Burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia in humans.

The aim of the present study was to compare the efficacy of burst-like conditioning electrical stimulation vs. continuous stimulation of cutaneous nociceptors for inducing increased pinprick sensitivity in the surrounding unstimulated skin (a phenomenon referred to as secondary hyperalgesia). In a first experiment (n = 30), we compared the increase in mechanical pinprick sensitivity induced by 50-Hz burst-like stimulation (n = 15) vs. 5-Hz continuous stimulation (n = 15) while maintaining constant the total number of stimuli and the total duration of stimulation. We found a significantly greater increase in mechanical pinprick sensitivity in the surrounding unstimulated skin after 50-Hz burst-like stimulation compared with 5-Hz continuous stimulation (P = 0.013, Cohen's d = 0.970). Importantly, to control for the different frequency of stimulation, we compared in a second experiment (n = 40) 5-Hz continuous stimulation (n = 20) vs. 5-Hz burst-like stimulation (n = 20), this time while keeping the total number of stimuli as well as the frequency of stimulation identical. Again, we found a significantly greater increase in pinprick sensitivity after 5-Hz burst-like stimulation compared with 5-Hz continuous stimulation (P = 0.009, Cohen's d = 0.868). To conclude, our data indicate that burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia.NEW & NOTEWORTHY Burst-like electrical conditioning stimulation of cutaneous nociceptors is more efficacious than continuous stimulation for inducing heterosynaptic facilitation of mechanical nociceptive input in humans.

Early gamma-oscillations as correlate of localized nociceptive processing in primary sensorimotor cortex.

Recent studies put forward the idea that stimulus-evoked gamma-band oscillations (GBOs; 30-100 Hz) play a specific role in nociception. So far, evidence for the specificity of GBOs for nociception, their possible involvement in nociceptive sensory discriminatory abilities, and knowledge regarding their cortical sources is just starting to grow. To address these questions, we used electroencephalography (EEG) to record brain activity evoked by phasic nociceptive laser stimuli and tactile stimuli applied at different intensities to the right hand and foot of 12 healthy volunteers. The EEG was analyzed in the time domain to extract phase-locked event-related brain potentials (ERPs) and in three regions of interest in the time-frequency domain (delta/theta, 40-Hz gamma, 70-Hz gamma) to extract stimulus-evoked changes in the magnitude of non-phase-locked brain oscillations. Both nociceptive and tactile stimuli, matched with respect to subjective intensity, elicited phase locked ERPs of increasing amplitude with increasing stimulus intensity. In contrast, only nociceptive stimuli elicited a significant enhancement of GBOs (65-85 Hz, 150-230 ms after stimulus onset), whose magnitude encoded stimulus intensity, whereas tactile stimuli led to a GBO decrease. Following nociceptive hand stimulation, the topographical distribution of GBOs was maximal at contralateral electrode C3, whereas maximum activity following foot stimulation was recorded at the midline electrode Cz, compatible with generation of GBOs in the representations of the hand and foot of the primary sensorimotor cortex, respectively. The differential behavior of high-frequency GBOs and low-frequency 40-Hz GBOs is indicating different functional roles and regions in sensory processing.NEW & NOTEWORTHY Gamma-band oscillations show hand-foot somatotopy compatible with generation in primary sensorimotor cortex and are present following nociceptive but not tactile stimulation of the hand and foot in humans.

Spatial Patterns of Brain Activity Preferentially Reflecting Transient Pain and Stimulus Intensity.

How pain emerges in the human brain remains an unresolved question. Neuroimaging studies have suggested that several brain areas subserve pain perception because their activation correlates with perceived pain intensity. However, painful stimuli are often intense and highly salient; therefore, using both intensity- and saliency-matched control stimuli is crucial to isolate pain-selective brain responses. Here, we used these intensity/saliency-matched painful and non-painful stimuli to test whether pain-selective information can be isolated in the functional magnetic resonance imaging responses elicited by painful stimuli. Using two independent datasets, multivariate pattern analysis was able to isolate features distinguishing the responses triggered by (1) intensity/saliency-matched painful versus non-painful stimuli, and (2) high versus low-intensity/saliency stimuli regardless of whether they elicit pain. This indicates that neural activity in the so-called "pain matrix" is functionally heterogeneous, and part of it carries information related to both painfulness and intensity/saliency. The response features distinguishing these aspects are spatially distributed and cannot be ascribed to specific brain structures.

