Stimulation Period Research Articles

What is the analgesic range of acupuncture stimulus for treating acute pain?

Since the analgesic effect of acupuncture stimulation is derived from different mechanisms depending on the type of pain, it is important to know which acupuncture points to stimulate. In this study, to confirm the effect of acupuncture stimulation on acute pain from a neurological point of view, somatosensory evoked potential and sensory threshold changes were evaluated to identify the nerve range that is affected by acupuncture stimulation on LI4 (Hapgok acupuncture point, of the radial nerve) during acute pain. The subjects were 40 healthy men and women aged 19-35 years. The study was designed as a randomly controlled, crossover trial with acupuncture stimulation at LI4 as the intervention. The washout period for acupuncture stimulation was 2 weeks, and the subjects were divided into two groups, i.e., an acupuncture stimulation group and a nonstimulation group, with 10 men and 10 women in each group. Somatosensory evoked potential measurement was carried out for 5 min by alternately applying 2 HZ-pulse electrical stimulation to the thumb and the little finger of the hand acupunctured with a 64-channel electroencephalogram. The verbal rating scale was used before and after each acupuncture stimulation session. The results of the study confirmed that the somatosensory evoked potential amplitude value of the thumb was significantly decreased and that the intensity of sensory stimulation corresponding to a verbal rating scale score of 6 was significantly increased only in the thumb after acupuncture stimulation. Therefore, the results show that acupuncture treatment for acute pain is more effective when direct acupuncture stimulation is applied to the painful area.

Establishment and identification of a skin cell line from Chinese tongue sole (Cynoglossus semilaevis) and analysis of the changes in its transcriptome upon LPS stimulation

The Chinese tongue sole (Cynoglossus semilaevis) holds significant economic importance within the fishing industry along the eastern coasts of China. In recent years, the frequent outbreaks of bacterial diseases have become a common concern as the aquaculture scale expands. The majority of the diseased fish exhibit symptoms such as skin congestion, damage and skin ulceration. As the skin serves as the first line of defense against bacterial infections, establishing a skin cell line for immunological research on Chinese tongue sole's response to bacterial infection is of utmost importance. In this study, a cell line named CSS (derived from the skin of the Chinese tongue sole) was successfully established. The cells have demonstrated stability during passages and exhibit a multipolar fibroblast-like morphology. They were cultured in L-15 medium with 20% serum and have been successfully passed through 60 passages over a period of 20 months. The identification of the mitochondrial CO1 gene confirmed that the cell originated from Chinese tongue sole. The karyotype detection revealed that the cell had a chromosome number of 2n = 42. After being stored in liquid nitrogen for 15 months, the cells can maintain more than 75% viability upon recovery. After transfecting with cy3-labeled scramble siRNA and pEGFP-N3 plasmid, clear fluorescence was observed in the transfected cells. We observed that lipopolysaccharide (LPS) from Escherichia coli significantly upregulate the gene expression of various immune-related pathways at 2 h in the CSS cell line. Additionally, the differentially expressed genes showed a higher enrichment in immune-related pathways at 2 and 6 h after stimulation compared to the 24 h point. Moreover, we identified 347 genes that exhibited a gradual increase in expression during the 0–24 h stimulation period. These genes were primarily enriched in pathways related to Autophagy, GABAergic synapse, Apelin signaling and Ferroptosis. In general, the CSS cell line established in this study exhibits stable growth and can serve as a valuable tool for in vitro studies of immunology and other basic biologies of Chinese tongue sole.

Dual-site beta tACS over rIFG and M1 enhances response inhibition: A parallel multiple control and replication study

