Neuromodulation Method Research Articles

Modulating nociception networks: the impact of low-intensity focused ultrasound on thalamocortical connectivity

Abstract Pain engages multiple brain networks, with the thalamus serving as a critical subcortical hub. This study aims to explore the effects of low-intensity transcranial focused ultrasound (FUS) induced suppression on the organization of thalamocortical nociceptive networks. We employed MR-guided focused ultrasound (MRgFUS), a potential non-invasive therapy, with real-time ultrasound beam localization feedback and fMRI monitoring. We first functionally identified the focused ultrasound target at the thalamic ventroposterior lateral nucleus by mapping the whole brain blood oxygenation level-dependent responses to nociceptive heat stimulation of the hand using fMRI in each individual macaque monkey under light anesthesia. The blood oxygenation level-dependent fMRI signals from the heat-responsive thalamic ventroposterior lateral nucleus were analyzed to derive thalamocortical effective functional connectivity network using the psychophysical interaction method. Nineteen cortical regions across sensorimotor, cognitive, associative, and limbic networks exhibited strong effective functional connectivity to the thalamic ventroposterior lateral during heat nociceptive processing. Focused ultrasound-induced suppression of heat activity in the thalamic VPL altered nociceptive responses in most of the nineteen regions. Data-driven hierarchical clustering analyses of blood oxygenation level-dependent time courses across all thalamocortical ROI pairs identified two effective functional connectivity subnetworks. The concurrent suppression of thalamic heat response with focused ultrasound reorganized these subnetworks and modified thalamocortical connection strength. Our findings suggest that the thalamic ventroposterior lateral nucleus has extensive and causal connections to a wide array of cortical areas during nociceptive processing. The combination of MRgFUS with fMRI enables precise dissection and modulation of nociceptive networks in the brain, a capability that no other device-based neuromodulation methods have achieved. This presents a promising non-invasive tool for modulating pain networks with profound clinical relevance. The robust modulation of nociceptive effective functional connectivity networks by focused ultrasound strongly supports the thalamic ventroposterior lateral as a viable target for pain management strategies.

Advancing Neuroscience and Therapy: Insights into Genetic and Non-Genetic Neuromodulation Approaches.

Neuromodulation stands as a cutting-edge approach in the fields of neuroscience and therapeutic intervention typically involving the regulation of neural activity through physical and chemical stimuli. The purpose of this review is to provide an overview and evaluation of different neuromodulation techniques, anticipating a clearer understanding of the future developmental trajectories and the challenges faced within the domain of neuromodulation that can be achieved. This review categorizes neuromodulation techniques into genetic neuromodulation methods (including optogenetics, chemogenetics, sonogenetics, and magnetogenetics) and non-genetic neuromodulation methods (including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, transcranial ultrasound stimulation, photobiomodulation therapy, infrared neuromodulation, electromagnetic stimulation, sensory stimulation therapy, and multi-physical-factor stimulation techniques). By systematically evaluating the principles, mechanisms, advantages, limitations, and efficacy in modulating neuronal activity and the potential applications in interventions of neurological disorders of these neuromodulation techniques, a comprehensive picture is gradually emerging regarding the advantages and challenges of neuromodulation techniques, their developmental trajectory, and their potential clinical applications. This review highlights significant advancements in applying these techniques to treat neurological and psychiatric disorders. Genetic methods, such as sonogenetics and magnetogenetics, have demonstrated high specificity and temporal precision in targeting neuronal populations, while non-genetic methods, such as transcranial magnetic stimulation and photobiomodulation therapy, offer noninvasive and versatile clinical intervention options. The transformative potential of these neuromodulation techniques in neuroscience research and clinical practice is underscored, emphasizing the need for integration and innovation in technologies, the optimization of delivery methods, the improvement of mediums, and the evaluation of toxicity to fully harness their therapeutic potential.

Neuromodulation as a Potential Intervention for Children With Attention-Deficit/Hyperactivity Disorder.

