Stimulus Intensity Research Articles

Adaptive spike threshold dynamics associated with sparse spiking of hilar mossy cells are captured by a simple model.

Hilar mossy cells (hMCs) in the dentate gyrus (DG) receive inputs from DG granule cells (GCs), CA3 pyramidal cells and inhibitory interneurons, and provide feedback input to GCs. Behavioural and in vivo recording experiments implicate hMCs in pattern separation, navigation and spatial learning. Our experiments link hMC intrinsic excitability to their synaptically evoked in vivo spiking outputs. We performed electrophysiological recordings from DG neurons and found that hMCs displayed an adaptative spike threshold that increased both in proportion to the intensity of injected currents, and in response to spiking itself, returning to baseline over a long time scale, thereby instantaneously limiting their firing rate responses. The hMC activity is additionally limited by a prominent medium after-hyperpolarizing potential (AHP) generated by small conductance K+ channels. We hypothesize that these intrinsic hMC properties are responsible for their low in vivo firing rates. Our findings extend previous studies that compare hMCs, CA3 pyramidal cells and hilar inhibitory cells and provide novel quantitative data that contrast the intrinsic properties of these cell types. We developed a phenomenological exponential integrate-and-fire model that closely reproduces the hMC adaptive threshold nonlinearities with respect to their threshold dependence on input current intensity, evoked spike latency and long-lasting spike-induced increase in spike threshold. Our robust and computationally efficient model is amenable to incorporation into large network models of the DG that will deepen our understanding of the neural bases of pattern separation, spatial navigation and learning. KEY POINTS: Previous studies have shown that hilar mossy cells (hMCs) are implicated in pattern separation and the formation of spatial memory, but how their intrinsic properties relate to their in vivo spiking patterns is still unknown. Here we show that the hMCs display electrophysiological properties that distinguish them from the other hilar cell types including a highly adaptive spike threshold that decays slowly. The spike-dependent increase in threshold combined with an after-hyperpolarizing potential mediated by a slow K+ conductance is hypothesized to be responsible for the low-firing rate of the hMC observed in vivo. The hMC's features are well captured by a modified stochastic exponential integrate-and-fire model that has the unique feature of a threshold intrinsically dependant on both the stimulus intensity and the spiking history. This computational model will allow future work to study how the hMCs can contribute to spatial memory formation and navigation.

A reliable and reproducible protocol for sound-evoked vestibular myogenic potentials in rattus norvegicus.

Cervical vestibular evoked myogenic potentials (cVEMPs) provide an objective measure of the integrity of the sacculo-collic pathway leading to their widespread use as a clinical tool in the diagnostic vestibular test battery. Though the application of cVEMPs in preclinical models to assess vestibular function, as performed in relevant clinical populations, remains limited. The present study aimed to establish a rodent model of cVEMP with standardized methods and protocols, examine the neural basis of the responses, and characterize and validate important features for interpretation and assessment of vestibular function. We compared air-conducted sound (ACS)-evoked VEMPs from the sternocleidomastoid muscles in naïve Brown Norway rats. A custom setup facilitated repeatable and reliable measurements which were carried out at multiple intensities with ACS between 1 and 16 kHz and over 7 days. The myogenic potentials were identified by the presence of a positive (P1)-negative (N1) waveform at 3-5 ms from the stimulus onset. Threshold, amplitude, and latency were compared with intensity- and frequency-matched responses within and between animals. cVEMP responses were repeatedly evoked with stimulus intensities between 50-100 dB SPL with excellent test-retest reliability and across multiple measurements over 7 days for all frequencies tested. Suprathreshold, cVEMP responses at 90 dB SPL for 6-10 kHz stimuli demonstrated significantly larger amplitudes (p < 0.01) and shorter latencies (p < 0.001) compared to cVEMP responses for 1-4 kHz stimuli. Latency of cVEMP showed sex-dependent variability, but no significant differences in threshold or amplitude between males and females was observed. The results provide a replicable and reliable setup, test protocol, and comprehensive characterization of cVEMP responses in a preclinical model which can be used in future studies to elucidate pathophysiological characteristics of vestibular dysfunctions or test efficacy of therapeutics.

