Electrophysiological Correlates of Vigilance During a Continuous Performance Test in Healthy Adults

The present study evaluated patterns of electrophysiological activity associated with sustained vigilance in healthy adults. Quantitative electroencephalographs (QEEG) were recorded during the performance of a Continuous Performance Test (CPT). Participants were divided into low and high vigilance groups based upon their reaction time changes between the early and late portions of the CPT. Coherence measures were calculated from the QEEG across the baseline, early CPT, and late CPT experimental conditions. Participants in the low vigilance group had higher baseline and CPT frontal to posterior coherence in the alpha and beta bands suggestive of a less vigilant state throughout the entire study. Additionally, the low vigilance group had a significantly greater beta 1 band coherence drop from baseline to the initial portion of the CPT than the high vigilance group. The combined groups had significantly lower amounts of right hemisphere frontal to posterior coherence across a number of frequency bands throughout all of the phases of the study when compared to the homologous left hemisphere sites. These interhemispheric coherence differences are consistent with vigilance network theories that implicate the right frontal and parietal lobes in the maintenance of sustained attention (M. I. Posner & M. E. Raichle, 1994).     

EEG Topographic Mapping of Visual and Kinesthetic Imagery in Swimmers

This study investigated differences in QEEG measures between kinesthetic and visual imagery of a 100-m swim in 36 elite competitive swimmers. Background information and post-trial checks controlled for the modality of imagery, swimming skill level, preferred imagery style, intensity of image and task equality. Measures of EEG relative magnitude in theta, low (7–9 Hz) and high alpha (8–10 Hz), and low and high beta were taken from 19 scalp sites during baseline, visual, and kinesthetic imagery. QEEG magnitudes in the low alpha band during the visual and kinesthetic conditions were attenuated from baseline in low band alpha but no changes were seen in any other bands. Swimmers produced more low alpha EEG magnitude during visual versus kinesthetic imagery. This was interpreted as the swimmers having a greater efficiency at producing visual imagery. Participants who reported a strong intensity versus a weaker feeling of the image (kinesthetic) had less low alpha magnitude, i.e., there was use of more cortical resources, but not for the visual condition. These data suggest that low band (7–9 Hz) alpha distinguishes imagery modalities from baseline, visual imagery requires less cortical resources than kinesthetic imagery, and that intense feelings of swimming requires more brain activity than less intense feelings.     

Developing a Performance Brain Training™ Approach for Baseball: A Process Analysis with Descriptive Data

Neurofeedback may be useful for improving sports performance but few studies have examined this potential. Here we present data of five development players from a major league baseball team. The aims were to evaluate the feasibility of conducting sessions within a professional organization, assess changes in quantitative electroencephalograph (QEEG), NeuroPerformance Profile?, and report qualitative self-report data before and after brain training. The EEG was recorded with 19 electrodes for 20 min of baseline conditions and approximately 21 min of a continuous performance test. The fast Fourier transform analysis provided average cross-spectral matrices for bands delta (1–3.5 Hz), theta (4–7.5 Hz), alpha (8–12 Hz), low beta (13–16 Hz), beta 1 (13–21 Hz), beta 2 (22–32 Hz), and gamma (32–45 Hz) from the pre and post intervention evaluations in the baseline condition of eyes open. The continuous performance test metrics included the errors of omission, errors of commission, response time and response time variability. The 9 scales of the NeuroPerformance Profile? were examined. The QEEG data, CPT data and NeuroPerformance Profile? data were all compared between the pre and post 15 sessions of brain training using a within subject paired t test design corrected for multiple comparisons using false discovery rate method. Following brain training, comparative QEEG, CPT and NeuroPerformance Profile? analyses illustrated significant differences. The QEEG findings of all participants illustrated significant changes within the training parameters but also across other frequency bands and electrode sites. Overall, the positive findings in both objective and subjective measures suggest further inquiry into the utility of brain training for performance enhancement with the specific application of sport is warranted. Particularly QEEG and CPT gains were noted in the areas that correspond to client self-report data demonstrating improvement in attention, decreased intrusive thought patterns and improvements in sleep patterns.     