This review examines the therapeutic potential of neuromodulation methods, including neurofeedback, transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS), as non-pharmacological interventions for children with attention-deficit/hyperactivity disorder (ADHD). A comprehensive review of current studies was conducted, focusing on each technique's mechanism, application, and efficacy in managing ADHD symptoms and cognitive deficits. Studies included human participants with ADHD, evaluating changes in symptom severity and cognitive outcomes. Neurofeedback demonstrated efficacy in symptom reduction, particularly when combined with pharmacotherapy, yielding sustained improvements. tDCS showed moderate efficacy, especially in attention and impulsivity control; however, variability in protocols and pediatric response highlights the need for standardization. TMS exhibited mixed outcomes, with high-frequency TMS targeting the dorsolateral prefrontal cortex indicating potential cognitive benefits, though results were inconsistent across studies. Neuromodulation presents a promising complementary approach for ADHD treatment in children, potentially addressing limitations of pharmacotherapy. Future research should focus on optimizing stimulation parameters, increasing sample sizes, and refining methodologies to establish neuromodulation as part of standard ADHD treatment protocols.

An Integrative Review of Brainwave Entrainment Benefits for Human Health.

Brainwave Entrainment (BWE) is a noninvasive method of neuromodulation based on the principle that auditory or visual stimulation at a specific frequency can lead the brain's electrocortical activity to oscillate at the frequency of the external signal or its multiples. This phenomenon could be used to alter physiological and psychological states. Therefore, we conducted an integrative review to answer the question: "What are the observed benefits of BWE on human health and well-being?" We searched for studies published in the last ten years in the Directory of Open Access Journals (DOAJ), EMBASE, Virtual Health Library (BVS), PubMed, SciELO, and Cochrane Library databases in April 2024. Searches were conducted in English, Portuguese, and Spanish. A total of 84 studies were included in our review. Studies showed improvements in various conditions, such as pain, sleep disturbances, mood disorders, cognition, and neurodegenerative disorders. In conclusion, our findings align with previous reviews and underscore the need for further research on BWE, particularly with larger sample sizes, robust control groups, and randomized clinical trial designs. Nevertheless, BWE demonstrates promising therapeutic potential and may support the management of various health conditions, enhancing individuals' quality of life.

The mechanism of action of neuromodulation in the treatment of overactive bladder.

Neuromodulation has been used in the treatment of various pelvic organ dysfunctions for almost 40 years and several placebo-controlled studies have confirmed its clinical effect. Many neuromodulation methods using different devices and stimulation parameters, targeting different neural structures have been introduced, but only a limited number have been adopted into routine clinical use. A substantial volume of basic research and clinical studies addressing specific effects of neuromodulation in the treatment of overactive bladder (OAB) have been published to date; however, their mechanistic implications have not been comprehensively summarized. Thus, our understanding of the mechanism of action of neuromodulation in OAB treatment is mainly based on postulated theories. Results from animal experiments suggest that different neuromodulation methods used to treat OAB share the same basic principles. The most likely explanation for the effect of neuromodulation in OAB therapy is the suppression of bladder afferent signalling, promotion of spinal guarding reflexes and modulation of non-specific supraspinal regulatory circuits.

Neuromodulation techniques for modulating cognitive function: enhancing stimulation precision and intervention effects.

Neuromodulation techniques effectively intervene in cognitive function, holding considerable scientific and practical value in fields such as aerospace, medicine, life sciences, and brain research. These techniques utilize electrical stimulation to directly or indirectly target specific brain regions, modulating neural activity and influencing broader brain networks, thereby regulating cognitive function. Regulating cognitive function involves an understanding of aspects such as perception, learning and memory, attention, spatial cognition, and physical function. To enhance the application of cognitive regulation in the general population, this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions. This review covers various neuromodulation techniques for cognitive intervention, including deep brain stimulation, vagus nerve stimulation, and invasive methods using microelectrode arrays. The non-invasive techniques discussed include transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcutaneous electrical acupoint stimulation, and time interference stimulation for activating deep targets. Invasive stimulation methods, which are ideal for studying the pathogenesis of neurological diseases, tend to cause greater trauma and have been less researched in the context of cognitive function regulation. Non-invasive methods, particularly newer transcranial stimulation techniques, are gentler and more appropriate for regulating cognitive functions in the general population. These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets. This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology. It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation. Additionally, researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.

