Increasing Stimulus Intensity Research Articles

Calibrating position and orientation of multiple ultrasound phased array units using Bayesian optimization.

Airborne ultrasound phased arrays (AUPAs) generate non-contact tactile sensations and enable acoustic levitation with specific focus fields. Using multiple units together offers numerous advantages, such as increased stimulus intensity and the ability to overcome occlusion. The AUPA units are typically mounted on a fixed frame, with their poses manually measured using tools such as a ruler for calibration. However, to increase the degrees of freedom for these units, a more flexible calibration method is required. With a wavelength of 8.5 mm, a 4 mm deviation in propagation distance from the two phased arrays can weaken the pressure at the focus position. Hence, in this study, calibration based on pose and focus information obtained through image processing was performed. First, augmented reality markers are attached to each AUPA unit for rough estimation of pose parameters. Second, using these approximate poses, the pressure distribution generated on a specific plane is estimated through thermal imaging. Finally, Bayesian optimization is employed to efficiently explore the pose parameters to minimize the error between the desired position and generated focal point. This approach enables the efficient calibration of the relative poses of AUPA units, even when they are placed in challenging-to-measure locations.

Pain tolerance and the thresholds of human sensory and motor axons to single and repetitive bursts of kilohertz-frequency stimulation.

Transcutaneous electrical stimulation with repetitive bursts of a kilohertz carrier frequency is thought to be less painful than conventional pulsed currents by reducing the sensitivity of pain receptors. However, no purported benefit has been shown unequivocally. We compared the effects of carrier-frequency stimulation and conventional stimulation on pain tolerance and the thresholds for sensory and motor axons in twelve participants. The ulnar nerve was stimulated transcutaneously with a conventional single pulse and 5 and 10kHz carrier-frequency waveforms that had 5 and 10 pulses, respectively, when delivered in bursts of ∼1ms duration. Phase durations were adjusted across waveform types to match the total charge for a given current amplitude. Single bursts of stimulation were delivered from 1mA up until no longer tolerable. This was repeated with repetitive bursts of stimulation at 20Hz for 1s. Participants tolerated higher current amplitudes with both carrier-frequency waveforms than conventional stimulation, with repetitive bursts more painful than single bursts. However, compared to conventional stimulation, carrier-frequency waveforms required more current to produce sensory and motor-threshold responses and to obtain a maximal motor response (Mmax). When the current at pain tolerance was normalised to the current at Mmax, participants tolerated lower stimulus intensities with carrier-frequency waveforms than conventional stimulation. These findings indicate that there is little to no benefit in using carrier-frequency waveforms to minimise the discomfort from electrical stimulation as the increase in stimulus intensity at pain tolerance is more than offset by reduced effectiveness in the activation of sensory and motor axons. KEY POINTS: Transcutaneous electrical stimulation with repetitive bursts of a kilohertz carrier-frequency waveform is thought to be less painful than conventional pulsed currents. For ulnar nerve stimulation, when stimulus waveforms were matched for total phase charge, participants tolerated higher current amplitudes with carrier-frequency stimulation than conventional stimulation. However, compared to conventional stimulation, carrier-frequency waveforms required more current to produce a threshold response in both sensory and motor axons and to produce a maximal motor response (Mmax). When current at pain tolerance was normalised to current at Mmax, participants tolerated lower stimulus intensities with carrier-frequency waveforms than conventional stimulation. Carrier-frequency waveforms provide little to no benefit in minimising the discomfort from transcutaneous electrical stimulation as the increase in stimulus intensity at pain tolerance is more than offset by reduced effectiveness in activating sensory and motor axons.

Temporal resolution relates to sensory hyperreactivity independently of stimulus detection sensitivity in individuals with autism spectrum disorder.

