Threshold Stimulus Research Articles

Real-world outcomes of Voretigene Neparvovec: a single-centre consecutive case series.

To present functional and anatomical outcomes of subretinal therapy with Voretigene Neparvovec (VN) in patients treated in one of the four specialist UK gene therapy centres. Single-centre, retrospective case series of patients affected by an inherited retinal dystrophy (IRD) caused by a pathogenic biallelic RPE65 mutation and treated with VN. Complete ophthalmic examination was planned preoperatively and 2, 4 and 8 weeks and 3, 6, 12, 18 and 24 months after surgery, and included visual acuity (VA) assessment (normal and low luminance), colour vision, contrast sensitivity, dark-adapted full-field stimulus threshold, macular optical coherence tomography (OCT) and fundus autofluorescence. Fourteen eyes of 8 patients were included with a mean follow-up of 26 months. Mean final VA improved by 2 lines, and improvements were noted in most other functional tests. Central retina thickness (CRT) remained fairly stable in the majority of patients, whereas 2 eyes experienced a reduction >30 μm. The status of ellipsoid band and external limiting membrane remained stable in all patients, except one. Peripapillary atrophy (PPA) was present in 5 eyes of 3 patients at the baseline; postoperative progression was noted in both eyes of one patient. No patient developed new PPA or chorioretinal atrophy (CRA) involving the macular area after treatment. Five eyes of 3 patients developed CRA at the retinotomy site, that progressed in 3 of them. Our study confirmed the effectiveness of subretinal VN therapy in terms of improvement of visual function. CRA was confirmed as a common postoperative complication, with limited functional impact.

Poor fixation stability does not account for motion perception deficits in amblyopia

People with amblyopia show deficits in global motion perception, especially at slow speeds. These observers are also known to have unstable fixation when viewing stationary fixation targets, relative to healthy controls. It is possible that poor fixation stability during motion viewing interferes with the fidelity of the input to motion-sensitive neurons in visual cortex. To probe these mechanisms at a behavioral level, we assessed motion coherence thresholds in adults with amblyopia while measuring fixation stability. Consistent with prior work, participants with amblyopia had elevated coherence thresholds for the slow speed stimuli, but not the fast speed stimuli, using either the amblyopic or the fellow eye. Fixation stability was elevated in the amblyopic eye relative to controls across all motion stimuli, and not selective for conditions on which perceptual deficits were observed. Fixation stability was not related to visual acuity, nor did it predict coherence thresholds. These results suggest that motion perception deficits might not be a result of poor input to the motion processing system due to unstable fixation, but rather due to processing deficits in motion-sensitive visual areas.

Relationship between the full-field stimulus test and self-reported visual function in patients with retinitis pigmentosa: REPEAT Study report No. 3.

To determine the relationship between the full-field stimulus test (FST) and self-reported visual function using the Michigan Retinal Degeneration Questionnaire (MRDQ) in patients with retinitis pigmentosa (RP). In this cross-sectional study, patients with clinically diagnosed RP (n = 31) performed FST to determine retinal sensitivity thresholds for blue, red and white stimuli. The difference between the blue and red thresholds was used to identify photoreceptor mediation type. Patients completed the MRDQ from which disability (Θ) scores were derived across seven visual function domains. Correlations between the FST thresholds and MRDQ domain Θ-scores were analysed using Spearman's rank correlation. The median age was 38.0 years, and photoreceptor mediation was rod-based in 11 patients (35.5%), cone-based in seven patients (22.6%) and mixed in 13 patients (41.9%). The highest disability scores were reported in the domains of 'mesopic peripheral function' and 'scotopic function'. Significant correlations were found between all chromatic stimuli thresholds and the MRDQ domains of 'scotopic function', 'mesopic peripheral function' and 'photopic peripheral function'. The strongest correlations of these domains were observed with the blue FST (p < 0.001). The threshold on blue stimulus FST and age were significant predictors of the domain scores on 'scotopic function' (p < 0.001), 'mesopic peripheral function' (p < 0.001) and 'photopic peripheral function' (p < 0.001). Strong correlations between MRDQ domains related to rod function and FST were found in patients with RP. These findings confirm that FST can be used as an informative and clinically relevant endpoint in RP trials when evaluating therapeutic interventions.

