Effects of Respiratory Rate on Heart Rate Variability in Neurologic Outpatients with Epilepsies or Migraine: A Preliminary Study.

BACKGROUND: Variation of spontaneous respiratory rates and influences of spontaneous and paced breathing rates on heart rate variability (HRV) were assessed in patients with epilepsy or migraine, and HRV parameters were compared between the groups. MATERIALS AND METHODS: Thirty neurologic outpatients, 16 diagnosed with epilepsies and 14 with migraine, were included. Autonomic testing consisted of short-term HRV, the deep breathing test (DBT), and measurement of HRV at systematically changed breathing rates (paced breathing, 5-18 breaths per minute, bpm). RESULTS: Spontaneous respiratory rate during short-term HRV varied from 9 to 23 bpm in the epileptic group and from 5 to 21 bpm in migraine patients and was significantly and negatively correlated with SD of all normal RR intervals (SDNN) and total power (TP) in epileptic patients but not in migraine patients. Paced breathing rate had a significant effect on all HRV parameters assessed in both groups. HRV (SD1, SDNN, TP) and DBT (E-I, SD1, SDNN) parameters were significantly lower in the epileptic group. Group differences were significantly greater during slow compared to fast breathing. CONCLUSIONS: An important and new finding is the wide variation of spontaneous respiratory rate in both groups, along with the significant negative correlation with the assessed HRV parameters. The reduction of HRV during slow breathing in epileptic patients may indicate a diminished cardiorespiratory coupling caused by a probable loss of sensitivity within the cardiovagal brainstem circuitry.

Association between Weather-Related Factors and Cardiac Arrest of Presumed Cardiac Etiology: A Prospective Observational Study Based on Out-of-Hospital Care Data.

OBJECTIVE: The objective of this study was to determine the association between weather-related factors and out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology. METHODS: This was a prospective observational study performed in a prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany) and data from the local weather station were evaluated over a 5-year period. Weather data (temperature, humidity, air pressure, wind speed) were obtained every minute and matched with the associated rescue mission data. Lowess-Regression analysis was performed to assess the relationship between the above-mentioned weather-related factors and OHCA of presumed cardiac etiology. Additionally, varying measuring-ranges were defined for each weather-related factor in order to compare them with each other with regard to the probability of occurrence of OHCA. RESULTS: During the observation period 1,558 OHCA with presumed cardiac etiology were registered (age: 67 ± 19 yrs; 62% male; hospital admission: 37%; survival to hospital discharge: 6.7%). Compared to moderate temperatures (5 - 25°C), probability of OHCA-occurrence increased significantly at temperatures above 25°C (p = 0.028) and below 5°C p = 0.011). Regarding air humidity, probability of OHCA-occurrence increased below a threshold-value of 75% compared to values above this cut-off (p = 0.006). Decreased probability was seen at moderate atmospheric pressure (1000 hPa - 1020 hPa), whereas increased probability was seen above 1020 hPa (p = 0.023) and below 1000 hPa (p = 0.035). Probability of OHCA-occurrence increased continuously with increasing wind speed (p < 0.001). CONCLUSIONS: There are associations between several weather-related factors such as temperature, humidity, air pressure, and wind speed, and occurrence of OHCA of presumed cardiac etiology. Particularly dangerous seem to be cold weather, dry air and strong wind.

Heart rate variability (HRV) in deep breathing tests and 5-min short-term recordings: agreement of ear photoplethysmography with ECG measurements, in 343 subjects.

PURPOSE: We analyzed heart rate variability (HRV) taken by ECG and photoplethysmography (PPG) to assess their agreement. We also analyzed the sensitivity and specificity of PPG to identify subjects with low HRV as an example of its potential use for clinical applications. METHODS: The HRV parameters: mean heart rate (HR), amplitude, and ratio of heart rate oscillation (E-I difference, E/I ratio), RMSSD, SDNN, and Power LF, were measured during 1-min deep breathing tests (DBT) in 343 individuals, followed by a 5-min short-term HRV (s-HRV), where the HRV parameters: HR, SD1, SD2, SDNN, Stress Index, Power HF, Power LF, Power VLF, and Total Power, were determined as well. Parameters were compared through correlation analysis and agreement analysis by Bland-Altman plots. RESULTS: PPG derived parameters HR and SD2 in s-HRV showed better agreement than SD1, Power HF, and stress index, whereas in DBT HR, E/I ratio and SDNN were superior to Power LF and RMSSD. DBT yielded stronger agreement than s-HRV. A slight overestimation of PPG HRV over HCG HRV was found. HR, Total Power, and SD2 in the s-HRV, HR, Power LF, and SDNN in the DBT showed high sensitivity and specificity to detect individuals with poor HRV. Cutoff percentiles are given for the future development of PPG-based devices. CONCLUSION: HRV measured by PPG shows good agreement with ECG HRV when appropriate parameters are used, and PPG-based devices can be employed as an easy screening tool to detect individuals with poor HRV, especially in the 1-min DBT test.