Researchers have been focusing on perceptual characteristics of autism spectrum disorder (ASD) in terms of sensory hyperreactivity. Previously, we demonstrated that temporal resolution, which is the accuracy to differentiate the order of two successive vibrotactile stimuli, is associated with the severity of sensory hyperreactivity. We currently examined whether an increase in the perceptual intensity of a tactile stimulus, despite its short duration, is derived from high temporal resolution and high frequency of sensory temporal summation. Twenty ASD and 22 typically developing (TD) participants conducted two psychophysical experimental tasks to evaluate detectable duration of vibrotactile stimulus with same amplitude and to evaluate temporal resolution. The sensory hyperreactivity was estimated using self-reported questionnaire. There was no relationship between the temporal resolution and the duration of detectable stimuli in both groups. However, the ASD group showed severe sensory hyperreactivity in daily life than TD group, and the ASD participants with severe sensory hyperreactivity tended to have high temporal resolution, not high sensitivity of detectable duration. Contrary to the hypothesis, there might be different processing between temporal resolution and sensitivity for stimulus detection. We suggested that the atypical temporal processing would affect to sensory reactivity in ASD.

Temporal Summation of the Thermal Grill Illusion is Comparable to That Observed Following Noxious Heat

The thermal grill illusion (TGI) describes a peculiar or even painful percept caused by non-noxious, interlaced warm and cold stimuli. It involves the glutamatergic system and is affected in putatively nociplastic syndromes such as fibromyalgia. The glutamatergic system is also involved in wind-up, that is, the increased activation of spinal neurons following repeated noxious stimulation leading to a temporal summation of perceived stimulus intensity. Here we combined both stimulation methods to further investigate whether non-noxious stimuli as employed in the TGI can lead to a similar summation of perceived stimulus intensity. In an experiment using a full crossover within-subjects design, 35 healthy volunteers received repeated stimuli, either in a thermal grill configuration or simply noxious heat. Both modalities were presented as sequences of 1 lead-in contact, followed by 11 consecutive contacts (each between 1.5 and 3 seconds), with either fast repetition (“wind-up” condition), or 2 slow-repeating control conditions. The main analyses concerned the relative pre-to-post sequence changes to quantify putatively wind-up-related effects. Pain ratings and skin conductance level (SCL) increased more strongly in “wind-up” than in control conditions. Interestingly, wind-up-related effects were of the same magnitude in TGI as compared to the pain control modality. Further, contact-by-contact SCL tracked how the effect emerged over time. These results indicate that although TGI does not involve noxious stimuli it is amenable to temporal summation and wind-up-like processes. Since both phenomena involve the glutamatergic system, the combination of wind-up with the TGI could yield a promising tool for the investigation of chronic pain conditions. PerspectiveUsing thermal stimuli in an experimental protocol to combine 1) the TGI (painful or peculiar percept from simultaneous cold/warm stimulation) and 2) wind-up (increase in stimulus intensity after repeated exposure) holds promise to investigate pain and thermoceptive mechanisms, and chronic pain conditions.

Neural envelope tracking predicts speech intelligibility and hearing aid benefit in children with hearing loss

Early assessment of hearing aid benefit is crucial, as the extent to which hearing aids provide audible speech information predicts speech and language outcomes. A growing body of research has proposed neural envelope tracking as an objective measure of speech intelligibility, particularly for individuals unable to provide reliable behavioral feedback. However, its potential for evaluating speech intelligibility and hearing aid benefit in children with hearing loss remains unexplored. In this study, we investigated neural envelope tracking in children with permanent hearing loss through two separate experiments. EEG data were recorded while children listened to age-appropriate stories (Experiment 1) or an animated movie (Experiment 2) under aided and unaided conditions (using personal hearing aids) at multiple stimulus intensities. Neural envelope tracking was evaluated using a linear decoder reconstructing the speech envelope from the EEG in the delta band (0.5-4 Hz). Additionally, we calculated temporal response functions (TRFs) to investigate the spatio-temporal dynamics of the response. In both experiments, neural tracking increased with increasing stimulus intensity, but only in the unaided condition. In the aided condition, neural tracking remained stable across a wide range of intensities, as long as speech intelligibility was maintained. Similarly, TRF amplitudes increased with increasing stimulus intensity in the unaided condition, while in the aided condition significant differences were found in TRF latency rather than TRF amplitude. This suggests that decreasing stimulus intensity does not necessarily impact neural tracking. Furthermore, the use of personal hearing aids significantly enhanced neural envelope tracking, particularly in challenging speech conditions that would be inaudible when unaided. Finally, we found a strong correlation between neural envelope tracking and behaviorally measured speech intelligibility for both narrated stories (Experiment 1) and movie stimuli (Experiment 2). Altogether, these findings indicate that neural envelope tracking could be a valuable tool for predicting speech intelligibility benefits derived from personal hearing aids in hearing-impaired children. Incorporating narrated stories or engaging movies expands the accessibility of these methods even in clinical settings, offering new avenues for using objective speech measures to guide pediatric audiology decision-making.

