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Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05205915?tab= results, identifier NCT05205915. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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 100 µA amplitude, starting at six weeks 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. Results: 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. Discussion: 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. [ABSTRACT FROM AUTHOR]

Background: Galvanic Vestibular Stimulation (GVS) is a non-invasive electrical stimulation technique that is typically used to probe the vestibular system. When using direct current or very low frequency sine, GVS causes postural sway or perception of illusory (virtual) motions. GVS is commonly delivered using two electrodes placed at the mastoids, however, placements involving additional electrodes / locations have been employed. Our objective was to systematically evaluate all known GVS electrode placements, compare induced current flow, and how it relates to the archetypal sway and virtual motions. The ultimate goal is to help users in having a better understanding of the effects of different placements. Methods: We simulated seven GVS electrode placements with same total injected current using an ultra-high resolution model. Induced electric field (EF) patterns at the cortical and the level of vestibular organs (left and right) were determined. A range of current flow metrics including potential factors such as inter-electrode separation, percentage of current entering the cranial cavity, and symmetricity were calculated. Finally, we relate current flow to reported GVS motions. Results: As expected, current flow patterns are electrode placement specific. Placements with two electrodes generally result in higher EF magnitude. Placements with four electrodes result in lower percentage of current entering the cranial cavity. Symmetric placements do not result in similar EF values in the left and the right organs respectively- highlighting inherent anatomical asymmetry of the human head. Asymmetric placements were found to induce as much as ~3-fold higher EF in one organ over the other. The percentage of current entering the cranial cavity varies between ~15% and ~40% depending on the placement. Conclusions: We expect our study to advance understanding of GVS and provide insight on probable mechanism of action of a certain electrode placement choice. The dataset generated across several metrics will support hypothesis testing relating empirical outcomes to current flow patterns. Further, the differences in current flow will guide stimulation strategy (what placement and how much scalp current to use) and facilitate a quantitatively informed rational / optimal decision. [ABSTRACT FROM AUTHOR]

Background: Cluster headache (CH) is a significant health concern due to its major socioeconomic consequences and most patients being refractory to conventional strategies. For treatment resistant CH, occipital nerve stimulation (ONS) is considered an effective treatment option. Whereas most patients do not adjust the amplitude of the ONS system, a subset changes the amplitude on a regular basis using their remote control, and are therefore referred to as 'voltage tuners'. Anxiety and self-control are thought to be central themes to this behavior. Research on this voltage tuning behavior could provide new insights in the use of ONS as acute attack treatment. To date, voltage tuning has not been assessed for CH. Hence this is a unique study aiming to investigate the occurrence and efficacy of voltage tuning in patients with CH and ONS. Methods: For this analysis, patients with CH who received ONS from 2020–2024, at our university medical center, were included. All patients underwent bilateral ONS implantation. Data on attack frequency, intensity and duration were collected retrospectively. Outcomes on the response, frequency, moment during the day, duration, rationale, sensation, average increase in amplitude, and efficacy of voltage tuning were collected with prospective interviews. Results: Thirty-three patients (M = 20) (42 ± 12.7 years) were included in the current analysis. At 1y follow-up, an overall response rate of 70% (23/33) was found for ONS. In total, 48% (18/33) of patients were defined as voltage tuners. Voltage tuning was performed with an average increase in amplitude of 92 (20–360)%, a frequency of 1–20 times/month and duration of 20 minutes-48 hours. Sensations of voltage tuning were described as "tingling" and/or "pinching". The rationale for voltage tuning in patients varied from prevention and ceasing to lowering the intensity and enhance control of CH attack. Conclusions: Outcomes show that voltage tuning may cease and/or terminate CH attacks and therefore raise interests in the use of ONS as acute attack treatment for patients with resistant CH treated with ONS. Future research on the occurrence and potential of voltage tuning will provide valuable insights for achieving optimal efficacy of ONS and quality of life in patients with CH. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high‐gamma power modulations (HGM) during a visual naming task, although these sites were found language‐negative on standard‐of‐care electrical stimulation mapping (ESM).In drug‐resistant epilepsy patients who underwent resection/ablation after stereo‐electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1‐year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming‐related HGM. The analyses were adjusted for 1‐year seizure freedom, operated hemispheres, and the volumes of surgical lesions.In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [β] = −.10), working memory (β = −.10), VLI (β = −.14), and letter–word identification (LWI; β = −.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (β = −.31), story memory immediate (β = −.27), verbal learning recognition (β = −.18), LWI (β = −.16), spelling (β = −.49), and passage comprehension (β = −.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere.HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits. [ABSTRACT FROM AUTHOR]

Electrical stimulation (ES) techniques, such as deep brain and transcranial electrical stimulation, have shown promise in alleviating the symptoms of depression and other neurological disorders in vivo. A new noninvasive ES method called temporal interference stimulation (TIS), possesses great potential as it can be used to steer the stimulation and possibly selectively modulate different brain regions. To study TIS in a controlled environment, we successfully established an in vitro 'TIS on a chip' setup using rat cortical neurons on microelectrode arrays (MEAs) in combination with a current stimulator. We validated the developed TIS system and demonstrated the spatial steerability of the stimulation by direct electric field measurements in the chip setup. We stimulated cultures of rat cortical neurons at 28 days in vitro (DIV) by two-channel stimulation delivering 1) TIS at 653 Hz and 643 Hz, resulting in a 10 Hz frequency envelope, 2) low-frequency stimulation (LFS) at 10 Hz and 3) high-frequency stimulation (HFS) at 653 Hz. Unstimulated cultures were used as control/sham. We observed the differences in the electric field strengths during TIS, HFS, and LFS. Moreover, HFS and LFS had the smallest effects on neuronal activity. Instead, TIS elicited neuronal electrophysiological responses, especially 24 hours after stimulation. Our 'TIS on a chip' approach eludicates the applicability of TIS as a method to modulate neuronal electrophysiological activity. The TIS on a chip approach provides spatially steerable stimuli while mitigating the effects of high stimulus fields near the stimulation electrodes. Thus, the approach opens new avenues for stimulation on a chip applications, allowing the study of neuronal responses to gain insights into the potential clinical applications of TIS in treating various brain disorders. [ABSTRACT FROM AUTHOR]

The availability of high-power lasers open new frontiers of Terahertz (THz) optics. In this paper, we present a mechanism for the enhanced THz field generation from the laser wakefield excitation during the interaction of an amplitude-modulated laser filament with a magnetized plasma. The derivation of electric and magnetic wakefields in axially magnetized plasma is obtained using the perturbative approach. Amplitude-modulated laser filament generates a significantly stronger transverse current due to laser intensity redistribution by the amplitude modulation. The modulation index of the amplitude modulated laser pulse is used to control the transverse current at THz frequency. Fourfold enhancement takes place in THz field strength for higher values of the modulation index (0–0.4). Also, the conversion efficiency of this mechanism is estimated as 1 0 − 4 that can be enhanced for higher modulation index. Scaling laws are provided for controlling and optimization of generated THz field. This work may be crucial in exploring THz optical phenomena such as THz field-induced Kerr effects and many other nonlinear effects. [ABSTRACT FROM AUTHOR]

Gel‐based adhesives show promising prospects in epidermal bioelectronics because of their potential applications in physiological signal collection and electrical stimulation. An ideal epidermal adhesive should exhibit robust adhesion for lamination and poor adhesion for easy peeling, in addition to strain‐insensitivity in electrical properties for motion‐artifact‐free physiological signal collection. Here, lignosulfonate‐derived organohydrogel adhesives with anisotropic and tunable adhesion, together with unprecedented strain‐insensitivity are synthesized. The organohydrogel exhibits a high interfacial toughness of 728 J m−2 on fresh porcine skin, while the adhesion can be screened by covering a denatured silk fibroin. An anisotropic adhesive with an adhesion heterogeneity is designed, showing a 14.2‐fold difference in adhesion strength along two different directions for on‐demand attachment and removal. The adhesive can transform into a highly porous structure, which has only a 3% resistance increase at 100% strain. The strain‐insensitivity of the adhesive lies in the strong interaction of ions and the 3D porous structure, which enables motion‐artifact‐free and high‐quality electrophysiological signal collection within the strain range of the human skin. The lignosulfonate‐derived on‐demand organohydrogel adhesive is expected to be used in epidermal bioelectronics, human‐machine interaction, metaverse, and beyond. [ABSTRACT FROM AUTHOR]

