Augmented pain inhibition and higher integration of pain modulatory brain networks in women with self-injury behavior.

Individuals who engage in nonsuicidal self-injury (NSSI) have demonstrated insensitivity to pain compared with individuals without NSSI. Yet, the neural mechanisms behind this difference are unknown. The objective of the present study was to determine which aspects of the pain regulatory system that account for this decreased sensitivity to pain. In a case-control design, 81 women, aged 18-35 (mean [SD] age, 23.4 [3.9]), were included (41 with NSSI and 40 healthy controls). A quantitative sensory testing protocol, including heat pain thresholds, heat pain tolerance, pressure pain thresholds, conditioned pain modulation (assessing central down-regulation of pain), and temporal summation (assessing facilitation of pain signals) was used. Pain-evoked brain responses were assessed by means of fMRI scanning during thermal pain. NSSI participants showed a more effective central down-regulation of pain, compared to controls, assessed with conditioned pain modulation. The neural responses to painful stimulation revealed a stronger relation between nociceptive and pain modulatory brain regions in NSSI compared to controls. In line with previous studies, pressure and heat pain thresholds were higher in participants with NSSI, however, there were no correlations between pain outcomes and NSSI clinical characteristics. The augmented pain inhibition and higher involvement of pain modulatory brain networks in NSSI may represent a pain insensitive endophenotype associated with a greater risk for developing self-injurious behavior.

Brain network segregation and integration during painful thermal stimulation.

The present study aimed to determine changes in brain network integration/segregation during thermal pain using methods optimized for network connectivity events with high temporal resolution. Participants (n = 33) actively judged whether thermal stimuli applied to the volar forearm were painful or not and then rated the warmth/pain intensity after each trial. We show that the temporal evolution of integration/segregation within trials correlates with the subjective ratings of pain. Specifically, the brain shifts from a segregated state to an integrated state when processing painful stimuli. The association with subjective pain ratings occurred at different time points for all networks. However, the degree of association between ratings and integration/segregation vanished for several brain networks when time-varying functional connectivity was measured at lower temporal resolution. Moreover, the increased integration associated with pain is explained to some degree by relative increases in between-network connectivity. Our results highlight the importance of investigating the relationship between pain and brain network connectivity at a single time point scale, since commonly used temporal aggregations of connectivity data may result in that fine-scale changes in network connectivity may go unnoticed. The interplay between integration/segregation reflects shifting demands of information processing between brain networks and this adaptation occurs both for cognitive tasks and nociceptive processing.

Genetic Influence on Nociceptive Processing in the Human Brain-A Twin Study.

Nociceptive processing in the human brain is complex and involves several brain structures and varies across individuals. Determining the structures that contribute to interindividual differences in nociceptive processing is likely to improve our understanding of why some individuals feel more pain than others. Here, we found specific parts of the cerebral response to nociception that are under genetic influence by employing a classic twin-design. We found genetic influences on nociceptive processing in the midcingulate cortex and bilateral posterior insula. In addition to brain activations, we found genetic contributions to large-scale functional connectivity (FC) during nociceptive processing. We conclude that additive genetics influence specific brain regions involved in nociceptive processing. The genetic influence on FC during nociceptive processing is not limited to core nociceptive brain regions, such as the dorsal posterior insula and somatosensory areas, but also involves cognitive and affective brain circuitry. These findings improve our understanding of human pain perception and increases chances to find new treatments for clinical pain.

A neuroimaging study of interpersonal distance in identical and fraternal twins.

Keeping appropriate interpersonal distance is an evolutionary conserved behavior that can be adapted based on learning. Detailed knowledge on how interpersonal space is represented in the brain and whether such representation is genetically influenced is lacking. We measured brain function using functional magnetic resonance imaging in 294 twins (71 monozygotic, 76 dizygotic pairs) performing a distance task where neural responses to human figures were compared to cylindrical blocks. Proximal viewing distance of human figures was compared to cylinders facilitated responses in the occipital face area (OFA) and the superficial part of the amygdala, which is consistent with these areas playing a role in monitoring interpersonal distance. Using the classic twin method, we observed a genetic influence on interpersonal distance related activation in the OFA, but not in the amygdala. Results suggest that genetic factors may influence interpersonal distance monitoring via the OFA whereas the amygdala may play a role in experience-dependent adjustments of interpersonal distance.

