Temporal summation of second pain is affected by cognitive load.

This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtained from 21 healthy participants during the presentation of four experimental conditions that differed in the manipulation of attention to painful stimuli or working memory load (Attention to hand & TSSP; 0-back & TSSP (low cognitive load); 2-back & TSSP (high cognitive load); 2-back (without pain)). We found that the TSSP was reduced when the attention was diverted and the cognitive load increased, and this reduction was accompanied by higher midfrontal theta activity and lower posterior alpha and central beta activity. Although it is well established that TSSP is a phenomenon that occurs at the spinal level, here we show that it is also affected by supraspinal attentional mechanisms. Delivery of painful repeated stimuli did not affect the performance of the 2-back task but was associated with smaller amplitudes of attentional event-related potentials (ERPs) after standard stimuli (not the target). The study of brain activity during TSSP allowed to clarify the role of top-down attentional modulation in pain sensitization processes. Results contribute to a better understanding of cognitive dysfunction in pain conditions and reinforce the use of therapeutic strategies based on distracting attention away from pain.

The polymorphism Val158Met in the COMT gene: disrupted dopamine system in fibromyalgia patients?

ABSTRACT: The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene ( COMT ) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial results on its role in fibromyalgia (FM). Here, the SNP Val158Met was analyzed in 294 FM patients (without comorbidities) and 209 healthy controls (without chronic pain). The concurrent impact of Val158Met genotypes and FM comorbid disorders (depression and sleep impairment) on FM risk were tested. In addition, the genotypic distribution of FM patients in relation to pain intensity was evaluated. The G allele (Val) resulted in being more represented in the FM group (57.8%) compared with the control group (48.8%; P = 0.037). Logistic regression highlighted that having the G/G (Val/Val) homozygous genotype was associated with 2 times higher risk of having FM compared with the A/A (Met/Met) carriers ( P = 0.038), whereas depression and sleep impairment increased FM risk by 12 and 8 times, respectively ( P < 0.001). However, considering only the FM patient group, the A/A homozygous genotype was significantly associated with severe pain intensity ( P = 0.007). This study highlighted associations between the SNP Val158Met and both FM and pain intensity, suggesting a link between dopaminergic dysfunction and vulnerability to chronic pain. Further studies should explore this SNP in FM patients in conjunction with COMT enzymatic activity and other symptoms connected with the dopaminergic system such as depression or sleep impairment.

Quality of life in patients with fibromyalgia: Contributions of disease symptoms, lifestyle and multi-medication.

Fibromyalgia (FM) is a disease characterized by the presence of chronic and widespread musculoskeletal pain, which causes a high negative impact on the quality of life (QoL). Although there are many studies about the QoL of patients with FM, it is unknown which variables have a main influence on it. Therefore, in the present study, we aimed to determine which FM symptoms predict a worse QoL and also to establish whether lifestyle and multi-medication are associated to QoL. We assessed a sample of 134 women with FM using a semi-structured clinical interview to explore lifestyle (diet, exercise, smoking) and medication use, and questionnaires to cover the main symptoms of this disease and QoL (SF-36). We found that the patients with FM had a poor QoL, being "physical pain" and "vitality" the most affected domains. A linear regression analysis showed that depression and anxiety assessed by HADS were the FM symptoms which most significantly predicted QoL, explaining 49% of the variance. Concerning lifestyle/medication influences, we found that multiple drug treatment and smoking also predicted a worse QoL (14%). Moreover, patients who practiced exercise regularly showed better QoL than patients who did not (regardless of the severity of FM). Thus, our results suggest that treatment strategies to improve QoL in FM should be focused on improving psychological distress, promoting regular exercise and reducing smoking and multi-medication. The data highlights the role of positive self-management practices to improve QoL in FM.

Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity.

Ovarian cancer (OC) is the most lethal gynecological malignancy; therefore, more effective treatments are urgently needed. We recently reported that chloroquine (CQ) increased reactive oxygen species (ROS) in OC cell lines (OCCLs), causing DNA double-strand breaks (DSBs). Here, we analyzed whether these lesions are repaired by nonhomologous end joining (NHEJ), one of the main pathways involved in DSB repair, and if the combination of CQ with NHEJ inhibitors (NHEJi) could be effective against OC. We found that NHEJ inhibition increased the persistence of γH2AX foci after CQ-induced DNA damage, revealing an essential role of this pathway in the repair of the lesions. NHEJi decreased the proliferation of OCCLs and a strong in vitro synergistic effect on apoptosis induction was observed when combined with CQ. This effect was largely abolished by the antioxidant N-Acetyl-L-cysteine, revealing the critical role of ROS and DSB generation in CQ/NHEJi-induced lethality. We also found that the NHEJ efficiency in OCCLs was not affected by treatment with Panobinostat, a pan-histone deacetylase inhibitor that also synergizes with CQ in OCCLs by impairing homologous recombination. Accordingly, the triple combination of CQ-NHEJi-Panobinostat exerted a stronger in vitro synergistic effect. Altogether, our data suggest that the combination of these drugs could represent new therapeutic strategies against OC.

