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1.
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2.
  • Bang, Peter, 1992- (author)
  • Beyond Categories : A Dimensional Approach to Autism and Sensorimotor Differences
  • 2024
  • Doctoral thesis (other academic/artistic)abstract
    • Autism spectrum conditions (ASC) encompass a range of sensory, motor, and social-communicative differences, reflecting the considerable heterogeneity within the autism spectrum. This diversity underscores the limitations of categorical diagnostic approaches, which often fail to capture the individualized manifestations of autism. Advances in genetics and neuroscience have driven a shift towards dimensional frameworks that emphasize the spectrum nature of autism and the broad autism phenotype (BAP). BAP encapsulates subclinical traits that mirror those of autism in the general population, challenging the conventional boundaries between clinical and non-clinical populations. Furthermore, sensorimotor differences, which are particularly prevalent in individuals with ASC, follow a spectrum-like pattern similar to the BAP and are predictive of developmental outcomes related to social participation, communication, and overall quality of life in people with and without ASC. However, specific descriptions of these relationships are lacking.This dissertation investigated the complex relationships between sensorimotor differences and autistic traits (ATs). Through a series of five interconnected studies, we examined broad sensory processing patterns and specific sensory modalities, namely auditory processing and motor/proprioception, to explore their roles in autistic phenotypes.Study 1 of the dissertation validated a Swedish translation of the Broad Autism Phenotype Questionnaire (BAPQ). By examining parents' BAP traits, the study highlighted significant associations between higher ATs and having a child with ASC. Furthermore, it confirmed the presence of all three AT domains—social interaction (ATSOC), communication (ATCOM), and cognitive rigidity (ATRIG), reinforcing the genetic and phenotypic continuity between clinical and subclinical ATs.Study 2 and Study 3 served as broader investigations into all seven sensory modalities and their associations with ATs. Study 2 explored these modality-specific associations, using Bayesian stochastic search variable selection (SSVS) and dominance analysis. This study highlighted auditory processing difficulties as the most consistent predictor of all three AT domains. Additionally, proprioceptive and tactile processing difficulties were specifically associated with ATCOM and ATSOC, respectively.Study 3 extended this analysis to a developing population, focusing on the relationship between sensorimotor processing, ATs, and anxiety in children aged 6-11 years. Identical to Study 2, we found tactile symptoms as a predictor of ATSOC, proprioceptive symptoms for ATCOM, and auditory symptoms for ATRIG. In addition, olfactory symptoms were selected as a predictor of ATCOM, and motor coordination was a consistent predictor of all AT domains. Using SSVS, this study also identified that auditory and olfactory processing difficulties were strong predictors of anxiety symptoms.Building on the previous studies, Study 4 narrowed the focus to auditory processing differences, investigating specific auditory problems and their associations with the AT domains. All AT domains significantly predicted affective reactions to sounds, while difficulties with speech perception, spatial perception, and auditory stream segregation were most strongly predicted by ATCOM.Study 5 focused on the previously found links between motor coordination and proprioceptive processing and ATCOM. Using causal mediation analysis within a counterfactual framework, this study found that cerebellar error correction deficits, measured through a finger tapping task, significantly impacted ATCOM through motor skills in childhood.Together, this dissertation provides a comprehensive overview of the sensory processing dimensions related to the core AT domains. Specifically, the studies underscored the clinical significance of monitoring auditory and olfactory complaints in children, as these were predictive of anxiety, and emphasized that early motor deficits impact social communication development. The findings advocate for the inclusion of detailed sensory and motor assessments in neurodevelopmental evaluations to identify children at risk for poor mental health outcomes. Future research should continue to explore the mechanisms underlying sensory processing differences. Particular focus should be placed on auditory and motor/proprioceptive functions and their contributions to ATs and clinical outcomes, such as anxiety. Emphasis should also be given to longitudinal studies that track these relationships over time.
