Primary sensory cortices contain distinguishable spatial patterns of activity for each sense

Whether primary sensory cortices are essentially multisensory or whether they respond to only one sense is an emerging debate in neuroscience. Here we use a multivariate pattern analysis of functional magnetic resonance imaging data in humans to demonstrate that simple and isolated stimuli of one sense elicit distinguishable spatial patterns of neuronal responses, not only in their corresponding primary sensory cortex, but in other primary sensory cortices. These results indicate that primary sensory cortices, traditionally regarded as unisensory, contain unique signatures of other senses and, thereby, prompt a reconsideration of how sensory information is coded in the human brain

Distinct Features of Auditory Steady-State Responses as Compared to Transient Event-Related Potentials

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The search for pain biomarkers in the human brain

Non-invasive functional brain imaging is used more than ever to investigate pain in health and disease, with the prospect of finding new means to alleviate pain and improve patient wellbeing. The observation that several brain areas are activated by transient painful stimuli, and that the magnitude of this activity is often graded with pain intensity, has prompted researchers to extract features of brain activity that could serve as biomarkers to measure pain objectively. However, most of the brain responses observed when pain is present can also be observed when pain is absent. For example, similar brain responses can be elicited by salient but non-painful auditory, tactile and visual stimuli, and such responses can even be recorded in patients with congenital analgesia. Thus, as argued in this review, there is still disagreement on the degree to which current measures of brain activity exactly relate to pain. Furthermore, whether more recent analysis techniques can be used to identify distributed patterns of brain activity specific for pain can be only warranted using carefully designed control conditions. On a more general level, the clinical utility of current pain biomarkers derived from human functional neuroimaging appears to be overstated, and evidence for their efficacy in real-life clinical conditions is scarce. Rather than searching for biomarkers of pain perception, several researchers are developing biomarkers to achieve mechanism-based stratification of pain conditions, predict response to medication and offer personalized treatments. Initial results with promising clinical perspectives need to be further tested for replicability and generalizability

Touch uses frictional cues to discriminate flat materials

In a forced-choice task, we asked human participants to discriminate by touch alone glass plates from transparent polymethyl methacrylate (PMMA) plastic plates. While the surfaces were flat and did not exhibit geometric features beyond a few tens of nanometres, the materials differed by their molecular structures. They produced similar coefficients of friction and thermal effects were controlled. Most participants performed well above chance and participants with dry fingers discriminated the materials especially well. Current models of tactile surface perception appeal to surface topography and cannot explain our results. A correlation analysis between detailed measurements of the interfacial forces and discrimination performance suggested that the perceptual task depended on the transitory contact phase leading to full slip. This result demonstrates that differences in interfacial mechanics between the finger and a material can be sensed by touch and that the evanescent mechanics that take place before the onset of steady slip have perceptual value

Non-invasive multi-channel electrophysiology of the human spinal cord: Assessing somatosensory processing from periphery to cortex

The spinal cord is of fundamental importance for somatosensory processing and plays a significant role in various pathologies, such as chronic pain. However, knowledge on spinal cord processing in humans is limited due to the vast technical challenges involved in its investigation via non-invasive recording approaches. Here, we aim to address these challenges by developing an electrophysiological approach – based on a high-density electrode-montage – that allows for characterizing spinal cord somatosensory evoked potentials (SEPs) and combining this with concurrent recordings of the spinal cord’s input (peripheral nerve action potentials) and output (SEPs in brainstem and cortex). In two separate experiments, we first methodologically validate the approach (including replication and robustness analyses) and then assess its application in the context of a neuroscientific question (integrative processes along the neural hierarchy). Critically, we demonstrate the benefits of multi-channel recordings in terms of enhancing sensitivity via spatial filtering, which also allows for obtaining spinal cord SEPs at the single-trial level. We make use of this approach to demonstrate the feasibility of recording spinal cord SEPs in low-signal scenarios (single-digit stimulation) and – most importantly – to provide evidence for bottom-up signal integration already at the level of the spinal cord. Taken together, our approach of concurrent multi-channel recordings of evoked responses along the neural hierarchy allows for a comprehensive assessment of the functional architecture of somatosensory processing at a millisecond timescale