Relationship between ambient temperature and severe acute poisoning by alcohol and drugs.

AIM: To test the hypothesis that severe acute poisoning by alcohol and drugs is more frequent at higher rather than at lower ambient temperatures. METHOD: This was a prospective observational study performed in a prehospital setting under marine west coast climate conditions. Data from the Emergency Medical Service in Hamburg (Germany) and data from the local weather station were evaluated over a 5-year period. Temperature data were obtained and matched with the associated rescue mission data, which were divided into the following groups: 1) alcohol poisoning, 2) opioid poisoning, 3) poisoning by sedatives/hypnotics, multiple drugs, volatile solvents, and other psychoactive substances. Lowess-Regression analysis was performed to assess the relationship between ambient temperature and frequency of severe acute poisoning. Additionally, three temperature ranges were defined in order to compare them with each other with regard to frequency of severe poisoning (<10 °C vs. 10-20 °C vs. >20 °C). The severity of emergencies was assessed using the National Advisory Committee for Aeronautics (NACA) scoring system. RESULTS: In 1535 patients, severe acute alcohol or drug poisoning associated with loss of consciousness, hypotension, and impaired respiratory function was treated (alcohol: n = 604; opioids: n = 295; sedatives/hypnotics/multiple drugs: n = 636). Compared to mild temperatures (10-20 °C), the frequency of poisoning increased in all three groups at higher temperatures and decreased at lower temperatures (p < 0.01). No significant correlation was found between severity of emergencies and temperature. CONCLUSIONS: Our results suggest a continuously increasing probability of occurrence of severe acute poisoning by alcohol and drugs with rising temperature.

A novel algorithm for 3-D visualization of electrogram duration for substrate-mapping in patients with ischemic heart disease and ventricular tachycardia.

BACKGROUND: Myocardial slow conduction is a cornerstone of ventricular tachycardia (VT). Prolonged electrogram (EGM) duration is a useful surrogate parameter and manual annotation of EGM characteristics are widely used during catheter-based ablation of the arrhythmogenic substrate. However, this remains time-consuming and prone to inter-operator variability. We aimed to develop an algorithm for 3-D visualization of EGM duration relative to the 17-segment American Heart Association model. METHODS: To calculate and visualize EGM duration, in sinus rhythm acquired high-density maps of patients with ischemic cardiomyopathy undergoing substrate-based VT ablation using a 64-mini polar basket-catheter with low noise of 0.01 mV were analyzed. Using a custom developed algorithm based on standard deviation and threshold, the relationship between EGM duration, endocardial voltage and ablation areas was studied by creating 17-segment 3-D models and 2-D polar plots. RESULTS: 140,508 EGMs from 272 segments (n = 16 patients, 94% male, age: 66±2.4, ejection fraction: 31±2%) were studied and 3-D visualization of EGM duration was performed. Analysis of signal processing parameters revealed that a 40 ms sliding SD-window, 15% SD-threshold and >70 ms EGM duration cutoff was chosen based on diagnostic odds ratio of 12.77 to visualize rapidly prolonged EGM durations. EGMs > 70 ms matched to 99% of areas within dense scar (<0.2 mV), in 95% of zones within scar border zone (0.2-1.0 mV) and detected ablated areas having resulted in non-inducibility at the end of the procedure. Ablation targets were identified with a sensitivity of 65.6% and a specificity of 94.6% avoiding false positive labeling of prolonged EGMs in segments with healthy myocardium. CONCLUSION: The novel algorithm allows rapid visualization of prolonged EGM durations. This may facilitate more objective characterization of arrhythmogenic substrate in patients with ischemic cardiomyopathy.

Laser-evoked potentials: prognostic relevance of pain pathway defects in patients with acute radiculopathy.

