Patients with fibromyalgia show increased beta connectivity across distant networks and microstates alterations in resting-state electroencephalogram.

Fibromyalgia (FM) is a chronic condition characterized by widespread pain of unknown etiology associated with alterations in the central nervous system. Although previous studies demonstrated altered patterns of brain activity during pain processing in patients with FM, alterations in spontaneous brain oscillations, in terms of functional connectivity or microstates, have been barely explored so far. Here we recorded the EEG from 43 patients with FM and 51 healthy controls during open-eyes resting-state. We analyzed the functional connectivity between different brain networks computing the phase lag index after group Independent Component Analysis, and also performed an EEG microstates analysis. Patients with FM showed increased beta band connectivity between different brain networks and alterations in some microstates parameters (specifically lower occurrence and coverage of microstate class C). We speculate that the observed alterations in spontaneous EEG may suggest the dominance of endogenous top-down influences; this could be related to limited processing of novel external events and the deterioration of flexible behavior and cognitive control frequently reported for FM. These findings provide the first evidence of alterations in long-distance phase connectivity and microstate indices at rest, and represent progress towards the understanding of the pathophysiology of fibromyalgia and the identification of novel biomarkers for its diagnosis.

Brain Electrical Activity Associated With Visual Attention and Reactive Motor Inhibition in Patients With Fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a generalized chronic pain condition associated with multiple cognitive impairments, including altered inhibitory processes. Inhibition is a key component of human executive functions and shares neural substrate with pain processing, which may explain the inhibitory deficits in FM. Here, we investigated the integrity of brain inhibitory mechanisms in these patients. METHODS: We recorded the electroencephalographic activity of 27 patients with FM and 27 healthy controls (HCs) (all women) while they performed a reactive motor inhibition task (the stop-signal paradigm). We analyzed task-induced modulations in electrophysiological markers related to inhibition (N2, P3, and midfrontal theta oscillations) and visual attention (posterior alpha oscillations). RESULTS: The FM group performed the task correctly, with no differences relative to HCs at the behavioral level. We did not find any between-group differences in N2 amplitude (F(1,52) = 0.01, p = .93), P3 amplitude (F(1,52) = 3.46; p = .068), or theta power (F(1,52) = 0.05; p = .82). However, modulation of posterior alpha power after presentation of either the go or stop stimuli was lower in patients than in HCs (F(1,52) = 7.98; p = .007). CONCLUSIONS: N2, P3, theta power, and behavioral results indicate that the mechanisms of motor inhibition are sufficiently preserved to enable correct performance of the stop-signal task in patients with FM. Nevertheless, the lower modulation of alpha suggests greater difficulty in mobilizing and maintaining visual attentional resources, a result that may explain the cognitive dysfunction observed in FM.

Electroencephalographic Evidence of Altered Top-Down Attentional Modulation in Fibromyalgia Patients During a Working Memory Task.

Fibromyalgia (FM) is a chronic syndrome involving widespread pain of unclear pathophysiology. FM patients frequently complain about cognitive symptoms that interfere with their daily life activities. Several studies have reported attentional deficits and working memory impairment in FM patients. Nevertheless, the mechanisms involved in these alterations are still poorly understood. In this study we recorded electroencephalographic activity in 32 women with FM and 30 matched controls while they performed a 2-back working memory task. We analyzed behavioural data, posterior alpha and midfrontal theta frequency power, and theta phase synchronization between midfrontal locations and the remaining scalp-recorded areas. Task performance was similar in patients and controls; however, time-frequency analysis showed a smaller decrease in the amplitude of the posterior alpha (related to attentional processing) and a smaller increase in midfrontal theta power (related to mental effort) in FM patients than in healthy controls. The FM patients also showed lower functional connectivity between midfrontal locations and rest of the scalp-recorded areas in the theta band (related to information transfer across distant brain regions when top-down control is required). To our knowledge, this is the first study relating alterations in oscillatory activity and impaired connectivity to attentional working memory complaints in FM patients. Reduced power in the theta band during performance of the task suggests that the medial frontal cortex may play an important role in the attentional deficits reported in FM.

When the brain simulates stopping: Neural activity recorded during real and imagined stop-signal tasks.

It has been suggested that mental rehearsal activates brain areas similar to those activated by real performance. Although inhibition is a key function of human behavior, there are no previous reports of brain activity during imagined response cancellation. We analyzed event-related potentials (ERPs) and time-frequency data associated with motor execution and inhibition during real and imagined performance of a stop-signal task. The ERPs characteristic of stop trials-that is, the stop-N2 and stop-P3-were also observed during covert performance of the task. Imagined stop (IS) trials yielded smaller stop-N2 amplitudes than did successful stop (SS) and unsuccessful stop (US) trials, but midfrontal theta power similar to that in SS trials. The stop-P3 amplitude for IS was intermediate between those observed for SS and US. The results may be explained by the absence of error-processing and correction processes during imagined performance. For go trials, real execution was associated with higher mu and beta desynchronization over motor areas, which confirms previous reports of lower motor activation during imagined execution and also with larger P3b amplitudes, probably indicating increased top-down attention to the real task. The similar patterns of activity observed for imagined and real performance suggest that imagination tasks may be useful for training inhibitory processes. Nevertheless, brain activation was generally weaker during mental rehearsal, probably as a result of the reduced engagement of top-down mechanisms and limited error processing.