The Potential of Non‐invasive Neurostimulation, tDCS for Cognitive Decline in Alzheimer’s Disease: Through the Lens of an Ongoing Clinical Trial

AbstractBackgroundTranscranial direct current stimulation (tDCS) is a non‐invasive neuromodulation method. Short‐term tDCS protocols have shown positive effects on cognitive outcomes in Alzheimer’s Disease (AD) populations1‐5. Less is known about the long‐term benefits of tDCS on cognition in AD. Here, we discuss the evidence on efficacy of tDCS in AD and the potential of this novel technique applied in home settings6‐8 through the lens of our ongoing long‐term, large‐scale (N = 100) randomized controlled clinical trial in patients with mild‐to‐moderate AD. This RCT aims to determine the effects of tDCS on cognition, mood, quality of life and functional/structural brain connectivity, and to explore the durability of these effects after 9‐months.MethodParticipants age ≥60 years with mild‐to‐moderate stage AD and the ability to provide informed consent are eligible. Participants receiving/have received monoclonal antibody treatment for AD or have history or head trauma or seizures are excluded. Participants are randomized to receive active tDCS at 2mA or sham delivered with two saline‐soaked electrodes placed over the dorsolateral prefrontal cortex for 30 minutes/day, 5 days/week for 6‐months at home.ResultThe study protocol has been developed and approved by the IRB. It includes 6 study visits (V1‐6) over 9 months. Eligible participants undergo in‐person tDCS training (V2), followed by a refresh training and the first tDCS session under supervision of study personnel (V3). Daily tDCS sessions proceed at home for 6 months, with a daily remote supervision via phone/video. Outcome assessments post‐intervention occur at 6, 7 and 9‐months (V4‐6). Our team developed and implemented an enhanced remote monitoring procedure (ERMP) that promotes safety and protocol adherence by monitoring skin condition and allowing for quality checks of electrode placement. The study protocol has been successfully implemented and is ongoing. To date, 101 participants have been consented/screened; of those, 62 were eligible and randomized to apply tDCS at‐home for 6‐months. Enrollment will continue until 2025.ConclusionThere is preliminary evidence on the potential of tDCS for symptom management in AD. Our study will expand the understanding of the long‐term benefits of tDCS in AD. If effective, this non‐pharmacological intervention could become an important strategy for symptom management in AD patients.

Medical Ultrasound Application Beyond Diagnosis: Insights From Ultrasound Sensing and Biological Response.

Ultrasound (US) can easily penetrate media with excellent spatial precision corresponding to its wavelength. Naturally, US plays a pivotal role in the echolocation abilities of certain mammals such as bats and dolphins. In addition, medical US generated by transducers interact with tissues via delivering ultrasonic energy in the modes of heat generation, exertion of acoustic radiation force (ARF), and acoustic cavitation. Based on the principle of echolocation, various assistive devices for visual impairment people have been developed. High-Intensity Focused Ultrasound (HIFU) are developed for targeted ablation and tissue destruction. Besides thermal ablation, histotripsy with US is designed to damage tissue purely via mechanical effect without thermal coagulation. Low-Intensity Focused Ultrasound (LIFU) has been proven to be an effective stimulation method for neuromodulation. Furthermore, US has been reported to transiently increase the permeability of biological membranes, enabling acoustic transfection and blood-brain barrier open. All of these advances in US are changing the clinic. This review mainly introduces the advances in these aspects, focusing on the physical and biological principles, challenges, and future direction.

Investigating the Possibilities of Applying the TENS as a Neurostimulation Method

Transcranial electrical stimulation (TES) is a non-invasive technology used to change the functions of the nervous system as one of the methods of neuromodulation. This method modulates brain activity by applying low-intensity electrical current to different regions of the brain. The use of transcranial electrical stimulation has shown promising results in the treatment of depression, chronic pain, neurodegenerative diseases and other neurological problems. Research shows that the application of transcranial electrical stimulation can be effective in areas such as improving memory, developing motor skills and increasing cognitive functions. However, safety, efficacy, and individual differences should be considered when using this method in clinical practice. The article examines the clinical and scientific basis, applications, and potential benefits of transcranial electrical stimulation. It is very important to study the parameters such as the shape, amplitude and frequency of the influencing signal used for the optimal solution of the treatment process. In the article, the types of the effective signal in transcranial electrical stimulation were investigated. The role of different forms of affective signals on the effectiveness of neurostimulation was investigated. In addition, it was concluded that electroacupuncture stimulation belongs to neurostimulation in terms of its essence and parameters.