The radicular pain syndrome is a major problem in public health care that can lead to chronic back and leg pain in 30%. Ischalgia and back pain are the most prominent signs of dorsal root affection. Until now, no clinical or neurophysiological test procedure exists that evaluates the function of the dorsal root and predicts the prognosis of patients suffering from RPS. We have recently demonstrated that laser-evoked potentials (LEP) are able to demonstrate dorsal root damage. With this study, we investigated 54 patients with acute radicular symptoms and compared LEP parameters (side to side difference of latency and amplitude, transformed to a z-score) with their state of health after 3 months to calculate their predictive value for outcome prognosis. Most significantly, the latency difference between the LEP of the affected dermatome relative to the contralateral healthy dermatome was able to predict the prognosis. Latency z score above two demonstrates a 91% specificity (33% sensitivity) for a poor outcome at 3 months. A significant relation between amplitude changes and the main outcome measure could not be shown. Only extreme changes (z score >10) in amplitude show a high specificity for the persistence of ischialgia in particular (specificity 0.94; sensitivity 0.35). All other parameters, such as clinical scores or other LEP parameters, were not able to predict the outcome of patients. We propose that clinical testing using LEP with latency analysis is a useful tool for estimating the course of disease, so that patients with poor predictive parameters can be treated more invasively at early disease stages to avoid persistence of radiculopathy.

Subjective Evaluation of Performance in a Collaborative Task Is Better Predicted From Autonomic Response Than From True Achievements.

Whereas the fundamental role of the body in social cognition seems to be generally accepted, elucidating the bodily mechanisms associated with non-verbal communication and cooperation between two or more persons is still a challenging endeavor. In this article we propose a fresh approach for investigating the function of the autonomic nervous system that is reflected in parameters of heart rate variability, respiration, and electrodermal activity in a social setting. We analyzed autonomic parameters of dyads solving a target-tracking task together with the partner or individually. A machine classifier was trained to predict the subjects' rating of performance and collaboration either from tracking error data or from the set of autonomic parameters. When subjects collaborated, this classifier could predict the subjective performance ratings better from the autonomic response than from the objective performance of the subjects. However, when they solved the task individually, predictability from autonomic parameters dropped to the level of objective performance, indicating that subjects were more rational in rating their performance in this condition. Moreover, the model captured general knowledge about the population that allows it to predict the performance ratings of an unseen subject significantly better than chance. Our results suggest that, in particular in situations that require collaboration with others, evaluation of performance is shaped by the bodily processes that are quantified by autonomic parameters. Therefore, subjective performance assessments appear to be modulated not only by the output of a rational or discriminative system that tracks the objective performance but to a significant extent also by interoceptive processes.

Chemosensory Event-Related Potentials in Response to Nasal Propylene Glycol Stimulation.

Propylene glycol, also denoted as 1.2 propanediol (C3H8O2), often serves as a solvent for dilution of olfactory stimuli. It is supposed to serve as a neutral substance and has been used in many behavioral and electrophysiological studies to dilute pure olfactory stimuli. However, the effect of propylene glycol on perception and on neuronal responses has hitherto never been studied. In this study we tested by means of a threshold test, whether a nasal propylene glycol stimulation is recognizable by humans. Participants were able to recognize propylene glycol at a threshold of 42% concentration and reported a slight cooling effect. In addition to the threshold test, we recorded electroencephalography (EEG) during nasal propylene glycol stimulation to study the neuronal processing of the stimulus. We used a flow olfactometer and stimulated 15 volunteers with three different concentrations of propylene glycol (40 trials each) and water as a control condition (40 trials). To evaluate the neuronal response, we analyzed the event-related potentials (ERPs) and power modulations. The task of the volunteers was to identify a change (olfactory, thermal, or tactile) in the continuous air flow generated by the flow olfactometer. The analysis of the ERPs showed that propylene glycol generates a clear P2 component, which was also visible in the frequency domain as an evoked power response in the theta-band. The source analysis of the P2 revealed a widespread involvement of brain regions, including the postcentral gyrus, the insula and adjacent operculum, the thalamus, and the cerebellum. Thus, it is possible that trigeminal stimulation can at least partly account for sensations and brain responses elicited by propylene glycol. Based on these results, we conclude that the use of high propylene glycol concentrations to dilute fragrances complicates the interpretation of presumed purely olfactory effects.

A unique representation of heat allodynia in the human brain.