Zebrafish larvae use stimulus intensity and contrast to estimate distance to prey

The ability to determine the distance to objects is an important feature of most visual systems, but little is known about the neuronal mechanisms for distance estimation. Larval zebrafish execute different visual behaviors depending on distance; at medium distances, they converge their eyes and approach, but when the prey is close enough, they execute a strike and suck the prey into their mouths. To study distance estimation, we developed a head-fixed strike assay. We found that we could evoke strike behavior in head-fixed larvae and quantify head movements to classify the behavior as a strike. Strikes were dependent on distance to prey, allowing us to use them to study distance estimation. Light intensity is rapidly attenuated as it travels through water, so we hypothesized that larvae could use intensity as a distance cue. We found that increasing stimulus intensity could cause larvae to strike at prey that would normally be out of range, and decreasing the intensity could lower the strike rate even for very proximal stimuli. In addition, stimulus contrast is a key parameter, and this could allow larvae to estimate distance over the range of natural illumination. Finally, we presented prey in the binocular vs. monocular visual field and found that monocular prey did evoke strikes, although the binocular input produced more. These results suggest that strike behavior is optimally evoked by bright UV dots in the binocular zone with minimal UV background light and provide a foundation to study the neuronal mechanisms of distance estimation.

Principal neuron diversity in the murine lateral superior olive supports multiple sound localization strategies and segregation of information in higher processing centers

Principal neurons (PNs) of the lateral superior olive nucleus (LSO) in the brainstem of mammals compare information between the two ears and enable sound localization on the horizontal plane. The classical view of the LSO is that it extracts ongoing interaural level differences (ILDs). Although it has been known for some time that LSO PNs have intrinsic relative timing sensitivity, recent reports further challenge conventional thinking, suggesting the major function of the LSO is detection of interaural time differences (ITDs). LSO PNs include inhibitory (glycinergic) and excitatory (glutamatergic) neurons which differ in their projection patterns to higher processing centers. Despite these distinctions, intrinsic property differences between LSO PN types have not been explored. The intrinsic cellular properties of LSO PNs are fundamental to how they process and encode information, and ILD/ITD extraction places disparate demands on neuronal properties. Here we examine the ex vivo electrophysiology and cell morphology of inhibitory and excitatory LSO PNs in mice. Although overlapping, properties of inhibitory LSO PNs favor time coding functions while those of excitatory LSO PNs favor integrative level coding. Inhibitory and excitatory LSO PNs exhibit different activation thresholds, potentially providing further means to segregate information in higher processing centers. Near activation threshold, which may be physiologically similar to the sensitive transition point in sound source location for LSO, all LSO PNs exhibit single-spike onset responses that can provide optimal time encoding ability. As stimulus intensity increases, LSO PN firing patterns diverge into onset-burst cells, which can continue to encode timing effectively regardless of stimulus duration, and multi-spiking cells, which can provide robust individually integrable level information. This bimodal response pattern may produce a multi-functional LSO which can encode timing with maximum sensitivity and respond effectively to a wide range of sound durations and relative levels.

Synchrony-Division Neural Multiplexing: An Encoding Model

Cortical neurons receive mixed information from the collective spiking activities of primary sensory neurons in response to a sensory stimulus. A recent study demonstrated an abrupt increase or decrease in stimulus intensity and the stimulus intensity itself can be respectively represented by the synchronous and asynchronous spikes of S1 neurons in rats. This evidence capitalized on the ability of an ensemble of homogeneous neurons to multiplex, a coding strategy that was referred to as synchrony-division multiplexing (SDM). Although neural multiplexing can be conceived by distinct functions of individual neurons in a heterogeneous neural ensemble, the extent to which nearly identical neurons in a homogeneous neural ensemble encode multiple features of a mixed stimulus remains unknown. Here, we present a computational framework to provide a system-level understanding on how an ensemble of homogeneous neurons enable SDM. First, we simulate SDM with an ensemble of homogeneous conductance-based model neurons receiving a mixed stimulus comprising slow and fast features. Using feature-estimation techniques, we show that both features of the stimulus can be inferred from the generated spikes. Second, we utilize linear nonlinear (LNL) cascade models and calculate temporal filters and static nonlinearities of differentially synchronized spikes. We demonstrate that these filters and nonlinearities are distinct for synchronous and asynchronous spikes. Finally, we develop an augmented LNL cascade model as an encoding model for the SDM by combining individual LNLs calculated for each type of spike. The augmented LNL model reveals that a homogeneous neural ensemble model can perform two different functions, namely, temporal- and rate-coding, simultaneously.

