Neural correlates of unpredictable Stop and non-Stop cues in overt and imagined execution.

The ability to inhibit incorrect behaviors is crucial for survival. In real contexts, cues that require stopping usually appear intermixed with indications to continue the ongoing action. However, in the classical Stop-signal task (SST), the unpredictable stimuli are always signals that require inhibition. To understand the neural mechanisms activated by low-probability nonstop cues, we recorded the electroencephalography from 23 young volunteers while they performed a modified SST where the unpredictable stimuli could be either Stop or confirmatory Go signals (CGo). To isolate the influence of motor output, the SST was performed during overt and covert execution. We found that, paradoxically, CGo stimuli activated motor inhibition processes, and evoked patterns of brain activity similar to those obtained after Stop signals (N2/P3 event-related potentials and midfrontal theta power increase), though in lesser magnitude. These patterns were also observed during the imagined performance. Finally, applying machine learning procedures, we found that the brain activity evoked after CGo versus Stop signals can be classified above chance during both, overt and imagined execution. Our results provide evidence that unpredictable signals cause motor inhibition even when they require to continue an ongoing action.

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.

Effects of the COVID-19 pandemic on chronic pain in Spain: a scoping review.

The COVID-19 outbreak has been a great challenge in the management of chronic pain patients. We have conducted a rapid scoping review to assess the impact of the pandemic (and the associated public health measures) on the health status and management practices of chronic pain patients in Spain. To this end, we performed a bibliographic search in LitCOVID and PubMed, and reviewed official websites and documents, and expert reports. The review showed that (1) the studies consistently indicate that the pandemic has had a very negative impact on the physical and psychological health of chronic pain patients; (2) there are scarce data on how the pandemic affected pain unit consultations and a lack of protocols to organize health care in the face of future waves of contagion, with little implementation of telehealth. We make proposals to improve management of chronic pain patients in pandemic situations, which should pivot around 3 axes: (1) a coordinated response of all the relevant stakeholders to define a future roadmap and research priorities, (2) a biopsychosocial approach in pain management, and (3) development and implementation of novel telemedicine solutions.

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.

Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity.

Conditioned pain modulation (CPM) is a promising psychophysical biomarker of central pain mechanisms because it significantly discriminates patients with chronic pain from healthy controls. Nevertheless, it is unclear in what extent CPM assessed experimentally is correlated with clinical manifestations of pain. To assess the concurrent validity of CPM, we performed a systematic review of the literature reporting correlations between CPM responses and pain intensity, disability, duration, and area in patients with different chronic pain conditions. We included 32 studies that altogether encompassed data from 1958 patients and provided 62 correlations. The majority of the results (69%) reported nonsignificant correlations between CPM efficiency and clinical manifestations of pain, whereas the remaining results showed a correlation between CPM reduction and worse clinical symptoms of pain. The modality of stimulation, the type of pain, and the stimulation site appear to be critical variables that influenced the pattern of results. Given that most of the studies were conducted with highly heterogeneous methodologies and unclear risk of bias, the findings highlight the need for future studies using standardized measures of clinical and experimental pain before considering CPM as a valid biomarker of pain. We discuss some guidelines to overcome the constraints in this promising line of research.

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.

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.

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.

Suicidality in chronic pain: predictors of suicidal ideation in fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) has been associated with a higher prevalence of suicidal behavior. Nevertheless, much remains unknown about suicide risk factors for this chronic pain disorder. In the present study, the relationship of suicidal ideation in FM with a number of sociodemographic, clinical, and psychological variables was analyzed. METHODS: One hundred seventeen women with Fibromyalgia were assessed. The procedure included the exploration of sleep problems (Pittsburgh Sleep Quality Index), depression (Beck Depression Inventory [BDI]), health-related quality of life (SF-36 and Fibromyalgia Impact Questionnaire), the core symptoms of FM (visual analogue scales), and algometry of tender points. Suicidal ideation was evaluated by item 9 of the BDI. Patients with presence vs. absence of suicidal ideation were compared in all the variables studied. RESULTS: The prevalence of suicidal ideation among FM patients was 32.5%. Significant differences between patients with vs. without suicidal ideas emerged mainly for the various indices of depression. Patients with suicidal ideation also reported higher levels of anxiety, more day dysfunction due to sleepiness and more limitations due to emotional and physical problems. Logistic regression analysis revealed that cognitive depression symptoms such as BDI Self-Blame cluster are the more closely related to suicide ideation. CONCLUSIONS: The presence of suicidal ideation in FM patients is closely related to comorbid depression, anxiety and to a higher impact of the disease in daily life.

Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.

The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

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.

Effects of stimuli intensity and frequency on auditory p50 and n100 sensory gating.

Sensory gating is the brain's ability to adjust its sensitivity to incoming stimuli, i.e., to diminish its response to irrelevant or repetitive stimuli (gating out) and to increase it when a novel stimulus is presented (gating in). Most of the existing studies have investigated the gating out mechanism, giving little attention to the gating in function. Although both the P50 and N100 components of the auditory ERPs (event related potentials) show amplitude reductions to stimuli repetition, it is not clear if both components are part of a common gating system or if their sensory modulation is uncorrelated. In order to respond to these questions and to further characterize the sensory gating functions, we examined to what extent P50 and N100 are influenced by changes in the stimuli parameters and whether the sensory modulation of both components are interrelated. To this end, we obtained ERPs from 23 healthy volunteers using pairs of auditory stimuli which could be identical (S1 = S2), different in frequency (S1 = 1000 Hz; S2 = 2000 Hz) or different in intensity (S1 = 80 dB SPL; S2 = 100 dB SPL). As expected, the amplitudes of P50 and N100 decreased in response to the second stimuli of the identical pairs. With non-identical pairs, amplitude increases of P50 and N100 were observed only in pairs with different intensity, but not frequency. Thus, the results showed that both P50 and N100 are sensory modulated, showing that amplitude decreased to stimuli repetition (gating out) and increased when the two stimuli of a pair differed in intensity (gating in). A correlational analysis of the sensory gating indices (S2/S1 ratio and S1-S2 difference) obtained for P50 and N100 suggested that the sensory gating function of both components may be of a different nature. The reliability of the ratio and the difference indices of sensory gating is also discussed.

Formative assessment and academic achievement in pre-graduate students of health sciences.

Although educational experts recommend the use of formative assessment, there is a dearth of empirical studies on its impact on academic achievement. In this research the authors analyse to what extent participation and performance in formative assessment are associated with positive academic outcomes of pre-graduate students of health sciences. A total of 548 students from three health science degrees (Medicine, Psychology and Biology) from four Spanish universities were involved in this study. The students who carried out mid-term formative assessment got better marks and had higher success rates in final summative assessment that the students who did not participate. In addition, success in formative assessment tests was associated with better summative marks. Interestingly, participation in formative assessment was a better predictor of final outcome than success in formative assessment, a result that supports the key role of feedback in formative assessment. Students who took the mid-term examination, irrespective of their success, obtained feedback about their achievement and probably this determined their greater involvement in the learning process. Although causal relationships between formative and summative assessment cannot be established from this research, the generalized benefits of formative assessments found here encourage the practice of them in health sciences education.

ERP evidence of MI activation without motor response execution.

There has been controversy concerning the activity of the primary motor cortex (MI) during the mental rehearsal of movement (motor imagination). In this study we found that the lateralized readiness potential (LRP), an event-related potential probably generated in MI, appeared with similar latencies during both trials requiring execution of hand movements and trials requiring only their mental rehearsal, regardless of whether misleading pre-cues that increased latency were employed. However, LRPs obtained during imagination trials had smaller amplitudes. We conclude that MI is involved in motor imagination as well as in preparing overt movement, and that in overt movement the LRP sums neural activity common to these two situations and neural activity exclusive to overt movement.