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.

Working Memory Performance, Pain and Associated Clinical Variables in Women With Fibromyalgia.

Working memory (WM) is a critical process for cognitive functioning in which fibromyalgia (FM) patients could show cognitive disturbances. Dyscognition in FM has been explained by interference from pain processing, which shares the neural substrates involved in cognition and may capture neural resources required to perform cognitive tasks. However, there is not yet data about how pain is related to WM performance, neither the role that other clinical variables could have. The objectives of this study were (1) to clarify the WM status of patients with FM and its relationship with nociception, and (2) to determine the clinical variables associated to FM that best predict WM performance. To this end, 132 women with FM undertook a neuropsychological assessment of WM functioning (Digit span, Spatial span, ACT tests and a 2-Back task) and a complete clinical assessment (FSQ, FIQ-R, BDI-1A, HADS, PSQI, MFE-30 questionnaires), including determination of pain thresholds and tolerance by pressure algometry. Patients with FM seem to preserve their WM span and ability to maintain and manipulate information online for both visuospatial and verbal domains. However, up to one-third of patients showed impairment in tasks requiring more short-term memory load, divided attention, and information processing ability (measured by the ACT task). Cognitive performance was spuriously related to the level of pain experienced, finding only that pain measures are related to the ACT task. The results of the linear regression analyses suggest that sleep problems and fatigue were the variables that best predicted WM performance in FM patients. Future research should take these variables into account when evaluating dyscognition in FM and should include dynamic measures of pain modulation.

DNA Methylation Changes in Fibromyalgia Suggest the Role of the Immune-Inflammatory Response and Central Sensitization.

Fibromyalgia (FM) has been explained as a result of gene-environment interactions. The present study aims to verify DNA methylation differences in eleven candidate genome regions previously associated to FM, evaluating DNA methylation patterns as potential disease biomarkers. DNA methylation was analyzed through bisulfite sequencing, comparing 42 FM women and their 42 healthy sisters. The associations between the level of methylation in these regions were further explored through a network analysis. Lastly, a logistic regression model investigated the regions potentially associated with FM, when controlling for sociodemographic variables and depressive symptoms. The analysis highlighted significant differences in the GCSAML region methylation between patients and controls. Moreover, seventeen single CpGs, belonging to other genes, were significantly different, however, only one cytosine related to GCSAML survived the correction for multiple comparisons. The network structure of methylation sites was different for each group; GRM2 methylation represented a central node only for FM patients. Logistic regression revealed that depressive symptoms and DNA methylation in the GRM2 region were significantly associated with FM risk. Our study encourages better exploration of GCSAML and GRM2 functions and their possible role in FM affecting immune, inflammatory response, and central sensitization of pain.

DNA methylation changes in genes involved in inflammation and depression in fibromyalgia: a pilot study.

OBJECTIVES: The present pilot study aims to investigate DNA methylation changes of genes related to fibromyalgia (FM) development and its main comorbid symptoms, including sleep impairment, inflammation, depression and other psychiatric disorders. Epigenetic modifications might trigger or perpetuate complex interplay between pain transduction/transmission, central pain processing and experienced stressors in vulnerable individuals. METHODS: We conducted DNA methylation analysis by targeted bisulfite NGS sequencing testing differential methylation in 112 genomic regions from leukocytes of eight women with FM and their eight healthy sisters as controls. RESULTS: Tests for differentially methylated regions and cytosines brought focus on the GRM2 gene, encoding the metabotropic glutamate receptor2. The slightly increased DNA methylation observed in the GRM2 region of FM patients may confirm the involvement of the glutamate pathway in this pathological condition. Logistic regression highlighted the simultaneous association of methylation levels of depression and inflammation-related genes with FM. CONCLUSIONS: Altogether, the results evidence the glutamate pathway involvement in FM and support the idea that a combination of methylated and unmethylated genes could represent a risk factor to FM or its consequence, more than single genes. Further studies on the identified biomarkers could contribute to unravel the causative underlying FM mechanisms, giving reliable directions to research, improving the diagnosis and effective therapies.

A family-based study to identify genetic biomarkers of fibromyalgia: consideration of patients' subgroups.