Study on after-effect of electroacupuncture with different time intervals on corticospinal excitability in primary motor cortex.

To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture. Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*). The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05). Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

Intraoperative nerve stimulation during vagal nerve stimulator placement.

Vagal nerve stimulation (VNS) is a palliative treatment for refractory epilepsy and intraoperative nerve stimulation is applied to the vagal and other nerves to prevent electrode misplacement. We evaluated these thresholds to establish intraoperative monitoring procedures for VNS surgery. Forty-six patients who underwent intraoperative nerve stimulation during VNS placement were enrolled. The vagal nerve and other exposed nerves were electrically stimulated during surgery, and muscle contraction was confirmed by electromyography of the vocal cords and visual recognition of cervical muscle contraction. The nerve thresholds and the most sensitive parts of the vagal nerve were analyzed retrospectively. The stimulation of vagal nerves induced vocal cord responses in all 46 patients; the median thresholds of the most sensitive parts and all parts were 0.2 mA (range: 0.05-0.75 mA) and 0.25 mA (range: 0.15-1.5 mA), respectively. The medial middle region was identified as the most sensitive part of the vagal nerve in the majority of participants (82.5%). In 11 patients, other cervical nerves were stimulated and sternohyoid muscle contraction was induced with a median threshold of 0.35 mA (range: 0.1-0.7 mA) in eight patients, while sternocleidomastoid muscle contraction was induced with a median threshold of 0.2 mA (range: 0.1-0.2 mA) in three. Intraoperative stimulation of vagal nerves induces vocal cord responses with locational variations, and the middle part stimulation could minimize the stimulus intensities. The nerves innervating the sternohyoid and sternocleidomastoid muscles may be exposed during the procedure. Knowledge of these characteristics will enhance the effectiveness of this technique in future applications.

Effect of 2% Topical Lidocaine Gel on Discomfort from Electrical Stimulation During Nerve Conduction Studies- A Prospective Double-Blind Placebo-Controlled Study.

Procedure discomfort can limit electrodiagnostic studies. Reducing discomfort can maximize the benefits of these diagnostic tools. This study targeted the discomfort associated with nerve conduction studies (NCS). This was a prospective randomized double-blind placebo-controlled study comparing the effect of topical lidocaine gel (2%) versus analgesic-free lubricant gel (K-Y gel) on pain perception during NCS. Sequential patients (n=130) referred for routine NCS participated in the study. We applied 1 mL of lidocaine gel to one palm, and 1 mL of K-Y gel to the other as a control. After 20-45 min of application, graded increments of electrical stimulation intensity were delivered to record the median and ulnar mixed palmar nerve responses. Patients were then asked to score the degree of pain felt from electrical stimulation over each palm using the Wong-Baker Faces Pain Scale (WBFPS) and the Numeric Rating Scale (NRS), independent of baseline pain. Mean WBFPS and NRS scores for lidocaine-treated palms were significantly lower than those for controls using parametric paired t-test (3.79 vs 4.37 and 3.35 vs 3.78 respectively, all p-values<0.05). Subgroup analysis showed a significant decrease in mean scores in females, patients aged ≤50 years, patients without a history of previous NCS, and patients without comorbidities (all p-values<0.05). Median scores using nonparametric Wilcoxon ranked test also showed statistically significant differences (all p-values<0.05). The results indicate that topical lidocaine 2% gel reduces discomfort associated with NCS. However, despite the statistical significance, clear clinical significance may be lacking. Clinical implementation may be considered for the subgroups that showed the greatest benefit. Further studies that incorporate more efficient drug delivery methods may yield better results.