Different regulative effects of high- and low-frequency external trigeminal nerve stimulation (eTNS) on sleep activity: Preliminary study

Study objectiveWith the growing prominence of peripheral nerve stimulation technology, the clinical applications and potential neurophysiological mechanisms of external trigeminal nerve stimulation (eTNS) have garnered increasing attention. Despite its status as the sole neuromodulation method commonly employed in sleep, no studies have explored the effects of eTNS at varying frequencies on sleep activities. This study aims to investigate the regulatory effects of high-frequency and low-frequency eTNS on sleep activities using polysomnography. MethodsIn this within-subjects experiment, 20 participants underwent a night of adaptation sleep, followed by 8-h sessions of sham, 120Hz-, and 2Hz-eTNS interventions in a randomized order in the sleep laboratory, with polysomnographic signals collected throughout. ResultsThe results indicated that 120Hz-eTNS significantly improved sleep efficiency, increased N2 sleep proportion, and reduced sleep latency, without significantly affecting sleep stage transition probabilities, sleep duration, or sleep-specific wave activities. Conversely, while 2Hz-eTNS did not impact sleep efficiency or latency, it increased the proportion of N3 sleep, stabilizes N3 sleep, and enhanced the survival probability of N3 and REM sleep duration. Additionally, it increases the density of slow oscillations (SOs), improved the coupling ratio of SO-spindles, and enhanced coupling timing accuracy. ConclusionsThese findings suggest that eTNS during sleep can indeed modulate sleep activities, with different frequencies exerting distinct regulatory effects. This may hold significant value for advancing the clinical application and efficacy of eTNS.

An innovative electrical neurostimulation approach to mimic reflexive urination control in spinal cord injury models

Neurogenic lower urinary tract dysfunction (NLUTD) is a frequent consequence of spinal cord injury (SCI), leading to symptoms that significantly impact quality of life. Although many life-saving techniques are available, current treatment strategies for managing NLUTD still exhibit limitations and drawbacks. Here, we introduce a new electrical neuromodulation strategy involving electrical stimulation of the major pelvic ganglion (MPG) to initiate bladder contraction, in conjunction with innovative programmable (IPG) electrical stimulation on the pudendal nerve (PN) to induce external urethral sphincter (EUS) relaxation in freely moving or anesthetized SCI mice. Furthermore, we conducted the void spot assay, and cystometry coupled with EUS electromyography (EMG) recordings to evaluate voiding function, and monitor bladder pressure and EUS activity. Our findings demonstrate that our novel electrical neuromodulation approach effectively triggers coordinated bladder muscle contraction and EUS relaxation, effectively counteracting SCI-induced NLUTD. Additionally, this electrical neuromodulation method enhances voiding efficiency, closely resembling natural reflexive urination in SCI mice. Thus, our study offers a promising electrical neurostimulation approach aimed at restoring physiological coordination and potentially offering personalized treatment for improving voiding efficiency in individuals with SCI-associated NLUTD.

Effects of vagal nerve stimulation parameters on heart rate variability in epilepsy patients.

Vagal nerve stimulation (VNS) is used as an alternative treatment in drug-resistant epilepsy patients. Effects of VNS on the cardiac autonomic system are controversial. In this study, we aimed to investigate the relationship between VNS parameters and heart rate variability (HRV) in epilepsy patients who underwent VNS treatment. Our study included 31 patients who underwent VNS for drug-resistant epilepsy. Patients were divided into groups according to response to VNS and VNS parameters. All patients underwent 24-h Holter ECG. The mean age of 31 VNS-treated epilepsy patients included in the study was 33.87 ± 7.6 years. When patients were grouped according to VNS response, 25 patients were in the VNS responder group and six patients were in the VNS-nonresponder group. When comparing Holter parameters in the VNS responder and non-responder groups, the median HF was significantly lower in the VNS responder group. VNS duration and signal frequency had a positive effect on LF/HF, while output and off time had a negative effect on LF/HF. When ROC analysis was performed to determine the cut-off values of the parameters for the VNS-responsive state, the AUC value of the HF parameter was 0.780, which was statistically significant. The cut-off value to distinguish response to VNS was 156.9. In conclusion, the effects of VNS parameters on HRV parameters are quite complex. However, the conclusion is that VNS is a neuromodulation method that affects the autonomic system in a complex way. Different levels of VNS parameters may also contribute to this effect. Furthermore, HRV parameters can be used as biomarkers to predict the patient population that may benefit from VNS.

Research hotspots and trends in transcranial magnetic stimulation for cognitive impairment: A bibliometric analysis from 2014 to 2023.