Assessment of intraluminal impedance for the detection of pharyngeal bolus flow during swallowing in healthy adults

Intraluminal impedance, a nonradiological method for assessing bolus flow within the gut, may be suitable for investigating pharyngeal disorders. This study evaluated an impedance technique for the detection of pharyngeal bolus flow during swallowing. Patterns of pharyngoesophageal pressure and impedance were simultaneously recorded with videofluoroscopy in 10 healthy volunteers during swallowing of liquid, semisolid, and solid boluses. The timing of bolus head and tail passage recorded by fluoroscopy was correlated with the timing of impedance drop and recovery at each recording site. Bolus swallowing produced a drop in impedance from baseline followed by a recovery to at least 50% of baseline. The timing of the pharyngeal and esophageal impedance drop correlated with the timing of the arrival of the bolus head. In the pharynx, the timing of impedance recovery was delayed relative to the timing of clearance of the bolus tail. In contrast, in the upper esophageal sphincter (UES) and proximal esophagus, the timing of impedance recovery correlated well with the timing of clearance of the bolus tail. Impedance-based estimates of pharyngoesophageal bolus clearance time correlated with true pharyngoesophageal bolus clearance time. Patterns of intraluminal impedance recorded in the pharynx during bolus swallowing are therefore more complex than those in the esophagus. During swallowing, mucosal contact between the tongue base and posterior pharyngeal wall prolongs the duration of pharyngeal impedance drop, leading to overestimation of bolus tail timing. Therefore, we conclude that intraluminal impedance measurement does not accurately reflect the bolus transit in the pharynx but does accurately reflect bolus transit across the UES and below.     

Traumatic Brain Injury Rehabilitation: QEEG Biofeedback Treatment Protocols

Interventions for improvement of cognitive problems in patients with traumatic brain injury (TBI) include electroencephalography biofeedback, also known as neurofeedback. Quantitative electroencephalography (QEEG) patterns are assessed in TBI patients and then compared to a database obtained from a normative population. Deviations in QEEG patterns from the normative group are the basis for an intervention plan. While QEEG patterns, obtained under an eyes closed, resting condition, provide information about deviations at rest, QEEG patterns obtained while the patient engages in cognitive tasks reflect specific deficiencies in brain functioning. This paper reviews and assesses QEEG patterns collected under both resting conditions as well as cognitive tasks. The article provides a theoretical and empirical base for QEEG interventions with TBI.     

Episodic hypoxia induces long-term facilitation of neural drive to tongue protrudor and retractor muscles.

Hypoxic episodes can evoke a prolonged augmentation of inspiratory motor output called long-term facilitation (LTF). Hypoglossal (XII) LTF has been assumed to represent increased tongue protrudor muscle activation and pharyngeal airway dilation. However, recent studies indicate that tongue protrudor and retractor muscles are coactivated during inspiration, a behavior that promotes upper airway patency by reducing airway compliance. These experiments tested the hypothesis that XII LTF is manifest as increased inspiratory drive to both tongue protrudor and retractor muscles. Neurograms were recorded in the medial XII nerve branch (XIIMED; contains tongue protrudor motor axons), the lateral XII nerve branch (XIILAT; contains tongue retractor motor axons), and the phrenic nerve in anesthetized, vagotomized, paralyzed, ventilated male rats. Strict isocapnia was maintained for 60 min after five 3-min hypoxic episodes (arterial Po(2) = 35 +/- 2 Torr) or sham treatment. Peak inspiratory burst amplitude showed a persistent increase in XIIMED, XIILAT, and phrenic nerves during the hour after episodic hypoxia (P < 0.05 vs. sham). This effect was present regardless of the quantification method (e.g., % baseline vs. percent maximum); however, comparisons of the relative magnitude of LTF between neurograms (e.g., XIIMED vs. XIILAT) varied with the normalization procedure. There was no persistent effect of episodic hypoxia on inspiratory burst frequency (P > 0.05 vs. sham). These data demonstrate that episodic hypoxia induces LTF of inspiratory drive to both tongue protrudor and retractor muscles and underscore the potential contribution of tongue muscle coactivation to regulation of upper airway patency.     

New Insight into the Time-Course of Motor and Sensory System Changes in Pain

Background

Pain-related interactions between primary motor (M1) and primary sensory (S1) cortex are poorly understood. In particular, the time-course over which S1 processing and corticomotor output are altered in association with muscle pain is unclear. We aimed to examine the temporal profile of altered processing in S1 and altered corticomotor output with finer temporal resolution than has been used previously.

