Spatio-temporal modulation of cortical activity during motor deadaptation depends on the feedback of task-related error.

Motor adaptations are responsible for recalibrating actions and facilitating the achievement of goals in a constantly changing environment. Once consolidated, the decay of motor adaptation is a process affected by available sensory information during deadaptation. However, the cortical response to task error feedback during the deadaptation phase has received little attention. Here, we explored changes in brain cortical responses due to feedback of task-related error during deadaptation. Twelve healthy volunteers were recruited for the study. Right hand movement and EEG were recorded during repetitive trials of a hand reaching movement. A visuomotor rotation of 30° was introduced to induce motor adaptation. Volunteers participated in two experimental sessions organized in baseline, adaptation, and deadaptation blocks. In the deadaptation block, the visuomotor rotation was removed, and visual feedback was only provided in one session. Performance was quantified using angle end-point error, averaged speed, and movement onset time. A non-parametric spatiotemporal cluster-level permutation test was used to analyze the EEG recordings. During deadaptation, participants experienced a greater error reduction when feedback of the cursor was provided. The EEG responses showed larger activity in the left centro-frontal parietal areas during the deadaptation block when participants received feedback, as opposed to when they did not receive feedback. Centrally distributed clusters were found for the adaptation and deadaptation blocks in the absence of visual feedback. The results suggest that visual feedback of the task-related error activates cortical areas related to performance monitoring, depending on the accessible sensory information.

Pseudogap of metallic layered nickelate R(2-x)Sr(x)NiO4 (R = Nd, Eu) crystals measured using angle-resolved photoemission spectroscopy.

We have investigated charge dynamics and electronic structures for single crystals of metallic layered nickelates, R(2-x)Sr(x)NiO4 (R = Nd, Eu), isostructural to La(2-x)Sr(x)CuO4. Angle-resolved photoemission spectroscopy on the barely metallic Eu(0.9)Sr(1.1)NiO4 (R = Eu, x = 1.1) has revealed a large hole surface of x2-y2 character with a high-energy pseudogap of the same symmetry and comparable magnitude with those of underdoped (x<0.1) cuprates, although the antiferromagnetic interactions are 1 order of magnitude smaller. This finding strongly indicates that the momentum-dependent pseudogap feature in the layered nickelate arises from the real-space charge correlation.

Inequivalent routes across the Mott transition in V2O3 explored by X-ray absorption.

The changes in the electronic structure of V2O3 across the metal-insulator transition induced by temperature, doping, and pressure are identified using high resolution x-ray absorption spectroscopy at the V pre-K edge. Contrary to what has been taken for granted so far, the metallic phase reached under pressure is shown to differ from the one obtained by changing doping or temperature. Using a novel computational scheme, we relate this effect to the role and occupancy of the a{1g} orbitals. This finding unveils the inequivalence of different routes across the Mott transition in V2O3.

Directional discrimination is better for noxious laser stimuli than for innocuous laser stimuli.

BACKGROUND: The directional discrimination is lower for painful laser heat compared to non-painful mechanical stimulation. The aim of the current study was to investigate how the directional discrimination of radiant heat stimulation depends on stimulation intensity and displacement velocity. METHODS: Fifteen healthy subjects were stimulated in the right volar forearm with a CO2 laser at intensities that were expected to be either painful (46°C) or non-painful (39°C). The laser beam was continuously displaced distal-proximally along the arm during the stimulation. After the stimulation, subjects indicated the perceived direction and intensity (NRS: 0: perception 3: pain 10: maximum pain). Stimulations were delivered with five lengths (20, 40, 60, 80 and 100 mm) and three velocities (10, 30 and 100 mm/s). To estimate the directional discrimination threshold (DDT) the data were fitted to a sigmoidal curve. RESULTS: For the lower intensity (39°C) the DDT was 81.8 mm for the slowest velocity, and above 100 mm for the two faster velocities. For the higher intensity (46°C) the DDT was 58.8 and 69.6 mm for the slowest velocity and middle velocity, respectively, and above 100 mm for the fastest velocity. The perceived intensity increased with stimulation length, stimulation intensity and decreasing velocity (LMM, p < .001). CONCLUSIONS: This study shows how the DDT for thermal stimuli is shorter for higher intensity and lower displacement velocities. Additionally, it was shown that for the velocity where directional discrimination is optimal for mechanical stimuli it is not possible to discriminate a thermal stimulus. SIGNIFICANCE: This study showed that the directional discrimination of painful laser stimuli is better than that for non-painful laser stimuli. These findings supplements our current knowledge regarding the tempo-spatial discrimination in the nociceptive system, where evidence from previous discrimination studies differs somewhat regarding difference between painful and non-painful discrimination. This, therefore, indicates that there is lacking knowledge regarding the discrimination within the nociceptive system.