Cognitive impairment, which manifests as a limited deterioration of specific functions associated with a particular disease, can lead to a general deterioration of the patient's standard of living. Transcranial magnetic stimulation, a non-invasive neuromodulation technique, is frequently employed to treat cognitive impairment in neuropsychiatric disorders. To analyzed the state of international research on neuromodulation methods for treating cognitive impairment between 2014 and 2023, with the aim of exploring the state of research worldwide and the most recent developments in this particular area. Articles and reviews pertaining to neuromodulation methods for cognitive impairment were examined using the web of science database between January 2014 and December 2023. Publications, nations, organizations, writers, journals, citations, and keywords data from the identified studies were systematically analyzed using the CiteSpace 6.3. R1 software. A total of 2371 documents with 11750 authors and 9461 institutions, with some co-occurrences, were retrieved. The quantity of yearly publications is showing an increasing trend. The United States and China have emerged as important contributors. Among the institutes, Harvard University had the highest number of publications, while Rossi S an author who is frequently cited. Initially, the primary keywords included human motor cortex, placebo-controlled trials, and serotonin reuptake inhibitors. However, the emphasis gradually moved to substance use disorders, supplementary motor areas, neural mechanisms, and exercise. The use of neuromodulation techniques to treat cognitive impairment has drawn interest from academics all around the world. This study revealed hotspots and new trends in the research of transcranial magnetic stimulation as a cognitive impairment rehabilitation treatment. These findings are hold significant potential to guide further research and thus promote transcranial magnetic stimulation as a treatment method for cognitive impairment.

Suppression of Visceral Nociception by Selective C-Fiber Transmission Block Using Temporal Interference Sinusoidal Stimulation.

Chronic visceral pain management remains challenging due to limitations in selective targeting of C-fiber nociceptors. This study investigates temporal interference stimulation (TIS) on dorsal root ganglia (DRG) as a novel approach for selective C-fiber transmission block. We employed (1) GCaMP6 recordings in mouse whole DRG using a flexible, transparent microelectrode array for visualizing L6 DRG neuron activation, (2) ex vivo single-fiber recordings to assess sinusoidal stimulation effects on peripheral nerve axons, (3) in vivo behavioral assessment measuring visceromotor responses (VMR) to colorectal distension in mice, including a TNBS-induced visceral hypersensitivity model, and (4) immunohistological analysis to evaluate immediate immune responses in DRG following TIS. We demonstrated that TIS (2000 Hz and 2020 Hz carrier frequencies) enabled tunable activation of L6 DRG neurons, with the focal region adjustable by altering stimulation amplitude ratios. Low-frequency (20-50 Hz) sinusoidal stimulation effectively blocked C-fiber and Aδ-fiber transmission while sparing fast-conducting A-fibers, with 20 Hz showing highest efficacy. TIS of L6 DRG reversibly suppressed VMR to colorectal distension in both control and TNBS-induced visceral hypersensitive mice. The blocking effect was fine-tunable by adjusting interfering stimulus signal amplitude ratios. No apparent immediate immune responses were observed in DRG following hours-long TIS. In conclusion, TIS on lumbosacral DRG demonstrates promise as a selective, tunable approach for managing chronic visceral pain by effectively blocking C-fiber transmission. This technique addresses limitations of current neuromodulation methods and offers potential for more targeted relief in chronic visceral pain conditions.

Strength of activation and temporal dynamics of bioluminescent-optogenetics in response to systemic injections of the luciferin

BioLuminescent OptoGenetics (“BL-OG”) is a chemogenetic method that can evoke optogenetic reactions in the brain non-invasively. In BL-OG, an enzyme that catalyzes a light producing reaction (i.e., a luciferase) is tethered to an optogenetic element that is activated in response to bioluminescent light. Bioluminescence is generated by injecting a chemical substrate (luciferin, e.g., h-Coelenterazine; h-CTZ) that is catalyzed by the luciferase. By directly injecting the luciferin into the brain, we show that bioluminescent light is proportional to spiking activity, and this relationship scales as a function of luciferin dosage. Here, we build on these previous observations by characterizing the temporal dynamics and dose response curves of bioluminescence generated by luminopsins (LMOs), a proxy of BL-OG effects, to intravenous (IV) injections of the luciferin. We imaged bioluminescence through a thinned skull of mice running on a wheel, while delivering h-CTZ via the tail vein with different dosage concentrations and injection rates. The data reveal a systematic relationship between strength of bioluminescence and h-CTZ dosage, with higher concentration generating stronger bioluminescence. We also found that bioluminescent activity occurs rapidly (< 60 s after IV injection) regardless of concentration dosage. However, as expected, the onset time of bioluminescence is delayed as the injection rate decreases. Notably, the strength and time decay of bioluminescence is invariant to the injection rate of h-CTZ. Taken together, these data show that BL-OG effects are highly consistent across injection parameters of h-CTZ, highlighting the reliability of BL-OG as a minimally invasive neuromodulation method.