Skin inflammation causes innocuous heat to become painful. This condition, called heat allodynia, is a common feature of pathological pain states. Here, we show that heat allodynia is functionally and neuroanatomically distinct from normal heat pain. We subtracted positron emission tomography scans obtained during painful heating of normal skin from scans during equally intense but normally innocuous heating of capsaicin-treated skin. This comparison reveals the specific activation of a medial thalamic pathway to the frontal lobe during heat allodynia. The results suggest that different central pathways mediate the intensity and certain qualitative aspects of pain. In making this differentiation, the brain recognizes unique physiological features of different painful conditions, thus permitting adaptive responses to different pain states.

Attention to painful stimulation enhances gamma-band activity and synchronization in human sensorimotor cortex.

A number of cortical regions are involved in processing pain-related information. The SI and SII somatosensory cortices process mainly sensory discriminative attributes but also play an important role in recognition and memory of painful events. Regions such as SII and the posterior insula appear to be the first stations that house processes by which attention profoundly shapes both behavioral responses and subjective pain experience. We investigated the influence of directed attention on pain-induced oscillations and synchronization processes using magnetoencephalogram in combination with an oddball paradigm in 20 healthy subjects. The subject's task was to count rare painful electrical stimuli applied to one finger, while ignoring frequent stimuli at a different finger. A high detection ratio was observed for all blocks and subjects. Early evoked oscillations in the delta-band increased with higher stimulus intensity and directed attention, most prominently at contralateral sensorimotor sites. Furthermore, suppression and rebound of beta activity were observed after painful stimulation. Moreover, induced oscillatory activity in the high gamma-band increased with directed attention, an effect being significantly stronger for high compared with low stimulus intensity. Coupling analysis performed for this high gamma response revealed stronger functional interactions between ipsilateral and contralateral sites during attention. We conclude that pain-induced high-frequency activity in sensorimotor areas may reflect an attentional augmentation of processing, leading to enhanced saliency of pain-related signals and thus to more efficient processing of this information by downstream cortical centers.

Role of synchronized oscillatory brain activity for human pain perception.

The understanding of cortical pain processing in humans has significantly improved since the development of modern neuroimaging techniques. Non-invasive electrophysiological approaches such as electro- and magnetoencephalography have proven to be helpful tools for the real-time investigation of neuronal signals and synchronous communication between cortical areas. In particular, time-frequency decomposition of signals recorded with these techniques seems to be a promising approach because different pain-related oscillatory changes can be observed within different frequency bands, which are likely to be linked to specific sensory and motor functions. In this review we discuss the latest evidence on pain-induced time-frequency signals and propose that changes in oscillatory activity reflect an essential communication mechanism in the brain that is modulated during pain processing. The importance of synchronization processes for normal and pathological pain processing, such as chronic pain states, is discussed.

Process Variability-Technological Challenge and Design Issue for Nanoscale Devices.

Current advanced transistor architectures, such as FinFETs and (stacked) nanowires and nanosheets, employ truly three-dimensional architectures. Already for aggressively scaled bulk transistors, both statistical and systematic process variations have critically influenced device and circuit performance. Three-dimensional device architectures make the control and optimization of the device geometries even more important, both in view of the nominal electrical performance to be achieved and its variations. In turn, it is essential to accurately simulate the device geometry and its impact on the device properties, including the effect caused by non-idealized processes which are subject to various kinds of systematic variations induced by process equipment. In this paper, the hierarchical simulation system developed in the SUPERAID7 project to study the impact of variations from equipment to circuit level is presented. The software system consists of a combination of existing commercial and newly developed tools. As the paper focuses on technological challenges, especially issues resulting from the structuring processes needed to generate the three-dimensional device architectures are discussed. The feasibility of a full simulation of the impact of relevant systematic and stochastic variations on advanced devices and circuits is demonstrated.

Pain draws visual attention to its location: experimental evidence for a threat-related bias.