Bandstructure meets many-body theory: the LDA+DMFT method.

Ab initio calculation of the electronic properties of materials is a major challenge for solid-state theory. Whereas 40 years' experience has proven density-functional theory (DFT) in a suitable form, e.g. local approximation (LDA), to give a satisfactory description when electronic correlations are weak, materials with strongly correlated electrons, say d- or f-electrons, remain a challenge. Such materials often exhibit 'colossal' responses to small changes of external parameters such as pressure, temperature, and magnetic field, and are therefore most interesting for technical applications. Encouraged by the success of dynamical mean-field theory (DMFT) in dealing with model Hamiltonians for strongly correlated electron systems, physicists from the bandstructure and many-body communities have joined forces and developed a combined LDA+DMFT method for treating materials with strongly correlated electrons ab initio. As a function of increasing Coulomb correlations, this new approach yields a weakly correlated metal, a strongly correlated metal, or a Mott insulator. In this paper, we introduce the LDA+DMFT method by means of an example, LaMnO(3). Results for this material, including the 'colossal' magnetoresistance of doped manganites, are presented. We also discuss the advantages and disadvantages of the LDA+DMFT approach.

Exploration of conditioned pain modulation effect on long-term potentiation-like pain amplification in humans.

BACKGROUND: This study aimed to explore conditioned pain modulation (CPM) effect on long-term potentiation (LTP)-like pain amplification induced by cutaneous 10-Hz conditioning electrical stimulation (CES). METHODS: Conditioned pain modulation was induced by cold pressor conditioning stimulus (CPCS) (4 °C) which was applied immediately before CES in the active session. In the control session, water with a temperature of 32 °C was used. Twenty subjects participated in two sessions in a randomized crossover design with at least 1-week interval. Perceptual intensity ratings to single electrical stimulation (SES) at the conditioned skin site and to pinprick and light-stroking stimuli in the immediate vicinity of the CES electrodes were measured . Superficial blood flow (SBF), skin temperature (ST) and heat pain threshold (HPT) were measured covering both homotopic and heterotopic skin. The pain intensities during CES process were measured and short-form McGill Pain Questionnaire (SF-MPQ) was used for assessing CES pain experience. RESULTS: Cold pressor conditioning stimulus reduced pain perception increments to weak pinprick and light-stroking stimuli after 10-Hz CES compared with the control session. Moreover, CPCS resulted in lower pain intensity ratings during CES process but without affecting the SF-MPQ scores between two sessions. The SBF and ST increased after CES and then gradually declined but without differences between CPCS and control sessions. CPM did not affect HPT and pain intensity increments to SES. CONCLUSIONS: The CPCS inhibited heterotopic perception amplification to weak mechanical stimuli after CES. The results indicate that endogenous descending inhibitory systems might play a role against development of non-nociceptive perception amplificatory states (e.g. allodynia). SIGNIFICANCE: Conditioned pain modulation (CPM) may play a role in inhibiting the pain amplificatory process at the central nervous system and prompting central desensitization. CPM has a special inhibition effect for the development of perception amplification to non-painful mechanical stimuli.