Distribution and statistical analysis of major and trace elements in the bee pollen from the territory of Republic of Kosovo.

The objective of this study was the determination of major and trace elements in the bee pollen samples from the whole territory of Republic of Kosovo. Pollen, as a natural plant product, is exposed to different contaminations absorbed by plants from the soil through the root system or with water intake, as well as to pollutants of different origins, including anthropogenic ones, deposited directly on pollen. In total 67 pollen samples were collected in 2019. The samples were analyzed for 27 macro and microelements by using ICP-AES and ICP-MS. The mean content of major elements in bee pollen was 4065, 3455, 1375 and 549 mg/kg for K, P, Ca and Mg, respectively. The range of the contents for some potentially toxic elements was 11.9-139.1, 1.9-16, 0.11-6.25, 0.01-0.329 and 0.001-0.38 mg/kg for Zn, Cu, Pb, Cd and As, respectively. Three groups of elements of mixed origin were identified through factor analysis: the first and the third Factors, are mostly of geogenic origin (Ag, Li, Al, Fe, Ca, Sr, K, Mg and P and Co, Ni, Cr, Cu and Mn) and the second Factor association is related to anthropogenic processes (Sb, As, Pb, Tl, Sn and Cd).

Time-varying nodal measures with temporal community structure: A cautionary note to avoid misinterpretation.

In network neuroscience, temporal network models have gained popularity. In these models, network properties have been related to cognition and behavior. Here, we demonstrate that calculating nodal properties that are dependent on temporal community structure (such as the participation coefficient [PC]) in time-varying contexts can potentially lead to misleading results. Specifically, with regards to the participation coefficient, increases in integration can be inferred when the opposite is occurring. Further, we present a temporal extension to the PC measure (temporal PC) that circumnavigates this problem by jointly considering all community partitions assigned to a node through time. The proposed method allows us to track a node's integration through time while adjusting for the possible changes in the community structure of the overall network.

Social, proximal and conditioned threat.

Responding to threats in the environment is crucial for survival. Certain types of threat produce defensive responses without necessitating previous experience and are considered innate, whereas other threats are learned by experiencing aversive consequences. Two important innate threats are whether an encountered stimulus is a member of the same species (social threat) and whether a stimulus suddenly appears proximal to the body (proximal threat). These threats are manifested early in human development and robustly elicit defensive responses. Learned threat, on the other hand, enables adaptation to threats in the environment throughout the life span. A well-studied form of learned threat is fear conditioning, during which a neutral stimulus acquires the ability to eliciting defensive responses through pairings with an aversive stimulus. If innate threats can facilitate fear conditioning, and whether different types of innate threats can enhance each other, is largely unknown. We developed an immersive virtual reality paradigm to test how innate social and proximal threats are related to each other and how they influence conditioned fear. Skin conductance responses were used to index the autonomic component of the defensive response. We found that social threat modulates proximal threat, but that neither proximal nor social threat modulates conditioned fear. Our results suggest that distinct processes regulate autonomic activity in response to proximal and social threat on the one hand, and conditioned fear on the other.

Recurrent processing enhances visual awareness but is not necessary for fast categorization of natural scenes.

Humans are rapid in categorizing natural scenes. Electrophysiological recordings reveal that scenes containing animals can be categorized within 150 msec, which has been interpreted to indicate that feedforward flow of information from V1 to higher visual areas is sufficient for visual categorization. However, recent studies suggest that recurrent interactions between higher and lower levels in the visual hierarchy may also be involved in categorization. To clarify the role of recurrent processing in scene categorization, we recorded EEG and manipulated recurrent processing with object substitution masking while the participants performed a go/no-go animal/nonanimal categorization task. The quality of visual awareness was measured with a perceptual awareness scale after each trial. Masking reduced the clarity of perceptual awareness, slowed down categorization speed for scenes that were not clearly perceived, and reduced the electrophysiological difference elicited by animal and nonanimal scenes after 150 msec. The results imply that recurrent processes enhance the resolution of conscious representations and thus support categorization of stimuli that are difficult to categorize on the basis of the coarse feedforward representations alone.

