Detrusor relaxing agents for neurogenic detrusor overactivity: a systematic review, meta-analysis and network meta-analysis.

OBJECTIVE: To evaluate the evidence regarding the therapeutic benefits and safety of oral detrusor relaxing agents (DRAs) in treating neurogenic detrusor overactivity (NDO). METHODS: A comprehensive search was performed on 1 September 2022. Two authors independently reviewed the articles to extract data using a pre-designed form. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A common-effect or random-effects model was used based on the heterogeneity among studies. Bayesian network meta-analysis (NMA) was further performed to make indirect comparisons of antimuscarinics and mirabegron. RESULTS: A total of 23 randomised controlled trials (RCTs) comprising 1697 patients were included in our analysis. Compared to placebo, the clinical benefits of oral DRAs, along with more adverse events (AEs), were demonstrated in the treatment of NDO. In the subgroup analysis, antimuscarinics significantly improved both urodynamic and bladder diary outcomes (including urinary incontinence episodes, urinary frequency, and residual volume), with a higher rate of AEs, such as xerostomia. Mirabegron improved some of the parameters and had fewer bothersome side-effects in patients with NDO. The NMA showed that none of the antimuscarinics or mirabegron was superior or inferior to the other. CONCLUSIONS: Detrusor relaxing agents are associated with improved outcomes in patients with NDO and our analysis has added new evidence regarding antimuscarinics. Evidence concerning mirabegron as first-line therapy for NDO is still limited. Well-designed RCTs are still required in this specific population.

Efficacy and safety of tibial nerve stimulation using a wearable device for overactive bladder.

OBJECTIVE: To evaluate the efficacy and safety of a wearable, smartphone-controlled, rechargeable transcutaneous tibial nerve stimulation (TTNS) device in patients with overactive bladder (OAB). PATIENTS AND METHODS: This multicentre, prospective, single-blind, randomised clinical trial included eligible patients with OAB symptoms who were randomly assigned to the stimulation group or sham group. The primary efficacy outcome was change from baseline in voiding frequency/24 h after 4 weeks of treatment. The secondary efficacy outcomes included changes in bladder diary outcomes (urgency score/void, nocturia episodes/day, micturition volume/void, and incontinence episodes/day), questionnaires on Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder Condition (PPBC), and American Urological Association Symptom Index Quality of Life Score (AUA-SI-QoL) at baseline and after 4 weeks of treatment. Device-related adverse events (AEs) were also evaluated. RESULTS: In the full analysis set (FAS), the mean (sd) change of voiding frequency/24 h in the stimulation group and sham group at 4 weeks were -3.5 (2.9) and -0.6 (2.4), respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -3.5 (2.9) vs -0.4 (2.3) (P < 0.01). In the FAS and PPS, micturition volume/void significantly improved at 4 weeks (P = 0.01 and P = 0.02). PPBC improvement almost reached significance in the FAS (P = 0.05), while it was significant in the PPS (P = 0.02). In the FAS and PPS, AUA-SI-QoL significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas there were no significant differences in urgency score/void, nocturia episodes/day or OABSS between the groups. Also, no device-related serious AEs were reported. CONCLUSIONS: The non-invasive neuromodulation technique using the novel ambulatory TTNS device is effective and safe for treating OAB. Its convenience and easy maintenance make it a new potential home-based treatment modality. Future studies are warranted to confirm its longer-term efficacy.

Mechanism of Action of Tibial Nerve Stimulation in the Treatment of Lower Urinary Tract Dysfunction.