Bimodal neuromodulation is emerging as a nonsurgical treatment for tinnitus. Bimodal treatment combining sound therapy with electrical tongue stimulation using the Lenire device is evaluated in a controlled pivotal trial (TENT-A3, NCT05227365) consisting of 6-weeks of sound-only stimulation (Stage 1) followed by 6-weeks of bimodal treatment (Stage 2) with 112 participants serving as their own control. The primary endpoint compares the responder rate observed in Stage 2 versus Stage 1, where a responder exceeds 7 points in the Tinnitus Handicap Inventory. In participants with moderate or more severe tinnitus, there is a clinically superior performance of bimodal treatment (58.6%; 95% CI: 43.5%, 73.6%; p = 0.022) compared to sound therapy alone (43.2%; 95% CI: 29.7%, 57.8%), which is not observed in the full cohort across all severity groups. Consistent results are observed for the secondary endpoint based on the Tinnitus Functional Index (bimodal treatment: 45.5%; 95% CI: 31.7%, 59.9%; sound-only stimulation: 29.6%; 95% CI: 18.2%, 44.2%; p = 0.010), where a responder exceeds 13 points. There are no device related serious adverse events. These positive outcomes led to FDA De Novo approval of the Lenire device for tinnitus treatment. Bimodal neuromodulation combining sound therapy with electrical tongue stimulation using the Lenire device is a nonsurgical treatment for tinnitus. Here, the authors show the positive efficacy and safety results of a controlled one-arm pivotal trial that led to FDA De Novo approval of the Lenire device. [ABSTRACT FROM AUTHOR]

Objective: In addition to the well-established advantage that strengthened pelvic musculature increases urethral resistance in stress urinary incontinence (SUI) patients, intra-vaginal electrical stimulation (iVES) has been shown in preclinical studies to improve bladder capacity via the pudendal-hypogastric mechanism. This study investigated whether iVES also benefits bladder storage in SUI patients by focusing on compliance, a viscoelastic parameter critically defining the bladder's storage function, in a clinical study. Moreover, the potential involvement of stimulation-induced neuromodulation in iVESmodified compliance was investigated by comparing the therapeutic outcomes of SUI patients treated with iVES to those who underwent a trans-obturator tape (TOT) implantation surgery, where a mid-urethral sling was implanted without electric stimulation. Patients and methods: Urodynamic and viscoelastic data were collected from 21 SUI patients treated with a regimen combining iVES and biofeedbackassisted pelvic floor muscle training (iVES-bPFMT; 20-min iVES and 20-min bPFMT sessions, twice per week, for 3 months). This regimen complied with ethical standards. Data from 21 SUI patients who received TOT implantation were retrospectively analyzed. Mean compliance (Cm), infused volume (Vinf), and threshold pressure (Pthr) from the pressure-flow/volume investigations were assessed. Results: Compared with the pretreatment control, iVES-bPFMT consistently and significantly increased Cm (18/21; 85%, p = 0.017, N = 21) and Vinf (16/21; 76%, p = 0.046; N = 21) but decreased Pthr (16/21; 76%, p = 0.026, N = 21). In contrast, TOT implantation did not result in consistent or significant changes in Cm, Vinf, or Pthr (p = 0.744, p = 0.295, p = 0.651, respectively; all N = 21). Conclusion: Our results provide viscoelastic and thermodynamic evidence supporting an additional benefit of iVES-bPFMT to bladder storage in SUI patients by modifying bladder compliance, possibly due to the potentiated hypogastric tone, which did not occur in TOT-treated SUI patients. [ABSTRACT FROM AUTHOR]

Background: Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis constitutes a pivotal response by surgical trauma, manifesting as a critical aspect of the acute stress reaction. This hyperactivity resulted in adverse surgical outcomes and is often associated with increased postoperative anxiety. Increased evidence suggests that Nesfatin-1 plays a crucial role in stress responses and stress-related psychiatric disorders. Electroacupuncture (EA) is widely used to alleviate stress responses and anxiety, although its mechanism of action remains unclear. This study aimed to assess the mechanisms by which hypothalamic Nesfatin-1 contribute to the alleviation of HPA axis hyperactivity and anxiety by EA. Methods: Partial hepatectomy (HT) was performed to simulate surgical trauma, and EA was applied at Zusanli (ST36) and Sanyinjiao (SP6). The levels of hypothalamic Nesfatin-1, c-Fos, and corticotropin-releasing hormone (CRH) were detected, and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were regarded as indicators of HPA axis activity. Anxiety levels were assessed through open field tests (OFT), elevated plus maze (EPM), and light–dark box tests (LDBT). To investigate the role of Nesfatin-1, its expression was modulated using stereotactic viral injections or plasmid transfections. Transcriptome sequencing was employed to explore the downstream signaling pathways of Nesfatin-1. Additionally, brain cannula implantation was performed to facilitate targeted drug administration. Results: Our findings demonstrated that EA reduced the hypothalamic overexpression of CRH and Nesfatin-1, as well as serum levels of ACTH and CORT. Additionally, it alleviated anxiety-like behaviors resulting from surgical trauma. We observed that overexpression of Nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) triggered hyperactivity of the HPA axis and anxiety. Conversely, knocking down Nesfatin-1 in the PVN reversed these effects caused by surgical trauma. Transcriptome sequencing identified the extracellular regulated protein kinases (ERK)/cAMP-response element binding protein (CREB) pathway as a key mediator in the impacts of surgical trauma and EA on the hypothalamus. Both in vivo and in vitro studies showed that overexpression of Nesfatin-1 activated the ERK/CREB pathway. Furthermore, administering ERK or CREB inhibitors into the PVN mitigated HPA axis hyperactivity and anxiety-like behaviors induced by surgical trauma. Finally, EA was observed to decrease the phosphorylation levels of ERK and CREB in the PVN. Conclusion: EA alleviates HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma through inhibition of Nesfatin-1/ERK/CREB pathway in the hypothalamus. [ABSTRACT FROM AUTHOR]

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aβ-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aβ tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aβ fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50–150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aβ-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aβ-fiber inputs in pain and reflex signaling. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is characterized by cognitive deficits that are linked to prefrontal cortex dysfunction. While transcranial direct current stimulation (tDCS) shows promise for improving cognition, the effects of intensified 3mA tDCS protocols on brain physiology are unknown. This project aims to elucidate the neurophysiological and cognitive effects of an intensified prefrontal tDCS protocol in SCZ. Methods: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, trial. Forty-eight participants with SCZ and cognitive impairment (measured via a set of executive functions tests) will be randomly allocated to receive either a single session of active (n = 24) or sham (n = 24) tDCS (20-min, 3-mA). The anodal and cathodal electrodes are positioned over the left and right DLPFC respectively. The stimulation occurs concurrently with the working memory task, which is initiated precisely 5 minutes after the onset of tDCS. Structural and resting-state (rs-fMRI) scans are conducted immediately before and after both active and sham tDCS using a 3 Tesla scanner (Siemens Prisma model) equipped with a 64-channel head coil. The primary outcome will be changes in brain activation (measures vis BOLD response) and working memory performance (accuracy, reaction time). Discussion: The results of this study are helpful in optimizing tDCS protocols in SCZ and inform us of neurocognitive mechanisms underlying 3 mA stimulation. This study will additionally provide initial safety and efficacy data on a 3 mA tDCS protocol to support larger clinical trials. Positive results could lead to rapid and broader testing of a promising tool for debilitating symptoms that affect the majority of patients with SCZ. The results will be made available through publications in peer-reviewed journals and presentations at national and international conferences. [ABSTRACT FROM AUTHOR]