A New Method to Measure Ocular Surface Sensitivity: Repeatability and Reproducibility of the Liquid Jet Esthesiometer.

To assess the reliability of the liquid jet esthesiometer (LJA) for measurement of corneal sensitivity. Two separate studies were conducted to assess intrasession repeatability (study 1) and intersession reproducibility (study 2) of corneal sensitivity measured using the LJA. Thirty participants (13 female and 17 male participants, age 23±6 years) participated in study 1 and another 30 (18 female and 12 male participants, 35±10 years) participated in study 2. For study 1, mechanical sensation threshold of the central cornea was measured three times on the same day, with a 30-min break between repeats. For study 2, central corneal sensation threshold was measured on five different days by one of eight randomly assigned examiners. Corneal sensation thresholds obtained in studies 1 and 2 were 2.3±1.0 and 2.5±1.2 μL, respectively. No significant differences between repeated measurements were obtained in either study (P≥0.19). Thresholds were lower (i.e., corneal sensitivity was higher) in female than male participants (2.1±1.0 vs. 2.7±0.9 μL in male participants, P=0.02) but were not affected by contact lens wear. Clinical reliability of the LJA was good for intrasession repeatability (coefficient of repeatability ±1.6 μL, intraclass correlation coefficient 0.74, within-subject coefficient of variation (CVW) 24%) and moderate for intersession reproducibility (Coefficient of Reproducibility ±2.2 μL, CVW 32%). Measurement variability was independent of threshold level (P=0.84). The LJA offers good clinical repeatability and is a reliable tool to measure corneal sensitivity in different population groups, regardless of stimulus thresholds. Day-to-day fluctuations in corneal sensitivity probably account for the relatively lower reproducibility.

Intraoperative Acoustic Monitoring Using Threshold and Suprathreshold Pure Tone Audiometry during Cochlear Implantation Under Local Anesthesia: A Simple and Novel Method to Potentially Enhance Hearing Preservation Cochlear Implant Surgery.

To report the feasibility and potential utility of monitoring acoustic hearing on awake patients using intraoperative behavioral responses to threshold and suprathreshold stimuli while undergoing cochlear implantation (CI) under local anesthesia, without any form of sedation. Retrospective review of the first five cases performed by one surgeon. Tertiary care academic medical center. Adult patients with residual acoustic hearing undergoing CI. CI under local anesthesia, without any form of sedation. Procedural tolerance, reliability of intraoperative pure tone threshold and suprathreshold audiometry, and correlation of intraoperative findings with early postoperative residual hearing. Five ears in four patients underwent CI, including three males and one female, with a median age of 61 years. Intraoperatively, patients reported reliable behavioral responses to pure tone threshold and suprathreshold stimuli and provided real-time feedback on perceived stimulus change to the surgeon just prior to, during, and immediately following electrode insertion. All patients were able to complete the operation under local anesthesia. During electrode insertion, three cases reported no change and two cases reported diminished stimulus perception that reversed with limited electrode pull back near terminal insertion. Immediate postoperative audiograms demonstrated preservation of bone conduction thresholds within 10 dB of their preoperative baseline for all cases, suggesting hearing preservation. Three-month postoperative AzBio in quiet scores were available for two patients, measuring 45% and 94%, respectively. This report describes the feasibility of intraoperative behavioral audiometry during CI under local anesthesia, using patient feedback during electrode insertion to optimize hearing preservation surgery. Akin to other surgical subspecialties that use real-time patient feedback where objective intraoperative measures of neurofunction are imperfect, we demonstrate feasibility and potential utility of live acoustic monitoring during CI.

Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in the USH2A-associated Retinal Degeneration RUSH2A Study

PurposeTo describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the RUSH2A study and to assess their suitability as clinical trial endpoints. DesignProspective natural history study. ParticipantsParticipants (n=105) with biallelic disease-causing sequence variants in USH2A and BCVA letter score of ≥54 were included. MethodsBCVA, FST, fundus-guided microperimetry, static perimetry and spectral domain optical coherence tomography were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals (CI). Associations of change from baseline to 4 years between BCVA, FST, ERG and other metrics were assessed with Spearman correlation coefficients (rs). Main Outcome MeasuresBCVA, FST, ERG. ResultsThe annual rate of decline in BCVA was 0.83 (95% CI: 0.65, 1.02) letters/year. For FST, the change was 0.09 (0.07, 0.11) log cd.s/m2/year for white threshold, 0.10 (0.08, 0.12) log cd.s/m2/year for blue threshold and 0.05 (0.04, 0.06) log cd.s/m2/year for red threshold. Changes were 22.6 (17.4, 28.2) %/year for white threshold, 26.0 (20.3, 32.1) %/year for blue threshold, and 12.3 (8.7, 16.0) %/year for red threshold. The high percentage of eyes with undetectable ERGs at baseline limited assessment of change. ConclusionBCVA was not a sensitive measure of progression over 4 years. FST was a more sensitive measure; however, additional information on the clinical relevance of changes in FST is needed before this test can be adopted as an endpoint for clinical trials.

Perception Threshold for Pressure by a Soft Textile Actuator.

Electroactive textile (EAT) has the potential to apply pressure stimuli to the skin, e.g. in the form of a squeeze on the arm. To present a perceivable haptic sensation we need to know the perception threshold for such stimuli. We designed a set-up based on motorized ribbons around the arm with five different widths (range 3 - 49 mm) for psychophysical studies. We investigated the perception threshold of force pressure and ribbon reduction in two studies, using two methods (PSI and 1up/3down staircase), comparing sex, the left and right arm, the lower and upper arm, and stimulated surface area with a total of 57 participants. We found that larger stimulation surfaces require less pressure to reach the perception threshold (0.151 N per cm 2 for 3 mm width, 0.00972 N per cm 2 for 49 mm width on the lower arm). This indicates a spatial summation effect for these pressure stimuli. We did not find significant differences in perception threshold for the left and right arm and, the upper and lower arm. Between male and female participants we found significant differences for two conditions (10 mm and 25 mm) in Experiment 1, but we could not reproduce this in Experiment 2.

Interoceptive signals shape the earliest markers and neural pathway to awareness at the visual threshold

Variations in interoceptive signals from the baroreceptors (BRs) across the cardiac and respiratory cycle can modulate cortical excitability and so affect awareness. It remains debated at what stages of processing they affect awareness-related event-related potentials (ERPs) in different sensory modalities. We investigated the influence of the cardiac (systole/diastole) and the respiratory (inhalation/exhalation) phase on awareness-related ERPs. Subjects discriminated visual threshold stimuli while their electroencephalogram, electrocardiogram, and respiration were simultaneously recorded. We compared ERPs and their intracranial generators for stimuli classified correctly with and without awareness as a function of the cardiac and respiratory phase. Cyclic variations of interoceptive signals from the BRs modulated both the earliest electrophysiological markers and the trajectory of brain activity when subjects became aware of the stimuli: an early sensory component (P1) was the earliest marker of awareness for low (diastole/inhalation) and a perceptual component (visual awareness negativity) for high (systole/exhalation) BR activity, indicating that BR signals interfere with the sensory processing of the visual input. Likewise, activity spread from the primary visceral cortex (posterior insula) to posterior parietal cortices during high and from associative interoceptive centers (anterior insula) to the prefrontal cortex during low BR activity. Consciousness is thereby resolved in cognitive/associative regions when BR is low and in perceptual centers when it is high. Our results suggest that cyclic fluctuations of BR signaling affect both the earliest markers of awareness and the brain processes underlying conscious awareness.