Brain regions preferentially responding to transient and iso-intense painful or tactile stimuli.

How pain emerges from cortical activities remains an unresolved question in pain neuroscience. A first step toward addressing this question consists in identifying brain activities that occur preferentially in response to painful stimuli in comparison to non-painful stimuli. A key confound that has affected this important comparison in many previous studies is the intensity of the stimuli generating painful and non-painful sensations. Here, we compared the brain activity during iso-intense painful and tactile sensations sampled by functional MRI in 51 healthy participants. Specifically, the perceived intensity was recorded for every stimulus and only the stimuli with rigorously matched perceived intensity were selected and compared between painful and tactile conditions. We found that all brain areas activated by painful stimuli were also activated by tactile stimuli, and vice versa. Neural responses in these areas were correlated with the perceived stimulus intensity, regardless of stimulus modality. More importantly, among these activated areas, we further identified a number of brain regions showing stronger responses to painful stimuli than to tactile stimuli when perceived intensity was carefully matched, including the bilateral opercular cortex, the left supplementary motor area and the right frontal middle and inferior areas. Among these areas, the right frontal middle area still responded more strongly to painful stimuli even when painful stimuli were perceived less intense than tactile stimuli, whereas in this condition other regions showed stronger responses to tactile stimuli. In contrast, the left postcentral gyrus, the visual cortex, the right parietal inferior gyrus, the left parietal superior gyrus and the right cerebellum had stronger responses to tactile stimuli than to painful stimuli when perceived intensity was matched. When tactile stimuli were perceived less intense than painful stimuli, the left postcentral gyrus and the right parietal inferior gyrus still responded more strongly to tactile stimuli while other regions now showed similar responses to painful and tactile stimuli. These results suggest that different brain areas may be engaged differentially when processing painful and tactile information, although their neural activities are not exclusively dedicated to encoding information of only one modality but are strongly determined by perceived stimulus intensity regardless of stimulus modality.

Central sensitization increases the pupil dilation elicited by mechanical pinprick stimulation.

High-frequency electrical stimulation (HFS) of skin nociceptors triggers central sensitization (CS), manifested as increased pinprick sensitivity of the skin surrounding the site of HFS. Our aim was to assess the effect of CS on pinprick-evoked pupil dilation responses (PDRs) and pinprick-evoked brain potentials (PEPs). We hypothesized that the increase in the positive wave of PEPs following HFS would result from an enhanced pinprick-evoked phasic response of the locus coeruleus-noradrenergic system (LC-NS), indicated by enhanced PDRs. In 14 healthy volunteers, 64- and 96-mN pinprick stimuli were delivered to the left and right forearms, before and 20 minutes after HFS was applied to one of the two forearms. Both PEPs and pinprick-evoked PDRs were recorded. After HFS, pinprick stimuli were perceived as more intense at the HFS-treated arm compared with baseline and control site, and this increase was similar for both stimulation intensities. Importantly, the pinprick-evoked PDR was also increased, and the increase was stronger for 64- compared with 96-mN stimulation. This is in line with our previous results showing a stronger increase of the PEP positivity at 64 vs. 96-mN stimulation and suggests that the increase in PEP positivity observed in previous studies could relate, at least in part, to enhanced LC-NS activity. However, there was no increase of the PEP positivity in the present study, indicating that enhanced LC-NS activity is not the only determinant of the HFS-induced enhancement of PEPs. Altogether, our results indicate that PDRs are more sensitive for detecting CS than PEPs. NEW & NOTEWORTHY We provide the first demonstration in humans that activity-dependent central sensitization increases pinprick-evoked autonomic arousal measured by enhanced pupil dilation response.

Heterosynaptic facilitation of mechanical nociceptive input is dependent on the frequency of conditioning stimulation.