Modulation of the withdrawal reflex during hemiplegic gait: effect of stimulation site and gait phase.

OBJECTIVE: The objective of the study was to investigate the sensitivity of the nociceptive withdrawal reflex to stimulation of different locations on the sole of the foot during hemiplegic gait. METHODS: Reflexes were evoked by cutaneous electrical stimulation of 4 locations on the sole of the foot of 7 hemiplegic and 6 age-matched healthy persons. The stimuli were delivered at heel-contact, during foot-flat, at heel-off, and during mid-swing. Reflexes were recorded from muscles of the stimulated and the contralateral leg. Ankle, knee, and hip joints angles were recorded using goniometers. RESULTS: In the hemiplegic persons, the size of tibialis anterior reflexes, and the latency of soleus reflexes were site- and phase-modulated. In both groups, the tibialis anterior reflexes were significantly smaller with stimulation to the fifth metatarsophalangeal joint and the heel compared with the first metatarsophalangeal joint and the arch of the foot. The tibialis anterior reflexes evoked at heel-off and mid-swing were larger in hemiplegic persons than in healthy persons. Reflexes in the proximal and contralateral limb muscles were not site-modulated during hemiplegic gait. The kinematic response at the ankle joint was also different in the two groups during mid-swing. CONCLUSIONS: Hemiplegic and healthy middle-aged people presented different phase-modulation of the kinematic and muscle nociceptive reflex responses evoked by stimulation delivered on the sole of the foot. SIGNIFICANCE: The results have potential application in programs to rehabilitate hemiplegic gait.

The potential of ecotoxicoproteomics in environmental monitoring: biomarker profiling in mussel plasma using ProteinChip array technology.

New global technologies, allowing simultaneous analysis of thousands of genes, proteins, and metabolites (so-called "omics" technologies), are being adopted rapidly by industry, academia, and regulatory agencies. This study evaluated the potential of proteomics in ecotoxicological research (i.e., ecotoxicoproteomics). Filter-feeding mussels (Mytilus edulis) were exposed continuously for 3 wk to oil, or oil spiked with alkylphenols and extra polycyclic aromatic hydrocarbons. The influence of chronic exposure on mussel plasma protein expression was investigated utilizing ProteinChip array technology in combination with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS). Results indicated that exposure to spiked oil had a more significant effect on protein expression in mussels than oil alone. In total, 83 mass peaks (intact or modified proteins/peptides) were significantly altered by spiked oil, while 49 were altered by oil. In exposed organisms, the majority of peaks were upregulated compared to controls (i.e., 69% in oil and 71% in spiked oil). Some peaks (32 in total) were affected by both treatments; however, the degree of response was higher in the spiked oil group for 25 of the 32 commonly affected features. Additionally, certain peaks revealed exposure- or gender-specific responses. Multivariate analysis with regression tree-based methods detected protein patterns associated with exposure that correctly classified masked samples with 90-95% accuracy. Similarly, 92% of females and 85% of males were correctly classified (independent of exposure). Results indicate that proteomics have the potential to make a valuable contribution to environmental monitoring and risk assessment.

An overview of the BEEP Stavanger workshop.

Within the three-year European Research Project BEEP (Biological Effects of Environmental Pollution in marine ecosystems), a workshop was carried out at the facility of Akvamiljø a.s. with the scientific support of IRIS (International Research Institute of Stavanger) researchers. Validation of newly developed biomarkers, especially at the molecular level, was the core part of the activity. Two large scale mesocosm exposures were done and samples shared between the participants (about 30 Institute), allowing an integrated approach for studying the effects of several pollutants selected as environmentally important issues (i.e. PAHs, alkyl phenols, bisphenol A, diallyl phthalate and polybrominated diphenyl ether). In addition, a field study (Visne, Norway) has been performed for the validations of biomarkers under environmental conditions. The Stavanger workshop demonstrates the importance of collaboration between researchers to establish common ways to proceed in biomarker analysis. The common exposures encourage a joint strategy for planning biomonitoring activity. A clarification in this direction is needed to coordinate results from numerous studies about the environmental impact of pollutants which are currently carried out all over Europe and around the world. Expertise in various disciplines is required to plan and perform a successful monitoring activity and to study/predict the effect of environmental pollutants. Biologists, chemists, statisticians and environmental researchers should always be included. The Stavanger workshop also indicated the importance of developing multivariate statistical methods to enable interpretation of complex data sets. It is of interest to develop statistical tools which can integrate the results from a battery of biomarkers in order to obtain a more complete picture of environmental impact.