Methods

In 10 healthy individuals we recorded somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in separate sessions at multiple time-points before, during and immediately after pain induced by hypertonic saline infusion in a hand muscle, and at 15 and 25 minutes follow-up.

Results

Participants reported an average pain intensity that was less in the session where SEPs were recorded (SEPs: 4.0±1.6; MEPs: 4.9±2.3). In addition, the time taken for pain to return to zero once infusion of hypertonic saline ceased was less for participants in the SEP session (SEPs: 4.7±3.8 mins; MEPs 9.4±7.4 mins). Both SEPs and MEPs began to reduce almost immediately after pain reached 5/10 following hypertonic saline injection and were significantly reduced from baseline by the second (SEPs) and third (MEPs) recording blocks during pain. Both parameters remained suppressed immediately after pain had resolved and at 15 and 25 minutes after the resolution of pain.

Conclusions

These data suggest S1 processing and corticomotor output may be co-modulated in association with muscle pain. Interestingly, this is in contrast to previous observations. This discrepancy may best be explained by an effect of the SEP test stimulus on the corticomotor pathway. This novel finding is critical to consider in experimental design and may be potentially useful to consider as an intervention for the management of pain.     

The level of serotonin in the superficial masseter muscle in relation to local pain and allodynia.

The aim of this study was to investigate if serotonin is present in the human masseter muscle and if so, whether it is involved in the modulation of local muscle pain or allodynia. Thirty-five patients with pain and tenderness of the masseter muscle as well as ten healthy individuals were included in the study. Of the patients, 18 suffered from fibromyalgia and 17 had localized myalgia, e.g. myofascial pain in the temporomandibular system. The participants were examined clinically with special consideration to the masseter muscle and the pressure pain threshold as well as tolerance levels of this muscle were assessed. Intramuscular microdialysis was performed in order to sample serotonin and a venous blood sample was collected for analysis of the serum level of serotonin. Serotonin was present in the masseter muscle and the level was significantly higher in the initial sample than in the sample collected during steady state. The level of serotonin in the masseter muscle in relation to the level of serotonin in the blood serum was calculated. This fraction of serotonin was higher in the patients with fibromyalgia than in healthy individuals and high level of serotonin was associated with pain as well as allodynia of the masseter muscle. In conclusion, the results of this study show that serotonin is present in the human masseter muscle both immediately following puncture and in a subsequent steady state and that it is associated with pain and allodynia. The origin of the serotonin seems partly to be the blood, but our results indicate that peripheral release also occurs.     

Experimental Muscle Pain Impairs the Synergistic Modular Control of Neck Muscles

A motor task can be performed via different patterns of muscle activation that show regularities that can be factorized in combinations of a reduced number of muscle groupings (also referred to as motor modules, or muscle synergies). In this study we evaluate whether an acute noxious stimulus induces a change in the way motor modules are combined to generate movement by neck muscles. The neck region was selected as it is a region with potentially high muscular redundancy. We used the motor modules framework to assess the redistribution of muscular activity of 12 muscles (6 per side) in the neck region of 8 healthy individuals engaged in a head and neck aiming task, in non-painful conditions (baseline, isotonic saline injection, post pain) and after the injection of hypertonic saline into the right splenius capitis muscle. The kinematics of the task was similar in the painful and control conditions. A general decrease of activity was noted for the injected muscle during the painful condition together with an increase or decrease of the activity of the other muscles. Subjects did not adopt shared control strategies (motor modules inter subject similarity at baseline 0.73±0.14); the motor modules recorded during the painful condition could not be used to reconstruct the activation patterns of the control conditions, and the painful stimulus triggered a subject-specific redistribution of muscular activation (i.e., in some subjects the activity of a given muscle increased, whereas in other subjects it decreased with pain). Alterations of afferent input (i.e., painful stimulus) influenced motor control at a multi muscular level, but not kinematic output. These findings provide new insights into the motor adaptation to pain.     

