spasm and spasticity may develop following spinal cord injury (SCI), causing hyper-excitability and increased tone, which can impact function and quality of life. Pharmaceutical interventions for spasticity may cause unwanted side effects such as drowsiness and weakness. Invasive and non-invasive electrical stimulation has been shown to reduce spasticity without these side effects. The aim of this study was to investigate the effect of sacral afferent stimulation (SAS), through surface electrical stimulation of the dorsal genital nerve (N=7), and through implanted electrodes on the sacral afferent nerve roots, on lower limb spasm and spasticity (N=2). Provoked spasms were interrupted with conditional SAS, where stimulation commenced following a provoked spasm, or unconditional stimulation, which was applied continuously. Conditionally and unconditionally applied SAS was shown to suppress acute provoked spasms in people with SCI. There was a statistically significant reduction in area under the curve of quadriceps electromyography during acute spasm with SAS compared to a control spasm. These results show that SAS may provide a safe, low-cost method of reducing acute spasm and spasticity in people living with SCI. SAS through implanted electrodes may also provide an additional function to sacral nerve stimulation devices.

Let's Shape Learning Into Lasting Memories.

Recent experiments in rats and humans have indicated that the effects of non-invasive electrical stimulation are primarily due to transcutaneous stimulation of peripheral nerves, specifically the greater occipital nerve. This stimulation pathway activates communication gateways from the periphery to the brain, impacting memory consolidation. In this invited commentary, I delve into and offer additional insights concerning the enhancement of episodic memory through transcutaneous electrical stimulation of the greater occipital nerve, building upon the findings published by my laboratory in both Science Advances and Elife. Our research on non-invasive transcutaneous electrical stimulation of the greater occipital nerve (NITESGON) has shown to enhance episodic memory consolidation and promote communication between the locus coeruleus (LC) pathway and the hippocampus based on resting connectivity functional MRI. The LC, primarily responsible for releasing noradrenaline and dopamine, plays a crucial role in post-encoding memory stabilization. This suggests that NITESGON can improve memory but does not affect immediate learning. The concept of behavioural tagging, where weak memories can be stabilized through strong or novel events, and how NITESGON activates a memory consolidation through this mechanism are discussed. The role of NITESGON in enhancing memory stabilization is highlighted, providing a non-pharmaceutical solution with minimal side effects. The potential application of NITESGON in neurological conditions, including Alzheimer's disease, attention deficit hyperactivity disorder and post-traumatic stress disorder, is also discussed, emphasizing its promising therapeutic prospects.

TRANSCRANIAL ELECTRICAL STIMULATION AS A TOOL TO UNDERSTAND AND ENHANCE MOBILITY IN OLDER ADULTS

Abstract Standing and walking are complex cognitive-motor tasks that rely on the function of numerous brain networks. This reliance upon supraspinal elements of the motor control system increases with age and many age-related diseases, especially when an individual must navigate unfamiliar environments and/or simultaneously perform cognitive tasks like talking, reading signs, or making decisions. Noninvasive transcranial electrical stimulation (tES) can safely and selectively induce both acute and longer-term changes in brain network function. It thus enables cause-and-effect study of the motor control system and moreover, holds promise as a therapeutic strategy to counteract age- and disease-related alterations in standing, walking, and mobility. The purpose of this talk is to introduce the fundamentals of tES, describe the effects of tES on the neural control of mobility in older adults, and finally, discuss current limitations and related avenues for future research and development within this rapidly-growing field of study.

Neuromodulator approaches to depression: The potential of transcranial electric stimulation

Depression, a widespread mental health disorder, presents significant challenges in diagnosis and treatment. Amidst the myriad treatments, non-invasive Transcranial Electric Stimulation (tES), encompassing Transcranial Alternating Current Stimulation (tACS) and Transcranial Direct Current Stimulation (tDCS), has emerged as a promising intervention for Major Depressive Disorder (MDD). This review delineates the mechanisms of these modalities, their distinctions, and their potential to modulate neural oscillations and influence cognitive functions. Studies showcased the efficacy of these techniques in ameliorating depressive symptoms, with EEG and fNIRS employed to gauge their neurological impact. Observations suggest the potential in modulating for specific brain rhythms to enhance memory functions in older adults and influence working memory processes. The dynamic interplay between tDCS and tACS in altering cortical activities and their interaction with neurotransmitters like GABA further underscores their potential. However, the need for extensive research, particularly double-blind randomized control trials, remains paramount to ascertain their safety and efficacy. This review provides a comprehensive insight into the prospective role of tES in the clinical landscape of MDD treatment.

Innervation of an Ultrasound-Mediated PVDF-TrFE Scaffold for Skin-Tissue Engineering.

In this work, electrospun polyvinylidene-trifluoroethylene (PVDF-TrFE) was utilized for its biocompatibility, mechanics, and piezoelectric properties to promote Schwann cell (SC) elongation and sensory neuron (SN) extension. PVDF-TrFE electrospun scaffolds were characterized over a variety of electrospinning parameters (1, 2, and 3 h aligned and unaligned electrospun fibers) to determine ideal thickness, porosity, and tensile strength for use as an engineered skin tissue. PVDF-TrFE was electrically activated through mechanical deformation using low-intensity pulsed ultrasound (LIPUS) waves as a non-invasive means to trigger piezoelectric properties of the scaffold and deliver electric potential to cells. Using this therapeutic modality, neurite integration in tissue-engineered skin substitutes (TESSs) was quantified including neurite alignment, elongation, and vertical perforation into PVDF-TrFE scaffolds. Results show LIPUS stimulation promoted cell alignment on aligned scaffolds. Further, stimulation significantly increased SC elongation and SN extension separately and in coculture on aligned scaffolds but significantly decreased elongation and extension on unaligned scaffolds. This was also seen in cell perforation depth analysis into scaffolds which indicated LIPUS enhanced perforation of SCs, SNs, and cocultures on scaffolds. Taken together, this work demonstrates the immense potential for non-invasive electric stimulation of an in vitro tissue-engineered-skin model.

Audiovisual gamma stimulation for the treatment of neurodegeneration.

Alzheimer's disease (AD) is the most common type of neurodegenerative disease and a health challenge with major social and economic consequences. In this review, we discuss the therapeutic potential of gamma stimulation in treating AD and delve into the possible mechanisms responsible for its positive effects. Recent studies reveal that it is feasible and safe to induce 40Hz brain activity in AD patients through a range of 40Hz multisensory and noninvasive electrical or magnetic stimulation methods. Although research into the clinical potential of these interventions is still in its nascent stages, these studies suggest that 40Hz stimulation can yield beneficial effects on brain function, disease pathology, and cognitive function in individuals with AD. Specifically, we discuss studies involving 40Hz light, auditory, and vibrotactile stimulation, as well as noninvasive techniques such as transcranial alternating current stimulation and transcranial magnetic stimulation. The precise mechanisms underpinning the beneficial effects of gamma stimulation in AD are not yet fully elucidated, but preclinical studies have provided relevant insights. We discuss preclinical evidence related to both neuronal and nonneuronal mechanisms that may be involved, touching upon the relevance of interneurons, neuropeptides, and specific synaptic mechanisms in translating gamma stimulation into widespread neuronal activity within the brain. We also explore the roles of microglia, astrocytes, and the vasculature in mediating the beneficial effects of gamma stimulation on brain function. Lastly, we examine upcoming clinical trials and contemplate the potential future applications of gamma stimulation in the management of neurodegenerative disorders.