Devising a framework of optogenetic coding in the auditory pathway: Insights from auditory midbrain recordings

Cochlear implants (CIs) restore activity in the deafened auditory system via electrical stimulation of the auditory nerve. As the spread of electric current in biological tissues is rather broad, the spectral information provided by electrical CIs is limited. Optogenetic stimulation of the auditory nerve has been suggested for artificial sound coding with improved spectral selectivity, as light can be conveniently confined in space. Yet, the foundations for optogenetic sound coding strategies remain to be established. Here, we parametrized stimulus-response-relationships of the auditory pathway in gerbils for optogenetic stimulation. Upon activation of the auditory pathway by waveguide-based optogenetic stimulation of the spiral ganglion, we recorded neuronal activity of the auditory midbrain, in which neural representations of spectral, temporal, and intensity information can be found. Screening a wide range of optical stimuli and taking the properties of optical CI emitters into account, we aimed to optimize stimulus paradigms for potent and energy-efficient activation of the auditory pathway. We report that efficient optogenetic coding builds on neural integration of millisecond stimuli built from microsecond light pulses, which optimally accommodate power-efficient laser diode operation. Moreover, we performed an activity-level-dependent comparison of optogenetic and acoustic stimulation in order to estimate the dynamic range and the maximal stimulation intensity amenable to single channel optogenetic sound encoding, and indicate that it complies well with speech comprehension in a typical conversation (65 dB). Our results provide a first framework for the development of coding strategies for future optogenetic hearing restoration.

The Effects of Conformity on Perceived Intensity of Stimuli

Conformity serves as the baseline for how one conducts themselves within a society. While a vital component to communal functioning, what transpires consequently is the question of how one’s own perceived cognition compares to that of the world around them, creating a conflict within experienced and expressed reaction. This study examines the ways in which group conformity may influence a person’s private perception of a reaction to a stimulus, aiming to determine the intrinsic effects of conformity through the examination of 122 participants and their rating of sourness when given a gumball. Throughout 41 trials, participants were placed in either the control or experimental group; those in the control group were isolated and given either a sweet or sour gumball, while those in the experimental group were placed into groups of three, wherein two participants were given sweet gumballs and the remaining participant was given a sour gumball. Participants in both groups were then asked to privately rate their perceived level of sourness on a scale of one to ten. In experimental trials, each group was given a brief period of time to discuss their experiences prior to the rating. A 22% increase in sourness rating between the control and experimental groups was found through this process, establishing that group conformity could not only influence how one outwardly expressed themselves in a given setting but could additionally alter how a person perceives their own physiological experience to given stimuli.

Identifying spinal tracts transmitting distant effects of trans-spinal magnetic stimulation.

Estimating the state of tract-specific inputs to spinal motoneurons is critical to understand movement deficits induced by neurological injury and potential pathways to recovery, but remains challenging in humans. In this study we explored the capability of trans-spinal magnetic stimulation (TSMS) to modulate distal reflex circuits in young adults. TSMS was applied over thoracic spine to condition soleus H-reflexes involving sacral-level motoneurons. Three TSMS intensities below motor threshold were applied at inter-stimulus intervals (ISIs) between 2-20 ms relative to peripheral nerve stimulation (PNS). While low intensity TSMS yielded no changes in H-reflexes across ISIs, the two higher stimulus intensities yielded two phases of H-reflex inhibition: a relatively long-lasting period at 2-9 ms ISIs, and a short phase at 11-12 ms ISIs. H-reflex inhibition at 2 ms ISI was uniquely dependent on TSMS intensity. To identify the candidate neural pathways contributing to H-reflex suppression, we constructed a tract-specific conduction time estimation model. Based upon our model, H-reflex inhibition at 11-12 ms ISIs is likely a manifestation of orthodromic transmission along the lateral reticulospinal tract. In contrast, the inhibition at 2 ms ISI likely reflects orthodromic transmission along sensory fibers with activation reaching brain, before descending along motor tracts. Multiple pathways may contribute to H-reflex modulation between 4-9 ms ISIs, orthodromic transmission along sensorimotor tracts and antidromic transmission of multiple motor tracts. Our findings suggest that non-invasive TSMS can influence motoneuron excitability at distal segments and that the contribution of specific tracts to motoneuron excitability may be distinguishable based upon conduction velocities.

Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix

Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats. The basolateral amygdala (BLA) was identified as a region of interest, demonstrating differential Fos responsivity to ER and having an established role in stress processing and adaptation. A comprehensive multi-omics investigation of the BLA, spanning multiple cohorts, platforms, and analyses, revealed alterations in microglia and the extracellular matrix (ECM). Follow-up studies indicated that ER decreased microglia size, complexity, and phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, suggesting decreased plasticity and increased inhibition within the BLA following loss. Behavioral analyses suggest that these molecular effects are linked to impaired BLA salience evaluation, leading to a mismatch between stimulus and reaction intensity. These loss-like behaviors could be rescued by depleting BLA ECM during the removal period, helping us understand the mechanisms underlying loss and revealing novel molecular targets to ameliorate its impact.

The Effect of taVNS on the Cerebello-Thalamo-Cortical Pathway: a TMS Study

fMRI studies show activation of cerebellum during transcutaneous auricular vagal nerve stimulation (taVNS); however, there is no evidence whether taVNS induced activation of the cerebellum translates to the cerebellar closed loops involved in motor functions. We assessed the propensity of taVNS at 25 Hz (taVNS25) and 100 Hz (taVNS100) to modulate cerebello-thalamo-cortical pathways using transcranial magnetic stimulation. In our double blind within-subjects study thirty-two participants completed one visit during which cerebellar brain inhibition (CBI) was assessed at baseline (no stimulation) and in a randomized order during taVNS100, taVNS25, and sham taVNS (xVNS). Generalized linear mixed models with gamma distribution were built to assess the effect of taVNS on CBI. The estimated marginal means of linear trends during each taVNS condition were computed and compared in a pairwise fashion with Benjamini-Hochberg correction for multiple comparisons. CBI significantly increased during taVNS100 compared to taVNS25 and xVNS (p = 0.0003 and p = 0.0465, respectively). The taVNS current intensity and CBI conditioning stimulus intensity had no significant effect on CBI. taVNS has a frequency dependent propensity to modulate the cerebello-thalamo-cortical pathway. The cerebellum participates in closed-loop circuits involved in motor, cognitive, and affective operations and may serve as an entry for modulating effects of taVNS.

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis

Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.

Variability in Motor Threshold during Transcranial Magnetic Stimulation Treatment for Depression: Neurophysiological Implications.

The measurement of the motor threshold (MT) is an important element in determining stimulation intensity during Transcranial Magnetic Stimulation treatment (rTMS). The current recommendations propose its realization at least once a week. The variability in this motor threshold is an important factor to consider as it could translate certain neurophysiological specificities. We conducted a retrospective naturalistic study on data from 30 patients treated for treatment-resistant depression in an rTMS-specialized center. For each patient, weekly motor-evoked potential (MEP) was performed and several clinical elements were collected as part of our clinical interviews. Regarding response to treatment (Patient Health Questionnaire-9 (PHQ-9) before and after treatment), there was a mean difference of -8.88 (-21 to 0) in PHQ9 in the Theta Burst group, of -9.00 (-18 to -1) in the High-Frequency (10 Hz) group, and of -4.66 (-10 to +2) in the Low-Frequency (1 Hz) group. The mean improvement in depressive symptoms was 47% (p < 0.001, effect-size: 1.60). The motor threshold changed over the course of the treatment, with a minimum individual range of 1 point and a maximum of 19 points (total subset), and a greater concentration in the remission group (4 to 10) than in the other groups (3 to 10 in the response group, 1 to 8 in the partial response group, 3 to 19 in the stagnation group). We also note that the difference between MT at week 1 and week 6 was statistically significant only in the remission group, with a different evolutionary profile showing an upward trend in MT. Our findings suggest a potential predictive value of MT changes during treatment, particularly an increase in MT in patients who achieve remission and a distinct "break" in MT around the 4th week, which could predict nonresponse.