Contact heat evoked potentials using simultaneous EEG and fMRI and their correlation with evoked pain

Background

The Contact Heat Evoked Potential Stimulator (CHEPS) utilises rapidly delivered heat pulses with adjustable peak temperatures to stimulate the differential warm/heat thresholds of receptors expressed by Aδ and C fibres. The resulting evoked potentials can be recorded and measured, providing a useful clinical tool for the study of thermal and nociceptive pathways. Concurrent recording of contact heat evoked potentials using electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has not previously been reported with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable, as it provides an opportunity to exploit the high temporal resolution of EEG and the high spatial resolution of fMRI to study the reaction of the human brain to thermal and nociceptive stimuli.

Methods

In this study we have recorded evoked potentials stimulated by 51°C contact heat pulses from CHEPS using EEG, under normal conditions (baseline), and during continuous and simultaneous acquisition of fMRI images in ten healthy volunteers, during two sessions. The pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS).

Results

Analysis of EEG data revealed that the latencies and amplitudes of evoked potentials recorded during continuous fMRI did not differ significantly from baseline recordings. fMRI results were consistent with previous thermal pain studies, and showed Blood Oxygen Level Dependent (BOLD) changes in the insula, post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and pre-central gyrus. There was a significant positive correlation between the evoked potential amplitude (EEG) and the psychophysical perception of pain on the VAS.

Conclusion

The results of this study demonstrate the feasibility of recording contact heat evoked potentials with EEG during continuous and simultaneous fMRI. The combined use of the two methods can lead to identification of distinct patterns of brain activity indicative of pain and pro-nociceptive sensitisation in healthy subjects and chronic pain patients. Further studies are required for the technique to progress as a useful tool in clinical trials of novel analgesics.     

Neurofeedback training for a patient with thalamic and cortical infarctions

One year after a left posterior and thalamic stroke, a 52-year-old male participant was treated with 14 weeks of theta reduction neurofeedback training. Imaging studies revealed left temporal, parietal, occipital, and bilateral thalamic infarctions along the distribution of the posterior cerebral artery. Neuropsychological testing demonstrated severe verbal memory, naming, visual tracking, and fine motor deficits. Additionally, alexia without agraphia was present. A pretraining quantitative electroencephalograph (QEEG) found alpha attenuation, lack of alpha reactivity to eye opening, and excessive theta activity from the left posterior head region. Neurofeedback training to inhibit 4–8 Hz theta activity was conducted for 42 sessions from left hemisphere sites. Over the course of the training, significant reductions in theta amplitude occurred from the training sites as assessed from the postsession baseline periods. Posttraining, a relative normalization of the QEEG was observed from the left posterior head region.     

The Relative Efficacy of Connectivity Guided and Symptom Based EEG Biofeedback for Autistic Disorders

Autism is a neurodevelopmental disorder characterized by deficits in communication, social interaction, and a limited range of interests with repetitive stereotypical behavior. Various abnormalities have been documented in the brains of individuals with autism, both anatomically and functionally. The connectivity theory of autism is a recently developed theory of the neurobiological cause of autisic symptoms. Different patterns of hyper- and hypo-connectivity have been identified with the use of quantitative electroencephalogray (QEEG), which may be amenable to neurofeedback. In this study, we compared the results of two published controlled studies examining the efficacy of neurofeedback in the treatment of autism. Specifically, we examined whether a symptom based approach or an assessment/connectivity guided based approach was more effective. Although both methods demonstrated significant improvement in symptoms of autism, connectivity guided neurofeedback demonstrated greater reduction on various subscales of the Autism Treatment Evaluation Checklist (ATEC). Furthermore, when individuals were matched for severity of symptoms, the amount of change per session was significantly higher in the Coben and Padolsky (J Neurother 11:5–23, 2007) study for all five measures of the ATEC. Our findings suggest that an approach guided by QEEG based connectivity assessment may be more efficacious in the treatment of autism. This permits the targeting and amelioration of abnormal connectivity patterns in the brains of people who are autistic.     