Response inhibition is a core component of cognitive control. Past electrophysiology and neuroimaging studies have identified beta oscillations and inhibitory control cortical regions correlated with response inhibition, including the right inferior frontal gyrus (rIFG) and primary motor cortex (M1). Hence, increasing beta activity in multiple brain regions is a potential way to enhance response inhibition. Here, a novel dual-site transcranial alternating current stimulation (tACS) method was used to modulate beta activity over the rIFG-M1 network in a sample of 115 (excluding 2 participants) with multiple control groups and a replicated experimental design. In Experiment 1, 70 healthy participants were randomly assigned to three dual-site beta-tACS groups, including in-phase, anti-phase or sham stimulation. During and after stimulation, participants were required to complete the stop-signal task, and electroencephalography (EEG) was collected before and after stimulation. The Barratt Impulsiveness Scale was completed before the experiment to evaluate participants' impulsiveness. In addition, we conducted an active control experiment with a sample size of 20 to exclude the potential effects of the dual-site tACS “return” electrode. To validate the behavioural findings of Experiment 1, 25 healthy participants took part in Experiment 2 and were randomized into two groups, including in-phase and sham stimulation groups. We found that compared to the sham group, in-phase but not anti-phase beta-tACS significantly improved both response inhibition performance and beta synchronization of the inhibitory control network in Experiment 1. Furthermore, the increased beta synchronization was correlated with enhanced response inhibition. In an independent sample of Experiment 2, the enhanced response inhibition performance observed in the in-phase group was replicated. After combining the data from the above two experiments, the time dynamics analysis revealed that the in-phase beta-tACS effect occurred in the post-stimulation period but not the stimulation period. The state-dependence analysis showed that individuals with poorer baseline response inhibition or higher attentional impulsiveness had greater improvement in response inhibition for the in-phase group. These findings strongly support that response inhibition in healthy adults can be improved by in-phase dual-site beta-tACS of the rIFG-M1 network, and provide a new potential treatment targets of synchronized cortical network activity for patients with clinically deficient response inhibition.

Association between ambient air pollutants and birthweight of singletons following assisted reproductive technologies

ObjectiveTo investigate the associations between exposure to ambient air pollutants and birthweight following ART treatment. DesignRetrospective cohort study. MethodsWe included 11,599 singletons derived from fresh cycles or frozen-thawed embryo transfer (FET) cycles between Jan 2013 and Dec 2019. Exposure to six air pollutants (SO2, NO2, CO, O3, PM2.5, and PM10) at patients` residences and the clinic site were estimated using the inverse distance weighting interpolation method based on data obtained from monitor sites. The daily mean levels of pollutants were estimated in potential exposure windows (the period from three months before treatment to oocyte retrieval, the period of ovarian stimulation, the period of in vitro culture, the period from embryo transfer to hCG test, the period of entire pregnancy, the 1st, 2nd, and 3rd trimester) were calculated. Generalized additive models adjusted for confounders including maternal age, BMI, and parity were used to evaluate the association between exposures and birthweight. Interaction of exposures and ART-associated factors, such as supraphysiologic estradiol and frozen-thawed, were explored in an XGboost model. Main outcome measuresBirthweight and z-score of singletons. ResultsIn fresh cycles, O3 exposure during the period from three months before treatment to oocyte retrieval and SO2 exposure during in vitro culture at the ART clinic showed a linear association with birthweight (7.24, 95% CI: 1.18–13.31 g per 10 μg/m3 increase in O3; 25.92, 95% CI: 8.26–43.58 g per 10 μg/m3 increase in SO2, respectively). For patients receiving single blastocyst transfer with exposures below the China standard of 20 μg/m3, an increase of 10 μg/m3 in SO2 was associated with a 61.52 (95% CI: 1.13–121.91) g increase in birthweight. In FET cycles, no significant association was found between air pollution and birthweight. XGboost model did not reveal a strong interaction between the exposures and ART-related factors, except for the interactions between O3 exposure and BMI. However, none of the interactions reached a higher rank of importance. ConclusionsAir pollution exposure during ART treatment may affect the birthweight of the offspring.

BEHAVIORAL RESPONSES OF CAPTIVE MANED WOLVES TO OLFACTORY ENRICHMENT

Environmental enrichment (EE) is a technique that increases animal welfare. The behavior of maned wolves when exposed to four odors hidden outside the enclosure was investigated. Using the focal animal method and recording all occurrences, their behavior was analyzed for five minutes in each baseline phase (Basal), during exposure (Exp), and after withdrawal of the stimulus (Pos). Behavioral responses were categorized as positive (P+), negative (N-), and other (Ot). The average P+ increased significantly (P < 0.05) from the Basal to the Exp, but it was not statistically different (P = 0.60) between the Basal and the Pos. Neither N- nor Ot changed statistically in any of the phases (P > 0.5). Maned wolves appeared to be sensitive to this EE with the olfactory stimuli used during the period of olfactory stimulation. The method used is practical, safe, and flexible, and can be useful in sensory enrichment programs.