Back morphology and walking patterns mean 13.8 years after surgery for lumbar disk herniation in adolescents.

Introduction: In many pain conditions, there is lingering pain despite healed tissue damage. Our previous study shows that individuals who underwent surgery for lumbar disk herniation (LDH) during adolescence have worse health, more pain, and increased disk degeneration mean 13 years after surgery compared with controls. It is unclear if walking patterns segregate surgically treated LDH adolescents and controls at mean 13-year follow-up. Objectives: Here, we analyzed the relationship between gait, back morphology and other health outcomes in a cohort of individuals treated surgically because of lumbar disk herniation compared with controls. Methods: We analyzed gait during a walking paradigm, back morphology at the site of surgery, and standardized health outcomes, among individuals who received surgery for LDH as adolescents, "cases" (n = 23), compared with "controls" (n = 23). Results: There were gait differences in head (P = 0.021) and trunk angle (P = 0.021) between cases and controls in a direction where cases exhibited a posture associated with sickness. The gait variance was explained by subjective pain and exercise habits rather than objective disk degeneration. Conclusion: Over a decade after surgery for LDH during adolescence, health among cases is worse compared with controls. The head and trunk angles differ between cases and controls, indicating that the residual pain lingers and may cause changes in movement patterns long after a painful episode in early life. Gait may be a useful target for understanding maintenance of pain and disability among individuals treated surgically for LDH during adolescence.

Whole brain correlates of individual differences in skin conductance responses during discriminative fear conditioning to social cues.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

Investigation of Concentration and Distribution of Elements in Three Environmental Compartments in the Region of Mitrovica, Kosovo: Soil, Honey and Bee Pollen.

The abundances of selected elements in different environmental compartments, namely soil, honey, and bee pollen, was determined in this study. For that purpose, sixteen soil and honey samples, and nine pollen samples were taken in the region of Mitrovica, Kosovo. The concentration of elements was measured by ICP-AES and ICP-MS. Pollution level concentrations of Pb, Zn, As, and Cd were observed in soil. The level of soil pollution was estimated by calculating pollution indices. Pb was also observed at high concentrations in honey, as was Cd and Pb in pollen. Pearson's correlation coefficients revealed mostly weak and moderate correlations of the concentrations of the eight selected elements among the soil, honey, and pollen samples. Several groups of elements with geogenic and anthropogenic origin were identified by hierarchical cluster analysis. The concentrations of selected heavy metals for soil and honey were compared to those in neighboring countries, and those for pollen with samples from Turkey, Serbia, and Jordan.

MRI Characteristics at a Mean of Thirteen Years After Lumbar Disc Herniation Surgery in Adolescents: A Case-Control Study.

