No relevant differences in conditioned pain modulation effects between parallel and sequential test design. A cross-sectional observational study

Background Conditioned pain modulation (CPM) is measured by comparing pain induced by a test stimulus with pain induced by the same test stimulus, either during (parallel design) or after (sequential design) the conditioning stimulus. Whether design, conditioning stimulus intensity and test stimulus selection affect CPM remains unclear. Methods CPM effects were evaluated in healthy participants (N = 89) at the neck, forearm and lower leg using the cold pressor test as the conditioning stimulus. In three separate experiments, we compared the impact of (1) design (sequential versus parallel), (2) conditioning stimulus intensity (VAS 40/100 versus VAS 60/100), and (3) test stimulus selection (single versus dual, i.e., mechanical and thermal). Statistical analyses of the main effect of design (adjusted for order) and experiment were conducted using linear mixed models with random intercepts. Results No significant differences were identified in absolute CPM data. In relative CPM data, a sequential design resulted in a slightly lower CPM effect compared to a parallel design, and only with a mechanical test stimulus at the neck (−6.1%; 95% CI [−10.1 to −2.1]) and lower leg (−5.9%; 95% CI [−11.7 to −0.1]) but not forearm (−4.5%; 95% CI [−9.0 to 0.1]). Conditioning stimulus intensity and test stimulus selection did not influence the CPM effect nor the difference in CPM effects derived from parallel versus sequential designs. Conclusions Differences in CPM effects between protocols were minimal or absent. A parallel design may lead to a minimally higher relative CPM effect when using a mechanical test stimulus. The conditioning stimulus intensities assessed in this study and performing two test stimuli did not substantially influence the differences between designs nor the magnitude of the CPM effect.

Response triggering by an acoustic stimulus increases with stimulus intensity and is best predicted by startle reflex activation

In a simple reaction time task, the presentation of a startling acoustic stimulus has been shown to trigger the prepared response at short latency, known as the StartReact effect. However, it is unclear under what conditions it can be assumed that the loud stimulus results in response triggering. The purpose of the present study was to examine how auditory stimulus intensity and preparation level affect the probability of involuntary response triggering and the incidence of activation in the startle reflex indicator of sternocleidomastoid (SCM). In two reaction time experiments, participants were presented with an irrelevant auditory stimulus of varying intensities at various time points prior to the visual go-signal. Responses were independently categorized as responding to either the auditory or visual stimulus and those with or without SCM activation (i.e., SCM+/−). Both the incidence of response triggering and proportion of SCM+ trials increased with stimulus intensity and presentation closer to the go-signal. Data also showed that participants reacted to the auditory stimulus at a much higher rate on trials where the auditory stimulus elicited SCM activity versus those that did not, and a logistic regression analysis confirmed that SCM activation is a reliable predictor of response triggering for all conditions.

Light-stimulus intensity modulates startle reflex habituation in larval zebrafish

The startle reflex in larval zebrafish describes a C-bend of the body occurring in response to sudden, unexpected, stimuli of different sensory modalities. Alterations in the startle reflex habituation (SRH) have been reported in various human and animal models of neurological and psychiatric conditions and are hence considered an important behavioural marker of neurophysiological function. The amplitude, offset and decay constant of the auditory SRH in larval zebrafish have recently been characterised, revealing that the measures are affected by variation in vibratory frequency, intensity, and interstimulus-interval. Currently, no study provides a model-based analysis of the effect of physical properties of light stimuli on the visual SRH. This study assessed the effect of incremental light-stimulus intensity on the SRH of larval zebrafish through a repeated-measures design. Their total locomotor responses were normalised for the time factor, based on the behaviour of a (non-stimulated) control group. A linear regression indicated that light intensity positively predicts locomotor responses due to larger SRH decay constants and offsets. The conclusions of this study provide important insights as to the effect of light properties on the SRH in larval zebrafish. Our methodology and findings constitute a relevant reference framework for further investigation in translational neurophysiological research.

Development of an Advanced Sham Coil for Transcranial Magnetic Stimulation and Examination of Its Specifications

Transcranial magnetic stimulation (TMS) neurophysiology has been widely applied worldwide, but it is often contaminated by confounders other than cortical stimulus-evoked activities. Although advanced sham coils that elaborately mimic active stimulation have recently been developed, their performance is not examined in detail. Developing such sham coils is crucial to improve the accuracy of TMS neurophysiology. Herein, we examined the specifications of the sham coil by comparison with the active coil. The magnetic flux and click sound pressure changes were measured when the stimulus intensity was varied from 10% to 100% maximum stimulator output (MSO), and the changes in coil surface temperature over time with continuous stimulation at 50% MSO for each coil. The magnetic flux change at the center of the coil showed a peak of 12.51 (kT/s) for the active coil, whereas it was 0.41 (kT/s) for the sham coil. Although both coils showed a linear change in magnetic flux as the stimulus intensity increased, due to the difference in coil winding structure, the sham coil took less than half the time to overheat and had 5 dB louder coil click sounds than the active coil. The sham coil showed a sufficiently small flux change at the center of the coil, but the flux change from the periphery of the coil was comparable to that of the active coil. Future use of high-quality sham coil will extend our understanding of the TMS neurophysiology of the cortex at the stimulation site.

Neural excitability and sensory input determine intensity perception with opposing directions in initial cortical responses

Perception of sensory information is determined by stimulus features (e.g., intensity) and instantaneous neural states (e.g., excitability). Commonly, it is assumed that both are reflected similarly in evoked brain potentials, that is, larger amplitudes are associated with a stronger percept of a stimulus. We tested this assumption in a somatosensory discrimination task in humans, simultaneously assessing (i) single-trial excitatory post-synaptic currents inferred from short-latency somatosensory evoked potentials (SEPs), (ii) pre-stimulus alpha oscillations (8–13 Hz), and (iii) peripheral nerve measures. Fluctuations of neural excitability shaped the perceived stimulus intensity already during the very first cortical response (at ~20 ms) yet demonstrating opposite neural signatures as compared to the effect of presented stimulus intensity. We reconcile this discrepancy via a common framework based on the modulation of electro-chemical membrane gradients linking neural states and responses, which calls for reconsidering conventional interpretations of brain potential magnitudes in stimulus intensity encoding.

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

ABSTRACTNeurons 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 (100-600 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 in vitro experiments in which 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 physiological noise induces irregular skipping without disrupting phase locking, as required for temporal coding. This occurs because the reliability and precision of spikes evoked by small- amplitude, fast-onset signals are differentially sensitive to noise. Simulations confirmed that differences in stimulus intensity and frequency can be well discriminated based on differences in spike rate or timing, respectively, but only in the presence of noise. Our results show that multiplexed coding by S1 pyramidal neurons is facilitated rather than degraded by physiological levels of noise. In fact, multiplexing is optimal under physiologically noisy conditions.