Analysis of the Latency of Auditory Brainstem Response Wave V in Infants According to Age, Hearing Threshold and Stimulus Intensity

Background and Objectives The latency of auditory brainstem response (ABR) wave V shifts depending on age, hearing threshold, and stimulus intensity. This study was performed to examine the latencies of ABR wave V in infants with normal hearing and sensorineural hearing loss.Subjects and Method The retrospective review of ABR of 318 infants (539 ears) was performed. The patients were divided into four groups according to age at the time of the ABR test (group A: 0-2 months, group B: 3-5 months, group C: 6-8 months, and group D: 9-11 months). The test was performed using click sound under sedation, with the stimulus intensity adjusted by 10 dB intervals. The latency of wave V was analyzed according to age, hearing threshold, and stimulus intensity.Results Normal hearing was detected in 320 ears (wave V threshold of 20 dBnHL or less) and sensorineural hearing loss was found in 219 ears. Wave V latencies decreased with increase in age and stimulus intensity in both normal hearing infants and hearing-impaired infants. The ears with higher thresholds showed longer latencies at the same stimulus intensity. The normative data of wave V latency of infants with varying hearing thresholds according to age and stimulus intensity could be determined.Conclusion The present study examined the latencies of ABR wave V of hearing-impaired and normal hearing infants according to age and stimulus intensity. The data will help audiologists to evaluate the hearing of infants who are referred for ABR test.

Physiological noise facilitates multiplexed coding of vibrotactile-like signals in somatosensory cortex

Neurons can use different aspects of their spiking to simultaneously represent (multiplex) different features of a stimulus. For example, some pyramidal neurons in primary somatosensory cortex (S1) use the rate and timing of their spikes to, respectively, encode the intensity and frequency of vibrotactile stimuli. Doing so has several requirements. Because they fire at low rates, pyramidal neurons cannot entrain 1:1 with high-frequency (100 to 600 Hz) inputs and, instead, must skip (i.e., not respond to) some stimulus cycles. The proportion of skipped cycles must vary inversely with stimulus intensity for firing rate to encode stimulus intensity. Spikes must phase-lock to the stimulus for spike times (intervals) to encode stimulus frequency, but, in addition, skipping must occur irregularly to avoid aliasing. Using simulations and invitro experiments in which mouse S1 pyramidal neurons were stimulated with inputs emulating those induced by vibrotactile stimuli, we show that fewer cycles are skipped as stimulus intensity increases, as required for rate coding, and that intrinsic or synaptic noise can induce irregular skipping without disrupting phase locking, as required for temporal coding. This occurs because noise can modulate the reliability without disrupting the precision of spikes evoked by small-amplitude, fast-onset signals. Specifically, in the fluctuation-driven regime associated with sparse spiking, rate and temporal coding are both paradoxically improved by the strong synaptic noise characteristic of the intact cortex. Our results demonstrate that multiplexed coding by S1 pyramidal neurons is not only feasible under invivo conditions, but that background synaptic noise is actually beneficial.

Neural supersaturation explains attentional attenuation effects on contrast appearance.