UNLABELLED: It has been often demonstrated that pain interferes with the processing of other information. However, the initiation of protective behavior in response to pain also requires enhanced processing of potentially relevant information, such as stimuli sharing the same spatial coordinates. In this study we test whether pain draws visual attention to its location. We report 2 experiments in which healthy individuals detected visual stimuli at 2 possible locations. Each stimulus was preceded by painful stimulation at the corresponding (congruent trial) or noncorresponding (incongruent trial) location. Based on the probability ratio of congruent to incongruent trials, pain was either spatially informative (experiment 1) or uninformative (experiment 2) for visual target detection. The detection of visual stimuli was faster at the pain location than at the other location in both experiments suggesting efficient spatially guided orienting and responding to potential sources of somatic threat. However, when pain was spatially uninformative, visual attention was only drawn to the pain location when pain was perceived as threatening. This indicates that threatening pain prioritizes the processing of visual information at its location, even if the pain is irrelevant for the upcoming visual event. PERSPECTIVE: In this study a threat-related processing bias of visual information on a painful body location was demonstrated. This finding advances our knowledge on how pain modulates attention. More particularly, it seems that interruption by pain is not absolute and that pain prioritizes the processing of other perceptual information that it spatially related to the pain.

Reduced frequency of severe hypoglycemia at mild ambient temperatures between 10 and 20 °C: A population-based study under marine west coast climate conditions.

AIMS: To determine the association between ambient temperature and severe hypoglycemia. METHODS: This was a prospective observational study performed in a prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany) and data from the local weather station were evaluated over a 5-year period. Lowess-regression analysis was conducted to assess the relationship between ambient temperature and frequency of severe hypoglycemia. Additionally, three temperature-ranges were defined in order to compare them with each other with regard to frequency of severe hypoglycemia (<10°C vs. 10-20°C vs. >20°C). RESULTS: In 2592 patients severe hypoglycemia was diagnosed and treated by emergency physicians (T1DM: n=829/32%; T2DM: n=1763/68%). The median age of patients was 64 (57-72 [20-85]) years. Compared to mild temperatures (10-20°C) the frequency of severe hypoglycemia increased significantly at temperatures above 20°C (+18% (95%-CI: [7%; 22%], p=0.007) and below 10°C (+15% (95%-CI: [6%; 24%], p<0.001). CONCLUSIONS: The results suggest the existence of a "thermal comfort zone" covering a temperature range from 10 to 20°C in which the frequency of severe hypoglycemia was significantly lower than below 10°C and above 20°C.

Acupuncture analgesia involves modulation of pain-induced gamma oscillations and cortical network connectivity.

Recent studies support the view that cortical sensory, limbic and executive networks and the autonomic nervous system might interact in distinct manners under the influence of acupuncture to modulate pain. We performed a double-blind crossover design study to investigate subjective ratings, EEG and ECG following experimental laser pain under the influence of sham and verum acupuncture in 26 healthy volunteers. We analyzed neuronal oscillations and inter-regional coherence in the gamma band of 128-channel-EEG recordings as well as heart rate variability (HRV) on two experimental days. Pain ratings and pain-induced gamma oscillations together with vagally-mediated power in the high-frequency bandwidth (vmHF) of HRV decreased significantly stronger during verum than sham acupuncture. Gamma oscillations were localized in the prefrontal cortex (PFC), mid-cingulate cortex (MCC), primary somatosensory cortex and insula. Reductions of pain ratings and vmHF-power were significantly correlated with increase of connectivity between the insula and MCC. In contrast, connectivity between left and right PFC and between PFC and insula correlated positively with vmHF-power without a relationship to acupuncture analgesia. Overall, these findings highlight the influence of the insula in integrating activity in limbic-saliency networks with vagally mediated homeostatic control to mediate antinociception under the influence of acupuncture.

Relationship between ambient temperature and frequency and severity of cardiovascular emergencies: A prospective observational study based on out-of-hospital care data.

OBJECTIVE: To test the hypothesis that more cardiovascular emergencies occur at low rather than at high temperatures under moderate climatic conditions. METHODS: This was a prospective observational study performed in a prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany) and from the local weather station were evaluated over a 5-year period. Temperature data were matched with the associated rescue mission data. Lowess-Regression analysis was performed to assess the relationship between the temperature and the frequency of individual cardiovascular emergencies. In addition, three threshold-temperatures (0°C, 10°C, 20°C) were defined in order to determine the frequency of cardiovascular emergencies above and below each cut-off value. The severity of emergencies was assessed using the National Advisory Committee for Aeronautics (NACA) scoring system. RESULTS: A total of 35,390 cardiovascular emergencies were treated by Emergency Physicians. Transient Loss of Consciousness increased at high temperatures (above 20°C): +43% (95%-CI: [27%; 59%]). In contrast, Coronary Artery Disease +26% (95%-CI: [17%; 34%]), Cardiac Pulmonary Edema +21% (95%-CI: [14%; 27%]), Hypertensive Urgency +18% (95%-CI: [10%; 25%]) and Cerebrovascular Accident +17% (95%-CI: [8%; 24%]) increased at low temperatures, particularly below 10°C (significance level for all: p<0.001). No temperature-related effect was seen in Cardiac Arrhythmia and Pulmonary Embolism and no significant correlation was found between the severity of emergencies and temperature. CONCLUSIONS: Our findings suggest that some cardiovascular emergencies such as Coronary Artery Disease, Cardiac Pulmonary Edema, Hypertensive Urgency and Cerebrovascular Accident are more frequent in low temperatures even under mild climatic conditions.