The Role of Pupillometry in the Assessment of Pain in Children Under General Anesthesia: A Prospective Single-Blinded Observational Study.

Background and objective The management and treatment of nociception remain one of the major challenges in anesthesiology, and hemodynamic variations may occur due to inadequate analgesia, which at times can be injurious. Pupillometry is a new noninvasive tool to assess nociception during anesthesia. The amount of pupillary reflex dilation (PRD) is directly proportional to the intensity of nociceptive stimuli and inversely proportional to the opioid dosage. This study aimed to assess the use of pupillometry as reflex pupillary dilatation in response to surgical stimulus in children under general anesthesia and to guide intraoperative opioid consumption. Materials and methods After obtaining approval from the institutional ethics committee and written consent from parents, children with anAmerican Society of Anesthesiology (ASA) classification of I and II and aged 2-12 years who were undergoing surgery under general anesthesia were enrolled in this prospective randomized observational study. General anesthesia was standardized with propofol, sevoflurane, and O2 andN2O (50:50%), and fentanyl administration was guided by pupil diameter changes. The primary outcome was to measure pupillary dilatation in response to pain and fentanyl administration guided by it. Results A total of 72 patients were included in the study. The mean pupil diameter significantly increased after surgical stimulus from 1.37 ±0.87to 2.40 ±1.95 mm (p<0.001).The heart rate (116.2 ±12.25to 118.50 ±8.20 beats/minute, p=0.18) and systolic BP (114.60 ±17.73 to 118.50 ±12.25 mmHg, p=0.12)did not change significantly on stimulus. The mean fentanyl consumption was 2.4 ug/kg and the side effects were not remarkable. Conclusion Based on our findings, pain has a significant influence on the pupil dilatation reflex in anesthetized children, and opioid administration based on pupil diameter can be valuable in clinical settings. We recommend the use of pupillometry as a pain index in children undergoing surgery under general anesthesia, and it can be a beneficial tool for assessing intraoperative pain. Newer techniques and developments are required in this field.

SP11.15 Stress Exposure Training in Surgery – A Narrative and Systematic Review

Abstract Aim The operating theatre is an environment associated with intense cognitive stimulus. The coordinated application of technical and non-technical skills is necessary to achieve optimal patient care. Surgeons may undergo a significant “stress response”, activated when perceived demands of a situation exceed perceived resources, leading to measurable variations in physiological and biochemical parameters. This results in impaired performance, demonstrated most acutely in junior and trainee surgeons. Methods A narrative and literature was undertaken searching for stress response, exposure, inoculation in healthcare, medicine, or surgery. 1332 eligible papers were identified, refined to 100 on abstract, with 37 undergoing full text review. Results Stress Exposure Training (SET) facilitates high performances in acutely stressful situations by inoculating individuals from the psychological and physiological impacts of stress. SET was initially a clinical intervention to treat stress-induced psychopathology. Routed in cognitive-behavioural therapy principles, it is now a generalisable training approach implemented by other high-stress high-performance industries, including the military and aeronautics. High-fidelity simulation training is a recognised tool that is commonly applied in medical education. It promotes decision-making, team-working, and technical and communication skills in a controlled environment. Importantly, this tool has been shown to elicit an equivalent stress response to “live” clinical scenarios. Conclusion This review explores the current literature on mitigating stress responses in surgeons and SET, including its current applications and research localised to surgical education. Finally, we propose a high-fidelity simulation training programme, aimed at junior surgeons-in-training based on the principles of SET comprised of gradually increasing stressors and appropriate psychological training in stress-response management.

Rapid measurement and machine learning classification of colour vision deficiency.