Background Methods Key Results Conclusions and Inferences Increasing age increases the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to this phenotype is unclear. This study explored the effects of age on key motility patterns in the murine colon and determined the contribution that altered neurokinin 2 (NK2) ‐mediated signaling made to the aging phenotype.Mucosal reflexes, colonic migrating motor complexes (CMMCs) and colonic motility assays were explored in isolated ex vivo colons from 3, 12–14, 18‐ and 24‐months old mice and the NK2‐mediated response determined. Electrical field stimulation (EFS) or exogenous drug application were used to explore the role of the mucosa in colonic segments.Aging reduced the force of contraction of the distal colon mucosal reflex, the frequency and force of contraction of CMMCs and the NK2‐mediated component of both motility patterns. Ondansetron, a 5‐HT3 receptor antagonist, blocked a component of both motility patterns in full thickness but not in mucosa‐free segments of the distal colon. 5, hydroxytryptamine (5‐HT) and EFS‐evoked NK2‐dependent contractions were reduced with increasing age. Smooth muscle sensitivity to 5‐HT or neurokinin A (NKA) was not altered with age. In isolated colon motility assays application of NKA decreased transit time in 24‐months colon and the NK2 antagonist GR159897 increased transit times in both 3‐ and 24‐months old colons.Aging impairs key motility patterns in the murine colon. These changes involve a decrease in mucosally‐evoked NK2‐mediated signaling. Targeting NK2‐mediated signaling may provide a novel approach to treating age‐related motility disorders in the lower bowel. [ABSTRACT FROM AUTHOR]

Background: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACSrelated publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research. Material and methods: The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references. Results: A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford's law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends. Conclusion: tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field. [ABSTRACT FROM AUTHOR]

The consequences of short‐term disuse are well known, but effective countermeasures remain elusive. This study investigated the effects of neuromuscular electrical stimulation (NMES) during 5 days of bed rest on retaining lower limb muscle mass and muscle function in healthy young and old participants. One leg received NMES of the quadriceps muscle (3 × 30min/day) (NMES), and the other served as a control (CON). Isometric quadriceps strength (MVC), rate of force development (RFD), lower limb lean mass, and muscle thickness were assessed pre‐and post‐intervention. Muscle thickness remained unaltered with NMES in young and increased in old following bed rest, while it decreased in CON legs. In old participants, mid‐thigh lean mass (MTLM) was preserved with NMES while decreased in CON legs. In the young, only a tendency to change with bed rest was detected for MTLM. MVC and early‐phase RFD decreased in young and old, irrespective of NMES. In contrast, late‐phase RFD was retained in young participants with NMES, while it decreased in young CON legs, and in the old, irrespective of NMES. NMES during short‐term bed rest preserved muscle thickness but not maximal muscle strength. While young and old adults demonstrated similar adaptive responses in preventing the loss of skeletal muscle thickness, RFD was retained in the young only. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin–eosin) and immunohistochemistry for NeuN, β-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for β-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in β-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury. [ABSTRACT FROM AUTHOR]

Eccentric training induces greater hypertrophy while causing more muscle damage than concentric training. This study examined the effects of small-range eccentric contractions (SR-ECCs) and large-range eccentric contractions (LR-ECCs) on muscle morphology, contractility, and damage in rats. Thirty male Fischer 344 rats were divided into five groups: small-range ECC single-bout (SR-ECCSB, n = 4), large-range ECC single-bout (LR-ECCSB, n = 4), SR-ECC intervention (SR-ECCIntv, n = 7), LR-ECC intervention (LR-ECCIntv, n = 8), and control (Cont, n = 7). These groups underwent transcutaneous electrical stimulation involving 80 ECCs twice a week for four weeks. The results indicated that the LR-ECCSB group had more Evans blue dye-positive fibers than other groups. The SR-ECCIntv group showed no increase in the mean myofiber cross-sectional area. However, Pax7+ and Ki67+ cells significantly increased in both ECCIntv groups compared to the Cont group, and the connective tissue area was significantly greater in the LR-ECCIntv than in others. Muscle force was lower in both ECCIntv groups compared to the Cont group. These findings suggest that SR-ECC intervention may induce a smaller increase in the number of fibers with a large myofiber cross-sectional area and satellite cell proliferation with less muscle damage and myofibrosis compared to LR-ECCs. [ABSTRACT FROM AUTHOR]

The development of artificial tetrachromatic vision holds great potential to enhance human color perception and discrimination, thereby enabling more effective navigation in diverse environments. Herein, an artificial tetrachromatic synaptic device is presented built upon 2D‐3D vertically stacked semiconductors composed of tungsten diselenide (WSe2)‐gallium nitride (GaN) configuration, forming a dual‐channel floating gate transistor (FGT). Under the concerted influence of electrical and optical stimulation, the device successfully mimics fundamental tetrachromatic synaptic behaviors, including short‐term potentiation (STP), weak long‐term potentiation (wLTP), long‐term potentiation (LTP), paired‐pulse facilitation (PPF), spike number‐dependent plasticity (SNDP), and spike rate‐dependent plasticity (SRDP). Notably, the plasticity of the device can be further modulated under ultraviolet (UV) stimulation, providing insights into the modulation of synaptic plasticity through the photogenerated carrier dynamics in the GaN channel. These results imply that WSe2‐GaN‐based FGT architecture with dual‐channel characteristics seamlessly integrates optical sensing and synaptic simulation functionalities, representing a promising avenue for the development of next‐generation artificial visual perception systems (AVPS), with a particular advantage for the pursuit of high‐performance artificial tetrachromatic neuromorphic computing applications of the future. [ABSTRACT FROM AUTHOR]

[Display omitted] Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo , SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments. [ABSTRACT FROM AUTHOR]

Angiotensin receptor blockade has been linked to aspects of aversive learning and memory formation and to the prevention of posttraumatic stress disorder symptom development. We investigated the influence of the angiotensin receptor blocker losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized, placebo-controlled design, we tested 45 (18 female) healthy volunteers during a baseline session, after application of losartan or placebo (drug session), and during a follow-up session. During each session, participants engaged in a task in which they had to predict the probability of an electrical stimulation on every trial while the true shock contingencies switched repeatedly between phases of high and low shock threat. Computational reinforcement learning models were used to investigate learning dynamics. Acute administration of losartan significantly reduced participants' adjustment during both low-to-high and high-to-low threat changes. This was driven by reduced aversive learning rates in the losartan group during the drug session compared with baseline. The 50-mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out a general reduction in attention and engagement. Decreased adjustment of aversive expectations was maintained at a follow-up session 24 hours later. This study shows that losartan acutely reduces Pavlovian learning in aversive environments, thereby highlighting a potential role of the renin-angiotensin system in anxiety development. [ABSTRACT FROM AUTHOR]