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  • Koppel, Lina, 1988- (author)
  • Pain, Touch, and Decision Making : Behavioral and Brain Responses to Affective Somatosensory Stimulation
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • Stimulation of sensory nerves can give rise to powerful affective experiences. Noxious stimuli can give rise to pain, an unpleasant experience which, in turn, causes suffering and constitutes a major societal burden. Touch, on the other hand, can feel pleasant and plays an important role in social relationships and well-being. Slow, gentle stroking of the skin in particular has been shown to activate C-tactile (CT) afferents, which are thought to signal affective and socially relevant aspects of touch. However, little is known about how pain and affective touch influence everyday decision making.In Paper I, we investigated the effect of acute physical pain on risk taking and intertemporal choice. Participants (n = 109) performed a series of economic decision-making tasks, once while experiencing acute thermal pain and once in a no-pain control condition. Results indicated that pain increased risk taking for monetary gains but not for equivalent losses, and increased impatience.In Paper II, we investigated the effect of affective touch on betrayal aversion, altruism, and risk taking. Participants (n = 120) performed a series of economic decision-making tasks, once while being stroked on the forearm at CT-optimal speed using a soft painter’s brush and once in a no-touch control condition. Results indicated no effect of affective touch on any of the outcome measures.In Paper III, we investigated how the ability to affect an upcoming painful event via voluntary action influences cortical processing of ongoing somatosensory stimulation. fMRI data was collected from 30 participants while they performed a task that involved pressing a response button to reduce the duration of upcoming thermal stimuli. Whole-brain analyses revealed no significant task-related effects in brain regions typically involved in pain, except activation in a cluster in anterior cingulate cortex (ACC) was greater when upcoming stimulation was painful than when it was nonpainful. However, region-of-interest analyses in anterior insula (AI) and midcingulate cortex (MCC) indicated that the noxious nature of the upcoming stimulation, as well as the ability to affect it, influenced processing of ongoing stimulation in both of these regions. Activation in MCC, but not AI, also correlated with response times.Taken together, these studies contribute to the broader understanding of everyday decision making, and of how affective experiences such as pain and touch shape everyday decisions and behaviors.
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5.
  • Liljencrantz, Jaquette, et al. (author)
  • Altered C-tactile processing in human dynamic tactile allodynia
  • 2013
  • In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 154:2, s. 227-234
  • Journal article (peer-reviewed)abstract
    • Human unmyelinated (C) tactile afferents signal the pleasantness of gentle skin stroking on hairy (nonglabrous) skin. After neuronal injury, that same type of touch can elicit unpleasant sensations: tactile allodynia. The prevailing pathophysiological explanation is a spinal cord sensitization, triggered by nerve injury, which enables Aβ afferents to access pain pathways. However, a recent mouse knockout study demonstrates that C-tactile afferents are necessary for allodynia to develop, suggesting a role for not only Aβ but also C-tactile afferent signaling. To examine the contribution of C-tactile afferents to the allodynic condition in humans, we applied the heat/capsaicin model of tactile allodynia in 43 healthy subjects and in 2 sensory neuronopathy patients lacking Aβ afferents. Healthy subjects reported tactile-evoked pain, whereas the patients did not. Instead, patients reported their C-touch percept (faint sensation of pleasant touch) to be significantly weaker in the allodynic zone compared to untreated skin. Functional magnetic resonance imaging in 18 healthy subjects and in 1 scanned patient indicated that stroking in the allodynic and control zones evoked different responses in the primary cortical receiving area for thin fiber signaling, the posterior insular cortex. In addition, reduced activation in the medial prefrontal cortices, key areas for C-tactile hedonic processing, was identified. These findings suggest that dynamic tactile allodynia is associated with reduced C-tactile mediated hedonic touch processing. Nevertheless, because the patients did not develop allodynic pain, this seems dependent on Aβ signaling, at least under these experimental conditions.
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  • Lloyd, D. M., et al. (author)
  • Pleasant touch moderates the subjective but not objective aspects of body perception
  • 2013
  • In: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 7:207
  • Journal article (peer-reviewed)abstract
    • Un-myelinated C tactile afferents (CT afferents) are a key finding in affective touch. These fibers, which activate in response to a caress-like touch to hairy skin (CT afferents are not found in palm skin), may have more in common with interoceptive systems encoding body ownership, than afferent systems processing other tactile stimuli. We tested whether subjective embodiment of a rubber hand (measured through questionnaire items) was increased when tactile stimulation was applied to the back of the hand at a rate optimal for CT afferents (3 cm/s) vs. stimulation of glabrous skin (on the palm of the hand) or at a non-optimal rate (30 cm/s), which should not activate these fibers. We also collected ratings of tactile pleasantness and a measure of perceived limb position, proprioceptive drift, which is mediated by different mechanisms of multisensory integration than those responsible for feelings of ownership. The results of a multiple regression analysis revealed that proprioceptive drift was a significant predictor of subjective strength of the illusion when tactile stimuli were applied to the back of the hand, regardless of stroking speed. This relationship was modified by pleasantness, with higher ratings when stimulation was applied to the back of the hand at the slower vs. faster stroking speed. Pleasantness was also a unique predictor of illusion strength when fast stroking was applied to the palm of the hand. However, there were no conditions under which pleasantness was a significant predictor of drift. Since the illusion was demonstrated at a non-optimal stroking speed an integrative role for CT afferents within the illusion cannot be fully supported. Pleasant touch, however, does moderate the subjective aspects of the rubber hand illusion, which under certain tactile conditions may interact with proprioceptive information about the body or have a unique influence on subjective body perception.