Colour vision deficiencies (CVDs) indicate potential genetic variations and can be important biomarkers of acquired impairment in many neuro-ophthalmic diseases. However, CVDs are typically measured with tests which possess high sensitivity for detecting the presence of a CVD but do not quantify its type or severity. In this study, we introduce Foraging Interactive D-prime (FInD), a novel computer-based, generalisable, rapid, self-administered vision assessment tool and apply it to colour vision testing. This signal detection theory-based adaptive paradigm computed test stimulus intensity from d-prime analysis. Stimuli were chromatic Gaussian blobs in dynamic luminance noise, and participants clicked on cells that contained chromatic blobs (detection) or blob pairs of differing colours (discrimination). Sensitivity and repeatability of FInD colour tasks were compared against the Hardy-Rand-Rittler and the Farnsworth-Munsell 100 hue tests in 19 colour-normal and 18 inherited colour-atypical, age-matched observers. Rayleigh colour match was also completed. Detection and discrimination thresholds were higher for atypical than for typical observers, with selective threshold elevations corresponding to unique CVD types. Classifications of CVD type and severity via unsupervised machine learning confirmed functional subtypes. FInD tasks reliably detect inherited CVDs, and may serve as valuable tools in basic and clinical colour vision science.

Improving speech perception for hearing-impaired listeners using audio-to-tactile sensory substitution with multiple frequency channels

Cochlear implants (CIs) have revolutionised treatment of hearing loss, but large populations globally cannot access them either because of disorders that prevent implantation or because they are expensive and require specialist surgery. Recent technology developments mean that haptic aids, which transmit speech through vibration, could offer a viable low-cost, non-invasive alternative. One important development is that compact haptic actuators can now deliver intense stimulation across multiple frequencies. We explored whether these multiple frequency channels can transfer spectral information to improve tactile phoneme discrimination. To convert audio to vibration, the speech amplitude envelope was extracted from one or more audio frequency bands and used to amplitude modulate one or more vibro-tactile tones delivered to a single-site on the wrist. In 26 participants with normal touch sensitivity, tactile-only phoneme discrimination was assessed with one, four, or eight frequency bands. Compared to one frequency band, performance improved by 5.9% with four frequency bands and by 8.4% with eight frequency bands. The multi-band signal-processing approach can be implemented in real-time on a compact device, and the vibro-tactile tones can be reproduced by the latest compact, low-powered actuators. This approach could therefore readily be implemented in a low-cost haptic hearing aid to deliver real-world benefits.

Intense nano-pulse stimulation-induced dynamic changes in vesicle trafficking visualized by super-resolution fluorescence microscopy

Super-resolution fluorescence microscopy (SRFM) has revolutionized biomedical research by providing valuable information at the nanometer-scale within cells. Recent advances in SRFM enable researchers to probe dynamic processes in living cells with unprecedented spatiotemporal resolution. Vesicle trafficking plays a critical role in tumor proliferation and invasion. Understanding the dynamics of vesicle trafficking in cancer cells is essential for cancer therapy. This study visualized and quantified changes in vesicle trafficking dynamics in cancer cells induced by intense nano-pulse stimulation (NPS) using SRFM. As an emerging physical modality for cancer therapy, it remains unknown whether and how NPS affects vesicle trafficking during its interaction with cancer cells. Our results indicate that NPS decreases the number, velocity, and track length of vesicles while significantly increasing the average size of vesicles. Notably, vesicle trafficking between cancer cells and normal human lung bronchial epithelial cells was also inhibited. This study provides experimental evidence that NPS directly affects vesicle trafficking. Furthermore, the results of this study may shed light on a better understanding of the mechanism by which NPS inhibits cancer invasion and metastasis. Finally, this work provides a potential physical method to regulate vesicle transport.

Short-term plasticity in the spinal nociceptive system.