Altered Visual Function in Short-Wave-Sensitive 1 (sws1) Gene Knockout Japanese Medaka (Oryzias latipes) Larvae.

Visual perception plays a crucial role in foraging, avoiding predators, mate selection, and communication. The regulation of color vision is largely dependent on opsin, which is the first step in the formation of the visual transduction cascade in photoreceptor cells. Short-wave-sensitive 1 (sws1) is a visual pigment that mediates short-wavelength light transduction in vertebrates. The depletion of sws1 resulted in increased M-opsin in mice. However, there is still no report on the visual function of sws1 in teleost fish. Here, we constructed the sws1 knockout medaka using CRISPR/Cas9 technology. The 6 dph (days post-hatching) medaka sws1-/- larvae exhibited significantly decreased food intake and total length at the first feeding stage, and the mRNA levels of orexigenic genes (npy and agrp) were significantly upregulated after feeding. The swimming speed was significantly reduced during the period of dark-light transition stimulation in the sws1-mutant larvae. Histological analysis showed that the thickness of the lens was reduced, whereas the thickness of the ganglion cell layer (GCL) was significantly increased in sws1-/- medaka larvae. Additionally, the deletion of sws1 decreased the mRNA levels of genes involved in phototransduction (gnb3b, grk7a, grk7b, and pde6c). We also observed increased retinal cell apoptosis and oxidative stress in sws1 knockout medaka larvae. Collectively, these results suggest that sws1 deficiency in medaka larvae may impair visual function and cause retinal cell apoptosis, which is associated with the downregulation of photoconduction expression and oxidative stress.

Occipital transcranial direct current stimulation in episodic migraine patients: effect on cerebral perfusion

Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017).

Association between Patients' Body Mass Index and the Effect of Monophasic Pulsed Microcurrent Stimulation on Pressure Injury Healing.

This secondary analysis study aimed to detect individual variables that influence the efficacy of monophasic pulsed microcurrent on pressure injury healing. Eleven patients with pressure injuries showing delayed healing underwent a microcurrent stimulation period and a placebo period. We analyzed the correlation between the individual variables and the following three outcomes using monophasic pulsed microcurrent: the wound reduction rate in the electrical stimulation period, the reduction rate in the placebo period, and the difference between these two reduction rates. Furthermore, the patients were divided into two groups, one with a wound reduction rate of more than 10% and the other with less than 10%, and the relationship between each variable was compared. As a result, the wound reduction rate in the electrical stimulation period and the difference in the reduction rate between the two periods showed significant positive correlations with patients' body mass index. In addition, a significant difference was observed in the body mass index between subjects with a reduction rate of 10% or higher and those with a reduction rate of less than 10%. This study found a correlation between the effect of monophasic pulsed microcurrent for pressure injury healing and the level of patients' body mass index.

Unilateral optogenetic stimulation of Lhx6 neurons in the zona incerta increases REM sleep.