Spinal cord microglia drive sex differences in ethanol-mediated PGE2-induced allodynia

The mechanisms of how long-term alcohol use can lead to persistent pain pathology are unclear. Understanding how earlier events of short-term alcohol use can lower the threshold of non-painful stimuli, described as allodynia could prove prudent to understand important initiating mechanisms. Previously, we observed that short-term low-dose alcohol intake induced female-specific allodynia and increased microglial activation in the spinal cord dorsal horn. Other literature describes how chronic ethanol exposure activates Toll-like receptor 4 (TLR4) to initiate inflammatory responses. TLR4 is expressed on many cell types, and we aimed to investigate whether TLR4 on microglia is sufficient to potentiate allodynia during a short-term/low-dose alcohol paradigm. Our study used a novel genetic model where TLR4 expression is removed from the entire body by introducing a floxed transcriptional blocker (TLR4-null background (TLR4LoxTB)), then restricted to microglia by breeding TLR4LoxTB animals with Cx3CR1:CreERT2 animals. As previously reported, after 14 days of ethanol administration alone, we observed no increased pain behavior. However, we observed significant priming effects 3 hrs post intraplantar injection of a subthreshold dose of prostaglandin E2 (PGE2) in wild-type and microglia-TLR4 restricted female mice. We also observed a significant female-specific shift to pro-inflammatory phenotype and morphological changes in microglia of the lumbar dorsal horn. Investigations in pain priming-associated neuronal subtypes showed an increase of c-Fos and FosB activity in PKCγ interneurons in the dorsal horn of female mice directly corresponding to increased microglial activity. This study uncovers cell- and female-specific roles of TLR4 in sexual dimorphisms in pain induction among non-pathological drinkers.

Partial rescue of the full-field electroretinogram in patients with RPE65-related retinal dystrophy following gene augmentation therapy with voretigene neparvovec-rzyl.

To present a series of patients with RPE65-related retinal dystrophy showing a partial rescue of the full-field electroretinogram (ERG) following gene replacement therapy with voretigene neparovec-rzyl (Luxturna®). This retrospective chart review examined 17 patients treated with voretigene neparovec-rzyl (VN) at the Casey Eye Institute (2018-2022). The last pre-operative ERG and all available post-operative ERGs were analyzed to identify subjects with functional rescue. Measurements of amplitudes and implicit times were compared to data from age-matched controls and the attenuation relative to the lower limit of normal (LLN) was calculated. For comparison with other functional exams, the last pre-operative and all post-treatment best-corrected visual acuity (BCVA) data, visual field (VF) tests and full-field threshold stimulus tests (FST) were also described. Of patients who underwent ERGs, most had unrecordable ERGs that did not change after treatment. However, we identified three patients, treated bilaterally, who demonstrated partial rescue of the full-field ERG in both eyes which was sustained during the course of the study. This is the largest series of patients treated with VN showing a partial rescue of the ERG. This is also the first report of bilateral ERG rescue, as well as the first description of ERG recovery occurring in non-pediatric subjects. Full-field ERG could be used in combination with other psychophysical tests and imaging modalities to detect and deepen our understanding of the response to this gene therapy approach.

Myofascial pain syndrome-aneurovegetative complaints pattern

The diagnosis of myofascial pain syndrome is usually made after structural-morphological explanations have been ruled out. The lack of positive findings to guide treatment inevitably leaves room for interpretation despite the extensive use of all imaging, neurophysiological or serological diagnostics. Under these circumstances, acareful differential diagnosis must be made between functional and structural aspects, both of which in many cases must be assessed in their different relevance. Particular attention must be paid to indications of vegetative-sympathetic adjustment disorders.The great importance of aclinical, experience-based approach to this symptom pattern becomes clear here, especially if the technical diagnostic data is of no help. The dominance of imaging findings naturally promotes astructure-based, mechanistic understanding of the illness. In contrast, the emotional, vegetative mood of the patient should be given greater consideration as adiagnostic and therapeutic focus. Treatment measures should have ahigh success rate, as persistent reductions in stimulus thresholds may lead to prognostically unfavorable chronification.

