Nociceptive-Evoked Potentials Are Sensitive to Behaviorally Relevant Stimulus Displacements in Egocentric Coordinates.

Feature selection has been extensively studied in the context of goal-directed behavior, where it is heavily driven by top-down factors. A more primitive version of this function is the detection of bottom-up changes in stimulus features in the environment. Indeed, the nervous system is tuned to detect fast-rising, intense stimuli that are likely to reflect threats, such as nociceptive somatosensory stimuli. These stimuli elicit large brain potentials maximal at the scalp vertex. When elicited by nociceptive laser stimuli, these responses are labeled laser-evoked potentials (LEPs). Although it has been shown that changes in stimulus modality and increases in stimulus intensity evoke large LEPs, it has yet to be determined whether stimulus displacements affect the amplitude of the main LEP waves (N1, N2, and P2). Here, in three experiments, we identified a set of rules that the human nervous system obeys to identify changes in the spatial location of a nociceptive stimulus. We showed that the N2 wave is sensitive to: (1) large displacements between consecutive stimuli in egocentric, but not somatotopic coordinates; and (2) displacements that entail a behaviorally relevant change in the stimulus location. These findings indicate that nociceptive-evoked vertex potentials are sensitive to behaviorally relevant changes in the location of a nociceptive stimulus with respect to the body, and that the hand is a particularly behaviorally important site

A geometric model of defensive peripersonal space

Potentially harmful stimuli occurring within the defensive peripersonal space (DPPS), a protective area surrounding the body, elicit stronger defensive reactions. The spatial features of the DPPS are poorly defined and limited to descriptive estimates of its extent along a single dimension. Here we postulated a family of geometric models of the DPPS, to address two important questions with respect to its spatial features: What is its fine-grained topography? How does the nervous system represent the body area to be defended? As a measure of the DPPS, we used the strength of the defensive blink reflex elicited by electrical stimulation of the hand (hand-blink reflex, HBR), which is reliably modulated by the position of the stimulated hand in egocentric coordinates. We tested the goodness of fit of the postulated models to HBR data from six experiments in which we systematically explored the HBR modulation by hand position in both head-centered and body-centered coordinates. The best-fitting model indicated that 1) the nervous system's representation of the body area defended by the HBR can be approximated by a half-ellipsoid centered on the face and 2) the DPPS extending from this area has the shape of a bubble elongated along the vertical axis. Finally, the empirical observation that the HBR is modulated by hand position in head-centered coordinates indicates that the DPPS is anchored to the face. The modeling approach described in this article can be generalized to describe the spatial modulation of any defensive response

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

IES brain potentials reflect secondary hyperalgesia

Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS.This work was funded by the Wellcome Trust Pain Consortium (COLL JLARAXR to GDI and AHD), a UCL Grand Challenges studentship (to JON), the National Natural Science Foundation of China (81571659 to ML) and the Natural Science Foundation of Tianjin (15JCYBJC55100 to ML).This is the author accepted manuscript. The final version is available from the American Physiological Society via http://dx.doi.org/10.1152/jn.00013.201

Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways

Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronisation of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intra-epidermal electrical stimulation (IES) allows selective activation of type-II Aδ mechano-heat nociceptors (II-AMHs), and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and co-exists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the EEG responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intra-epidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES co-exists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES were significantly increased after the intra-epidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia, and therefore represent an objective correlate of CS

Nociceptive-Evoked Potentials Are Sensitive to Behaviorally Relevant Stimulus Displacements in Egocentric Coordinates.

Feature selection has been extensively studied in the context of goal-directed behavior, where it is heavily driven by top-down factors. A more primitive version of this function is the detection of bottom-up changes in stimulus features in the environment. Indeed, the nervous system is tuned to detect fast-rising, intense stimuli that are likely to reflect threats, such as nociceptive somatosensory stimuli. These stimuli elicit large brain potentials maximal at the scalp vertex. When elicited by nociceptive laser stimuli, these responses are labeled laser-evoked potentials (LEPs). Although it has been shown that changes in stimulus modality and increases in stimulus intensity evoke large LEPs, it has yet to be determined whether stimulus displacements affect the amplitude of the main LEP waves (N1, N2, and P2). Here, in three experiments, we identified a set of rules that the human nervous system obeys to identify changes in the spatial location of a nociceptive stimulus. We showed that the N2 wave is sensitive to: (1) large displacements between consecutive stimuli in egocentric, but not somatotopic coordinates; and (2) displacements that entail a behaviorally relevant change in the stimulus location. These findings indicate that nociceptive-evoked vertex potentials are sensitive to behaviorally relevant changes in the location of a nociceptive stimulus with respect to the body, and that the hand is a particularly behaviorally important site

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

Robust Digital Holography For Ultracold Atom Trapping

We have formulated and experimentally demonstrated an improved algorithm for design of arbitrary two-dimensional holographic traps for ultracold atoms. Our method builds on the best previously available algorithm, MRAF, and improves on it in two ways. First, it allows for creation of holographic atom traps with a well defined background potential. Second, we experimentally show that for creating trapping potentials free of fringing artifacts it is important to go beyond the Fourier approximation in modelling light propagation. To this end, we incorporate full Helmholtz propagation into our calculations.Comment: 7 pages, 4 figure

Developing a Digital Twin at Building and City Levels: A Case Study of West Cambridge Campus

A digital twin (DT) refers to a digital replica of physical assets, processes, and systems. DTs integrate artificial intelligence, machine learning, and data analytics to create living digital simulation models that are able to learn and update from multiple sources as well as represent and predict the current and future conditions of physical counterparts. However, current activities related to DTs are still at an early stage with respect to buildings and other infrastructure assets from an architectural and engineering/construction point of view. Less attention has been paid to the operation and maintenance (O&M) phase, which is the longest time span in the asset life cycle. A systematic and clear architecture verified with practical use cases for constructing a DT would be the foremost step for effective operation and maintenance of buildings and cities. According to current research about multitier architectures, this paper presents a system architecture for DTs that is specifically designed at both the building and city levels. Based on this architecture, a DT demonstrator of the West Cambridge site of the University of Cambridge in the UK was developed that integrates heterogeneous data sources, supports effective data querying and analysis, supports decision-making processes in O&M management, and further bridges the gap between human relationships with buildings/cities. This paper aims at going through the whole process of developing DTs in building and city levels from the technical perspective and sharing lessons learned and challenges involved in developing DTs in real practices. Through developing this DT demonstrator, the results provide a clear roadmap and present particular DT research efforts for asset management practitioners, policymakers, and researchers to promote the implementation and development of DT at the building and city levels

Errors in recall of age at first sex

Aims: To measure the degree and direction of errors in recall of age at first sex. Method: Participants were initially recruited in 1994–1995 (Wave I) with 3 subsequent follow-ups in: 1996 (Wave II); 2001– 2002 (Wave III); and 2007–2008 (Wave IV). Participants' individual errors in recall of their age at first sex at Wave IV were estimated by the paired difference between responses given for age at first sex in Wave I and Wave IV (recalled age at first sex obtained at Wave IV minus the age at first sex obtained at Wave I). Results: The mean of the recall-estimation of age at first sex at Wave IV was found to be slightly increased comparing to the age at first sex at Wave I (less than 1 year). The errors in the recalled age at first sex tended to increase in participants who had their first sex younger or older than the average, and the recalled age at first sex tended to bias towards the mean (i.e. participants who had first sex younger than the average were more likely to recall an age at first sex that was older than the age, and vice versa). Conclusions: In this U.S. population-based sample, the average recall error for age at first sex was small. However, the accuracy of recalled information varied significantly among subgroup populations