High-frequency burstlike electrical conditioning stimulation (HFS) applied to human skin induces an increase in mechanical pinprick sensitivity of the surrounding unconditioned skin (a phenomenon known as secondary hyperalgesia). The present study assessed the effect of frequency of conditioning stimulation on the development of this increased pinprick sensitivity in humans. In a first experiment, we compared the increase in pinprick sensitivity induced by HFS, using monophasic non-charge-compensated pulses and biphasic charge-compensated pulses. High-frequency stimulation, traditionally delivered with non-charge-compensated square-wave pulses, may induce a cumulative depolarization of primary afferents and/or changes in pH at the electrode-tissue interface due to the accumulation of a net residue charge after each pulse. Both could contribute to the development of the increased pinprick sensitivity in a frequency-dependent fashion. We found no significant difference in the increase in pinprick sensitivity between HFS delivered with charge-compensated and non-charge-compensated pulses, indicating that the possible contribution of charge accumulation when non-charge-compensated pulses are used is negligible. In a second experiment, we assessed the effect of different frequencies of conditioning stimulation (5, 20, 42, and 100 Hz) using charge-compensated pulses on the development of increased pinprick sensitivity. The maximal increase in pinprick sensitivity was observed at intermediate frequencies of stimulation (20 and 42 Hz). It is hypothesized that the stronger increase in pinprick sensitivity at intermediate frequencies may be related to the stronger release of substance P and/or neurokinin-1 receptor activation expressed at lamina I neurons after C-fiber stimulation.NEW & NOTEWORTHY Burstlike electrical conditioning stimulation applied to human skin induces an increase in pinprick sensitivity in the surrounding unconditioned skin (a phenomenon referred to as secondary hyperalgesia). Here we show that the development of the increase in pinprick sensitivity is dependent on the frequency of the burstlike electrical conditioning stimulation.

Development of a new psychophysical method to assess intranasal trigeminal chemosensory function.

BACKGROUND: The aim of this study was to develop a new psychophysical test to assess intranasal trigeminal chemosensory function. METHODOLOGY: The test is similar to the Sniffin’ Sticks test, but using pens impregnated with substances preferentially activating trigeminal afferents. Our test comprises detection threshold, discrimination, identification and lateralization tasks. In a first study, we evaluated healthy controls. In a second study, we evaluated the potential usefulness of this test in patients with rhinological conditions. RESULTS: Study 1: 86 controls were included. Threshold, identification and lateralization performance decreased with age. Test-retest reliability was similar to that of olfactory tests. Study 2: results of the controls group were compared to those of 59 patients (14 allergic rhinitis, 11 chronic rhinosinusitis with nasal polyps (CRSwNP), 9 without nasal polyps (CRSsNP), and 25 with an olfactory disorder (OD)). Controls had 1) lower detection thresholds compared to CRSwNP, CRSsNP and OD, 2) better discrimination and identification scores compared to OD, and 3) better lateralization scores compared to CRSwNP and CRSsNP. CONCLUSIONS: Our test allows to identify age-related changes in trigeminal chemosensory function. Trigeminal function seems to be differently affected in different pathologies. Further studies are necessary to validate our results and evaluate the impact of olfactory co-activation on the observed results.

Peripheral vs. central determinants of vibrotactile adaptation.

Long-lasting mechanical vibrations applied to the skin induce a reversible decrease in the perception of vibration at the stimulated skin site. This phenomenon of vibrotactile adaptation has been studied extensively, yet there is still no clear consensus on the mechanisms leading to vibrotactile adaptation. In particular, the respective contributions of 1) changes affecting mechanical skin impedance, 2) peripheral processes, and 3) central processes are largely unknown. Here we used direct electrical stimulation of nerve fibers to bypass mechanical transduction processes and thereby explore the possible contribution of central vs. peripheral processes to vibrotactile adaptation. Three experiments were conducted. In the first, adaptation was induced with mechanical vibration of the fingertip (51- or 251-Hz vibration delivered for 8 min, at 40× detection threshold). In the second, we attempted to induce adaptation with transcutaneous electrical stimulation of the median nerve (51- or 251-Hz constant-current pulses delivered for 8 min, at 1.5× detection threshold). Vibrotactile detection thresholds were measured before and after adaptation. Mechanical stimulation induced a clear increase of vibrotactile detection thresholds. In contrast, thresholds were unaffected by electrical stimulation. In the third experiment, we assessed the effect of mechanical adaptation on the detection thresholds to transcutaneous electrical nerve stimuli, measured before and after adaptation. Electrical detection thresholds were unaffected by the mechanical adaptation. Taken together, our results suggest that vibrotactile adaptation is predominantly the consequence of peripheral mechanoreceptor processes and/or changes in biomechanical properties of the skin.