An ecotoxicoproteomic approach (SELDI-TOF mass spectrometry) to biomarker discovery in crab exposed to pollutants under laboratory conditions.

Ciphergen ProteinChip Technology is a proteomic tool, used for the discovery of new and sensitive biomarkers. This approach was used to evaluate the protein profile of crabs exposed to various pollutants. Two different exposure experiments were performed: spider crabs (Hyas araneus) were exposed for 3 weeks to diallyl phatalate (DAP), bisphenol A (BisA) and polybrominated diphenyl ether (PBDE-47), while shore crabs (Carcinus maeanas) were exposed to crude oil, crude oil spiked with alkylphenols (APs) and 4-nonylphenol (NP). Gender and species-related protein pattern alterations were observed and compared to controls. Results showed different responses to pollutants by the two species. Major disruption in protein peak expression was observed in samples exposed to mixtures of pollutants, i.e. oil spiked with APs. Compared to shore crab, spider crab species showed a lower degree of response in terms of number of altered protein peaks following exposure. In general, female individuals of both species showed a larger number of significantly altered proteins compared to males. Data analysis by non-metric multi-dimensional scaling (MDS) was performed. Bi-dimesional-MDS plots revealed a good separation of groups for both spider and shore crabs. In some cases, a good discrimination can also be observed between the two genders within each treatment. Results highlight the potential of crabs as sentinel organisms for the aquatic environment. The results indicate that SELDI-ToF technology is a powerful tool to discover protein expression signatures for different pollutants and sex dependent responses.

Preliminary study of responses in mussel (Mytilus edilus) exposed to bisphenol A, diallyl phthalate and tetrabromodiphenyl ether.

Environmental pollutants with hormonal activity including bisphenol, diallyl phtalate and tetrabromodiphenyl ether, have the potential to alter gonadal development and reproduction in aquatic wildlife. Little is known about the biological impact of environmentally relevant concentrations in mussels. To investigate some aspects of their potential estrogenic action, mussels were continuously exposed during 3 weeks. Gonadal development and vitellogenin like protein levels were examined. Bisphenol (50 microg/l) induced the expression of phospho-proteins in females and spawning in both sexes. Diallyl phthalate and tetrabromodiphenyl ether decreased phospho-protein levels in both sexes and induced spawning in males. Moreover, severe damaging effects on ovarian follicles and ovocytes were observed in both bisphenol A- and tetrabromodiphenyl ether-exposed female mussels.

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.

Selective activation of small-diameter motor fibres using exponentially rising waveforms: a theoretical study.

The present study investigated the possibility of using exponentially rising waveforms for selectively activating small motor fibres in a nerve bundle enclosed by a cuff electrode. Exponentially rising waveforms were studied using models of motor fibres and a volume conductor model. With an exponentially rising waveform (duration: 2 ms, time constant: 1 ms) large (15.5 microm) and small (8 microm) nerve fibres located at the edge of the nerve bundle had a current threshold of 125 microA and 53 microA, respectively. These reversals in the recruitment order of large and small nerve fibres located at the edge of the nerve bundle were observed for exponentially rising waveforms of 2, 4, and 6 ms in duration with time constants of 0.9, 0.6 and 0.6 ms, respectively. Reversals of the same nerve fibres located at the centre of the nerve bundle were observed for exponentially rising waveforms of 4 and 6 ms in duration, with a time constant of 0.6 ms for both waveforms. The underlying mechanism for selective activation of small nerve fibres with exponentially rising waveforms was found to be a combination of a decrease in the size of the local excitations in the centre node due to sodium channel inactivation and blocking of action potentials in large nerve fibres due to their larger difference in the membrane potential of adjacent nodes. The exponentially rising waveforms were compared with both rectangular prepulses and ramp prepulses. The rectangular prepulses were found to be unable selectively to activate small nerve fibres with the volume conductor model and criteria used in the present study, whereas the ramp prepulses performed as well as the exponentially rising waveforms. In conclusion, a novel stimulation paradigm has been proposed that may provide smooth, gradual control of muscle force with minimum fatigue.