Purpose: Aphasia is an acquired language impairment that commonly results from stroke. Non-invasive brain stimulation (NIBS) might accelerate aphasia recovery trajectories and has seen mounting popularity in recent aphasia rehabilitation research. The present review aimed to: (1) summarise all existing literature on NIBS as a post-stroke aphasia treatment; and (2) provide recommendations for future NIBS-aphasia research. Materials and methods: Databases for published and grey literature were searched using scoping review methodology. 278 journal articles, conference abstracts/posters, and books, and 38 items of grey literature, were included for analysis. Results: Quantitative analysis revealed that ipsilesional anodal transcranial direct current stimulation and contralesional 1-Hz repetitive transcranial magnetic stimulation were the most widely used forms of NIBS, while qualitative analysis identified four key themes including: the roles of the hemispheres in aphasia recovery and their relationship with NIBS; heterogeneity of individuals but homogeneity of subpopulations; individualisation of stimulation parameters; and much remains under-explored in the NIBS-aphasia literature. Conclusions: Taken together, these results highlighted systemic challenges across the field such as small sample sizes, inter-individual variability, lack of protocol optimisation/standardisation, and inadequate focus on aphasiology. Four key recommendations are outlined herein to guide future research and refine NIBS methods for post-stroke aphasia treatment. IMPLICATIONS FOR REHABILITATION: A comprehensive review of non-invasive brain stimulation (NIBS) post-stroke aphasia literature, including all study designs, was required. Review of this literature revealed that anodal transcranial direct current stimulation is the mostly commonly used type of NIBS in aphasia treatment research. Systemic challenges across the field hinder prospective translation of NIBS into aphasia practice. Aphasia rehabilitation professionals should note that further research is required before NIBS is suitable for translation into clinical practice. [ABSTRACT FROM AUTHOR]

Functional electrical stimulation (FES) can support functional restoration of a paretic limb post-stroke. Hebbian plasticity depends on temporally coinciding pre- and post-synaptic activity. A tight temporal relationship between motor cortical (MC) activity associated with attempted movement and FES-generated visuo-proprioceptive feedback is hypothesized to enhance motor recovery. Using a brain–computer interface (BCI) to classify MC spectral power in electroencephalographic (EEG) signals to trigger FES-delivery with detection of movement attempts improved motor outcomes in chronic stroke patients. We hypothesized that heightened neural plasticity earlier post-stroke would further enhance corticomuscular functional connectivity and motor recovery. We compared subcortical non-dominant hemisphere stroke patients in BCI-FES and Random-FES (FES temporally independent of MC movement attempt detection) groups. The primary outcome measure was the Fugl-Meyer Assessment, Upper Extremity (FMA-UE). We recorded high-density EEG and transcranial magnetic stimulation-induced motor evoked potentials before and after treatment. The BCI group showed greater: FMA-UE improvement; motor evoked potential amplitude; beta oscillatory power and long-range temporal correlation reduction over contralateral MC; and corticomuscular coherence with contralateral MC. These changes are consistent with enhanced post-stroke motor improvement when movement is synchronized with MC activity reflecting attempted movement. [ABSTRACT FROM AUTHOR]

Background: Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). Case presentation: A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. Conclusion: Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia. [ABSTRACT FROM AUTHOR]

Objectives: While electrical stimulation has been demonstrated to improve medical research council (MRC) scores in critically ill patients, its effectiveness remains a subject of debate. This meta-analysis aimed to discuss recent insights into the effectiveness of electrical stimulation in improving muscle strength and its effects on different clinical outcomes in critically ill adults. Methods: A comprehensive search of major electronic databases, including PubMed, Cochrane Library, and Embase, was conducted from inception to June 15, 2024, to identify randomized controlled trials (RCTs) that evaluated the effects of electrical stimulation in critically ill patients. The analysis focused on comparing electrical stimulation to standard care, sham interventions, or placebo. Outcomes of interest included MRC scores, duration of mechanical ventilation (MV), mortality rate, and intensive care unit (ICU) and hospital length of stay (LOS). Results: A total of 23 RCTs, including 1798 patients, met the inclusion criteria. The findings demonstrated a significant benefit of electrical stimulation over usual care in enhancing global muscle strength, as measured by MRC scores (MD =3.62, 95% CI 0.94 to 6.30, p = 0.0008, I2 = 87%). While subgroup analysis of electrical muscle stimulation (EMS) demonstrated no significant effect on ICU LOS, sensitivity analysis indicated a potential reduction in ICU LOS for both EMS (MD = -11.0, 95% CI -21.12 to -0.88, p = 0.03) and electrical stimulation overall (MD = -1.02, 95% CI -1.96 to -0.08, p = 0.03) compared to the control group. In addition, sensitivity analysis suggested that both electrical stimulation (MD = -2.38, 95% CI -3.81 to -0.94, p = 0.001) and neuromuscular electrical stimulation (NMES) specifically (MD = -2.36, 95% CI -3.85 to -0.88, p = 0.002) may contribute to a decrease in hospital LOS. No statistically significant differences were observed in mortality or duration of MV. Conclusion: Electrical stimulation appears to be an effective intervention for improving MRC scores in critically ill patients. However, further research is warranted to explain the potential effects of electrical stimulation on hospital LOS and ICU LOS. [ABSTRACT FROM AUTHOR]

Background: After a stroke, damage to the part of the brain that controls movement results in the loss of motor function. Brain-computer interface (BCI)-based stroke rehabilitation involves patients imagining movement without physically moving while the system measures the perceptual-motor rhythm in the motor cortex. Visual feedback through virtual reality and functional electrical stimulation is provided simultaneously. The superiority of real BCI over sham BCI in the subacute phase of stroke remains unclear. Therefore, we aim to compare the effects of real and sham BCI on motor function and brain activity among patients with subacute stroke with weak wrist extensor strength. Methods: This is a double-blinded randomized controlled trial. Patients with stroke will be categorized into real BCI and sham BCI groups. The BCI task involves wrist extension for 60 min/day, 5 times/week for 4 weeks. Twenty sessions will be conducted. The evaluation will be conducted four times, as follows: before the intervention, 2 weeks after the start of the intervention, immediately after the intervention, and 4 weeks after the intervention. The assessments include a clinical evaluation, electroencephalography, and electromyography using motor-evoked potentials. Discussion: Patients will be categorized into two groups, as follows: those who will be receiving neurofeedback and those who will not receive this feedback during the BCI rehabilitation training. We will examine the importance of motor imaging feedback, and the effect of patients' continuous participation in the training rather than their being passive. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation (TBS), a patterned brain stimulation technique that mimics rhythmic bursts of 3–8 Hz endogenous brain rhythms, has emerged as a promising therapeutic approach for treating a wide range of brain disorders, though the neural mechanism of TBS action remains poorly understood. We investigated the neural effects of TBS using intracranial EEG (iEEG) in 10 pre-surgical epilepsy participants undergoing intracranial monitoring. Here we show that individual bursts of direct electrical TBS at 29 frontal and temporal sites evoked strong neural responses spanning broad cortical regions. These responses exhibited dynamic local field potential voltage changes over the course of stimulation presentations, including either increasing or decreasing responses, suggestive of short-term plasticity. Stronger stimulation augmented the mean TBS response amplitude and spread with more recording sites demonstrating short-term plasticity. TBS responses were stimulation site-specific with stronger TBS responses observed in regions with strong baseline stimulation effective (cortico-cortical evoked potentials) and functional (low frequency phase locking) connectivity. Further, we could use these measures to predict stable and varying (e.g. short-term plasticity) TBS response locations. Future work may integrate pre-treatment connectivity alongside other biophysical factors to personalize stimulation parameters, thereby optimizing induction of neuroplasticity within disease-relevant brain networks. Neural mechanisms underpinning theta burst stimulation (TBS) and its implications for neuropsychiatric disorders are not fully understood. Here authors show theta burst stimulation delivered by intracranial electrodes results in measurable responses that change over time, suggestive of neuroplasticity. These responses can be predicted by baseline biophysical parameters such as functional connectivity. [ABSTRACT FROM AUTHOR]