Multiple linear regression to estimate time-frequency electrophysiological responses in single trials.

Transient sensory, motor or cognitive event elicit not only phase-locked event-related potentials (ERPs) in the ongoing electroencephalogram (EEG), but also induce non-phase-locked modulations of ongoing EEG oscillations. These modulations can be detected when single-trial waveforms are analysed in the time-frequency domain, and consist in stimulus-induced decreases (event-related desynchronization, ERD) or increases (event-related synchronization, ERS) of synchrony in the activity of the underlying neuronal populations. ERD and ERS reflect changes in the parameters that control oscillations in neuronal networks and, depending on the frequency at which they occur, represent neuronal mechanisms involved in cortical activation, inhibition and binding. ERD and ERS are commonly estimated by averaging the time-frequency decomposition of single trials. However, their trial-to-trial variability that can reflect physiologically-important information is lost by across-trial averaging. Here, we aim to (1) develop novel approaches to explore single-trial parameters (including latency, frequency and magnitude) of ERP/ERD/ERS; (2) disclose the relationship between estimated single-trial parameters and other experimental factors (e.g., perceived intensity). We found that (1) stimulus-elicited ERP/ERD/ERS can be correctly separated using principal component analysis (PCA) decomposition with Varimax rotation on the single-trial time-frequency distributions; (2) time-frequency multiple linear regression with dispersion term (TF-MLRd) enhances the signal-to-noise ratio of ERP/ERD/ERS in single trials, and provides an unbiased estimation of their latency, frequency, and magnitude at single-trial level; (3) these estimates can be meaningfully correlated with each other and with other experimental factors at single-trial level (e.g., perceived stimulus intensity and ERP magnitude). The methods described in this article allow exploring fully non-phase-locked stimulus-induced cortical oscillations, obtaining single-trial estimate of response latency, frequency, and magnitude. This permits within-subject statistical comparisons, correlation with pre-stimulus features, and integration of simultaneously-recorded EEG and fMRI.

Single-trial time-frequency analysis of electrocortical signals: baseline correction and beyond.

Event-related desynchronization (ERD) and synchronization (ERS) of electrocortical signals (e.g., electroencephalogram [EEG] and magnetoencephalogram) reflect important aspects of sensory, motor, and cognitive cortical processing. The detection of ERD and ERS relies on time-frequency decomposition of single-trial electrocortical signals, to identify significant stimulus-induced changes in power within specific frequency bands. Typically, these changes are quantified by expressing post-stimulus EEG power as a percentage of change relative to pre-stimulus EEG power. However, expressing post-stimulus EEG power relative to pre-stimulus EEG power entails two important and surprisingly neglected issues. First, it can introduce a significant bias in the estimation of ERD/ERS magnitude. Second, it confuses the contribution of pre- and post-stimulus EEG power. Taking the human electrocortical responses elicited by transient nociceptive stimuli as an example, we demonstrate that expressing ERD/ERS as the average percentage of change calculated at single-trial level introduces a positive bias, resulting in an overestimation of ERS and an underestimation of ERD. This bias can be avoided using a single-trial baseline subtraction approach. Furthermore, given that the variability in ERD/ERS is not only dependent on the variability in post-stimulus power but also on the variability in pre-stimulus power, an estimation of the respective contribution of pre- and post-stimulus EEG variability is needed. This can be achieved using a multivariate linear regression (MVLR) model, which could be optimally estimated using partial least square (PLS) regression, to dissect and quantify the relationship between behavioral variables and pre- and post-stimulus EEG activities. In summary, combining single-trial baseline subtraction approach with PLS regression can be used to achieve a correct detection and quantification of ERD/ERS.

Bypassing primary sensory cortices--a direct thalamocortical pathway for transmitting salient sensory information.

