An intra-neural microstimulation system for ultra-high field magnetic resonance imaging and magnetoencephalography.

BACKGROUND: Intra-neural microstimulation (INMS) is a technique that allows the precise delivery of low-current electrical pulses into human peripheral nerves. Single unit INMS can be used to stimulate individual afferent nerve fibres during microneurography. Combining this with neuroimaging allows the unique monitoring of central nervous system activation in response to unitary, controlled tactile input, with functional magnetic resonance imaging (fMRI) providing exquisite spatial localisation of brain activity and magnetoencephalography (MEG) high temporal resolution. NEW METHOD: INMS systems suitable for use within electrophysiology laboratories have been available for many years. We describe an INMS system specifically designed to provide compatibility with both ultra-high field (7T) fMRI and MEG. Numerous technical and safety issues are addressed. The system is fully analogue, allowing for arbitrary frequency and amplitude INMS stimulation. RESULTS: Unitary recordings obtained within both the MRI and MEG screened-room environments are comparable with those obtained in 'clean' electrophysiology recording environments. Single unit INMS (current <7μA, 200μs pulses) of individual mechanoreceptive afferents produces appropriate and robust responses during fMRI and MEG. COMPARISON WITH EXISTING METHOD(S): This custom-built MRI- and MEG-compatible stimulator overcomes issues with existing INMS approaches; it allows well-controlled switching between recording and stimulus mode, prevents electrical shocks because of long cable lengths, permits unlimited patterns of stimulation, and provides a system with improved work-flow and participant comfort. CONCLUSIONS: We demonstrate that the requirements for an INMS-integrated system, which can be used with both fMRI and MEG imaging systems, have been fully met

A nociresponsive specific area of human somatosensory cortex within BA3a: BA3c?

© 2020 It is well recognized that in primates, including humans, noxious body stimulation evokes a neural response in the posterior bank of the central sulcus, in Brodmann cytoarchitectonic subdivisions 3b and 1 of the primary somatosensory cortex. This response is associated with the 1st/sharp pain and contributes to sensory discriminative aspects of pain perception and spatial localization of the noxious stimulus. However, neurophysiological studies in New World monkeys predict that in humans noxious stimulation also evokes a separate neural response—mediated by C-afferent drive and associated with the 2nd/burning pain—in the depth of the central sulcus in Brodmann area 3a (BA3a) at the transition between the somatosensory and motor cortices. To evoke such a response, it is necessary to use multi-second duration noxious stimulation, rather than brief laser pulses. Given the limited human pain-imaging literature on cortical responses induced by C-nociceptive input specifically within BA3a, here we used high spatial resolution 7T fMRI to study the response to thermonoxious skin stimulation. We observed the predicted response of BA3a in the depth of the central sulcus in five human volunteers. Review of the available evidence suggests that the nociresponsive region in the depth of the central sulcus is a structurally and functionally distinct cortical area that should not be confused with proprioceptive BA3a. It is most likely engaged in interoception and control of the autonomic nervous system, and contributes to the sympathetic response to noxious stimulation, arguably the most intolerable aspect of pain experience. Ablation of this region has been shown to reduce pain sensibility and might offer an effective means of ameliorating some pathological pain conditions

Regionally specific human GABA concentration correlates with tactile discrimination thresholds

The neural mechanisms underlying variability in human sensory perception remain incompletely understood. In particular, few studies have attempted to investigate the relationship between in vivo measurements of neurochemistry and individuals' behavioral performance. Our previous work found a relationship between GABA concentration in the visual cortex and orientation discrimination thresholds (Edden et al., 2009). In the present study, we used magnetic resonance spectroscopy of GABA and psychophysical testing of vibrotactile frequency thresholds to investigate whether individual differences in tactile frequency discrimination performance are correlated with GABA concentration in sensorimotor cortex. Behaviorally, individuals showed a wide range of discrimination thresholds ranging from 3 to 7.6 Hz around the 25 Hz standard. These frequency discrimination thresholds were significantly correlated with GABA concentration (r = −0.58; p < 0.05) in individuals' sensorimotor cortex, but not with GABA concentration in an occipital control region (r = −0.04). These results demonstrate a link between GABA concentration and frequency discrimination in vivo, and support the hypothesis that GABAergic mechanisms have an important role to play in sensory discrimination

Temporomandibular Disorder Modifies Cortical Response to Tactile Stimulation

Individuals with temporomandibular disorder (TMD) suffer from persistent facial pain and exhibit abnormal sensitivity to tactile stimulation. To better understand the pathophysiological mechanisms underlying TMD, we investigated cortical correlates of this abnormal sensitivity to touch. Using functional magnetic resonance imaging (fMRI), we recorded cortical responses evoked by low frequency vibration of the index finger in subjects with TMD and in healthy controls (HC). Distinct subregions of contralateral SI, SII, and insular cortex responded maximally for each group. Although the stimulus was inaudible, primary auditory cortex was activated in TMDs. TMDs also showed greater activation bilaterally in anterior cingulate cortex and contralaterally in the amygdala. Differences between TMDs and HCs in responses evoked by innocuous vibrotactile stimulation within SI, SII, and the insula paralleled previously reported differences in responses evoked by noxious and innocuous stimulation, respectively, in healthy individuals. This unexpected result may reflect a disruption of the normal balance between central resources dedicated to processing innocuous and noxious input, manifesting itself as increased readiness of the pain matrix for activation by even innocuous input. Activation of the amygdala in our TMD group could reflect the establishment of aversive associations with tactile stimulation due to the persistence of pain