The use of non-proven therapy among patients treated in Norwegian oncological departments. A cross-sectional national multicentre study.

A national multicentre study was performed to investigate the prevalent use of "alternative medicine", here called "non-proven therapies (NPT)", applied among Norwegian cancer patients. Of 911 patients invited to take part in the study, 642 were included in the analysis. Demographic characteristics were collected for all patients. The participating physicians gave information about the patients' clinical characteristics. Among 630 evaluable patients, 20% had been or were present users of NPTs for their oncological disease. The preferred methods were healing by hand and faith healing. Herbs, vitamins, diets and Iscador were other popular methods. As many as 40% of the users of NPTs had used NPTs earlier for non-malignant diseases. Elderly patients were less likely to use NPTs. Use was high in the northern part of Norway.

Spatial and temporal profiles of flare and hyperalgesia after intradermal capsaicin.

Intradermal injection of capsaicin induces a region of visual flare (neurogenic inflammation) and regions with modality specific hyperalgesia. Their temporal and spatial profiles have been studied to elucidate the mechanism behind neurogenic inflammation and hyperalgesia. Until today, the flare response has mainly been quantified by visual inspection. However, recent developments of thermography and laser-Doppler flowmetry have facilitated quantitative measurement of the neurogenic inflammation. The purpose of the present study was (1). to measure the temporal and spatial profiles of neurogenic inflammation and hyperalgesia induced by capsaicin by using thermography/laser-Doppler flowmetry and various sensory tests, and (2). to correlate the parameters related to neurogenic inflammation with the areas of secondary hyperalgesia. Eight healthy volunteers were injected intradermally with 250 microg of capsaicin. Five minutes after the injection, temperature and blood flow were measured by thermography and a laser-Doppler flowmetry, and followed by assessment of visual flare and hyperalgesia. Punctate hyperalgesia, stroking hyperalgesia, and heat hyperalgesia were assessed by von Frey hair, cotton swab, and radiant heat stimulator, respectively. This procedure was repeated 30 and 60 min after the injection. A significant increase in blood flow and temperature was detected by laser-Doppler flowmetry and thermography (F=102.08, P<0.001, and F=8.46, P=0.002, respectively). Throughout the experiment, the areas of visual flare, stroking hyperalgesia, and punctate hyperalgesia were covered by the area of significantly increased blood flow detected 5 min after the injection. The intensity of pain to heat stimuli significantly increased over time at the distal site and the proximal site (P<0.05). However, there was no significant difference between the pain intensity to radiant heat stimuli inside/outside the area of punctate hyperalgesia. These results seem to indicate that a possible contribution of neurogenic inflammation to secondary hyperalgesia (especially to radiant heat stimuli) must be reconsidered.

Hyperalgesia and temporal summation of pain after heat injury in man.