Detection and appropriate reaction to sudden and intense events happening in the sensory environment is crucial for survival. By combining Bayesian model selection with dynamic causal modeling of functional magnetic resonance imaging data, a novel analysis approach that allows inferring the causality between neural activities in different brain areas, we demonstrate that salient sensory information reaches the multimodal cortical areas responsible for its detection directly from the thalamus, without being first processed in primary and secondary sensory-specific areas. This direct thalamocortical transmission of multimodal salient information is parallel to the processing of finer stimulus attributes, which are transmitted in a modality-specific fashion from the thalamus to the relevant primary sensory areas. Such direct thalamocortical connections bypassing primary sensory cortices provide a fast and efficient way for transmitting information from subcortical structures to multimodal cortical areas, to allow the early detection of salient events and, thereby, trigger immediate and appropriate behavior.

Gamma-band oscillations in the primary somatosensory cortex--a direct and obligatory correlate of subjective pain intensity.

Electroencephalographic gamma band oscillations (GBOs) induced over the human primary somatosensory cortex (SI) by nociceptive stimuli have been hypothesized to reflect cortical processing involved directly in pain perception, because their magnitude correlates with pain intensity. However, as stimuli perceived as more painful are also more salient, an alternative interpretation of this correlation is that GBOs reflect unspecific stimulus-triggered attentional processing. In fact, this is suggested by recent observations that other features of the electroencephalographic (EEG) response correlate with pain perception when stimuli are presented in isolation, but not when their saliency is reduced by repetition. Here, by delivering trains of three nociceptive stimuli at a constant 1 s interval, and using different energies to elicit graded pain intensities, we demonstrate that GBOs recorded over SI always predict the subjective pain intensity, even when saliency is reduced by repetition. These results provide evidence for a close relationship between GBOs and the cortical activity subserving pain perception.

Novelty is not enough: laser-evoked potentials are determined by stimulus saliency, not absolute novelty.

Event-related potentials (ERPs) elicited by transient nociceptive stimuli in humans are largely sensitive to bottom-up novelty induced, for example, by changes in stimulus attributes (e.g., modality or spatial location) within a stream of repeated stimuli. Here we aimed 1) to test the contribution of a selective change of the intensity of a repeated stimulus in determining the magnitude of nociceptive ERPs, and 2) to dissect the effect of this change of intensity in terms of "novelty" and "saliency" (an increase of stimulus intensity is more salient than a decrease of stimulus intensity). Nociceptive ERPs were elicited by trains of three consecutive laser stimuli (S1-S2-S3) delivered to the hand dorsum at a constant 1-s interstimulus interval. Three, equally spaced intensities were used: low (L), medium (M), and high (H). While the intensities of S1 and S2 were always identical (L, M, or H), the intensity of S3 was either identical (e.g., HHH) or different (e.g., MMH) from the intensity of S1 and S2. Introducing a selective change in stimulus intensity elicited significantly larger N1 and N2 waves of the S3-ERP but only when the change consisted in an increase in stimulus intensity. This observation indicates that nociceptive ERPs do not simply reflect processes involved in the detection of novelty but, instead, are mainly determined by stimulus saliency.

Unmasking the obligatory components of nociceptive event-related brain potentials.

It has been hypothesized that the human cortical responses to nociceptive and nonnociceptive somatosensory inputs differ. Supporting this view, somatosensory-evoked potentials (SEPs) elicited by thermal nociceptive stimuli have been suggested to originate from areas 1 and 2 of the contralateral primary somatosensory (S1), operculo-insular, and cingulate cortices, whereas the early components of nonnociceptive SEPs mainly originate from area 3b of S1. However, to avoid producing a burn lesion, and sensitize or fatigue nociceptors, thermonociceptive SEPs are typically obtained by delivering a small number of stimuli with a large and variable interstimulus interval (ISI). In contrast, the early components of nonnociceptive SEPs are usually obtained by applying many stimuli at a rapid rate. Hence, previously reported differences between nociceptive and nonnociceptive SEPs could be due to differences in signal-to-noise ratio and/or differences in the contribution of cognitive processes related, for example, to arousal and attention. Here, using intraepidermal electrical stimulation to selectively activate Aδ-nociceptors at a fast and constant 1-s ISI, we found that the nociceptive SEPs obtained with a long ISI are no longer identified, indicating that these responses are not obligatory for nociception. Furthermore, using a blind source separation, we found that, unlike the obligatory components of nonnociceptive SEPs, the obligatory components of nociceptive SEPs do not receive a significant contribution from a contralateral source possibly originating from S1. Instead, they were best explained by sources compatible with bilateral operculo-insular and/or cingulate locations. Taken together, our results indicate that the obligatory components of nociceptive and nonnociceptive SEPs are fundamentally different.