BACKGROUND AND OBJECTIVE: Tibial nerve stimulation (TNS) has long been used to effectively treat lower urinary tract dysfunction (LUTD). Although numerous studies have concentrated on TNS, its mechanism of action remains elusive. This review aimed to concentrate on the mechanism of action of TNS against LUTD. MATERIALS AND METHODS: A literature search was performed in PubMed on October 31, 2022. In this study, we introduced the application of TNS for LUTD, summarized different methods used in exploring the mechanism of TNS, and discussed the next direction to investigate the mechanism of TNS. RESULTS AND CONCLUSIONS: In this review, 97 studies, including clinical studies, animal experiments, and reviews, were used. TNS is an effective treatment for LUTD. The study of its mechanisms primarily concentrated on the central nervous system, tibial nerve pathway, receptors, and TNS frequency. More advanced equipment will be used in human experiments to investigate the central mechanism, and diverse animal experiments will be performed to explore the peripheral mechanism and parameters of TNS in the future.

Patient-Reported Outcome Measure of Ataxia Correlates with Canonical Clinical Assessments in Chinese Spinocerebellar Ataxias.

Spinocerebellar ataxia (SCA) patients' reports of their own experiences are essential to the outcome evaluation in clinical trials. To better understand the health condition and well-being of ataxia population, Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) was developed. The aim of our study was to culturally adapt the PROM-Ataxia into Chinese version and assess its correlation with canonical clinical assessments. We translated the PROM-Ataxia into Chinese following the ISPOR TCA Task Force guidelines and evaluated its correlation with measures of motor ataxia, non-ataxia signs, quality of life, and mental health in 92 Chinese SCA participants. Nearly all the participants found this questionnaire complete and intelligible but some items were found repetitive or ambiguous. The total score of PROM-Ataxia from stage 0 to stage 3 was 23.24 ± 18.53, 79.11 ± 40.45, 144.30 ± 41.30, and 176.20 ± 31.74, respectively (p < 0.0001). It was strongly correlated with the Scale for the Assessment and Rating of Ataxia (SARA) (r = 0.832, p < 0.0001). Physical and activities domain of PROM-Ataxia were correlated with measures of motor ataxia, quality of life, and psychological health while mental health domain was correlated with all the clinical assessments including inventory of non-ataxia signs and cognitive assessment. We translated the PROM-Ataxia into Chinese for the first time, which allows transnational comparability in future studies. Our study validated the responsiveness of PROM-Ataxia to established clinical measures in Chinese SCA patients and implied its potential to evaluate the therapeutic effect and optimize the sensitivity of changes in clinical outcome assessments.

Typical value ranges and signal patterns in patients with neurogenic bladder: Quality control in urodynamics using an air-charged catheter system.

PURPOSE: To establish typical value ranges (TVRs) of the air-charged catheter (ACC) system, and analyze the typical signal patterns (TSPs) of cough under different bladder volumes for quality control of a urodynamic study using the ACC system. MATERIALS AND METHODS: The urodynamic traces of 1977 patients with neurogenic bladder (NB) were analyzed for intravesical pressure (pves ), abdominal pressure (pabd ), and detrusor pressure (pdet ) in the cough test at our center from July 2017 to December 2021. The pdet cough signals were described and classified. The pdet cough signal patterns in different bladder volumes and postures were analyzed. RESULTS: The 50% range of the initial resting pves , pabd , and pdet in the supine and sitting positions were 7-15, 7-14, and 0-0 cmH2 O, and 24-33, 24-33, and 0-0 cmH2 O, respectively. The cough amplitudes for pves and pabd were similar in the 50% range, as follows: 10-27 and 8-25 cmH2 O in the supine position, respectively; and 18-43 and 17-40 cmH2 O in the sitting position, respectively. The cough amplitude of pves and pabd was not related to bladder volume (p > 0.05). The cough spikes of pdet were divided into three types: type I, in which pdet has a minimal change (<5 cmH2 O); type II, a monophasic cough spike, in which could be a positive (IIa, ≥5 cmH2 O) or negative spike (IIb, ≥5 cmH2 O); and type III, a biphasic spike, in which could be a positive-to-negative biphasic (IIIa) or negative-to-positive spike (IIIb). Under different bladder volumes, the cough signals of pdet were all expressed as type I, II, or III, and the cough signals were unrelated to bladder volume (p > 0.05). CONCLUSIONS: TVRs of the initial resting state in patients with NB were established to provide guidance for quantitative quality control of the ACC system. The TSPs of the pdet cough signal under different bladder volume and posture were described, which could be used for qualitative quality control of the ACC system.

TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

Inhibitory effects of a smartphone-controlled wearable transcutaneous tibial nerve stimulation device on bladder reflexes in anesthetized cats.

OBJECTIVES: To explore the inhibitory effects of a novel, smartphone-controlled, and wearable tibial nerve stimulation device on nonnociceptive and nociceptive bladder reflexes in anesthetized cats and to compare the stimulus results of two current waveforms outputted by this new stimulator. MATERIALS AND METHODS: A novel, intelligent tibial nerve stimulator was put on the ankles of 14 cats and controlled by a mobile application. Cystometrograms (CMGs) were performed repeatedly by infusing 0.9% normal saline (NS) and 0.5% acetic acid (AA) through a urethral catheter. Inhibitory effects were explored by measuring the bladder capacity (BC) in two areas: (1) on nonnociceptive bladder reflex (infused with NS) and on nociceptive bladder reflex (filled with AA to induce overactive bladder [OAB] model); and (2) under the stimulation of two different current waveforms (waveforms A and B). RESULTS: In Group 1, the BC of AA-induced OAB (41.48 ± 8.40%) was significantly different compared with the capacity of a NS-infused bladder (104.89 ± 1.32%, p < 0.05). Both NS-filled (151.35 ± 5.71%, p < 0.05) and AA-instilled (71.41 ± 9.34%, p < 0.05) bladder volumes significantly increased after tibial nerve stimulation (TNS). In Group 2, the BC increased to 166.18 ± 15.17% (p = 0.026) and 127.64 ± 13.00% (p = 0.239), respectively, after TNS with waveforms A and B current. CONCLUSIONS: Results revealed that this novel, smartphone-based, wearable, and wireless tibial nerve stimulation system could inhibit the micturition reflex on physiological condition, serving as a potential option for OAB treatment. In addition, the waveforms of stimulation current had an important influence on the effects of TNS.

Reliability assessment of the upper urinary tract dilation grading system based on magnetic resonance urography in patients with neurogenic bladder.

BACKGROUND: To assess the inter-observer and intra-observer reliability of the magnetic resonance urography (MRU)-upper urinary tract dilation (UUTD) grading system. METHODS: A total of 40 patients with a diagnosis of NB were enrolled in this study. The images were assembled in an electronic presentation randomly. The presentations were reviewed and graded by 4 junior and 4 senior urologists. One week later, the images were randomized again and reassessed. The inter-observer reliability was estimated by Kendall's coefficient of concordance and intra-class correlation coefficient (ICC), and the intra-observer reliability was estimated by weighted Cohen's kappa. RESULTS: The inter-observer reliability strength was excellent for all urologists, with the ICC value of 0.939 (0.908-0.963) and Kendall's W value of 0.967. The highest agreement was shown in Grade 4 at 92.50%, and the lowest in Grade 2 at 82.14%. All disagreements were within one grade of difference. Moreover, the Intra-observer reliability was excellent, with the weighted kappa value ranging from 0.904 to 0.954. CONCLUSIONS: The inter-observer and intra-observer reliability of this novel MRU-UUTD grading system is confirmed, providing adequate evidence for broader clinical application.

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

A novel de novo mutation (p.Pro1310Glnfs*46) in KMT2A caused Wiedemann-Steiner Syndrome in a Chinese boy with postnatal growth retardation: a case report.

Wiedemann-Steiner Syndrome (WSS) is a very rare autosomal dominant disease. Mutations in the KMT2A gene have been shown to cause this disease. A 1-year-old Chinese boy exhibited growth delay, psychomotor retardation, limb hypotonia and facial dysmorphism that was consistent with WSS. His body weight started to drop below the normal range at 3 months old, and the decline persisted. Whole-exome sequencing showed a novel de novo mutation (p.Pro1310Glnfs*46) in KMT2A, which confirmed the diagnosis of WSS. We diagnosed a Chinese boy who presented postnatal growth retardation with WSS caused by a novel de novo mutation in KMT2A. Our findings expand the mutational and phenotypic spectra of WSS and will be valuable for the mutation-based pre- and postnatal screening for and genetic diagnosis of WSS.