Temporal summation of pain occurs when repeated stimuli become increasingly painful in spite of unchanged stimulus intensity. Summation can be quantified as the difference in pain between the first and the last stimulus in a train of stimuli. The aim of the study was to compare temporal summation of pain in normal skin with summation of pain in skin with primary and secondary hyperalgesia evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Measurements were made before, and 0, 1, 2, and 4 h after the heat injury, in three areas: primary and secondary mechanical hyperalgesia induced by the heat injury, and in a mirror image of the injury on the opposite leg. Temporal summation of pain was induced by repeated electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale (VAS). Primary hyperalgesia was evaluated by von Frey hairs and electrical stimuli, and the areas of secondary hyperalgesia with a rigid von Frey hair (314 mN). Significant primary (P < 0.000001) and secondary (P < 0.00006) mechanical hyperalgesia were evoked by the heat injury. The pain threshold to single electrical stimuli was reduced within the injury (P < 0.03), but not outside. The pain responses to single and repeated electrical stimuli were not significantly altered by the injury. Temporal summation of pain occurred in 418 stimulus trains out of 576 (73%), but no significant changes in summation developed in skin with primary or secondary mechanical hyperalgesia compared with normal skin (baseline measurements). Temporal summation at high stimulus intensities was more pronounced than at lower intensities (P < 0.0002). We found no correlation between either temporal summation and area of secondary hyperalgesia, or temporal summation and pain intensity during the induction of heat injury. We conclude that the development of primary and secondary mechanical hyperalgesia after heat injury in man was not associated with changes in temporal summation of painful electrical stimuli.

Convergence of nociceptive and non-nociceptive input onto the medullary dorsal horn in man.

Referred pain arising in orofacial pain states is probably due to convergence of different somatosensory input onto the medullary dorsal horn (MDH). To examine convergence between nociceptive and non-nociceptive input onto the MDH, the blink reflex (BR) was applied. R1- and R2-components can be evoked by innocuous stimuli, but only the R2 is elicited by painful heat. The BR was elicited by innocuous electrical stimuli applied to the supraorbital nerve. A conditioning painful heat pulse which did not evoke any BR was homotopically applied to the left forehead preceding the electrical stimulus by 75 ms. While R1 remained unchanged, the R2 was facilitated by about 30%. This study demonstrates a convergence of low-threshold mechanoreceptive and nociceptive inputs onto interneurons of the MDH in man.

Correlation between local vascular and sensory changes following tissue inflammation induced by repetitive application of topical capsaicin.

The aim of the present study was to investigate local vascular and sensory changes and their correlation in order to obtain a better understanding of the mechanisms of allodynia, hyperalgesia and vascular changes following tissue inflammation induced by repetitive application of capsaicin cream. This type of application was utilized as a controlled model of inflammation which was altered in intensity due to its repetitive applicability. Ten healthy volunteers participated in two experiments separated by at least five days. Each experiment consisted of a baseline session followed by five additional sessions. Before these sessions either 1.5 g capsaicin (1%) or placebo cream was applied to the volar site of the forearm for 15 min. The areas of stroking allodynia and pin-prick hyperalgesia were mapped and the intensity of spontaneous pain (VAS) was assessed after each application of the cream. In addition, the visible flare, temperature (IR-Thermography), and blood- flow (Laser-Doppler) were measured. The first application of capsaicin was perceived as painful; it induced both secondary hyperalgesia and allodynia. Compared to placebo, the first application of capsaicin cream also resulted in an increased blood-flow, elevated temperature and visible flare. The highest values of these sensory and vascular parameters were reached after the third application. A direct correlation between visible flare, secondary mechanical hyperalgesia and allodynia following repetitive application of capsaicin indicates that both common central and peripheral mechanisms were involved in these changes.

Brief, prolonged and repeated stimuli applied to hyperalgesic skin areas: a psychophysical study.

In this experimental study brief/prolonged and single/repeated, nociceptive stimuli (laser, thermode and electrical) were used to investigate sensory changes in capsaicin-induced primary and secondary hyperalgesia. The pain threshold to prolonged thermode stimulation was reduced in the primary area and remained constant in the secondary area. The pain thresholds to brief laser and electrical stimuli remained constant in the primary but reduced in the secondary area. The summation pain threshold to repeated (five stimuli delivered at 0.5, 1, 2 and 3 Hz) laser and electrical stimuli was reduced in the secondary area. The stimulus response functions to single laser and electrical stimuli were increased in the secondary area.