Clinical usefulness and feasibility of time-frequency analysis of chemosensory event-related potentials.

BACKGROUND: The clinical usefulness of olfactory event-related brain potentials (OERPs) to assess olfactory function is limited by the relatively low signal-to-noise ratio of the responses identified using conventional time-domain averaging. Recently, it was shown that time-frequency analysis of the obtained EEG signals can markedly improve the signal-to-noise ratio of OERPs in healthy controls, because it enhances both phase-locked and non phase-locked EEG responses. The aim of the present study was to investigate the clinical usefulness of this approach and evaluate its feasibility in a clinical setting. METHODOLOGY: We retrospectively analysed EEG recordings obtained from 45 patients (15 anosmic, 15 hyposmic and 15 normos- mic). The responses to olfactory stimulation were analysed using conventional time-domain analysis and joint time-frequency analysis. The ability of the two methods to discriminate between anosmic, hyposmic and normosmic patients was assessed using a Receiver Operating Characteristic analysis. RESULTS: The discrimination performance of OERPs identified using conventional time-domain averaging was poor. In contrast, the discrimination performance of the EEG response identified in the time-frequency domain was relatively high. Furthermore, we found a significant correlation between the magnitude of this response and the psychophysical olfactory score. CONCLUSION: Time-frequency analysis of the EEG responses to olfactory stimulation could be used as an effective and reliable diagnostic tool for the objective clinical evaluation of olfactory function in patients.

Pinprick-induced gamma-band oscillations are not a useful electrophysiological marker of pinprick hypersensitivity in humans.

OBJECTIVE: This study aimed to investigate scalp gamma-band oscillations (GBOs) induced by mechanical stimuli activating skin nociceptors before and after the induction of mechanical hypersensitivity using high-frequency electrical stimulation (HFS) of the skin. METHODS: In twenty healthy volunteers, we recorded the electroencephalogram during robot-controlled mechanical pinprick stimulation (512 mN) applied at the right ventral forearm before and after HFS. RESULTS: HFS induced a significant increase in mechanical pinprick sensitivity, but this increased pinprick sensitivity was, at the group level, not accompanied by a significant increase in GBOs. Visual inspection of the individual data revealed that possible GBOs were present in eight out of twenty participants (40%) and the frequency of these GBOs varied substantially across participants. CONCLUSIONS: Based on the low number of participants showing GBOs we question the (clinical) utility of mechanically-induced GBOs as an electrophysiological marker of pinprick hypersensitivity in humans. SIGNIFICANCE: Mechanical pinprick-induced scalp GBOs are not useful for evaluating mechanical pinprick hypersensitivity in humans.

Modulation of the spinal N13 SEP component by high- and low-frequency electrical stimulation. Experimental pain models matter.

OBJECTIVE: The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of cervical dorsal horn neurons. Neurophysiological studies in healthy participants showed that capsaicin-induced central sensitization causes an increase of the N13 SEP amplitude. Consequently, in human research, this spinal component may serve as a valuable readout of central sensitization. In this study, we wanted to verify if the sensitivity of the N13 SEP for detecting central sensitization is consistent across different experimental pain models inducing central sensitization and secondary hyperalgesia, namely high and low-frequency electrical stimulation (HFS and LFS). METHODS: In 18 healthy participants, we recorded SEP after bilateral ulnar nerve stimulation before and after secondary hyperalgesia was induced through HFS and LFS applied on the ulnar nerve territory of the hand of one side. The area of secondary hyperalgesia was mapped with a calibrated 128-mN pinprick probe, and the mechanical pain sensitivity with three calibrated 16-64-256-mN pinprick probes. RESULTS: Although both HFS and LFS successfully induced secondary hyperalgesia only LFS increased the amplitude of the N13 SEP. CONCLUSIONS: These findings suggest that the sensitivity of the N13 SEP for detecting dorsal horn excitability changes may critically depend on the different experimental pain models. SIGNIFICANCE: Our results indicate that LFS and HFS could trigger central sensitization at the dorsal horn level through distinct mechanisms, however this still needs confirmation by replication studies.