BACKGROUND: The purpose of this study was to describe the prevalence of lumbar spine degeneration in adult individuals who had undergone lumbar disc herniation surgery during adolescence. METHODS: Twenty-three individuals who had been surgically treated for lumbar disc herniation as adolescents (≤18 years of age) participated in this study at a mean of 13.8 years (range, 8.6 to 20.4 years) after the surgery; they were matched for age and sex to 23 controls without any known previous disc herniation or spinal surgery. Magnetic resonance imaging included sagittal T1-weighted, T2-weighted, and short tau inversion recovery (STIR) sequences of the lumbar spine. Disc degeneration was assessed with the Pfirrmann grading system. Changes in the vertebral end plate and body were assessed according to Modic changes and total end plate (TEP) score. Patient-reported outcome measures included the Oswestry Disability Index, a visual analog scale (VAS) for leg and back pain, the EuroQol-5 Dimension-3 Level (EQ-5D-3L) questionnaire, and the mental and physical component summary scores of the Short Form (SF)-36. Statistical analyses were made with the chi-square test and the Welch-Satterthwaite t test. RESULTS: Compared with the controls, the cases that underwent surgery had a higher prevalence of the following: severe degeneration according to the Pfirrmann grading system at the L4-L5 (p = 0.007) and L5-S1 (p = 0.002) levels, Modic changes at the L4-L5 (p = 0.022) and L5-S1 (p = 0.026) levels, and a TEP score of ≥6 at the L5-S1 level (p = 0.001). The surgical cases had a significantly worse patient-reported outcome compared with the controls (all p ≤ 0.010), with the exception of the VAS for leg pain (p = 0.093) and the mental component summary score of the SF-36 (p = 0.844). CONCLUSIONS: Lumbar disc herniation surgery that was performed during adolescence was associated with more frequent lumbar spine degeneration and lower health-related quality of life in adulthood when compared with the control group. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The effect of immersive virtual reality on proximal and conditioned threat.

Virtual reality lets the user be immersed in a 3-dimensional environment, which can enhance certain emotional responses to stimuli relative to experiencing them on a flat computer screen. We here tested whether displaying two different types of threats in immersive virtual reality enhanced threat related autonomic responses measured by skin conductance responses (SCRs). We studied innate and learned threat responses because these types of threats have been shown to depend on different neural circuits in animals. Therefore, it is possible that immersive virtual reality may modulate one of these threats but not the other. Innate threat responses were provoked by the sudden appearance of characters at proximal egocentric distance, which were compared to the sudden appearance of distant characters (proximal threat). Learned threat responses were studied by conditioning two of the characters to an electric shock (conditioned threat) and contrasting SCRs to these characters with SCRs to two other characters that were never paired with shock. We found that displaying stimuli in immersive virtual reality enhanced proximal threat responses but not conditioned threat responses. Findings show that immersive virtual reality can enhance an innate type of threat responses without affecting a learned threat response, suggesting that separate neural pathways serve these threat responses.

Biological preparedness and resistance to extinction of skin conductance responses conditioned to fear relevant animal pictures: A systematic review.

Preparedness theory is one of the most influential ideas in explaining the origin of specific phobias. The theory proposes that fear conditioning is selective to animals that have posed a threat to survival throughout human evolution, and that acquired fear memories to such threats are resistant to extinction. We reviewed fear conditioning studies testing whether autonomic responses conditioned to pictures of snakes and spiders show greater resistance to extinction than neutral cues. We identified 32 fear conditioning experiments published in 23 studies including 1887 participants. Increased resistance to extinction of conditioned responses to snake and spider pictures was found in 10 (31%) of the experiments, whereas 22 (69%) experiments did not support the hypothesis. Thus, the body of evidence suggests that preparedness theory does not explain the origin of specific phobias.

The Immersive Virtual Reality Lab: Possibilities for Remote Experimental Manipulations of Autonomic Activity on a Large Scale.

There is a need for large-scale remote data collection in a controlled environment, and the in-home availability of virtual reality (VR) and the commercial availability of eye tracking for VR present unique and exciting opportunities for researchers. We propose and provide a proof-of-concept assessment of a robust system for large-scale in-home testing using consumer products that combines psychophysiological measures and VR, here referred to as a Virtual Lab. For the first time, this method is validated by correlating autonomic responses, skin conductance response (SCR), and pupillary dilation, in response to a spider, a beetle, and a ball using commercially available VR. Participants demonstrated greater SCR and pupillary responses to the spider, and the effect was dependent on the proximity of the stimuli to the participant, with a stronger response when the spider was close to the virtual self. We replicated these effects across two experiments and in separate physical room contexts to mimic variability in home environment. Together, these findings demonstrate the utility of pupil dilation as a marker of autonomic arousal and the feasibility to assess this in commercially available VR hardware and support a robust Virtual Lab tool for massive remote testing.