Identification of HLA-A2-restricted immunogenic peptides derived from Vitamin D-Binding Protein.

T-cell-mediated destruction of pancreatic ß cells leads to Type 1 diabetes (TID). Vitamin D-Binding Protein (VDBP) has been identified as an autoantigen and T cell reactivity against VDBP increases in the development of T1D. Autoreactive cytotoxic T lymphocytes (CTLs) recognize ß-cell-derived peptides in the context of major histocompatibility complex class I molecules. However, little is known about the VDBP-derived immunogenic peptides that are presented in the context of human HLA molecules. Here, we predicted and identified VDBP derived immunogenic peptides that were presented in association with human HLA-A2 molecule. The VDBP derived peptides binding to HLA-A∗0201 were predicted by using a computer-assisted algorithm. The candidate peptides were synthesized, then affinity between peptides and HLA-A∗0201 were analyzed. In addition, the CTL activity of the peptides was detected by cytotoxicity assay and ELISPOT assay in vitro. Furthermore, HLA-A∗0201-transgenic mice were immunized with peptides to induce the CTL activity in vivo. The results demonstrated that peptides of VDBP containing residues 211-219 and 235-243 had high affinity with HLA-A∗0201. In addition, these peptides elicited potent CTL responses in vitro, and induced T1D in vivo. Therefore, this experiment identified immunogenic HLA-A∗0201-restricted epitopes derived from VDBP, and provided pathogenesis theory of T1D.

Epileptic seizures in nonalcoholic Wernicke's encephalopathy: a case report and literature review.

Wernicke encephalopathy (WE) is characterized by eye signs, cerebellar dysfunction, and confusion. Epileptic seizures are rare in nonalcoholic WE. We reviewed the clinical, laboratory, radiological, and prognostic characteristics of nonalcoholic WE accompanied by epileptic seizures. We reported 1 case and searched similar cases using PubMed, WoK, Ovid, and Embase. WE was diagnosed according to dietary deficiencies, clinical symptoms and brain magnetic resonance imaging (MRI). We reviewed 13 patients (median age, 27 years; 5 men) with clear histories of thiamine deficiency and symptoms of typical WE. The type of epileptic seizures reported in the 13 cases reviewed was generically reported as seizures or convulsions in 4 patients; 7 patients had generalized tonic-clonic seizures, 1 partial seizure, and 1 generalized convulsive status epileptics. Two patients had epileptic seizures as the first symptom of WE. Laboratory tests mainly indicated metabolic acidosis and electrolyte disturbances. Electroencephalography may present as normal patterns, increased slow waves or epileptic discharge. Six patients had cortical lesions on brain MRI. These lesions were usually diffuse and band-like, and sometimes involved all lobes either symmetrically or asymmetrically, with the frontal lobe as the most susceptible area. All cortical lesions were accompanied by non-cortical lesions typical of WE. Brain MRI abnormalities, after thiamine treatment, mostly disappeared on follow-up MRIs. The patients had good prognoses. Only 1 patient had repeated seizures, and there were no comas or deaths. Patients with nonalcoholic WE accompanied by seizures are young and generally have good prognoses. Most patients experienced generalized convulsive seizures, which may have been related to abnormal cerebral cortical metabolism due to subacute thiamine deficiency.

Effects of tetrathiomolybdate and penicillamine on brain hydroxyl radical and free copper levels: a microdialysis study in vivo.