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8.
  • Löken, Line Sofie, 1977, et al. (author)
  • Coding of pleasant touch by unmyelinated afferents in humans.
  • 2009
  • In: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 12:5, s. 547-8
  • Journal article (peer-reviewed)abstract
    • Pleasant touch sensations may begin with neural coding in the periphery by specific afferents. We found that during soft brush stroking, low-threshold unmyelinated mechanoreceptors (C-tactile), but not myelinated afferents, responded most vigorously at intermediate brushing velocities (1-10 cm s(-1)), which were perceived by subjects as being the most pleasant. Our results indicate that C-tactile afferents constitute a privileged peripheral pathway for pleasant tactile stimulation that is likely to signal affiliative social body contact.
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9.
  • Middleton, Steven J, et al. (author)
  • Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.
  • 2022
  • In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 145:10, s. 3637-3653
  • Journal article (peer-reviewed)abstract
    • Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.
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10.
  • Morrison, India, 1972, et al. (author)
  • Facets and mechanisms of adaptive pain behavior: predictive regulation and action
  • 2013
  • In: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 7
  • Research review (peer-reviewed)abstract
    • Neural mechanisms underlying nociception and pain perception are considered to serve the ultimate goal of limiting tissue damage. However, since pain usually occurs in complex environments and situations that call for elaborate control over behavior, simple avoidance is insufficient to explain a range of mammalian pain responses, especially in the presence of competing goals. In this integrative review we propose a Predictive Regulation and Action (PRA) model of acute pain processing. It emphasizes evidence that the nervous system is organized to anticipate potential pain and to adjust behavior before the risk of tissue damage becomes critical. Regulatory processes occur on many levels, and can be dynamically influenced by local interactions or by modulation from other brain areas in the network. The PRA model centers on neural substrates supporting the predictive nature of pain processing, as well as on finely-calibrated yet versatile regulatory processes that ultimately affect behavior. We outline several operational categories of pain behavior, from spinally-mediated reflexes to adaptive voluntary action, situated at various neural levels. An implication is that neural processes that track potential tissue damage in terms of behavioral consequences are an integral part of pain perception.
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11.
  • Morrison, India, 1972, et al. (author)
  • "Feeling" Others' Painful Actions: The Sensorimotor Integration of Pain and Action Information
  • 2013
  • In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 34:8, s. 1982-1998
  • Journal article (peer-reviewed)abstract
    • Sensorimotor regions of the brain have been implicated in simulation processes such as action understanding and empathy, but their functional role in these processes remains unspecified. We used functional magnetic resonance imaging (fMRI) to demonstrate that postcentral sensorimotor cortex integrates action and object information to derive the sensory outcomes of observed hand-object interactions. When subjects viewed others' hands grasping or withdrawing from objects that were either painful or nonpainful, distinct sensorimotor subregions emerged as showing preferential responses to different aspects of the stimuli: object information (noxious vs. innocuous), action information (grasps vs. withdrawals), and painful action outcomes (painful grasps vs. all other conditions). Activation in the latter region correlated with subjects' ratings of how painful each object would be to touch and their previous experience with the object. Viewing others' painful grasps also biased behavioral responses to actual tactile stimulation, a novel effect not seen for auditory control stimuli. Somatosensory cortices, including primary somatosensory areas 1/3b and 2 and parietal area PF, may therefore subserve somatomotor simulation processes by integrating action and object information to anticipate the sensory consequences of observed hand-object interactions.
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12.
  • Morrison, India, 1972, et al. (author)
  • Reduced C-afferent fibre density affects perceived pleasantness and empathy for touch.
  • 2011
  • In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 134:Pt 4, s. 1116-26
  • Journal article (peer-reviewed)abstract
    • We examined patients with a heritable disorder associated with a mutation affecting the nerve growth factor beta gene. Their condition has been classified as hereditary sensory and autonomic neuropathy type V. Carriers of the mutation show a reduction in density of thin and unmyelinated nerve fibres, including C afferents. A distinct type of unmyelinated, low-threshold mechanoreceptive C fibre, the C-tactile afferent, is present in hairy but not glabrous skin of humans and other mammals. They have been implicated in the coding of pleasant, hedonic touch of the kind that occurs in affiliative social interactions. We addressed the relationship between C fibre function and pleasant touch perception in 10 individuals from a unique population of mutation carriers in Sweden. We also investigated the effect of reduced C-fibre density on patients' evaluation of observed interpersonal touch (empathy). Results showed that patients perceived gentle, slow arm stroking, optimal for eliciting C-tactile afferent responses (1-10 cm/s), as less pleasant than did matched controls and also differed in their rating patterns across stimulation velocities. Further, patients' blood-oxygen-level-dependent responses in posterior insular cortex--a target for C afferents--were not modulated by stimulation optimal for activating C-tactile afferents. Hence, perception of the hedonic aspect of dynamic touch likely depends on C-tactile afferent density. Closely similar patterns between individuals' ratings of felt and seen touch suggest that appraisal of others' touch is anchored in one's own perceptual experience, whether typical or atypical.