A Comprehensive Review of Recent Trends in Surgical Approaches for Epilepsy Management.

Epilepsy is a neurological disorder that affects millions of people worldwide, with a significant proportion of patients experiencing drug-resistant epilepsy, where seizures remain uncontrolled despite medical treatment. This review evaluates the latest surgical techniques for managing epilepsy, focusing on their effectiveness, safety, and the ongoing challenges that hinder their broader adoption. We explored various databases including PubMed, Google Scholar, and Cochrane Library to look for relevant literature using the following keywords: Epilepsy, Resective Surgery, Corpus Collectumy, and Antiepileptic Drugs. A total of 54 relevant articles were found and thoroughly explored. Recent advancements in surgical interventions include resective procedures such as anterior temporal lobectomy, corpus callosotomy, and hemispherectomy, which have been particularly effective in reducing seizures for specific types of epilepsy. Minimally invasive techniques, including laser interstitial thermal therapy and focused ultrasound, are increasingly being used, offering promising outcomes for certain patient groups. Additionally, neuromodulation methods such as deep brain stimulation, vagus nerve stimulation, and responsive neurostimulation provide alternative treatment options, especially for patients who are not suitable candidates for resective surgery. Despite these advancements, the full potential of epilepsy surgery is often underutilized due to various challenges. Inconsistent referral practices, a lack of standardized surgical protocols, and significant socioeconomic barriers continue to limit access to these procedures. Addressing these issues through improved referral processes, better education for healthcare providers and patients, and ensuring equitable access to advanced surgical treatments is crucial for optimizing patient outcomes. Future research should focus on overcoming these barriers and assessing long-term outcomes to further enhance the care of patients with epilepsy.

Magnetogenetic stimulation inside MRI induces spontaneous and evoked changes in neural circuits activity in rats.

The ability to modulate specific neural circuits and simultaneously visualize and measure brain activity with MRI would greatly impact our understanding of brain function in health and disease. The combination of neurostimulation methods and functional MRI in animal models have already shown promise in elucidating fundamental mechanisms associated with brain activity. We developed an innovative magnetogenetics neurostimulation technology that can trigger neural activity through magnetic fields. Similar to other genetic-based neuromodulation methods, magnetogenetics offers cell-, area-, and temporal-specific control of neural activity. The magnetogenetic protein-Electromagnetic Perceptive Gene (EPG)-is activated by non-invasive magnetic fields, providing a unique way to target neural circuits by the MRI static and gradient fields while simultaneously measuring their effect on brain activity. EPG was expressed in rat's visual cortex and the amplitude of low-frequency fluctuation, resting-state functional connectivity (FC), and sensory activation was measured using a 7T MRI. The results demonstrate that EPG-expressing rats had significantly higher signal fluctuations in the visual areas and stronger FC in sensory areas consistent with known anatomical visuosensory and visuomotor connections. This new technology complements the existing neurostimulation toolbox and provides a means to study brain function in a minimally-invasive way which was not possible previously.

Diabetic peripheral neuropathy and neuromodulation techniques: a systematic review of progress and prospects.