Introduction: Lower leg pain and symptoms, and poor leg circulation are common in older adults. These can significantly affect their function and quality of life. Neuromuscular electrical stimulation (NMES) applied via the feet as 'foot NMES' activates the leg musculovenous pump. This study investigated the effects of foot NMES administered at home using Revitive® among community-dwelling older adults with lower leg pain and/or other lower leg symptoms such as cramps, or sensations of tired, aching, and heavy feeling legs. Methods: A randomised placebo-controlled study with three groups (2 NMES, 1 Sham) and three assessments (baseline, week 8, week 12 follow-up) was carried out. Self-reported function using Canadian occupational performance measure (COPM), leg pain, overall leg symptoms score (heaviness, tiredness, aching, or cramps), and ankle blood flow were assessed. Analysis of covariance (ANCOVA) and logistic regression were used to compare the groups. Statistical significance was set at p < 0.05 (two-sided 5%). Results: Out of 129 participants enrolled, 114 completed the study. The improvement in all outcomes were statistically significant for the NMES interventions compared to Sham at both week 8 (p < 0.01) and week 12 (p < 0.05). The improvement in COPM met the minimal clinically important difference (MCID) for the NMES interventions compared to Sham at both week 8 (p < 0.005) and week 12 (p < 0.05). Improvement in leg pain met MCID at week 8 compared to Sham (p < 0.05). Ankle blood flow increased approximately 3-fold during treatment compared to Sham. Compliance with the interventions was high and no device-related adverse events were reported. Conclusions: The home-based foot NMES is safe, and significantly improved self-reported function, leg pain and overall leg symptoms, and increased ankle blood flow compared to a Sham among older adults. Trial registration: The trial was prospectively registered in ISRCTN on 17/06/2019 with registration number ISRCTN10576209. It can be accessed at https://www.isrctn.com/ISRCTN10576209. Key points: • Eight weeks of daily home-based foot NMES therapy delivered using Revitive devices significantly improved self-reported function, leg pain and other leg symptoms in community-dwelling older adults when compared to a Sham. • Significant improvements in self-reported function and leg symptoms were sustained when measured at the follow-up four weeks after the intervention period. • During use, the foot NMES induced approximately a three-fold increase in ankle blood flow volume and intensity of blood flow when compared to a Sham. • No device-related adverse events were reported. • Compliance with the foot NMES intervention was high. [ABSTRACT FROM AUTHOR]

With electrical stimulation, retinal prostheses bypass dysfunctional photoreceptors and activate the surviving bipolar or retinal ganglion cells (RGCs). Therefore, the effective modulation of RGCs is crucial for developing retinal prostheses. Substantial research has been performed on the ability of an electrical stimulus to generate a reliable RGC response. However, different experimental conditions show varying levels of how well the electrical stimulation evokes RGC spikes. Therefore, in this study, we attempted to extract an indicator to understand how the electrical stimulation effectively evokes RGC spikes. Six cynomolgus monkeys were used: three as controls and three as an N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model. The retinal recordings were performed using 8 x 8 multi-electrode arrays (MEAs). Electrical stimulation consisted of symmetrical biphasic pulses of varying amplitudes and durations. The number of stimulation conditions that resulted in significantly higher post-stimulation firing rates than pre-stimulus firing rates was defined as the modulation efficiency ratio (MER). The MER was significantly lower in degenerated retinas than in normal retinas. We investigated the relationship between the variables and the MER in normal and degenerated primate RGCs. External variables, such as duration and inter-electrode distance, and internal variables, such as average firing rates and statistics (mean, standard deviation, and coefficient of variation [CV]) of inter-spike intervals (ISIs) of spontaneous spikes, were used. External variables had similar effects on MER in normal and degenerated RGCs. In contrast, internal variables affected MER differently in normal and degenerated RGCs. While in normal RGCs, they were not related to MER, in degenerated RGCs, the mean ISIs were positively correlated with MER, and the CV of ISIs was negatively correlated with MER. The most important variable affecting MER was the mean ISI. A shorter ISI indicates hyperactive firing in the degenerated retina, which prevents electrical stimulation from evoking more RGCs. We believe that this hyperactivity in degenerated retinas results in a lower MER than that in the normal retina. Our findings can be used to optimize the selection of stimulation channels for in vitro MEA experiments and practical calibration methods to achieve higher efficiency when testing retinal prostheses. [ABSTRACT FROM AUTHOR]

Ingestible electronics have the capacity to transform our ability to effectively diagnose and potentially treat a broad set of conditions. Current applications could be significantly enhanced by addressing poor electrode-tissue contact, lack of navigation, short dwell time, and limited battery life. Here we report the development of an ingestible, battery-free, and tissue-adhering robotic interface (IngRI) for non-invasive and chronic electrostimulation of the gut, which addresses challenges associated with contact, navigation, retention, and powering (C-N-R-P) faced by existing ingestibles. We show that near-field inductive coupling operating near 13.56 MHz was sufficient to power and modulate the IngRI to deliver therapeutically relevant electrostimulation, which can be further enhanced by a bio-inspired, hydrogel-enabled adhesive interface. In swine models, we demonstrated the electrical interaction of IngRI with the gastric mucosa by recording conductive signaling from the subcutaneous space. We further observed changes in plasma ghrelin levels, the "hunger hormone," while IngRI was activated in vivo, demonstrating its clinical potential in regulating appetite and treating other endocrine conditions. The results of this study suggest that concepts inspired by soft and wireless skin-interfacing electronic devices can be applied to ingestible electronics with potential clinical applications for evaluating and treating gastrointestinal conditions. Existing ingestible electronics suffer from poor tissue contact, short dwell time, and limited battery life. Here, the authors report an ingestible, battery- free, and tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut. [ABSTRACT FROM AUTHOR]

• Afferent stimulation elicited a greater corticospinal drive to lumbar multifidus muscles in CLBP in comparison to controls. • Afferent stimulation alone elicited a larger reduction in paravertebral muscles activity compared to controls. • These results suggest an alteration of sensorimotor integration in our sample of participants with chronic low back pain. Objective: Chronic low back pain (CLBP) impacts on spine movement. Altered sensorimotor integration can be involved. Afferents from the lumbo-pelvic area might be processed differently in CLBP and impact on descending motor control. This study aimed to determine whether afferents influence the corticomotor control of paravertebral muscles in CLBP. Fourteen individuals with CLBP (11 females) and 13 pain-free controls (8 females) were tested with transcranial magnetic stimulation (TMS) to measure the motor-evoked potential [MEP] amplitude of paravertebral muscles. Noxious and non-noxious electrical stimulation, and magnetic stimulation in the lumbo-sacral area were used as afferent stimuli and triggered 20 to 200 ms prior to TMS. EMG modulation elicited by afferent stimulation alone was measured to control net motoneuron excitability. MEP/EMG ratio was used as a measure of corticospinal excitability with control of net motoneuron excitability. MEP/EMG ratio was larger at 60, 80 and 100-ms intervals in CLBP compared to controls, and afferent stimulations alone reduced EMG amplitude greater in CLBP than controls at 100 ms. Our results suggest alteration in sensorimotor integration in CLBP highlighted by a greater facilitation of the descending corticospinal input to paravertebral muscles. Our results can help to optimise interventions by better targeting mechanisms. [ABSTRACT FROM AUTHOR]

For the human brain to operate, populations of neurons across anatomical structures must coordinate their activity within milliseconds. To date, our understanding of such interactions has remained limited. We recorded directly from the hippocampus (HPC), posteromedial cortex (PMC), ventromedial/orbital prefrontal cortex (OFC), and the anterior nuclei of the thalamus (ANT) during two experiments of autobiographical memory processing that are known from decades of neuroimaging work to coactivate these regions. In 31 patients implanted with intracranial electrodes, we found that the presentation of memory retrieval cues elicited a significant increase of low frequency (LF < 6 Hz) activity followed by cross-regional phase coherence of this LF activity before select populations of neurons within each of the four regions increased high-frequency (HF > 70 Hz) activity. The power of HF activity was modulated by memory content, and its onset followed a specific temporal order of ANT→HPC/PMC→OFC. Further, we probed cross-regional causal effective interactions with repeated electrical pulses and found that HPC stimulations cause the greatest increase in LF-phase coherence across all regions, whereas the stimulation of any region caused the greatest LF-phase coherence between that particular region and ANT. These observations support the role of the ANT in gating, and the HPC in synchronizing, the activity of cortical midline structures when humans retrieve self-relevant memories of their past. Our findings offer a fresh perspective, with high temporal fidelity, about the dynamic signaling and underlying causal connections among distant regions when the brain is actively involved in retrieving self-referential memories from the past. [ABSTRACT FROM AUTHOR]