Wilson disease is an inherited disorder of excessive copper accumulation. The commonly used drug d-penicillamine (PA) or trientine both cause a high incidence (10-50%) of neurological worsening, which rarely occurs with tetrathiomolybdate (TM) treatment. To investigate the mechanisms of neurologic deterioration after the initiation of chelation therapy, brain hydroxyl radical and free copper were assessed in vivo in this study. On days 3, 7, 14, and 21 after PA or TM administration, striatal hydroxyl radical levels of both TX mice and controls were assessed by terephthalic acid (TA) combined with microdialysis and high-performance liquid chromatography (HPLC). Within the same microdialysis samples, free copper was measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that both hydroxyl radical and free copper markedly increased in the striatum of TX mice during PA administration but were not elevated when administering TM. These results suggested that the further increased free copper in the brain and oxidative stress caused by some chelators might contribute to the neurological deterioration.

Characterizing brain mineral deposition in patients with Wilson disease using susceptibility-weighted imaging.

AIMS: The aim of this study was to evaluate the feasibility of characterizing the brain-mineral deposition in patients with Wilson disease (WD) using susceptibility-weighted imaging (SWI). MATERIALS AND METHODS: The study enrolled 30 WD patients and 20 age-matched healthy controls. Neurological symptoms were scored using the modified Young Scale. The hepatic function indices, serum and urinary copper content, and serum iron content were determined. All study objects received the magnetic resonance imaging (MRI) and SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. The relationship between CP values and the clinical status were evaluated. RESULTS: The serum iron content of WD patients was higher than the normal. The CP values of substantia nigra, caudate nucleus, and globus pallidus of WD were lower than the normal values, while the CP value of substantia nigra was the lowest. No correlations were determined between the CP values and the iron and copper parameters. There was negative correlation between the scores of dysarthria and the CP values of the globus pallidus. There was negative correlation between the scores of tremor and the CP values of caudate nucleus. Some regions, which had high signals on T2-weighted image, had low signals on SWI. CONCLUSIONS: There might be abnormal iron metabolism in patients with WD. The decreased CP values might reflect a deposition of both copper and iron. SWI may be more sensitive than the ordinary MRI. The mineral deposition may contribute to the neural symptoms.

A bibliometric profile of optogenetics: quantitative and qualitative analyses.

Introduction: Optogenetics is a rapidly developing field combining optics and genetics, with promising applications in neuroscience and beyond. However, there is currently a lack of bibliometric analyses examining publications in this area. Method: Publications on optogenetics were gathered from the Web of Science Core Collection Database. A quantitative analysis was conducted to gain insights into the annual scientific output, and distribution of authors, journals, subject categories, countries, and institutions. Additionally, qualitative analysis, such as co-occurrence network analysis, thematic analysis, and theme evolution, were performed to identify the main areas and trends of optogenetics articles. Results: A total of 6,824 publications were included for analysis. The number of articles has rapidly grown since 2010, with an annual growth rate of 52.82%. Deisseroth K, Boyden ES, and Hegemann P were the most prolific contributors to the field. The United States contributed the most articles (3,051 articles), followed by China (623 articles). A majority of optogenetics-related articles are published in high-quality journals, including NATURE, SCIENCE, and CELL. These articles mainly belong to four subjects: neurosciences, biochemistry and molecular biology, neuroimaging, and materials science. Co-occurrence keyword network analysis identified three clusters: optogenetic components and techniques, optogenetics and neural circuitry, optogenetics and disease. Conclusion: The results suggest that optogenetics research is flourishing, focusing on optogenetic techniques and their applications in neural circuitry exploration and disease intervention. Optogenetics is expected to remain a hot topic in various fields in the future.

Transdermal tibial nerve optogenetic stimulation targeting C-fibers.