Spatial attention is generally believed to increase contrast appearance of visual stimuli. A recent study, however, revealed that attention attenuates appearance of high-contrast stimuli. This puzzling attentional attenuation was ascribed to the attentional modulation on supersaturating neurons, whose response initially increases to peak and then decreases as stimulus intensity increases. Here, in two experiments (N = 22), we examined this hypothesis by testing how contrast adaptation affects attentional modulation on contrast appearance of high-contrast stimuli. We found that luminance-contrast adaptation reversed attentional effects from attenuation to enhancement, supporting the supersaturation model. Moreover, equiluminant red-green adaptation only vanished but could not reverse the attentional attenuation, implying that the parvocellular pathway was not the dominant pathway mediating the attentional attenuation. Our study indicates that supersaturation, as a pervasive phenomenon in neuronal responses, can be manifested in attentional modulation on perceived contrast, and the M-pathway may play an important role in this attentional processing. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Repetitive transcranial magnetic stimulation enhances the neuronal excitability of mice by regulating dynamic characteristics of Granule cells' Ion channels.

This study aims to explore the effects of acute high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) on neuronal excitability of granule cells in the hippocampal dentate gyrus, as well as the underlying intrinsic mediating mechanisms by which rTMS regulates neuronal excitability. First, high-frequency single TMS was used to measure the motor threshold (MT) of mice. Then, rTMS with different intensities of 0 MT (control), 0.8 MT, and 1.2 MT were applied to acute mice brain slices. Next, patch-clamp technique was used to record the resting membrane potential and evoked nerve discharge of granule cells, as well as the voltage-gated sodium current (I Na) of voltage-gated sodium channels (VGSCs), transient outward potassium current (I A) and delayed rectifier potassium current (I K) of voltage-gated potassium channels (Kv). Results showed that acute hf-rTMS in both 0.8 MT and 1.2 MT groups significantly activated I Na and inhibited I A and I K compared with control group, due to the changes of dynamic characteristics of VGSCs and Kv. Acute hf-rTMS in both 0.8 MT and 1.2 MT groups significantly increased membrane potential and nerve discharge frequency. Therefore, changing dynamic characteristics of VGSCs and Kv, activating I Na and inhibiting I A and I K might be one of the intrinsic mediating mechanisms by which rTMS enhanced the neuronal excitability of granular cells, and this regulatory effect increased with the increase of stimulus intensity.

Temporal activity patterns of layer II and IV rat barrel cortex neurons in healthy and injured conditions.

Neurons are known to encode information not just by how frequently they fire, but also at what times they fire. However, characterizations of temporal encoding in sensory cortices under conditions of health and injury are limited. Here we characterized and compared the stimulus‐evoked activity of 1210 online‐sorted units in layers II and IV of rat barrel cortex under healthy and diffuse traumatic brain injury (TBI) (caused by a weight‐drop model) conditions across three timepoints post‐injury: four days, two weeks, and eight weeks. Temporal activity patterns in the first 50 ms post‐stimulus recording showed four categories of responses: no response or 1, 2, or 3 temporally‐distinct response components, that is, periods of high unit activity separated by silence. The relative proportions of unit response categories were similar between layers II and IV in healthy conditions but not in early post‐TBI conditions. For units with multiple response components, inter‐component timings were reliable in healthy and late post‐TBI conditions but disrupted by injury. Response component times typically shifted earlier with increasing stimulus intensity and this was more pronounced in layer IV than layer II. Surprisingly, injury caused a reversal of this trend and in the late post‐TBI condition no stimulus intensity‐dependence differences were observed between layers II and IV. We speculate this indicates a potential compensatory mechanism in response to injury. These results demonstrate how temporal encoding features maladapt or functionally recover differently in sensory cortex after TBI. Such maladaptation or functional recovery is layer‐dependent, perhaps due to differences in thalamic input or local inhibitory neuronal makeup.

Reflection-Source Emissions Evoked with Clicks and Frequency Sweeps: Comparisons Across Levels.