Evidence for early activation of primary motor cortex and SMA after electrical lower limb stimulation using EEG source reconstruction.

Compared to median nerve somatosensory evoked potentials (SEP), less is known about activity evoked by nerve stimulation of the lower limb. To understand the mechanisms and the physiology of sensor- and motor control it is useful to investigate the sensorimotor functions as revealed by a standardized functional status. Therefore, we investigated SEPs of the lower limb in 6 healthy male volunteers. For each side, tibial and peroneal nerves were stimulated transcutaneously at the fossa poplitea. The tibial nerves were also stimulated further distally at the ankle joint. Source localization was applied to 64-EEG-channel data of the SEPs. In contrast to somatosensory areas, which are activated after median nerve stimulation, we found dipoles adjacent to motor areas near Brodmann area 4 (BA 4) for SEP components P 32/40 and P 54/60 and near the supplementary motor area (SMA) for the N 75/83 component. These sources could reliably be distinguished for each individual subject as well as for the grand mean data set. Our data show that afferent projections from the lower limb mainly reach primary motor areas (BA 4) and only subsequently, with a delay of 40 ms, higher order motor areas such as SMA. We conclude that a focused view on SEP of the lower limb could be a useful tool to investigate pathological states in motor control or peripheral deafferentiation.

Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis.

The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. On the dorsal hand, 51 degrees C stimulation produced painful pinprick sensations and 41 degrees C stimuli evoked warmth. On the glabrous thenar, 41 degrees C stimulation produced mild warmth and 51 degrees C evoked strong but painless heat sensations. We used CHEP responses to estimate the conduction velocities (CV) of peripheral fibers mediating these sensations. On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.

Top-down and bottom-up modulation of pain-induced oscillations.

Attention is an important factor that is able to strongly modulate the experience of pain. In order to differentiate cortical mechanisms underlying subject-driven (i.e., top-down) and stimulus-driven (bottom-up) modes of attentional pain modulation, we recorded electric brain activity in healthy volunteers during painful laser stimulation while spatial attention and stimulus intensity were systematically varied. The subjects' task was to evaluate the pain intensity at the attended finger, while ignoring laser stimuli delivered to the other finger. Top-down (attention) and bottom up (intensity) influences differed in their effects on oscillatory response components. Attention towards pain induced a decrease in alpha and an increase in gamma band power, localized in the insula. Pain intensity modulated delta, alpha, beta and gamma band power. Source localization revealed stimulus driven modulation in the cingulate gyrus (CG) and somatosensory areas for gamma power changes. Our results indicate that bottom-up and top-down modes of processing exert different effects on pain-induced slow and fast oscillatory activities. Future studies may examine pain-induced oscillations using this paradigm to test for altered attentional pain control in patients with chronic pain.

Cognitive performance, mood and experimental pain before and during morphine-induced analgesia in patients with chronic non-malignant pain.

This paper investigates subjective, behavioral and neurophysiological changes due to treatment with oral sustained-release morphine in six patients with severe non-malignant pain. Patients rated their mood and clinical pain on visual analog scales (VAS). Experimental pain reactions were quantified by ratings on categorical scales and evoked cerebral potentials (LEP) in response to standardized laser stimuli. A standard auditory oddball task provided reaction time (RT), errors, N1 and P2 of late auditory evoked potentials (AEP), and a P300 component. It was used to measure vigilance and cognitive performance. In parallel with clinical pain reduction, laser pain ratings and LEP amplitudes were significantly reduced. In contrast, auditory P2 and P300 amplitude were found to be even enlarged under morphine. RT and mood also failed to indicate any sedation. It is concluded that LEP indicated the analgesic morphine effects whereas late potentials and P300 from auditory stimuli reflected the perceptual-cognitive status which, instead of being deteriorated by morphine-induced sedation, improved probably due to the removal of pain as a mental stressor.