Evaluation of the accuracy of several symptoms and domains in distinguishing patients diagnosed with fibromyalgia from healthy controls.

OBJECTIVES: To assess the discriminative power of several symptoms and domains that may assist in the diagnosis of subjects with Fibromyalgia (FM). METHODS: 79 individuals with FM and 66 healthy controls participated in the study. The potential domains proposed by the American College of Rheumatology (ACR) criteria were considered (Wolfe et al., 1990). Binary logistic regression and area under a ROC curve (AUC) were used to rank the importance of the variables in distinguishing patients from pain-free controls. Z values were then calculated to compare the AUC values obtained for each variable with that which yielded the highest AUC (reference standard). For each measure, the cut-offs that maximise sensitivity and specificity were also calculated. RESULTS: The mean pressure pain threshold (PPT) yielded the highest discriminative power (AUC, 0.991) and was therefore chosen as the reference standard; considering an optimal cut- off ≤3.97, it correctly classified 95% of patients and 97% of controls. The discriminative powers of tender point count (cut-off ≥9), health-related quality of life (cut-off ≤63.27) and vitality (cut-off ≤46.97) were as good as that of the reference standard. Finally, items related to physical role and function, body pain, fatigue and memory loss showed adequate discriminative power, although slightly lower than that of the reference. CONCLUSIONS: In addition to pain, health-related quality of life and fatigue/vitality were confirmed as the best predictors of individuals with FM. The study findings indicate that tender point count and especially pressure pain threshold (measured with an algometer) continue to be key issues in the clinical assessment of subjects with FM relative to pain-free controls.

Brain processing of task-relevant and task-irrelevant emotional words: an ERP study.

Although there is evidence for preferential perceptual processing of written emotional information, the effects of attentional manipulations and the time course of affective processing require further clarification. In this study, we attempted to investigate how the emotional content of words modulates cerebral functioning (event-related potentials, ERPs) and behavior (reaction times, RTs) when the content is task-irrelevant (emotional Stroop Task, EST) or task-relevant (emotional categorization task, ECT), in a sample of healthy middle-aged women. In the EST, the RTs were longer for emotional words than for neutral words, and in the ECT, they were longer for neutral and negative words than for positive words. A principal components analysis of the ERPs identified various temporospatial factors that were differentially modified by emotional content. P2 was the first emotion-sensitive component, with enhanced factor scores for negative nouns across tasks. The N2 and late positive complex had enhanced factor scores for emotional relative to neutral information only in the ECT. The results reinforce the idea that written emotional information has a preferential processing route, both when it is task-irrelevant (producing behavioral interference) and when it is task-relevant (facilitating the categorization). After early automatic processing of the emotional content, late ERPs become more emotionally modulated as the level of attention to the valence increases.

The effects of C-tactile stimulation on temporal summation of second pain: A study of the central and peripheral neural correlates.

Affective touch is mediated by specialized receptors sensitive to gentle and slow touch called C-tactile afferents (CT). The activation of these receptors has shown promise in reducing subjective pain ratings, however, how this type of touch can affect central sensitization processes is poorly studied. This work aimed to investigate if affective touch is able to modulate pain sensitization and its electrophysiological correlates during Temporal Summation of Second Pain (TSSP), a phenomenon characterized by an increase in pain perception due to repeated noxious stimuli. Thirty-seven participants underwent a TSSP protocol involving three conditions: TSSP alone, TSSP during vibrotactile stimulation, and TSSP during CT stimulation (administered with a brush mounted in a robot arm). We measured subjective pain ratings, electroencephalographic (N2-P2 complex) and electrocardiographic activity during these conditions. Participants reported a significantly lower increase of pain during CT stimulation compared to vibrotactile stimulation, but not to TSSP alone. In addition, TSSP was reduced when administered in the ipsilateral arm compared to the other somatosensory stimulation. Subjective reports of attention towards painful stimuli, amplitude of the N2-P2 complex, and heart rate were also reduced during CT stimulation. Conclusion: Our results indicated that the activation of CT receptors may reduce sensitization compared to other types of somatosensory stimulation, which is possibly related to the reduction of the attention devoted to nociceptive stimulation. Our results suggest that activation of CT receptors may alleviate the occurrence of central pain sensitization.

Translation, validity, and reliability of the European Portuguese version of the Touch Experiences and Attitudes Questionnaire.