According to coherent reflection theory, otoacoustic emissions (OAE) evoked with clicks (clicked-evoked, CE) or tones (stimulus frequency, SF) originate via the same mechanism. We test this hypothesis in gerbils by investigating the similarity of CE- and SFOAEs across a wide range of stimulus levels. The results show that OAE transfer functions measured in response to clicks and sweeps have nearly equivalent time-frequency characteristics, particularly at low stimulus levels. At high stimulus levels, the two OAE types are more dissimilar, reflecting the different dynamic properties of the evoking stimulus. At mid to high stimulus levels, time-frequency analysis reveals contributions from at least two OAE source components of varying latencies. Interference between these components explains the emergence of strong spectral microstructure. Time-frequency filtering based on mean basilar-membrane (BM) group delays (τBM) shows that late-latency OAE components (latency ~ 1.6τBM) dominate at low stimulus intensities and exhibit highly compressive growth with increasing stimulus intensity. In contrast, early-latency OAE components (~ 0.7τBM) are small at low stimulus levels but can come to dominate the overall response at higher intensities. Although the properties of long-latency OAEs are consistent with an origin via coherent reflection near the peak of the traveling wave, the generation place and/or mechanisms responsible for the early-latency OAE components warrant further investigation. Because their delay remains in constant proportion to τBM across sound intensity, long-latency OAEs, whether evoked with tones or clicks, can be used to predict characteristics of cochlear processing, such as the sharpness of frequency tuning, even at high stimulus levels.

Influence of BDNF Val66Met polymorphism on excitatory-inhibitory balance and plasticity in human motor cortex

ObjectiveWhile previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human. MethodsUsing individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals. ResultsExcitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP- but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission. ConclusionsThe influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation. SignificanceThese novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex.

The residence of synaptically released dopamine on D2 autoreceptors.

SUMMARYNeuromodulation mediated by synaptically released endogenous transmitters acting in G-protein-coupled receptors (GPCRs) is slow primarily because of multistep downstream signaling. What is less well understood is the spatial and temporal kinetics of transmitter and receptor interaction. The present work uses the combination of the dopamine sensor, dLight, to detect the spatial release and diffusion of dopamine and a caged form of a D2-dopamine receptor antagonist, CyHQ-sulpiride, to rapidly block the D2 autoreceptors. Photoactivation of the CyHQ-sulpiride blocks receptors in milliseconds such that the time course of dopamine/receptor interaction is mapped onto the downstream signaling. The results show that highly localized release, but not dopamine diffusion, defines the time course of the functional interaction between dopamine and D2 autoreceptors, which determines downstream inhibition.

Implant- and anesthesia-related factors affecting cardiopulmonary threshold intensities for vagus nerve stimulation

Objective. Vagus nerve stimulation (VNS) is typically delivered at increasing stimulus intensity until a neurological or physiological response is observed (‘threshold’) for dose calibration, preclinically and therapeutically. Factors affecting VNS thresholds have not been studied systematically. In a rodent model of VNS we measured neural and physiological responses to increasing VNS intensity, determined neurological and physiological thresholds and examined the effect of implant- and anesthesia-related factors on thresholds. Approach. In acute and chronic vagus implants (45 and 20 rats, respectively) VNS was delivered under isoflurane, ketamine-xylazine, or awake conditions. Evoked compound action potentials (CAPs) were recorded and activation of different fiber types was extracted. Elicited physiological responses were registered, including changes in heart rate (HR), breathing rate (BR), and blood pressure (BP). CAP and physiological thresholds were determined. Main results. The threshold for evoking discernable CAPs (>10 µV) (CAP threshold) is significantly lower than what elicits 5%–10% drop in heart rate (heart rate threshold, HRT) (25 µA ± 1.8 vs. 80 µA ± 5.1, respectively; mean ± SEM). Changes in BP and small changes in BR (bradypnea) occur at lowest intensities (70 µA ± 8.3), followed by HR changes (80 µA ± 5.1) and finally significant changes in BR (apnea) (310 μA ± 32.5). HRT and electrode impedance are correlated in chronic (Pearson correlation r= 0.47; p< 0.001) but not in acute implants (r = −0.34; p NS); HRT and impedance both increase with implant age (r= 0.44; p< 0.001 and r = 0.64; p < 0.001, respectively). HRT is lowest when animals are awake (200 µA ± 35.5), followed by ketamine-xylazine (640 µA ± 151.5), and isoflurane (1000 µA ± 139.5). The sequence of physiological responses with increasing VNS intensity is the same in anesthetized and awake animals. Pulsing frequency affects physiological responses but not CAPs. Significance. Implant age, electrode impedance, and type of anesthesia affect VNS thresholds and should be accounted for when calibrating stimulation dose.