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

Thermal Detection Thresholds of Aδ- and C-Fibre Afferents Activated by Brief CO2 Laser Pulses Applied onto the Human Hairy Skin

Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively

How different experimental models of secondary hyperalgesia change the nociceptive flexion reflex

In this neurophysiological study in healthy humans, we assessed how central sensitization induced by either high-frequency stimulation (HFS) or topical capsaicin application modulates features of the RIII reflex response. The ability of these stimuli to engage the endogenous pain modulatory system was also tested. In 26 healthy participants we elicited an RIII reflex using suprathreshold stimulation of the sural nerve. Subsequently HFS or capsaicin were applied to the foot and the RIII reflex repeated after 15 minutes. Contact heating of the volar forearm served as the heterotopic test stimulus to probe activation of the endogenous pain modulatory system. HFS significantly reduced the pain threshold by 29% and the RIII reflex threshold by 20%. Capsaicin significantly reduced the pain threshold by 17% and the RIII reflex threshold by 18%. Both HFS and capsaicin left RIII reflex size unaffected. Numerical Rating Scale (NRS) pain scores elicited by the heterotopic noxious heat stimulus were unaffected by capsaicin and slightly increased by HFS. HFS and capsaicin similarly modulated the pain threshold and RIII reflex threshold, without a concomitant inhibitory effect of the endogenous pain modulatory system. Our neurophysiological study supports the use of the RIII reflex in investigating central sensitization in humans

Time-Frequency Analysis of Chemosensory Event-Related Potentials to Characterize the Cortical Representation of Odors in Humans

BACKGROUND: The recording of olfactory and trigeminal chemosensory event-related potentials (ERPs) has been proposed as an objective and non-invasive technique to study the cortical processing of odors in humans. Until now, the responses have been characterized mainly using across-trial averaging in the time domain. Unfortunately, chemosensory ERPs, in particular, olfactory ERPs, exhibit a relatively low signal-to-noise ratio. Hence, although the technique is increasingly used in basic research as well as in clinical practice to evaluate people suffering from olfactory disorders, its current clinical relevance remains very limited. Here, we used a time-frequency analysis based on the wavelet transform to reveal EEG responses that are not strictly phase-locked to onset of the chemosensory stimulus. We hypothesized that this approach would significantly enhance the signal-to-noise ratio of the EEG responses to chemosensory stimulation because, as compared to conventional time-domain averaging, (1) it is less sensitive to temporal jitter and (2) it can reveal non phase-locked EEG responses such as event-related synchronization and desynchronization. METHODOLOGY/PRINCIPAL FINDINGS: EEG responses to selective trigeminal and olfactory stimulation were recorded in 11 normosmic subjects. A Morlet wavelet was used to characterize the elicited responses in the time-frequency domain. We found that this approach markedly improved the signal-to-noise ratio of the obtained EEG responses, in particular, following olfactory stimulation. Furthermore, the approach allowed characterizing non phase-locked components that could not be identified using conventional time-domain averaging. CONCLUSION/SIGNIFICANCE: By providing a more robust and complete view of how odors are represented in the human brain, our approach could constitute the basis for a robust tool to study olfaction, both for basic research and clinicians

Thoughts of Death Modulate Psychophysical and Cortical Responses to Threatening Stimuli

Existential social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Therefore we explored whether reminders of mortality influence subjective ratings of intensity and threat of auditory and painful thermal stimuli and the associated electroencephalographic activity. Moreover, we explored whether personality and demographics modulate psychophysical and neural changes related to mortality salience (MS). Following MS induction, a specific increase in ratings of intensity and threat was found for both nociceptive and auditory stimuli. While MS did not have any specific effect on nociceptive and auditory evoked potentials, larger amplitude of theta oscillatory activity related to thermal nociceptive activity was found after thoughts of death were induced. MS thus exerted a top-down modulation on theta electroencephalographic oscillatory amplitude, specifically for brain activity triggered by painful thermal stimuli. This effect was higher in participants reporting higher threat perception, suggesting that inducing a death-related mind-set may have an influence on body-defence related somatosensory representations