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition. Diabetic peripheral neuropathy, a common complication of diabetes, is characterized by nerve damage due to high blood sugar levels that lead to symptoms, such as pain, tingling, and numbness, primarily in the hands and feet. The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy, while also examining recent developments in this domain. The investigation encompassed an array of neuromodulation methods, including frequency rhythmic electrical modulated systems, dorsal root ganglion stimulation, and spinal cord stimulation. This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy. Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments. Through these efforts, we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

Controlling action potentials with magnetoelectric nanoparticles

Non-invasive or minutely invasive and wireless brain stimulation that can target any region of the brain is an open problem in engineering and neuroscience with serious implications for the treatment of numerous neurological diseases. Despite significant recent progress in advancing new methods of neuromodulation, none has successfully replicated the efficacy of traditional wired stimulation and improved on its downsides without introducing new complications. Due to the capability to convert magnetic fields into local electric fields, MagnetoElectric NanoParticle (MENP) neuromodulation is a recently proposed framework based on new materials that can locally sensitize neurons to specific, low-strength alternating current (AC) magnetic fields (50Hz 1.7 kOe field). However, the current research into this neuromodulation concept is at a very early stage, and the theoretically feasible game-changing advantages remain to be proven experimentally. To break this stalemate phase, this study leveraged understanding of the non-linear properties of MENPs and the nanoparticles' field interaction with the cellular microenvironment. Particularly, the applied magnetic field's strength and frequency were tailored to the M − H hysteresis loop of the nanoparticles. Furthermore, rectangular prisms instead of the more traditional “spherical” nanoparticle shapes were used to: (i) maximize the magnetoelectric effect and (ii) improve the nanoparticle-cell-membrane surface interface. Neuromodulation performance was evaluated in a series of exploratory in vitro experiments on 2446 rat hippocampus neurons. Linear mixed effect models were used to ensure the independence of samples by accounting for fixed adjacency effects in synchronized firing. Neural activity was measured over repeated 4-min segments, containing 90 s of baseline measurements, 90 s of stimulation measurements, and 60 s of post stimulation measurements. 87.5 % of stimulation attempts produced statistically significant (P < 0.05) changes in neural activity, with 58.3 % producing large changes (P < 0.01). In negative controls using either zero or 1.7 kOe-strength field without nanoparticles, no experiments produced significant changes in neural activity (P > 0.05 and P > 0.15 respectively). Furthermore, an exploratory analysis of a direct current (DC) magnetic field indicated that the DC field could be used with MENPs to inhibit neuron activity (P < 0.01). These experiments demonstrated the potential for magnetoelectric neuromodulation to offer a near one-to-one functionality match with conventional electrode stimulation without requiring surgical intervention or genetic modification to achieve success, instead relying on physical properties of these nanoparticles as “On/Off” control mechanisms. One-sentence summaryThis in vitro neural cell culture study explores how to exploit the non-linear and anisotropic properties of magnetoelectric nanoparticles for wireless neuromodulation, the importance of magnetic field strength and frequency matching for optimization, and demonstrates, for the first time, that magnetoelectric neuromodulation can inhibit neural responses.

A preliminary study exploring the effects of transcutaneous spinal cord stimulation on spinal excitability and phantom limb pain in people with a transtibial amputation

Objective. Phantom limb pain (PLP) is debilitating and affects over 70% of people with lower-limb amputation. Other neuropathic pain conditions correspond with increased spinal excitability, which can be measured using reflexes andF-waves. Spinal cord neuromodulation can be used to reduce neuropathic pain in a variety of conditions and may affect spinal excitability, but has not been extensively used for treating PLP. Here, we propose using a non-invasive neuromodulation method, transcutaneous spinal cord stimulation (tSCS), to reduce PLP and modulate spinal excitability after transtibial amputation.Approach. We recruited three participants, two males (5- and 9-years post-amputation, traumatic and alcohol-induced neuropathy) and one female (3 months post-amputation, diabetic neuropathy) for this 5 d study. We measured pain using the McGill Pain Questionnaire (MPQ), visual analog scale (VAS), and pain pressure threshold (PPT) test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes andF-waves, respectively. We delivered tSCS for 30 min d-1for 5 d.Main Results. After 5 d of tSCS, MPQ scores decreased by clinically-meaningful amounts for all participants from 34.0 ± 7.0-18.3 ± 6.8; however, there were no clinically-significant decreases in VAS scores. Two participants had increased PPTs across the residual limb (Day 1: 5.4 ± 1.6 lbf; Day 5: 11.4 ± 1.0 lbf).F-waves had normal latencies but small amplitudes. PRM reflexes had high thresholds (59.5 ± 6.1μC) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 d of tSCS, reflex thresholds decreased significantly (38.6 ± 12.2μC;p< 0.001).Significance. These preliminary results in this non-placebo-controlled study suggest that, overall, limb amputation and PLP may be associated with reduced spinal excitability and tSCS can increase spinal excitability and reduce PLP.