Accurate reaction time methods demonstrate similar results from different sensory modalities

Over the past few decades, there has been a significant number of reports that suggested that reaction times for different sensory modalities were different – e.g., that visual reaction time was slower than tactile reaction time. A recent report by Holden and colleagues stated that (1) there has been a significant historic upward drift in reaction times reported in the literature, (2) that this drift or degradation in reaction times could be accounted for by inaccuracies in the methods used and (3) that these inaccurate methods led to inaccurate reporting of differences between visual and tactile based reaction time testing. The Holden study utilized robotics (i.e., no human factors) to test visual and tactile reaction time methods but did not assess how individuals would perform on different sensory modalities. This study utilized three different sensory modalities: visual, auditory, and tactile, to test reaction time. By changing the way in which the subjects were prompted and measuring subsequent reaction time, the impact of sensory modality could be analyzed. Reaction time testing for two sensory modalities, auditory and visual, were administered through an Arduino Uno microcontroller device, while tactile-based reaction time testing was administered with the Brain Gauge. A range of stimulus intensities was delivered for the reaction times delivered by each sensory modality. The average reaction time and reaction time variability was assessed and a trend could be identified for the reaction time measurements of each of the sensory modalities. Switching the sensory modality did not result in a difference in reaction time and it was concluded that this was due to the implementation of accurate circuitry used to deliver each test. Increasing stimulus intensity for each sensory modality resulted in faster reaction times. The results of this study confirm the findings of Holden and colleagues and contradict the results reported in countless studies that conclude that (1) reaction times are historically slower now than they were 50 years ago and (2) that there are differences in reaction times for different sensory modalities (vision, hearing, tactile). The implications of this are that utilization of accurate reaction time methods could have a significant impact on clinical outcomes and that many methods in current clinical use are basically perpetuating poor methods and wasting time and money of countless subjects or patients.

Distinct neuron phenotypes may serve object feature sensing in the electrosensory lobe of Gymnotus omarorum.

Early sensory relay circuits in the vertebrate medulla often adopt a cerebellum-like organization specialized for comparing primary afferent inputs with central expectations. These circuits usually have a dual output, carried by center ON and center OFF neurons responding in opposite ways to the same stimulus at the center of their receptive fields. Here, we show in the electrosensory lateral line lobe of Gymnotiform weakly electric fish that basilar pyramidal neurons, representing 'ON' cells, and non-basilar pyramidal neurons, representing 'OFF' cells, have different intrinsic electrophysiological properties. We used classical anatomical techniques and electrophysiological in vitro recordings to compare these neurons. Basilar neurons are silent at rest, have a high threshold to intracellular stimulation, delayed responses to steady-state depolarization and low pass responsiveness to membrane voltage variations. They respond to low-intensity depolarizing stimuli with large, isolated spikes. As stimulus intensity increases, the spikes are followed by a depolarizing after-potential from which phase-locked spikes often arise. Non-basilar neurons show a pacemaker-like spiking activity, smoothly modulated in frequency by slow variations of stimulus intensity. Spike-frequency adaptation provides a memory of their recent firing, facilitating non-basilar response to stimulus transients. Considering anatomical and functional dimensions, we conclude that basilar and non-basilar pyramidal neurons are clear-cut, different anatomo-functional phenotypes. We propose that, in addition to their role in contrast processing, basilar pyramidal neurons encode sustained global stimuli such as those elicited by large or distant objects while non-basilar pyramidal neurons respond to transient stimuli due to movement of objects with a textured surface.

Ephaptic coupling in white matter fibre bundles modulates axonal transmission delays.

Axonal connections are widely regarded as faithful transmitters of neuronal signals with fixed delays. The reasoning behind this is that extracellular potentials caused by spikes travelling along axons are too small to have an effect on other axons. Here we devise a computational framework that allows us to study the effect of extracellular potentials generated by spike volleys in axonal fibre bundles on axonal transmission delays. We demonstrate that, although the extracellular potentials generated by single spikes are of the order of microvolts, the collective extracellular potential generated by spike volleys can reach several millivolts. As a consequence, the resulting depolarisation of the axonal membranes increases the velocity of spikes, and therefore reduces axonal delays between brain areas. Driving a neural mass model with such spike volleys, we further demonstrate that only ephaptic coupling can explain the reduction of stimulus latencies with increased stimulus intensities, as observed in many psychological experiments.