Tactile Perception in Adults with Autism: a Multidimensional Psychophysical Study

Although sensory problems, including unusual tactile sensitivity, are heavily associated with autism, there is a dearth of rigorous psychophysical research. We compared tactile sensation in adults with autism to controls on the palm and forearm, the latter innervated by low-threshold unmyelinated afferents subserving a social/affiliative submodality of somatosensation. At both sites, the groups displayed similar thresholds for detecting light touch and innocuous sensations of warmth and cool, and provided similar hedonic ratings of the pleasantness of textures. In contrast, increased sensitivity to vibration was seen in the autism group on the forearm, along with increased sensitivity to thermal pain at both sites. These findings suggest normal perception along with certain areas of enhanced perception in autism, consistent with previous studies

Pain Processing in Psychiatric Conditions: A systematic review

©American Psychological Association, 2019. This paper is not the copy of record and may not exactly replicate the authoritative document published in the APA journal. Please do not copy or cite without author's permission. The final article is available, upon publication, at: https://doi.org/10.1177/1089268019842771Objective: Pain is a universal, multidimensional experience with sensory emotional, cognitive and social components, which is fundamental to our environmental learning when functioning typically. Understanding pain processing in psychiatric conditions could provide unique insight into the underlying pathophysiology or psychiatric disease, especially given the psychobiological overlap with pain processing pathways. Studying pain in psychiatric conditions is likely to provide important insights, yet, there is a limited understanding beyond the work outside depression and anxiety. This is a missed opportunity to describe psychiatric conditions in terms of neurobiological alterations. In order to examine the research into the pain experiences of these groups and the extent to which a-typicality is present, a systematic review was conducted. Methods: An electronic search strategy was developed and conducted in several databases. Results: The current systematic review included 46 studies covering five DSM-5 disorders: autism, attention deficit hyperactivity disorder, schizophrenia, personality disorder and eating disorders, confirming tentative evidence of altered pain and touch processing. Specifically, hyposensitivity is reported in schizophrenia, personality disorder and eating disorder, hypersensitivity in ADHD and mixed results for autism. Conclusions: Review of the research highlights a degree of methodological inconsistency in the utilisation of comprehensive protocols; the lack of which fails to allow us to understand whether a-typicality is systemic or modality-specific

Acute tryptophan depletion alters affective touch perception

RationaleAffiliative tactile interactions help regulate physiological arousal and confer resilience to acute and chronic stress. C-tactile afferents (CTs) are a population of unmyelinated, low threshold mechanosensitive cutaneous nerve fibres which respond optimally to a low force stimulus, moving at between 1 and 10 cm/s. As CT firing frequencies correlate positively with subjective ratings of touch pleasantness, they are hypothesised to form the first stage of encoding affiliative tactile interactions. Serotonin is a key modulator of social responses with known effects on bonding.ObjectivesThe aim of the present study was to determine the effect of acutely lowering central serotonin levels on perceptions of CT-targeted affective touch.MethodsIn a double blind, placebo-controlled design, the effect of acute tryptophan depletion (ATD) on 25 female participants' ratings of directly and vicariously experienced touch was investigated. Psychophysical techniques were used to deliver dynamic tactile stimuli; some velocities were targeted to optimally activate CTs (1-10 cm/s), whereas other, faster and slower strokes fell outside the CT optimal range. Discriminative tactile function, cold pain threshold and tolerance were also measured.ResultsATD significantly increased pleasantness ratings of both directly and vicariously experienced affective touch, increasing discrimination of the specific hedonic value of CT targeted velocities. While ATD had no effect on either tactile or cold pain thresholds, there was a trend for reduced tolerance to cold pain.ConclusionsThese findings are consistent with previous reports that depletion of central serotonin levels modulates neural and behavioural responsiveness to appetitive sensory signals

C-tactile afferent stimulating touch carries a positive affective value

The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major—smile muscle, positive affect & corrugator supercilii—frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli. These results offer the first empirical evidence in humans that tactile stimulation that optimally activates CTs carries a positive affective valence that can be measured implicitly

Touch localisation after nerve repair in the hand: Insights from a new measurement tool.

Errors of touch localisation after injury to the nerves of the hand are common, and their measurement is of considered importance for evaluating functional recovery. Available empirical accounts have significant methodological limitations, however, and a quantitatively rigorous and detailed description of touch localisation in nerve injury is lacking. Here we develop a new method of measuring touch localisation and evaluate its value for use in nerve injury. Eighteen patients with transection injuries to the median/ulnar nerves and thirty-three healthy controls were examined. The hand was blocked from the participant's view and points were marked on the volar surface using a UV pen. These points served as targets for touch stimulation. Two photographs were taken, one with and one without UV lighting, rendering targets seen and unseen, respectively. The experimenter used the photograph with visible targets to register their locations, and participants reported the felt position of each stimulation on the photograph with unseen targets. The error of localisation and its directional components were measured, separate from misreferrals-errors made across digits, or from a digit to the palm. Nerve injury was found to significantly increase the error of localisation. These effects were specific to the territory of the repaired nerve, and showed considerable variability at the individual level, with some patients showing no evidence of impairment. A few patients also made abnormally high numbers of misreferrals, and the pattern of misreferrals in patients differed from that observed in healthy controls