To determine how a waking brain falls asleep researchers have monitored and manipulated activity of neurons and glia in various brain regions. While imaging Gamma-Aminobutyric Acid (GABA) neurons in the zona incerta (ZI) we found a subgroup that anticipates onset of NREM sleep (Blanco-Centurion C, Luo S, Vidal-Ortiz A, Swank C, Shiromani PJ. Activity of a subset of vesicular GABA-transporter neurons in the ventral ZI anticipates sleep onset. Sleep. 2021;44(6):zsaa268. doi:10.1093/sleep/zsaa268.). To differentiate the GABA subtype we now image and optogenetically manipulate the ZI neurons containing the transcription factor, Lhx6. In the first study, Lhx6-cre mice (n = 5; female = 4) were given rAAV-DJ-EF1a-DIO-GCaMP6M into the ZI (isofluorane anesthesia), a GRIN lens implanted, and 21days later sleep and fluorescence in individual Lhx6 neurons were recorded for 4 hours. Calcium fluorescence was detected in 132 neurons. 45.5% of the Lhx6 neurons were REM-max; 30.3% were wake-max; 11.4% were wake + REM max; 9% were NREM-max; and 3.8% had no change. The NREM-max group of neurons fluoresced 30 seconds ahead of sleep onset. The second study tested the effects of unilateral optogenetic stimulation of the ZI Lhx6 neurons (n = 14 mice) (AAV5-Syn-FLEX-rc[ChrimsonR-tdTomato]. Stimulation at 1 and 5 Hz (1 minute on- 4 minutes off) significantly increased percent REM sleep during the 4 hours stimulation period (last half of day cycle). The typical experimental approach is to stimulate neurons in both hemispheres, but here we found that low-frequency stimulation of ZI Lhx6 neurons in one hemisphere is sufficient to shift states of consciousness. Detailed mapping combined with mechanistic testing is necessary to identify local nodes that can shift the brain between wake-sleep states.

Layer-fMRI VASO with short stimuli and event-related designs at 7 T

Layers and columns are the dominant processing units in the human (neo)cortex at the mesoscopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical surface. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing complementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period and sub-millimeter resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials (∼20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimulus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.

A Single Application of Cerebellar Transcranial Direct Current Stimulation Fails to Enhance Motor Skill Acquisition in Parkinson's Disease: A Pilot Study.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that leads to numerous impairments in motor function that compromise the ability to perform activities of daily living. Practical and effective adjunct therapies are needed to complement current treatment approaches in PD. Transcranial direct current stimulation applied to the cerebellum (c-tDCS) can increase motor skill in young and older adults. Because the cerebellum is involved in PD pathology, c-tDCS application during motor practice could potentially enhance motor skill in PD. The primary purpose was to examine the influence of c-tDCS on motor skill acquisition in a complex, visuomotor isometric precision grip task (PGT) in PD in the OFF-medication state. The secondary purpose was to determine the influence of c-tDCS on transfer of motor skill in PD. The study utilized a double-blind, SHAM-controlled, within-subjects design. A total of 16 participants completed a c-tDCS condition and a SHAM condition in two experimental sessions separated by a 7-day washout period. Each session involved practice of the PGT concurrent with either c-tDCS or SHAM. Additionally, motor transfer tasks were quantified before and after the practice and stimulation period. The force error in the PGT was not significantly different between the c-tDCS and SHAM conditions. Similarly, transfer task performance was not significantly different between the c-tDCS and SHAM conditions. These findings indicate that a single session of c-tDCS does not elicit acute improvements in motor skill acquisition or transfer in hand and arm tasks in PD while participants are off medications.

Long-term analgesic effect of trans-spinal direct current stimulation compared to non-invasive motor cortex stimulation in complex regional pain syndrome.

The aim of the present study was to compare the analgesic effect of motor cortex stimulation using high-frequency repetitive transcranial magnetic stimulation or transcranial direct current stimulation and transcutaneous spinal direct current stimulation in patients with complex regional pain syndrome. Thirty-three patients with complex regional pain syndrome were randomized to one of the three treatment groups (repetitive transcranial magnetic stimulation, n = 11; transcranial direct current stimulation, n = 10; transcutaneous spinal direct current stimulation, n = 12) and received a series of 12 sessions of stimulation for 3 weeks (induction phase) and 11 sessions for 4 months (maintenance therapy). The primary end-point was the mean pain intensity assessed weekly with a visual numerical scale during the month prior to treatment (baseline), the 5-month stimulation period and 1 month after the treatment. The weekly visual numerical scale pain score was significantly reduced at all time points compared to baseline in the transcutaneous spinal direct current stimulation group, at the last two time points in the repetitive transcranial magnetic stimulation group (end of the 5-month stimulation period and 1 month later), but at no time point in the transcranial direct current stimulation group. A significant pain relief was observed at the end of induction phase using transcutaneous spinal direct current stimulation compared to repetitive transcranial magnetic stimulation (P = 0.008) and to transcranial direct current stimulation (P = 0.003). In this trial, transcutaneous spinal direct current stimulation was more efficient to relieve pain in patients with complex regional pain syndrome compared to motor cortex stimulation techniques (repetitive transcranial magnetic stimulation, transcranial direct current stimulation). This efficacy was found during the induction phase and was maintained thereafter. This study warrants further investigation to confirm the potentiality of transcutaneous spinal direct current stimulation as a therapeutic option in complex regional pain syndrome.