AbstractThis paper aims to investigate the impact of conventional rehabilitation training and neuromuscular electrical stimulation (NMES) on the recovery of motor abilities in patients following ligament injury reconstruction. Forty postoperative patients who underwent surgery for anterior cruciate ligament reconstruction (ACLR) were randomly allocated to either the conventional rehabilitation group or the NMES group. The NMES group received NMES treatment in addition to the conventional rehabilitation program starting from eight weeks postoperatively. Various parameters, including knee joint function, stability, and balance, were compared between the two groups at eight weeks and 12 weeks postoperatively. Compared to the data at eight weeks postoperatively, both groups exhibited significant improvements in all measured indicators at 12 weeks postoperatively (p < 0.05). In the 12th week after the surgery, the NMES group demonstrated a Lysholm score of 93.18 ± 3.67 points, an IKDC score of 84.65 ± 2.33 points, a KT-2000 measurement of 0.88 ± 0.45 mm, a thigh circumference difference of −1.33 ± 0.55 cm, a knee flexion angle of 130.12 ± 4.21°, a single-leg standing time of 60.12 ± 9.33 s, a YBT score of 70.26 ± 2.68 points, and a Bulgarian split squat 1RM size of 58.07 ± 6.85 kg; all of these results were significantly superior to those observed in the conventional group (p < 0.05). NMES significantly enhances the recovery of athletic ability in patients following postoperative ACLR and can be effectively applied in clinical practice. [ABSTRACT FROM AUTHOR]

Neurofibromatosis Type 1 (NF1) is a complex genetic disorder characterized by the development of benign neurofibromas, which can cause significant morbidity in affected individuals. While the molecular mechanisms underlying NF1 pathogenesis have been extensively studied, the development of effective therapeutic strategies remains a challenge. This paper presents the development and validation of a novel biomaterial testing model to enhance our understanding of NF1 pathophysiology, disease mechanisms and evaluate potential therapeutic interventions. Our long-term goal is to develop an invitro model of NF1 to evaluate drug targets. We have developed an in vitro system to test the cellular behavior of NF1 patient derived cells on electroconductive aligned nanofibrous biomaterials with electrical stimulatory cues. We hypothesized that cells cultured on electroconductive biomaterial will undergo morphological changes and variations in cell proliferation that could be further enhanced with the combination of exogenous electrical stimulation (ES). In this study, we developed electrospun Hyaluronic Acid–Carbon Nanotube (HA-CNT) nanofiber scaffolds to mimic the axon's topographical and bioelectrical cues that influence neurofibroma growth and development. The cellular behavior was qualitatively and quantitively analyzed through immunofluorescent stains, Alamar blue assays and ELISA assays. Schwann cells from NF1 patients appear to have lost their ability to respond to electrical stimulation in the development and regeneration range, which was seen through changes in morphology, proliferation and NGF release. Without stimulation, the conductive material enhances NF1 SC behavior. Wild-type SC respond to electrical stimulation with increased cell proliferation and NGF release. Using this system, we can better understand the interaction between axons and SC that lead to tumor formation, homeostasis and regeneration. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectiveMethodsResultsDiscussionTo decide what programming parameters to use for cochlear implants (CIs) in partial deaf patients can be challenging.The processor programming form, categorised as electrical complement (EC), electro-acoustic-stimulation (EAS) or electric stimulation (ES), and difficulties switching programming form were investigated.A retrospective investigation of medical records and audiograms was conducted in adult patients intended for EC and EAS.Eighty-four ears (80 patients) were included. Twenty ears were initially fitted with EC, 32 with EAS, 30 with ES and 2 with both EC and EAS. Sixty-four ears met the criteria to use EC or EAS at initial fitting, however only 54 ears were fitted with EC or EAS initially. Twenty-eight patients altered between at least two programming forms and six of those experienced difficulties to adapt to a new form when their low-frequency hearing deteriorated. Twenty-five percent of patients initially fitted with EC or EAS switched programming form within two years.Further studies on how to choose the most beneficial sound processor programming parameters for EC and EAS, and when to change between programming forms, are warranted as well as clear guidance on choosing the right candidates for EC and EAS. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Essential tremor (ET) is a common debilitating condition, yet current treatments often fail to provide satisfactory relief. Transcutaneous spinal cord electrical stimulation (tSCS) has emerged as a potential noninvasive neuromodulation technique capable of disrupting the oscillatory activity underlying tremors.This study aimed to investigate the potential of tSCS to disrupt tremor in a frequency‐dependent manner in a cohort of patients with ET.Eighteen patients with ET completed the study. The experiment consisted of 60‐s postural tremor recording, during tSCS at tremor frequency, at 1 Hz, at 21 Hz, no stimulation, and trapezius stimulation. Tremor frequency and amplitude were analyzed and compared across the conditions.We found tremor amplitude reduction at tremor frequency stimulation significant only during the second half of the stimulation. The same stimulation resulted in the highest number of responders. tSCS at 1 Hz showed a trend toward decreased tremor amplitude in the latter half of stimulation. tSCS at 21 Hz did not produce any significant alterations in tremor, whereas trapezius stimulation exacerbated it. Notably, during tremor frequency stimulation, a subgroup of responders exhibited consistent synchronization between tremor phase and delivered stimulation, indicating tremor entrainment.Cervical tSCS holds promise for alleviating postural tremor in patients with ET when delivered at the subject's tremor frequency. The observed changes in tremor amplitude likely result from the modulation of spinal cord circuits by tSCS, which disrupts the oscillatory drive to muscles by affecting afferent pathways or spinal reflexes. However, the possibility of an interplay between spinal and supraspinal centers cannot be discounted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The development of high‐performance artificial synaptic neuromorphic devices poses a significant challenge in the creation of biomimetic sensing neural systems that seamlessly integrate both sensory and computational functionalities. In pursuit of this objective, promising bionic opto‐olfactory co‐sensory artificial synapse devices are constructed utilizing the BP‐C/CNT (2D/1D) hybrid filter membrane as the resistive layer. Experimental results demonstrated that the devices seamlessly integrated the light modulation, gas detection, and biological synaptic functions into a single device while addressing the challenge with separating artificial synaptic devices from sensors. These devices offered the following advantages: 1) Simulating visual synapses, they can effectively replicate fundamental synaptic functions under both electrical and optical stimulation. 2) By emulating olfactory synapse responses to specific gases, they can achieve ultra‐low detection limits and rapid identification of ethanol and acetone gases. 3) They enable photo‐olfactory co‐sensing simulations that mimic synaptic function under light‐modulated pulse conditions in distinct gas environments, facilitating the study of synaptic learning rules and Pavlovian responses. This work provides a pioneering approach for exploring highly stable 2D BP‐based optoelectronics and advancing the development of biomimetic neural systems. [ABSTRACT FROM AUTHOR]