Purpose: To explore whether stimulation of C-fibers in tibial nerves can induce bladder inhibition by optogenetic transdermal illumination. Methods: Ten rats were injected with AAV2/6-hSyn-ChR2(H134R)-EYFP into the tibial nerves. Transurethral cystometry was performed 4 weeks after the virus injection. Illumination (473-nm blue light at 100 mW) was performed with the fiber positioned above the right hind paw near the ankle. The light transmission efficiency was examined with a laser power meter. The effects on cystometry were compared before and after illumination with the bladder infused with normal saline and acetic acid, respectively. Result: Upon transdermal delivery of 473-nm light at a peak power of 100 mW, the irradiance value of 0.653 mW/mm2 at the target region was detected, which is sufficient to activate opsins. The photothermal effect of 473-nm light is unremarkable. Acute inhibitory responses were not observed during stimulation regarding any of the bladder parameters; whereas, after laser illumination for 30 min, a statistically significant increase in bladder capacity with the bladder infused with normal saline (from 0.53 ± 0.04 mL to 0.72 ± 0.05 mL, p < 0.001) and acetic acid (from 0.25 ± 0.02 mL to 0.37 ± 0.04 mL, p < 0.001) was detected. A similar inhibitory response was observed with pulsed illumination at both 10Hz and 50Hz. However, illumination did not significantly influence base pressure, threshold pressure, or peak pressure. Conclusion: In this preliminary study, it can be inferred that the prolonged bladder inhibition is mediated by the stimulation of C-fibers in the tibial nerves, with no frequency-dependent characteristics. Although the 473-nm blue light has limited penetration efficacy, it is sufficient to modulate bladder functions through transdermal illumination on the superficial peripheral nervous system.

Real-time changes in brain activity during tibial nerve stimulation for overactive bladder: Evidence from functional near-infrared spectroscopy hype scanning.

Purpose: To use functional near-infrared spectroscopy (fNIRS) to identify changes in brain activity during tibial nerve stimulation (TNS) in patients with overactive bladder (OAB) responsive to therapy. Methods: Eighteen patients with refractory idiopathic OAB patients were recruited consecutively for this pilot study. At baseline, all patients completed 3 days voiding diary, Quality-of-Life score, Perception-of-Bladder-Condition, and Overactive-Bladder-Symptom score. Then 4 region-of-interest (ROI) fNIRS scans with 3 blocks were conducted for each patient. The block design was used: 60 s each for the task and rest periods and 3 to 5 repetitions of each period. A total of 360 s of data were collected. During the task period, patients used transcutaneous tibial nerve stimulation (TTNS) of 20-Hz frequency and a 0.2-millisecond pulse width and 30-milliamp stimulatory current to complete the experiment. The initial scan was obtained with a sham stimulation with an empty bladder, and a second was obtained with a verum stimulation with an empty bladder. Patients were given water till strong desire to void, and the third fNIRS scan with a verum stimulation was performed. The patients then needed to urinate since they could not tolerate the SDV condition for a long time. After a period of rest, the patients then were given water until they exhibited SDV state. The fourth scan with sham fNIRS scan in the SDV state was performed. NIRS_KIT software was used to analyze prefrontal activity, corrected by false discovery rate (FDR, p < 0.05). Statistical analyses were performed using GraphPad Prism software; p < 0.05 was considered significant. Results: TTNS treatment was successful in 16 OAB patients and unsuccessful in 2. The 3 days voiding diary, Quality-of-Life score, Perception-of-Bladder-Condition, and Overactive-Bladder-Symptom score were significantly improved after TNS in the successfully treated group but not in the unsuccessfully treated group. The dorsolateral prefrontal cortex (DLPFC) (BA 9, Chapters 25 and 26) and the frontopolar area (FA) (BA 10, Chapters 35, 45, and 46) were significantly activated during TNS treatment with an empty bladder rather than with an SDV. Compared with the successfully treated group, the unsuccessfully treated group did not achieve statistical significance with an empty bladder and an SDV state. Conclusion: fNIRS confirms that TNS influences brain activity in patients with OAB who respond to therapy. That may be the central mechanism of action of TNS.

Corrigendum: A bibliometric profile of optogenetics: quantitative and qualitative analyses.

[This corrects the article DOI: 10.3389/fnins.2023.1221316.].