Disturbing the activity of the primary motor cortex by means of transcranial magnetic stimulation affects long term memory of sentences referred to manipulable objects.

Previous studies on embodied meaning suggest that simulations in the motor cortex play a crucial role in the processing of action sentences. However, there is little evidence that embodied meaning have functional impact beyond working memory. This study examines how the neuromodulation of the motor cortex (M1) could affect the processing of action-related language, measuring participants' performance in a long-term memory task. Participants were submitted to two sessions in separate days, one with low-frequency repetitive transcranial magnetic stimulation (rTMS) and the other with sham rTMS. The pulses were delivered for 15 minutes over M1 or over V1, used as a control area. After each stimulation or sham period, the participants were asked to memorize a list of simple sentences, with a manual action verb or an attentional verb, followed in both cases by a noun referred to a manipulable object (e.g., to hang a cane vs. to observe a cane). Finally, they received the verbs as cues with instructions to recall the nouns. The results showed that low frequency rTMS on M1, compared to sham stimulation, significantly improved the performance in the memory task, for both types of sentences. No change in performance was found after the rTMS stimulation of V1. These results confirm that the perturbation on the motor system, affect the memory of manipulable object names in the context of sentences, providing further evidence of the role played by the sensorimotor system in the encoding and recall of concrete sentences of action.

Clinical course of peripheral precocious puberty in girls due to autonomous ovarian cysts.

Peripheral precocious puberty (PPP) is the precocious development of secondary sexual characteristics without pulsatile gonadotropin-releasing hormone (GnRH) secretion. In girls, PPP suggests a hyper-oestrogenic state, such as autonomous ovarian cysts and McCune-Albright syndrome (MAS). We aimed to investigate PPP in girls with ovarian cysts, with or without MAS. A retrospective study design was used. The study included 12 girls diagnosed with ovarian cysts with PPP between January 2003 and May 2022. Pelvic sonography was performed in cases of vaginal bleeding or areolar pigmentation in PPP. The clinical characteristics, clinical courseand pelvic sonographic findings of girls with ovarian cysts were investigated. We found 18 episodes of ovarian cysts in the 12 girls. The median size of the ovarian cysts was 27.5 mm. Five of the girls were diagnosed with MAS. The median time to spontaneous regression was 6 months. Later, 4 out of 12 girls progressed to central precocious puberty (CPP), and three of them had a recurrence of ovarian cysts. Compared to the non-recurrent and recurrent groups, there was a difference in peak luteinizing hormone (LH) in the GnRH stimulation test and period to cyst regression. Most ovarian cysts in PPP spontaneously disappear. However, this couldbe one of the findings of MAS. Some girls progress from PPP to CPP. Therefore, follow-up isnecessary for ovarian cysts in patients with PPP. The recurrence of ovarian cysts may occur when spontaneous regression is prolonged.

High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke

Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties. To report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS. This randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. Patients were followed for 90 days. Primary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored. A total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 patients. Patients tolerated the HD C-tDCS with no permanent stimulation cessation. The hypoperfused region was reduced by a median (IQR) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -4% (-7% to 1%) sham patients and followed a dose-response pattern. Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in sham. In this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials. ClinicalTrials.gov Identifier: NCT03574038.