Immobilization following trauma or surgery induces skeletal muscle atrophy, and improvement in the muscle atrophy is critical for successful clinical outcomes. The purpose of this study is to evaluate the effect of electrical muscle stimulation (EMS) on muscle atrophy. The study design is a controlled laboratory study. Eighty rats (56 to establish the deltoid muscle atrophy [DMA] model and 24 to evaluate the effect of EMS on the model) were used. DMA was induced by completely immobilizing the right shoulder of each rat by placing sutures between the scapula and humeral shaft, with the left shoulder as a control. After establishing the DMA model, rats were randomly assigned into three groups: low‐frequency EMS (L‐EMS, 10 Hz frequency), medium‐frequency EMS (M‐EMS, 50 Hz frequency), and control (eight rats per group). After 3 weeks, the deltoid muscles of each rat were harvested, alterations in gene expression and muscle cell size were evaluated, and immunohistochemical analysis was performed. DMA was most prominent 3 weeks after shoulder immobilization. Murf1 and Atrogin were significantly induced at the initial phase and gradually decreased at approximately 3 weeks; however, MyoD expressed an inverse relationship with Murf1 and Atrogin. IL6 expression was prominent at 1 week. The time point for the EMS effect evaluation was selected at 3 weeks, when the DMA was the most prominent with a change in relevant gene expression. The M‐EMS group cell size was significantly larger than that of L‐EMS and control group in both the immobilized and intact shoulders (all p < 0.05), without significant differences between the L‐EMS and control groups. The M‐EMS group showed significantly lower mRNA expressions of Murf1 and Atrogin and higher expressions of MyoD and Col1A1 than that of the control group (all p < 0.05). In immunohistochemical analysis, similar results were observed with lower Atrogin staining and higher MyoD and Col1A1 staining in the M‐EMS group. DMA model was established by complete shoulder immobilization, with the most prominent muscle atrophy observed at 3 weeks. M‐EMS improved DMA with changes in the expression of relevant genes. M‐EMS might be a solution for strengthening atrophied skeletal muscles and facilitating rehabilitation after trauma or surgery. [ABSTRACT FROM AUTHOR]

Background Purpose Electrical stimulation of the gut has been investigated in recent decades with a view to treating various gastro‐intestinal motility disorders including, among others, gastric electrical stimulation to relieve nausea and vomiting associated with gastroparesis and sacral neuromodulation to treat fecal incontinence and/or constipation. Although their symptomatic efficacy has been ascertained by randomized controlled trials, their mechanisms of action are not fully understood.This review summarizes the past year's literature on the mechanisms of action of gut electrical stimulation therapies, including their impact on the gut‐brain axis. [ABSTRACT FROM AUTHOR]

Piezoelectric nanomaterials for wireless neuromodulation is a promising alternative to traditional electrical stimulation. However, the low‐avidity between piezoelectric nanomaterials and cellular membranes leads to low efficiency of electrical signal transmission, which requires high‐intensity thresholds of ultrasound stimulation (US). Here, lead‐free piezoelectric (K,Na)NbO3 (KNN) nanoparticles (NPs) with cholesterol coating (KNNC) are presented, in which Cholesterol can be accommodated in the membrane and make them append on the plasma membrane. Compared to non‐modified nanoparticles, cell‐anchored KNNC NPs highly resist convective washout owing to high affinity of cholesterol to biological membranes, which enables highly efficient wireless electrical stimulation to activate cell impulses under low‐intensity ultrasound. Meanwhile, after perfusion washing, the KNNC NPs distributed around the cells are washed away, while part of KNNC NPs remain on the surface of cell membrane still can induce significant Ca2+ influx under US, similar to the group without washing, indicating the KNNC NPs appended on the cell play a major role in wireless electrical stimulation. Furthermore, the highly efficient electrical transmission of KNNC enables neural differentiation of stem cells in regulating synaptic plasticity by modulating Ca2+ influx, demonstrating that KNNC NPs offer a perspective toward minimally invasive wireless neuromodulation therapies for neurological diseases. [ABSTRACT FROM AUTHOR]

Background & objective: Intensive Care Unit-Acquired Weakness (ICU-AW) is a weakness found in critically ill patients, and this weakness can persist even after discharge from the Intensive Care Unit (ICU). Various rehabilitation medicine procedures have been shown to be effective in prevention as well as managing the established weakness in this cohort of the patients. We analyzed the effect of Neuromuscular Electrical Stimulation (NMES) therapy on the global muscle strength, quadriceps femoris muscle, and creatine kinase examination in patients known to have ICU-AW. Methodology: The type of study used a pre-experimental one-group pre-posttest, and the study population consisted of 23 patients who experienced ICU-AW. Patients were given NMES therapy at the beginning of treatment in the ICU and then evaluated using the Medical Research Council Scale for Muscle Strength (MRC-SS), Manual Muscle Test (MMT), and creatine kinase levels. Results: NMES therapy provides significant results on increasing muscle strength on the fifth day with MRC-SS 42.78 (24-60) and MMT 3.57 (2-5) (P < 0.001), as well as a significant decrease in creatine kinase levels given therapy at the beginning of ICU admission. Conclusion: NMES therapy increases global muscle strength and quadriceps femoris muscle and decreases creatine kinase levels. [ABSTRACT FROM AUTHOR]

To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague–Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity. [ABSTRACT FROM AUTHOR]

Transcranial electrical brain stimulation techniques like transcranial direct current (tDCS) and transcranial alternating current (tACS) have emerged as potential tools for treating neurological diseases by modulating cortical excitability. These techniques deliver small electric currents to the brain non-invasively through electrodes on the scalp. tDCS uses constant direct current which weakly alters the membrane voltage of cortical neurons, while tACS utilizes alternating current to target and enhance cortical oscillations, though the underlying mechanisms are not fully understood more specifically. To elucidate how tACS perturbs endogenous network dynamics, we simulated spiking neuron network models. We identified distinct roles of the depolarizing and hyperpolarizing phases in driving network activity towards and away from the strong nonlinearity provided by pyramidal neurons. Exploring resonance effects, we found matching tACS frequency to the network's endogenous resonance frequency creates greater entrainment. Based on this, we developed an algorithm to determine the network's endogenous frequency, phase, and amplitude, then deliver optimized tACS to entrain network oscillations. Together, these computational results provide mechanistic insight into the effects of tACS on network dynamics and could inform future closed-loop tACS systems that dynamically tune stimulation parameters to ongoing brain activity. [ABSTRACT FROM AUTHOR]

(1) Background: Tinnitus involves the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source. For many people, tinnitus is a disorder associated with symptoms of emotional distress, cognitive dysfunction, autonomic arousal, behavioural changes, and functional disability. Many symptoms can be addressed effectively using education or cognitive behavioural therapy. However, there is no treatment that effectively reduces or alters tinnitus-related neurophysiological activity and thus the tinnitus percept. In this systematic review, we evaluated the effectiveness of neuromodulation therapies for tinnitus that explicitly target pathological synchronous neural activity. (2) Methods: Multiple databases were searched for randomised controlled trials of neuromodulation interventions for tinnitus in adults, with 24 trials included. The risk of bias was assessed, and where appropriate, meta-analyses were performed. (3) Results: Few trials used acoustic, vagal nerve, or transcranial alternating current stimulation, or bimodal stimulation techniques, with limited evidence of neuromodulation or clinical effectiveness. Multiple trials of transcranial direct current stimulation (tDCS) were identified, and a synthesis demonstrated a significant improvement in tinnitus symptom severity in favour of tDCS versus control, although heterogeneity was high. (4) Discussion: Neuromodulation for tinnitus is an emerging but promising field. Electrical stimulation techniques are particularly interesting, given recent advances in current flow modelling that can be applied to future studies. [ABSTRACT FROM AUTHOR]

(1) Background: Cochlear implants (CIs) are widely applied to recover audition for patients with severe degrees of or total hearing loss. Electrical stimulation using the electrically evoked ABR (E-ABR) can be recorded in CI recipients through the device. This work was designed to study E-ABR recorded individually from different channels located at the apical, middle, and basal cochlear regions in comparison to their simultaneous separated or adjacent combined recordings. (2) Methods: This study included 17 children fitted with unilateral cochlear implants. All children were subjected to impedance measurement, electrical compound action potentials (ECAP), and E-ABR recording of three channels located at the apical, middle, and basal cochlear regions. This was followed by simultaneous E-ABR recording of the three "separated" channels in comparison to E-ABR recording from three adjacent channels located at the middle cochlear region. (3) Results: Similar E-ABR latencies and amplitudes were found using either individual or simultaneously separated or adjacent combined recording. However, the mean amplitude measures of E-ABR for combined adjacent channels showed a positive correlation with the applied current level. (4) Conclusions: Combined E-ABR recording from adjacent channels is a faster and more reliable technique that can be used effectively without compromising the results of the recorded E-ABR. [ABSTRACT FROM AUTHOR]