Experimental morphology of the feeding mechanism in salamanders

The subarcualis rectus I muscle (SAR) in the feeding mechanism of four tiger salamanders (Ambystoma tigrinum) was removed early in ontogeny and these individuals were allowed to complete metamorphosis. This procedure resulted in postmetamorphic tiger salamanders which differed from control individuals in the size (and thus force generating capacity) of the SAR muscle. The experimental manipulation of muscle ontogeny allowed a test of previous hypotheses of SAR function in postmetamorphic individuals. Multivariate analysis of variance for kinematic variables measured from high-speed video records of feeding revealed that experimentally modified tiger salamanders did not protract the hyobranchial apparatus or project the tongue from the mouth during feeding. Removal of the SAR muscle resulted in significantly reduced hyobranchial elevation in the buccal cavity and reduced maximum tongue projection distance.     

Behavioural and electrophysiological experiments on the sense of taste in Saguinus midas tamarin (Callitrichidae) (author's transl)]

The activity in the gustatory nerve from the anterior part of the tongue, the chorda tympani proper nerve, has been recorded during stimulation of the tongue of a New World monkey, Saguinus midas tamarin. A series of 0.3 M sugars and 0.07 M NaCl, 0.07 M sucrose, 0.004 M acetic acid and 0.00005 M quinine hydrochloride were used as taste stimuli. The concentrations of the last four stimuli were the same as those earlier found to be the lowest concentrations at which this monkey in behavioural experiments discriminates between them and water. The records showed that these threshold concentrations all elicited a neural response. Further, the neural activities during stimulation with the series of 0.3 M sugars were recorded. Using the amplitudes of the responses as a measure, the order between them was found to be fructose greater than glucose greater than lactose greater than arabinose greater than sucrose = galactose greater than raffinose. This order was discussed and related with the order found in behavioural experiments. With both methods, fructose seemed to be the strongest stimulus, but then the order among the sugars differed.     

Characterization of a familial small supernumerary marker chromosome in a patient with adult-onset tongue cancer

Cytogenetic analysis in peripheral blood lymphocytes of a 50-year-old female with tongue cancer showed the presence of one to three copies of a small supernumerary marker chromosome (sSMC) in a mosaic state. Family studies also revealed the marker in mosaic form in four (age <29 years) of eleven clinically normal individuals studied from her family of 16 individuals spanning three generations. Due to the extremely small size of the marker chromosome, identification by classical cytogenetics was not informative. Multicolor FISH followed by whole chromosome painting identified the marker as a derivative of chromosome 21. This is the first report of sSMC21 in an adult-onset tongue cancer patient and some of her family members with no clinical symptoms.     

Differences in stress reactivity of laboratory macaques measured by heart period and respiratory sinus arrhythmia

Some laboratory primates are more likely than others to react to anxiety-provoking stressors. Individuals that overreact to stressors may experience diminished psychological well-being and would be inappropriate for some experiments. The differences between reactive and nonreactive individuals may be reflected in heart period and respiratory sinus arrhythmia (RSA). Using surface electrodes and radio telemetry, we measured these two cardiac variables in seven male and ten female singly caged longtailed macaques (Macaca fascicularis) when they were exposed to two stressors, a sudden noise (whistle test) and an unfamiliar technician wearing capture gloves (glove test). Behavior was videotaped during both tests. For the whistle test, cardiac data were recorded before, during, and after two 1 min whistle blasts separated by 90 min. For the glove test, data were recorded in 1 min blocks every 8 min over 96 min before, during, and after 1 min exposure to the gloved technician. Heart period was decreased and RSA was suppressed during both the whistle and glove exposures. After the whistle test, the cardiac activity of most subjects returned to baseline levels within 10 min. The glove test produced more extended suppression, with greater individual differences, than the whistle test. There were greater individual differences in RSA than in heart period. These enhanced individual differences were used to define stress reactors that differed from nonreactors in their cardiac data profiles. Of 16 subjects that completed the glove test, five were identified as reactors. Am. J. Primatol. 45:245–261, 1998. © 1998 Wiley-Liss, Inc.     