Continuous theta-burst stimulation in patients with drug-resistant epilepsy: A single-blind placebo-controlled cross-over pilot study

ObjectivesTo evaluate the effect of continuous theta-burst stimulation (cTBS) in patients with drug-resistant epilepsy (DRE). MethodsTwelve patients with DRE (five with idiopathic generalized and seven with focal epilepsy) were included in this cross-over design study and randomized to either first sham or first active stimulation, each applied for 5 consecutive days. A round coil over the vertex was used in generalized epilepsy or a figure-of-8 coil over the “epileptogenic area” in focal epilepsy. Sham stimulation was given by placing the coil 90° perpendicular to the head. The number of seizures, electroencephalography findings, Quality of Life in Epilepsy Inventory (QOLIE-84), and Symptom Check List (SCL-90) scores evaluated during the 8–12 weeks before and after active and sham stimulations were compared statistically. ResultsEight patients could complete both active and sham stimulation periods of 5 days and two patients completed active stimulation sessions, without any significant adverse effects. The number of seizures significantly reduced after active cTBS, but not after sham stimulation, when compared with those recorded before the stimulation period. QOLIE scores were increased, but interictal epileptiform discharges and SCL-90 scores showed no difference after cTBS. Active stimulation was stopped in one patient after he experienced an aggravation of myoclonic seizures. ConclusionscTBS seemed to be relatively safe and gave promising results in reducing the frequency of seizures in patients with both generalized and focal DRE. This time-saving technique may ease the introduction of repetitive transcranial magnetic stimulation into the routine practice of busy epilepsy clinics.

(058) Acute Dorsal Genital Neuromodulation can Improve Subjective Arousal: A Pilot Study in Women With and Without Spinal Cord Injury

Abstract Introduction Female sexual dysfunction (FSD) is a potentially life altering condition that impacts an estimated 40% of women. Unfortunately, the few treatment options available have limited success due to adverse events and an inability to improve subjective arousal. One potential treatment option, neuromodulation, has improved female sexual function index (FSFI) scores in small studies. The underlying mechanisms of how neuromodulation may improve FSD are not understood. We hypothesize that neuromodulation provides benefits by increasing genital blood flow. Objective Our primary objective is to determine if a single period of dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS) directly causes a change in vaginal blood flow (VBF). Our secondary objective is to assess if subjective arousal increases during a single period of DGNS or TNS. These interventions will be compared among three cohorts of women: women with C6–T10 spinal cord injury (SCI), women with FSD (FSFI lubrication sub-score < 4), and able-bodied women without FSD. Methods Participants attended two separate visits, one for each nerve target, randomly ordered and separated by 1–5 months. We are testing two experimental paradigms: without and with erotic audio-visual materials. The first experiments measured vaginal pulse amplitude (VPA) using a vaginal photoplethysmography transducer (VPP) before, during, and after 20 minutes of nerve stimulation. After data processing, we calculated average peak to peak (p2p) amplitudes for each time period and performed an ANOVA and post-hoc pairwise comparisons within each participant. For the second experiment we measured VPA during neutral and erotic videos both without stimulation and with stimulation. In both experiments we measured subjective arousal via a Likert-type scale at 4 timepoints and made comparisons across participants with a paired t-test. The first experiments are complete and data collection for the second experiments is ongoing. Results We recruited three participants in each cohort in the first experiments, with five participants completing both sessions. All participants saw significant changes in their p2p amplitude from before stimulation to after stimulation in DGNS trials (n = 3 increased, n = 4 decreased). Three of five participants had significant p2p increases in TNS trials and one participant had significant decreases. DGNS subject arousal scores increased significantly after stimulation, but TNS scores did not (Figure 1). Most participants reported genital sensations during DGNS (7 of 8) and TNS (3 of 6) sessions. Three participants have completed both visits in the second set of experiments, with similar trends. Conclusions Acute DGNS, but not TNS, increased subjective arousal across all participants. VPA responses to stimulation were heterogeneous and although most changes were significant, there may not be physiological or clinical relevance. It is possible that repeated stimulation sessions over time may enhance changes in VPA. Disclosure No

Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation are often compromised by adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-nanoelectronic threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stableICMS in awake, behaving mouse models. Invivo two-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2μA. Importantly, StimNETs evoke longitudinally stable behavioral responses for over 8months at a markedly low charge injection of 0.25 nC/phase. Quantified histological analyses show that chronic ICMS by StimNETs induces no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially selective neuromodulation at low currents, which lessens risk of tissue damage or exacerbation of off-target side effects.