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  • Morrison, India, 1972, et al. (author)
  • The skin as a social organ.
  • 2010
  • In: Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale. - : Springer Science and Business Media LLC. - 1432-1106. ; 204:3, s. 305-14
  • Research review (peer-reviewed)abstract
    • In general, social neuroscience research tends to focus on visual and auditory channels as routes for social information. However, because the skin is the site of events and processes crucial to the way we think about, feel about, and interact with one another, touch can mediate social perceptions in various ways. This review situates cutaneous perception within a social neuroscience framework by discussing evidence for considering touch (and to some extent pain) as a channel for social information. Social information conveys features of individuals or their interactions that have potential bearing on future interactions, and attendant mental and emotional states. Here, we discuss evidence for an affective dimension of touch and explore its wider implications for the exchange of social information. We consider three important roles for this affective dimension of the cutaneous senses in the transmission and processing of social information: first, through affiliative behavior and communication; second, via affective processing in skin-brain pathways; and third, as a basis for intersubjective representation.
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14.
  • Morrison, India, 1972, et al. (author)
  • Vicarious responses to social touch in posterior insular cortex are tuned to pleasant caressing speeds.
  • 2011
  • In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - Washington, DC, United States : Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 31:26, s. 9554-62
  • Journal article (peer-reviewed)abstract
    • Affective touch carries strong significance for social mammals, including humans. Gentle, dynamic touch of a kind that occurs during social interactions is preferentially encoded by a distinct neural pathway involving tactile C (CT) afferents, a type of unmyelinated afferent nerve found exclusively in hairy skin. CT afferents increase firing when the skin is stroked at a pleasant, caress-like speed of ∼3 cm/s, and their discharge frequency correlates with the subjective hedonic experience of the caress. In humans, the posterior insula is a cortical target for CT afferents. Since the potential social relevance of affective touch extends to the touch interactions of others, we postulated that information from CT afferents in posterior insular cortex provides a basis for encoding observed caresses.
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15.
  • Olausson, Håkan, 1965, et al. (author)
  • The neurophysiology of unmyelinated tactile afferents.
  • 2010
  • In: Neuroscience and biobehavioral reviews. - : Elsevier BV. - 1873-7528 .- 0149-7634. ; 34:2, s. 185-91
  • Research review (peer-reviewed)abstract
    • CT (C tactile) afferents are a distinct type of unmyelinated, low-threshold mechanoreceptive units existing in the hairy but not glabrous skin of humans and other mammals. Evidence from patients lacking myelinated tactile afferents indicates that signaling in these fibers activate the insular cortex. Since this system is poor in encoding discriminative aspects of touch, but well-suited to encoding slow, gentle touch, CT fibers in hairy skin may be part of a system for processing pleasant and socially relevant aspects of touch. CT fiber activation may also have a role in pain inhibition. This review outlines the growing evidence for unique properties and pathways of CT afferents.
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16.
  • Perini, Irene, et al. (author)
  • Where Pain Meets Action in the Human Brain
  • 2013
  • In: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 33:40, s. 15930-15939
  • Journal article (peer-reviewed)abstract
    • Pain's complex influence on behavior implies that it involves an action component, although little is known about how the human brain adaptively translates painful sensations into actions. The consistent activation of premotor and motor-related regions during pain, including the midcingulate cortex (MCC), raises the question of whether these areas contribute to an action component. In this fMRI experiment, we controlled for voluntary action-related processing during pain by introducing a motor task during painful or nonpainful stimulation. The MCC (particularly the caudal cingulate motor zone [CCZ]), motor cortex, thalamus, and cerebellum responded during action regardless of pain. Crucially, however, these regions did not respond to pain unless an action was performed. Reaction times were fastest during painful stimulation and correlated with CCZ activation. These findings are consistent with the results of an activation likelihood estimate meta-analysis in which activation across experiments involving pain, action execution, or action preparation (with a total of 4929 subjects) converged in a similar network. These findings suggest that specific motor-related areas, including the CCZ, play a vital role in the control and execution of context-sensitive behavioral responses to pain. In contrast, bilateral insular cortex responded to pain stimulation regardless of action.
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