Background: Positive touch experiences have proved to be extremely important throughout our lifespan, with cascading effects on our social life. However, few questionnaires are available to measure attitudes and experiences of touch in the Portuguese population. This study aimed to translate and validate the European Portuguese version of the Touch Experiences and Attitudes Questionnaire (TEAQ), as a reliable and valid instrument to measure different aspects of affective touch experiences and attitudes. Methods: Therefore, an online sample of 384 (299 females and 85 males) participants, aged between 18 and 75 years (M = 24.59; SD = 9.56) was collected. Multidimensional Rasch model and confirmatory factor analysis were carried out, and also reliability and convergent and discriminant validity were determined. In addition, we examined sex differences in attitudes and experiences of touch. Results: Results showed good fit indexes for the 52-item six-factor model structure (friends and family touch, current intimate touch, childhood touch, attitudes to self-care, attitudes to intimate touch, and attitudes to unfamiliar touch). This instrument also showed good reliability and acceptable convergent and discriminant validity. Significant sex differences were found, with female participants reporting more positive touch experiences (including childhood touch, friends and family touch, and current intimate touch) and a more favourable attitude to self-care, with males showing a more positive attitude towards unfamiliar touch. Regarding attitudes towards the intimate touch, scores for both groups were comparable. Conclusion: Overall, the European Portuguese version of the TEAQ presented good psychometric properties and appears to be a reliable and valid self-report measure, being a useful and beneficial instrument in research and clinical settings.

Transcranial direct current stimulation of 3 cortical targets is no more effective than placebo as treatment for fibromyalgia: a double-blind sham-controlled clinical trial.

ABSTRACT: Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and the dorsolateral prefrontal cortex seem to improve pain and other symptoms of fibromyalgia (FM), although the evidence on the effectiveness of tDCS and the optimal stimulation target is not robust enough. Our main objective was to establish the optimal area of stimulation, comparing the 2 classical targets and a novel pain-related area, the operculo-insular cortex, in a sham-controlled trial. Using a double-blind design, we randomly assigned 130 women with FM to 4 treatment groups (M1, dorsolateral prefrontal cortex, operculo-insular cortex, and sham), each receiving fifteen 20-minute sessions of 2 mA anodal tDCS over the left hemisphere. Our primary outcome was pain intensity. The secondary outcomes were the other core symptoms of FM (fatigue, mood, cognitive and sleep disorders, and hyperalgesia measured by the pressure pain threshold). We performed the assessment at 3 time points (before, immediately after treatment, and at 6 months follow-up). The linear mixed-model analysis of variances showed significant treatment effects across time for clinical pain and for fatigue, cognitive and sleep disturbances, and experimental pain, irrespective of the group. In mood, the 3 active tDCS groups showed a significantly larger improvement in anxiety and depression than sham. Our findings provide evidence of a placebo effect, support the use of tDCS for the treatment of affective symptoms, and challenge the effectiveness of tDCS as treatment of FM.

Brain electrical activity signatures during performance of the Multisource Interference Task.

The Multisource Interference Task (MSIT) was developed to test cognitive control in normal and pathological conditions and has become a reliable tool for exploring the integrity of cingulo-frontal-parietal cognitive/attentional networks in fMRI studies. Analysis of EEG recordings made during performance of the MSIT may provide additional information about the temporal dynamics of cognitive control. However, this has not yet been investigated in depth. In this study, we analyzed the ERPs and carried out time-frequency decomposition of EEG recorded during control and interference conditions of the MSIT. The N2 ERP component and midfrontal theta power (both considered neural signatures of conflict processing) were significantly larger in interference than in control trials. Theta also showed higher phase synchronization between midfrontal and right frontolateral scalp locations in the interference condition, supporting the view that this frequency band entrains additional brain resources when a need for greater control arises. In interference trials, we also observed longer P3 latency, larger P3 amplitude, and greater reduction of posterior alpha (modulations related to allocation of attentional resources), in addition to a greater reduction of central beta power (related to motor preparation). In conclusion, the MSIT reliably modulated brain electrical activity related to cognitive control and attention. The EEG indices obtained during the performance of this task may be useful for exploring the functioning of cognitive/attentional networks in healthy and clinical populations.

Functional Equivalence of Imagined vs. Real Performance of an Inhibitory Task: An EEG/ERP Study.

Early neuroimaging and electrophysiological studies suggested that motor imagery recruited a different network than motor execution. However, several studies have provided evidence for the involvement of the same circuits in motor imagery tasks, in the absence of overt responses. The present study aimed to test whether imagined performance of a stop-signal task produces a similar pattern of motor-related EEG activity than that observed during real performance. To this end, mu and beta event-related desynchronization (ERD) and the Lateralized Readiness Potential (LRP) were analyzed. The study also aimed to clarify the functional significance of the Stop-N2 and Stop-P3 event-related potential (ERPs) components, which were also obtained during both real and imagined performance. The results showed a common pattern of brain electrical activity, and with a similar time course, during covert performance and overt execution of the stop-signal task: presence of LRP and Stop-P3 in the imagined condition and identical LRP onset, and similar mu and beta ERD temporal windows for both conditions. These findings suggest that a similar inhibitory network may be activated during both overt and covert execution of the task. Therefore, motor imagery may be useful to improve inhibitory skills and to develop new communicating systems for Brain-Computer Interface (BCI) devices based on inhibitory signals.