(529) Etiology of Erectile Dysfunction in Patients who Underwent Endourological Procedures for Prostate vs. Robotic and Open Radical Prostatectomy.

Abstract Introduction Erectile dysfunction continues to be a concern for patients and physicians after surgical treatment of prostate pathology. Objective To analyze doppler diagnosis on patients who underwent prostate surgery for benign or malignant pathology of the prostate. Methods We retrospectively analyzed all patients who underwent either robotic assisted prostatectomy (RALP), open retropubic prostatectomy (RRP), endoscopic procedures such as greenlight procedure, laser resection of the prostate or transurethral resection of the prostate (TURP); and High Intensity Focused Ultrasound (HIFU) treatment for prostate pathology and who underwent intracavernous injection followed by Color Doppler Duplex Ultrasound (CDDU) at our institution between 2005 and 2019. CDDU findings were recorded following injection of low dose alprostadil (10-20 mcg) and again after a period of privacy and visual sexual stimulation. CCDU findings including peak systolic velocities (PSV), and resistive indices (RIs) were recorded. Arterial insufficiency (AI) was defined as either a post-stimulation PSV < 25 with any RI or a PSV 25-34.9 with RI≥0.9. Cavernous Venous Occlusion Disease (CVOD) was defined as post-stimulation PSV ≥35 with RI < 0.9. Mixed was defined as post-stimulation PSV 25-34.9 with RI < 0.9. Vascular normal was defined as post-stim PSV ≥ 35 with RI ≥ 0.9. Results 380/1917 (19.8%) patients had a past surgical history of prostate surgery. 111/380 (29.2%) underwent RRP, 168/380 (44.2%) patients underwent RALP, 85/380 (22.3%) underwent endourological resection of the prostate and 2/380 (0.5%) patients underwent HIFU. Median age for the RALP group was 60.5 (IQR 23.7-82.8), RRP group was 64.2 (29.7-87.7), endourological resection of the prostate 64.6 (30.8 – 85.6) and HIFU 65.0 (46.9-79.4). 87.1% of patients who had an endoscopic procedure were using phosphodiesterase-5 inhibitors at the time of CDDU. CVOD was the most common etiology of ED in patients who underwent RRP (28.8%) and Endourological procedures of the prostate (32.9%); In patient who underwent RALP the most common etiology of ED was noted to be AI (28.6%), however none of these values were statistically significant (p=0.428). Conclusions There is no difference in etiology of ED in patients who underwent open, robotic or endoscopic manipulation of the prostate as shown by CDDU. Disclosure No

Distinct neural signaling characteristics between fibromyalgia and provoked vestibulodynia revealed by means of functional magnetic resonance imaging in the brainstem and spinal cord.

Fibromyalgia and provoked vestibulodynia are two chronic pain conditions that disproportionately affect women. The mechanisms underlying the pain in these conditions are still poorly understood, but there is speculation that both may be linked to altered central sensitization and autonomic regulation. Neuroimaging studies of these conditions focusing on the brainstem and spinal cord to explore changes in pain regulation and autonomic regulation are emerging, but none to date have directly compared pain and autonomic regulation in these conditions. This study compares groups of women with fibromyalgia and provoked vestibulodynia to healthy controls using a threat/safety paradigm with a predictable noxious heat stimulus. Functional magnetic resonance imaging data were acquired at 3 tesla in the cervical spinal cord and brainstem with previously established methods. Imaging data were analyzed with structural equation modeling and ANCOVA methods during: a period of noxious stimulation, and a period before the stimulation when participants were expecting the upcoming pain. The results demonstrate several similarities and differences between brainstem/spinal cord connectivity related to autonomic and pain regulatory networks across the three groups in both time periods. Based on the regions and connections involved in the differences, the altered pain processing in fibromyalgia appears to be related to changes in how autonomic and pain regulation networks are integrated, whereas altered pain processing in provoked vestibulodynia is linked in part to changes in arousal or salience networks as well as changes in affective components of pain regulation.