Examining the lateralization of electrophysiological correlates of auditory awareness.

The neurological basis for perceptual awareness remains unclear, and theories disagree as to whether sensory cortices per se generate awareness. Critically, neural activity in the sensory cortices is only a neural correlate of consciousness (NCC) if it closely matches the contents of perceptual awareness. Research in vision and touch suggest that contralateral activity in sensory cortices is an NCC. Similarly, research in hearing with two sound sources (left and right) presented over headphones also suggests that a candidate NCC called the auditory awareness negativity (AAN) matches perceived location of sound. The current study used 13 different sound sources presented over loudspeakers for natural localization cues and measured event-related potentials to a threshold stimulus in a sound localization task. Preregistered Bayesian mixed models provided moderate evidence against an overall AAN and very strong evidence against its lateralization. Because of issues regarding data quantity and quality, exploratory analyses with aggregated data from multiple loudspeakers were conducted. Results provided moderate evidence for an overall AAN and strong evidence against its lateralization. Nonetheless, the interpretations of these results remain inconclusive. Therefore, future research should reduce the number of conditions and/or test over several sessions to procure a sufficient amount of data. Taken at face value, the results may suggest issues with AAN as an NCC of auditory awareness, as it does not laterally map onto experiences in a free-field auditory environment, in contrast to the NCCs of vision and touch.

Effect of Spatial and Temporal Prediction on Tactile Sensitivity.

The purpose of the present study was to examine whether spatial or temporal prediction of the tactile stimulus contributes to tactile sensitivity. To investigate the effect of spatial prediction on tactile sensitivity, electrical stimuli were provided for the digit nerve in one of five fingers, and advanced notice of the stimulating finger was provided before the stimulus in some trials but not in others. There was no significant effect of spatial prediction on the intensity at the perceptual threshold of the digit nerve stimulus. This indicates that spatial prediction of the tactile stimulus does not influence tactile sensitivity. To examine the effect of temporal prediction, an auditory warning cue was provided 0, 1, or 10 s before the electrical stimulus to the digit nerve. The stimulus intensity at the perceptual threshold in the trials with the 1 s warning cue was lower than those with the 0 s warning cue. This indicates that temporal prediction enhances tactile sensitivity. The stimulus intensity at the perceptual threshold in the trials with the 1 s warning cue was lower than those with the 10 s warning cue. This means that the contribution of temporal prediction to the tactile sensitivity is greater as the warning cue is closer to the time of the stimulus. This finding may be explained by a defense mechanism activated when humans predict that a tactile stimulus is coming soon.

Self-Regulation of the Posterior-Frontal Brain Activity with Real-Time fMRI Neurofeedback to Influence Perceptual Discrimination.

The Global Neuronal Workspace (GNW) hypothesis states that the visual percept is available to conscious awareness only if recurrent long-distance interactions among distributed brain regions activate neural circuitry extending from the posterior areas to prefrontal regions above a certain excitation threshold. To directly test this hypothesis, we trained 14 human participants to increase blood oxygenation level-dependent (BOLD) signals with real-time functional magnetic resonance imaging (rtfMRI)-based neurofeedback simultaneously in four specific regions of the occipital, temporal, insular and prefrontal parts of the brain. Specifically, we hypothesized that the up-regulation of the mean BOLD activity in the posterior-frontal brain regions lowers the perceptual threshold for visual stimuli, while down-regulation raises the threshold. Our results showed that participants could perform up-regulation (Wilcoxon test, session 1: p = 0.022; session 4: p = 0.041) of the posterior-frontal brain activity, but not down-regulation. Furthermore, the up-regulation training led to a significant reduction in the visual perceptual threshold, but no substantial change in perceptual threshold was observed after the down-regulation training. These findings show that the up-regulation of the posterior-frontal regions improves the perceptual discrimination of the stimuli. However, further questions as to whether the posterior-frontal regions can be down-regulated at all, and whether down-regulation raises the perceptual threshold, remain unanswered.