Somatosensory information is delivered to neuronal networks of the dorsal horn (DH) of the spinal cord by the axons of primary afferent neurons that encode the intensity of peripheral sensory stimuli under the form of a code based on the frequency of action potential firing. The efficient processing of these messages within the DH involves frequency-tuned synapses, a phenomenon linked to their ability to display activity-dependent forms of short-term plasticity (STP). By affecting differently excitatory and inhibitory synaptic transmissions, these STP properties allow a powerful gain control in DH neuronal networks that may be critical for the integration of nociceptive messages before they are forwarded to the brain, where they may be ultimately interpreted as pain. Moreover, these STPs can be finely modulated by endogenous signaling molecules, such as neurosteroids, adenosine, or GABA. The STP properties of DH inhibitory synapses might also, at least in part, participate in the pain-relieving effect of nonpharmacological analgesic procedures, such as transcutaneous electrical nerve stimulation, electroacupuncture, or spinal cord stimulation. The properties of target-specific STP at inhibitory DH synapses and their possible contribution to electrical stimulation-induced reduction of hyperalgesic and allodynic states in chronic pain will be reviewed and discussed.

Hybrid and adaptive control of functional electrical stimulation to correct hemiplegic gait for patients after stroke.

Introduction: Gait, as a fundamental human movement, necessitates the coordination of muscles across swing and stance phases. Functional electrical stimulation (FES) of the tibialis anterior (TA) has been widely applied to foot drop correction for patients with post-stroke during the swing phase. Although the gastrocnemius (GAS) during the stance phase is also affected, the Functional electrical stimulation of the gastrocnemius received less attention. Methods: To address this limitation, a timing- and intensity-adaptive Functional electrical stimulation control strategy was developed for both the TA and GAS. Each channel incorporates a speed-adaptive (SA) module to control stimulation timing and an iterative learning control (ILC) module to regulate the stimulation intensity. These modules rely on real-time kinematic or kinetic data during the swing or stance phase, respectively. The orthotic effects of the system were evaluated on eight patients with post-stroke foot drop. Gait kinematics and kinetics were assessed under three conditions: no stimulation (NS), Functional electrical stimulation to the ankle dorsiflexor tibialis anterior (SA-ILC DS) and FES to the tibialis anterior and the ankle plantarflexor gastrocnemius (SA-ILC DPS). Results: The ankle plantarflexion angle, the knee flexion angle, and the anterior ground reaction force (AGRF) in the SA-ILC DPS condition were significantly larger than those in the NS and SA-ILC DS conditions (p < 0.05). The maximum dorsiflexion angle during the swing phase in the SA-ILC DPS condition was similar to that in the SA-ILC DS condition, with both being significantly larger than the angle observed in the NS condition (p < 0.05). Furthermore, the angle error and force error relative to the set targets were minimized in the SA-ILC DPS condition. Discussion: The observed improvements can be ascribed to the appropriate stimulation timing and intensity provided by the SA-ILC DPS strategy. This study demonstrates that the hybrid and adaptive control strategy of functional electrical stimulation system offers a significant orthotic effect, and has considerable potential for future clinical application.

Prepulse inhibition deficit as a transdiagnostic process in neuropsychiatric disorders: a systematic review

BackgroundPsychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple pathologies. A phenomenon disrupted in several disorders is prepulse inhibition (PPI) of the startle response, in which startle to an intense sensory stimulus, or pulse, is reduced if a weak stimulus, or prepulse, is previously presented.Objective and methodsThe present systematic review analyzed the role of PPI deficit as a possible transdiagnostic process for four main groups of neuropsychiatric disorders: (1) trauma-, stress-, and anxiety-related disorders (2) mood-related disorders, (3) neurocognitive disorders, and (4) other disorders such as obsessive-compulsive, tic-related, and substance use disorders. We used Web of Science, PubMed and PsycInfo databases to search for experimental case-control articles that were analyzed both qualitatively and based on their potential risk of bias. A total of 64 studies were included in this systematic review. Protocol was submitted prospectively to PROSPERO 04/30/2022 (CRD42022322031).Results and conclusionThe results showed a general PPI deficit in the diagnostic groups mentioned, with associated deficits in the dopaminergic neurotransmission system, several areas implied such as the medial prefrontal cortex or the amygdala, and related variables such as cognitive deficits and anxiety symptoms. It can be concluded that the PPI deficit appears across most of the neuropsychiatric disorders examined, and it could be considered as a relevant measure in translational research for the early detection of such disorders.