Dishabituation of laser-evoked EEG responses: dissecting the effect of certain and uncertain changes in stimulus spatial location.

The repetition of nociceptive stimuli of identical modality, intensity and location at short (1 s) and constant inter-stimulus interval (ISI) determines a strong habituation of the corresponding electroencephalographic (EEG) responses. To understand what determines this response habituation, we (1) examined the effect of introducing a selective change in the spatial location of the repeated stimulus (i.e., without altering its modality, intensity and timing), and (2) dissected the relative contribution of bottom-up, stimulus-driven spatial changes and top-down, cognitive expectations of such a change. Multichannel EEG was recorded while participants received a triplet of stimuli (S1-S2-S3) delivered to the hand dorsum at 1-s ISI. S3 was delivered either to the same hand as S1 and S2 or to the other hand, and participants were either explicitly informed or not informed of the location of S3. We found that, unlike the introduction of a change in the sensory modality of the repeated stimulus (Valentini et al. in J Cogn Neurosci 23:2822-2837, 2011), introducing a change in its spatial location did not produce a significant dishabituation of the laser-evoked N1, N2 and P2 peaks, but only a small amplitude increase following the P2 peak, maximal on the hemisphere contralateral to the stimulated hand. Furthermore, the magnitude of the elicited responses was not significantly affected by cognitive expectations. Altogether, these results indicate that bottom-up, stimulus-driven novelty resulting from a change in stimulus spatial location does not revert the habituation caused by repetition suppression, but determines a small increase of neural activity over the contralateral central-parietal cortex, likely reflecting shifts in spatial attention.

Assessment of chemosensory function using electroencephalographic techniques.

Electroencephalographic techniques are widely used to provide an objective evaluation of the chemosensory function and to explore neural mechanisms related to the processing of chemosensory events. The most popular technique to evaluate brain responses to chemosensory stimuli is across trial time-domain averaging to reveal chemosensory event-related potentials (CSERP) embedded within the ongoing EEG. Nevertheless, this technique has a poor signal-to-noise ratio and cancels out stimulus-induced changes in the EEG signal that are not strictly phased-locked to stimulus onset. The fact that consistent CSERP are not systematically identifiable in healthy subjects currently constitutes a major limitation to the use of this technique for the diagnosis of chemosensory dysfunction. In this review, we will review the different techniques related to the recording and identification of CSERP, discuss some of their limitations, and propose some novel signal processing methods which could be used to enhance the signal-to-noise ratio of chemosensory event-related brain responses.

Olfactory Dysfunction Predicts Frailty and Poor Postoperative Outcome in Older Patients Scheduled for Elective Non-Cardiac Surgery.

OBJECTIVES: Frailty has been suggested to take part in the recently demonstrated link between olfactory dysfunction and overall mortality risk. Preoperative assessment of frailty is essential to detect the most vulnerable patients scheduled for surgery. The aim of this study was to evaluate whether olfactory dysfunction is a reliable predictor of preoperative frailty and postoperative outcome. DESIGN: This was a single-center prospective observational study conducted between July and October 2020 in Brussels, Belgium. SETTING AND PARTICIPANTS: 155 preoperative patients aged from 65 years old and scheduled for elective non-cardiac surgery. MEASUREMENTS: Olfactory function was examined using the Sniffin' Sticks 12-item identification test. Frailty was assessed using the Edmonton Frail Scale (EFS) and handgrip strength. The clock drawing test (CDT) from the EFS was also analyzed separately to evaluate cognitive function. Patients were followed for postoperative complications and mortality over one year. RESULTS: Olfactory dysfunction was significantly associated with the EFS score, anosmic patients having a higher median EFS score than normosmic patients (6[4-7] vs 4[2-5], p = .025). Anosmic patients had an increased odds of being frail after adjusting for possible confounding factors (OR: 6.19, 95% CI: 1.65-23.20, p = .007) and were more at risk of poor postoperative outcome (including complications and death) (OR: 4.33, 95% CI: 1.28-14.67, p = .018). CONCLUSIONS: Olfactory dysfunction is associated with preoperative frailty determined by the EFS and with poor post-surgical outcome at one-year.