Adverse childhood experiences, brain efficiency, and the development of pain symptoms in youth.

Adverse childhood experiences (ACEs) are often reported by youths with chronic pain, and both ACEs and chronic pain disrupt how information is processed. However, it is unknown whether changes to shared neural networks underlie the relationship between ACEs and the development of pain symptoms. This study explored the relationships between ACEs, brain efficiency, and pain symptomology in youth. A community sample of youths aged 14-18 years underwent MRIs, answered trauma and pain questionnaires, and underwent pain sensory testing, twice, 3 months apart (Nbaseline = 44; Nfollow-up = 42). Sensory testing determined thresholds for mechanical and thermal stimuli. Global and local network efficiencies were evaluated using graph theory. Generalized estimating equations were applied to examine whether brain efficiency moderated the relationships between ACEs, pain intensity, and pain sensitivity (i.e., mechanical detection, heat pain, and temperature change thresholds). There was a significant interaction between ACEs and global brain efficiency in association with pain intensity (β = -0.31, p = 0.02) and heat pain (β = -0.29, p = 0.004). Lower global brain efficiency exacerbated the relationship between ACEs and pain intensity (θX → Y|W = -1.16 = 0.37, p = 0.05), and heat pain sensitivity (θX → Y|W = -1.30 = 0.44, p = 0.05). Higher global brain efficiency ameliorated the relationship between ACEs and pain intensity (θX → Y|W = 1.75 = -0.53, p = 0.05). The relationship between ACEs and pain symptomology was comparable to chronic pain phenotypes (i.e., higher pain intensity and pain thresholds) and may vary as a function of brain efficiency in youth. This stresses the importance of assessing for pain symptoms in trauma-exposed youth, as earlier identification and intervention are critical in preventing the chronification of pain. This article explores the relationship between ACEs, pain symptomology, and brain efficiency in youth. ACEs may affect how the brain processes information, including pain. Youths with lower brain efficiencies that were exposed to more ACEs have pain symptomology comparable to youths with chronic pain. Understanding this relationship is important for the earlier identification of pain symptoms, particularly in vulnerable populations such as youths exposed to trauma, and is critical for preventing the chronification of pain.

Evaluation of Efficacy of 2 Extended-release Bupivacaine Products in a Porcine Model of Incisional Pain.

Extended-release (ER) local anesthetics are often incorporated in multi-modal analgesia or as an alternative when the effect of systemic analgesics may confound research. In this study, we compared the analgesic efficacy of 2 ER bupivacaine anesthetics with different ER mechanisms, a slow-release bupivacaine-meloxicam polymer (BMP) and a sucrose acetate isobutyrate bupivacaine (SABER-B) system. We used a full-thickness unilateral skin incision porcine model to evaluate the efficacy of these 2 ER bupivacaine analgesics. Eighteen male swine were randomized into 3 groups: control (saline; n = 6), bupivacaine:meloxicam (10 mg/kg, 0.3 mg/kg; n = 6), and SABER-B (10 mg/kg; n = 6). After surgery, pigs were assessed for changes in body weight, salivary cortisol level, and response to von Frey testing at 1, 3, 6, 24, 48, 72, 96, 120, and 168 h. Body weight and salivary cortisol levels were not significantly different between groups. Based on the von Frey testing, the pigs that received analgesics showed a significantly higher withdrawal threshold of nociceptive stimulus than those that received saline at 1, 3, 6, and 24 h after the surgery. At 48 h after surgery, the SABER-B group had a significantly higher withdrawal threshold than the saline group. The withdrawal threshold was not significantly different from the baseline measurement on intact skin at 3 and 6 h after surgery in the BMP group or 1 and 3 h for the SABERB group. The analgesic effects of BMP were greatest at 3 and 6 h after surgery and that of SABER-B as 1 and 3 h SABER-B provided an earlier onset of analgesia and longer analgesia duration than did BMP. This study demonstrates that ER bupivacaine can provide pigs with 24 to 48 h of analgesia for incisional pain.

Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector.

To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector. Single-center, retrospective chart review. In this case series, four patients between the ages of six and 11years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated. Three out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector. We observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes. Caution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

Wavelet transform of single-trial vestibular short-latency evoked potential reveals temporary reduction in signal detectability and temporal precision following noise exposure.

Our study presents a new method of VsEP quantification using wavelet transform on a single-trial basis. It also describes a novel approach to determine the stimulus threshold of the VsEP based on signal-detection theory and Rayleigh statistics. The present analysis could also be applied to analysis of auditory brain stem response (ABR). Thus, it has the potential to provide new insights into the physiological properties that underlie peripheral vestibular and auditory dysfunction.

Self-Reported Functional Vision in USH2A-Associated Retinal Degeneration as Measured by the Michigan Retinal Degeneration Questionnaire.

The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using a patient-reported outcome (PRO) measure, the Michigan Retinal Degeneration Questionnaire (MRDQ), to correlate MRDQ scores with well-established visual function measurements. An observational cross-sectional study (n = 93) of participants who had Usher Syndrome Type 2 (USH2, n = 55) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP; n = 38) associated with biallelic variants in the USH2A gene. The study protocol was approved by all ethics boards and informed consent was obtained from each participant. Participants completed the MRDQ at the 48-month study follow-up visit. Disease duration was self-reported by participants. One-way ANOVA was used to compare subgroups (clinical diagnosis, age, disease duration, and full-field stimulus threshold [FST] Blue-Red mediation) on mean scores per domain. Spearman correlation coefficients were used to assess associations between MRDQ domains and visual/retinal function assessments. Of the study sample, 58% were female participants and the median disease duration was 13years. MRDQ domains were sensitive to differences between subgroups of clinical diagnosis, age, disease duration, and FST Blue-Red mediation. MRDQ domains correlated with static perimetry, microperimetry, full-field stimulus testing, and best-corrected visual acuity (BCVA). Self-reported FV measured by the MRDQ, when applied to USH2 and ARRP participants, had good distributional characteristics and correlated well with visual function tests. MRDQ adds a new dimension of understanding on vision-related functioning and establishes this PRO tool as an informative measure in evaluating USH2A outcomes.

Feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array

Objective. Electrical stimulation of peripheral nerves has long been a treatment option to restore impaired neural functions that cannot be restored by conventional pharmacological therapies. Endovascular neurostimulation with stent-mounted electrode arrays is a promising and less invasive alternative to traditional implanted electrodes, which typically require invasive implantation surgery. In this study, we investigated the feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array and compared its performance to that of a commercially available pacing catheter. Approach. In acute animal experiments, a pacing catheter was implanted unilaterally in the femoral artery to stimulate the femoral nerve in a bipolar configuration. Electromyogram of the quadriceps and electroneurogram of a distal branch of the femoral nerve were recorded. After retrieval of the pacing catheter, a bipolar stent-mounted electrode array was implanted in the same artery and the recording sessions were repeated. Main Results. Stimulation of the femoral nerve was feasible with the stent-electrode array. Although the threshold stimulus intensities required with the stent-mounted electrode array (at 100–500 µs increasing pulse width, 2.17 ± 0.87 mA–1.00 ± 0.11 mA) were more than two times higher than the pacing catheter electrodes (1.05 ± 0.48 mA–0.57 ± 0.28 mA), we demonstrated that, by reducing the stimulus pulse width to 100 µs, the threshold charge per phase and charge density can be reduced to 0.22 ± 0.09 µC and 24.62 ± 9.81 µC cm−2, which were below the tissue-damaging limit, as defined by the Shannon criteria. Significance. The present study is the first to report in vivo feasibility and efficiency of peripheral nerve stimulation using an endovascular stent-mounted electrode array.