Purpose/Objective: Mixed urinary incontinence (MUI) is the coexistence of stress urinary incontinence (SUI) and urge urinary incontinence (UUI). MUI can be a challenging condition to treat, and there continues to be a demand for successful nonsurgical interventions if possible. This study evaluates the efficacy of combining bipolar radiofrequency (RF) energy to the vaginal canal, electrical muscle stimulation (EMS) of the pelvic floor, and patient education in the treatment of MUI in females. Methods: A prospective study that evaluates RF and EMS in female patients with moderate MUI. RF and EMS treatments were administered three times, 2 weeks apart. Patients were also educated on exactly what MUI is and how to appropriately utilize their pelvic floor muscles. Outcome measures assessed included both objective (cough stress test to measure pad weight) and subjective (Incontinence Quality of Life [iQOL]; Medical, Epidemiological, and Social Aspects of Aging [MESA] Urge Incontinence [UI], MESA Stress Incontinence [SI], Female Sexual Function Index [FsFI]; and Urogenital Distress Inventory-6 [UDI-6]). Results: In total, 31 women underwent the combination of RF, EMS, and patient education, resulting in significant improvement in MUI symptoms (PGI: 82% indicated feeling improvement) after 3 months of treatment in all measures. Conclusion: RF and EMS in conjunction with patient education via a three-treatment protocol was found to be efficacious and safe for treating women with MUI. Future studies should be done to further elucidate optimal treatment protocols for MUI and patients followed up for longer periods of time to determine the durability of this regimen. [ABSTRACT FROM AUTHOR]

Peak alpha frequency (PAF), the dominant oscillatory frequency within the alpha range (8–12 Hz), is associated with cognitive function and several neurological conditions, including chronic pain. Manipulating PAF could offer valuable insight into the relationship between PAF and various functions and conditions, potentially providing new treatment avenues. This systematic review aimed to comprehensively synthesise effects of non‐invasive brain stimulation (NIBS) on PAF speed. Relevant studies assessing PAF pre‐ and post‐NIBS in healthy adults were identified through systematic searches of electronic databases (Embase, PubMed, PsychINFO, Scopus, The Cochrane Library) and trial registers. The Cochrane risk‐of‐bias tool was employed for assessing study quality. Quantitative analysis was conducted through pairwise meta‐analysis when possible; otherwise, qualitative synthesis was performed. The review protocol was registered with PROSPERO (CRD42020190512) and the Open Science Framework (https://osf.io/2yaxz/). Eleven NIBS studies were included, all with a low risk‐of‐bias, comprising seven transcranial alternating current stimulation (tACS), three repetitive transcranial magnetic stimulation (rTMS), and one transcranial direct current stimulation (tDCS) study. Meta‐analysis of active tACS conditions (eight conditions from five studies) revealed no significant effects on PAF (mean difference [MD] = −0.12, 95% CI = −0.32 to 0.08, p = 0.24). Qualitative synthesis provided no evidence that tDCS altered PAF and moderate evidence for transient increases in PAF with 10 Hz rTMS. However, it is crucial to note that small sample sizes were used, there was substantial variation in stimulation protocols, and most studies did not specifically target PAF alteration. Further studies are needed to determine NIBS's potential for modulating PAF. [ABSTRACT FROM AUTHOR]

Following new concepts by Bichat in the early 19th century, of organic and animal life centered around the ganglionic nervous system, over 100 years of anatomic studies and physiologic experimentation eventually resulted in Gaskell's 1916 book entitled "The Involuntary Nervous System" and Langley's 1921 book entitled "The Autonomic Nervous System." Neurology and cardiology emerged as specialties of medicine in the early 20th century. Although neurology made several prominent discoveries in neurophysiology during the first half of the 20th century, cardiology developed coronary care units and cardiac catheterization in the 1960s. Programmed electrical stimulation of the heart and noninvasive ambulatory monitoring provided new methodologies to study clinical cardiac arrhythmias. Experimentally, direct cardiac nerve stimulation of sympathetic nerve endings, as well as parasympathetic control of the atrioventricular node, provided the background to new detailed autonomic studies of the heart. Neurocardiology, perhaps initially more directed towards our understanding of sudden cardiac death, ultimately embraced an even significantly more complex scheme of local circuit neurons and near‐endless loops of interconnecting neurons in the heart. Intrathoracic extracardiac and intracardiac ganglia have been recharacterized, both anatomically and physiologically, laying the groundwork for potential new therapies of cardiac neuromodulation. [ABSTRACT FROM AUTHOR]

Post-Acute sequelae of SARS-CoV-2 (PASC) is a multisystem disorder causing persistent musculoskeletal deconditioning and reduced lower extremity strength. Electrical stimulation (E-Stim) to the gastrocnemius muscle can enhance strength outcomes by increasing the frequency of muscle fiber activation. We investigated its effect on individuals with PASC. Participants were randomized into intervention (IG) or control (CG) groups. The IG self-administered daily one-hour E-Stim to both their gastrocnemius muscles using a functional device over 4-week, while the CG used a sham device. Primary outcomes were ankle dorsiflexion strength assessed via dynamometry during maximum voluntary contractions, and gastrocnemius voluntary activation (GVA) via surface electromyography. The secondary outcome assessed activities of daily living (ADL), instrumental ADL, and mobility queries. Percentage improvement was calculated. Eighteen patients were analyzed (IG = 10; CG = 8). After 4 week, the IG showed a significantly higher improvement in ankle dorsiflexion strength (222.64%) compared to the CG (51.27%, p = 0.002). Additionally, the IG's ankle dorsiflexion strength improvement significantly correlated with GVA improvement (rho = 0.782) at 4 week. The secondary outcomes did not reveal significant changes in neither group. Self-administered gastrocnemius E-Stim improves ankle dorsiflexion strength in individuals with PASC. However, larger sample sizes and longer interventions are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Introduction: Diagnostic procedures for pulp vitality assessment are a crucial aspect of routine dental practice. This review aims to provide a comprehensive overview of nontraditional techniques and methodologies for assessing pulp vitality, specifically exploring promising approaches that are currently not used in dental practice. Methods: The study protocol was registered a priori (https://osf.io/3m97z/). An extensive electronic search was conducted across multiple databases, including MEDLINE via PubMed, Scopus, Web of Science, and Embase. Inclusion criteria were guided by the research question based on the PCC model as follows: "What are the potential nontraditional techniques (Concept) for assessing pulp vitality (Population) in the field of endodontics or clinical practice (Context)?" Studies were included that explored possible approaches to pulp vitality assessment, utilizing a range of techniques, whilst any studies using traditional pulp tests (cold, heat, and electric stimulation) or well‐known methods (pulse oximetry and laser Doppler flowmetry) were excluded. Reviewers independently screened articles and extracted data. A patent search was also performed. Results: Of 3062 studies, 65 were included that described nontraditional approaches for assessing pulp vitality. These included a range of optical diagnostic methods, ultrasound Doppler flowmetry (UDF), magnetic resonance imaging (MRI), terahertz imaging, tooth temperature measurements, as well as invasive methodologies, including 133xenon washout, radioisotope‐labelled tracers, hydrogen gas desaturation, intravital microscopy and fluorescent microspheres isotope clearance. The patent search included artificial intelligence and biomarkers methods. Conclusions: This review provides details for potential innovative tests that may directly describe pulp vitality. Importantly, these methods range from clinically impractical through to promising methods that may transform clinical practice. Several nontraditional techniques have the potential to enhance diagnostic accuracy and could provide valuable insights into the assessment of pulp vitality in challenging clinical scenarios. [ABSTRACT FROM AUTHOR]