Effects of different recovery interventions on anaerobic performances following preseason soccer training

In the preseason soccer training, morning and afternoon training sessions often are scheduled daily. The high frequency of training sessions could place heavy strain on biological systems, and it is necessary to apply proper recovery strategies for improving the players' capability to regain an adequate working state for subsequent training units. However, the effect of recovery interventions following soccer training units is debatable, due to a lack of studies performed in field situations. The aim of this study was to examine, during a 21-day preseason soccer training, the most effective recovery intervention (i.e., passive, dry-aerobic exercises, water-aerobic exercises, electrostimulation) on anaerobic performances (i.e., squat jump, countermovement jump, bounce jumping, and 10-m sprint) and subjective ratings (i.e., perceived exertion and muscle pain), with the conditions before the intervention controlled and standardized. Twelve young (age: 18.1 +/- 1.2 years) elite soccer players participated. Data were collected on 4 occasions 2 days apart and at the same time of the day. Activity and dietary intake were replicated on each occasion. After baseline measurements, participants performed a standardized training during which their heart rates and ratings of perceived exertion were recorded. This was followed by a 20-minute recovery intervention. After a 5-hour rest, athletes' ratings of muscle pain were recorded prior to a second test session. There were no significant differences in exercise intensities and baseline anaerobic performances. Significantly (p < 0.01) better performances were observed in the afternoon. Although no main effect of recovery intervention was observed on anaerobic performances, dry-aerobic exercises (0.6 +/- 0.9) and electrostimulation (0.6 +/- 1.2) were more beneficial (p < 0.01) than water-aerobic exercises (2.1 +/- 1.1) and passive rest (2.1 +/- 1.7) for reducing muscle pain, which could affect the player's working ability.     

THE SHORT-TERM BEHAVIORAL REACTIONS OF BOTTLENOSE DOLPHINS TO INTERACTIONS WITH BOATS IN DOUBTFUL SOUND, NEW ZEALAND

Doubtful Sound is home to one of the southernmost resident populations of bottlenose dolphins ( Tursiops sp.). This population regularly interacts with scenic cruises. During these interactions, dolphins tend to horizontally and vertically avoid vessels, especially when the behavior of these vessels is intrusive. This study aimed at understanding the behavioral reactions of individuals to these interactions that lead to the disruption of the school's behavioral state. Observing the behavioral events performed by individuals during an interaction can help define the short-term reactions elicited by the boat presence. I recorded the behavioral events performed by all individuals of focal schools. The frequency of occurrence of all events was compared depending on the presence of vessels, their behavior, and the behavioral state of the focal school. Dolphins tended to perform more side flops while interacting with powerboats, a behavior which may be used as a non-vocal communication tool. Moreover, the movement of dolphins became more erratic during interactions with all types of vessels. These effects increased when the boats were more intrusive while interacting. This study shows that the impact of interaction with boats can be minimized if the vessels respect the guidelines in place.     

Increased Sensitivity to Thermal Pain Following a Single Opiate Dose Is Influenced by the COMT val158met Polymorphism

Increased pain sensitivity after opioid administration (opioid-induced hyperalgesia) and/or repeated painful stimuli is an individually varying and clinically important phenomenon. The functional polymorphism (val¹⁵⁸met) of the Catechol-O-methyltransferase (COMT) gene regulates the metabolism of dopamine/noradrenaline. Individuals homozygous for the met¹⁵⁸ allele have been reported to have increased pain sensitivity and there are findings of lower µ-opioid system activation during sustained pain. We hypothesized that met/met individuals would exhibit higher pain sensitization and opioid-induced hyperalgesia in response to repeated pain stimuli and an intravenous injection of an opioid drug.Participants were 43 healthy subjects who went through an experiment where five blocks of pain were induced to the hand using a heat probe. After each stimulus subjects rated the pain on a visual analogue scale (VAS) from 0 mm (no pain) to 100 mm (worst possible pain). Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug.At baseline there was no difference in pain ratings between the COMTval¹⁵⁸met genotypes, F(2, 39)<1. However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval¹⁵⁸met genotype, F(2, 36) = 4.17, p = 0.024. Met/met individuals reported significantly more pain compared to val/val, p = 0.010. A pairwise comparison of baseline and the opioid intervention demonstrated that analgesia was induced in all groups (p = 0.042) without a separating effect for genotype (n.s).We suggest that the initial response of the descending pain system is not influenced by the COMTval¹⁵⁸met polymorphism but when the system is challenged the difference is revealed. An important clinical implication of this may be that the COMTval¹⁵⁸met related differences may be more expressed in individuals where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients. This has to be proven in future studies where the impact of the COMTval¹⁵⁸met polymorphism on opioid treatment in patients is addressed.