OBJECTIVES: Evidence from genome-wide and candidate gene association studies, familial aggregation and linkage analyses demonstrate the genetic contribution to fibromyalgia (FM) disease. This study aimed to identify genetic biomarkers of FM and its related comorbid disorders, by exploring 41 polymorphisms potentially involved in FM pathogenesis in families with at least one patient with FM. METHODS: Core symptoms were assessed, and blood samples collected from 556 patients with FM and 395 healthy relatives. For the genetic study, a final sample of 401 FM patients and 232 healthy controls was selected, discarding patients with concomitant pathologies and controls with chronic pain. A family-based approach using DFAM test (Plink) and SNPs (single nucleotide polymorphisms) combination analyses to compare FM patients vs. controls were first applied. Second, the genotypic distribution of subgroups of FM patients, stratified by severe vs. mild symptoms of pain, depression and sleep impairment, was considered. RESULTS: No evidence of associations with FM per se were detected, using either a family-based approach or SNPs combination analyses. However, considering the subgroups of FM patients, the SNP rs6454674 (CNR1, cannabinoid receptor 1 gene) was found as a potential genetic marker of FM correlated with depression (p<.001). CONCLUSIONS: No significant associations using either the family-based analysis or the SNPs combination tests dissociated FM patients and their healthy relatives. FM patients with and without depression showed a significant difference in the genotypic distribution related to the SNP rs6454674 in the cannabinoid receptor 1 gene (CNR1) indicating that FM is not a homogenous disorder.

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.

Chronic kidney disease of unknown cause in Mexico: The case of Poncitlan, Jalisco.

Chronic kidney disease of unknown cause (CKDu) is relatively common in low- and middle-income countries. A high prevalence of CKDu has been reported among the inhabitants of Poncitlan, Mexico. We did a cross-sectional study to compare the characteristics of residents in Poncitlan, a very poor municipality, with those from other municipalities in Jalisco state. We also estimated the prevalence of renal replacement therapy (RRT) in this region. We assessed 51,789 individuals in Jalisco: 16,351 (32.1%) were men, mean age 51.8 ± 15.3 years; 650 (1.3%) were aged < 18 years. Overall the prevalence of CKD (10.5%) and proteinuria (11.5%), were similar to the overall Mexican population. There were 283 adult and 144 child participants who resided in Poncitlan: adults were more likely to be female (78.0 vs. 67.9%, p = 0.000) but were of similar age as compared to those from other municipalities; children were younger (8.78 ± 3.97 vs. 15.03 ± 2.57 years, p = 0.000) but had a similar proportion of females compared to children from other municipalities. In Poncitlan, the prevalence of CKD and proteinuria were both higher in adults compared to those from other municipalities (CKD: 20.1 vs. 10.4%, p = 0.002; proteinuria: 36.1 vs. 11.0%, p = 0.000), and the prevalence of proteinuria in children was also higher (44.4 vs. 4.8%, p = 0.000). However, the prevalence of diabetes mellitus and obesity were lower in Poncitlan than elsewhere. The prevalence of RRT in Poncitlan was 2,228 pmp, twice as high as the prevalence for Jalisco state as a whole. In conclusion, CKD and proteinuria were detected frequently in residents of the Poncitlan community. Future studies should consider the possibility that CKDu is due to multifactorial causes, especially in poor communities.
.

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.

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.

Broad cognitive complaints but subtle objective working memory impairment in fibromyalgia patients.

BACKGROUND: Cognitive dysfunction in fibromyalgia (FM) encompasses objective cognitive difficulties, as measured in neuropsychological tests, and self-reported cognitive complaints. Although it has been suggested that FM patients display problems in working memory, the data are inconsistent, and the overall working memory status of the patients is unclear. It is also not clear whether the working memory problems are related to cognitive complaints or how the dyscognition is affected by the characteristic clinical symptoms of FM. METHODS: To clarify these aspects, we explored the neuropsychological performance for different components of working memory and the subjective self-perception of cognitive status in a sample of 38 women with FM. They were compared with a matched group of 32 healthy women. RESULTS: Our findings suggested that the FM patients do not differ from healthy controls in their overall working memory functioning. Only a poor performance was found in a single task of visuospatial working memory, mediated by the presence of depressive symptoms, fatigue and pain. The FM patients also displayed a higher level of perception of cognitive difficulties than healthy controls, and this difference was mediated by depression and fatigue. Furthermore, cognitive complaints in FM patients were only associated with a lower verbal WM capacity. DISCUSSION: FM patients have a subtle specific impairment in their working memory functioning, as well as elevated concern about their cognitive status. These findings suggest a disconnection between neuropsychological performance and subjective complaints. In FM patients, clinical variables such as pain, fatigue, and depression play an important role in dyscognition, as assessed by both objective and subjective measures, and should be taken into account in future research.

Prevention of low bone mass to achieve high bone density in Mexico: position of the Mexican Association for Bone and Mineral Metabolism.

In Mexico, osteoporosis is a public health problem. In this document, the Mexican Association for Bone and Mineral Metabolism defines its position on calcium, vitamin D supplement use, and physical activity as an effective, safe, and cost-effective initiatives to prevent low bone mass. INTRODUCTION: In Mexico, osteoporosis is a public health problem that is expected to increase in the decades ahead. Generally, modifiable risk factors for bone health are related with lifestyles, especially nutrition and physical activity. METHODS: In this position paper, the Mexican Association for Bone and Mineral Metabolism (AMMOM, by its acronym in Spanish), which is a multidisciplinary group of researchers, dietitians, epidemiologists, nurses, and physicians who study bone and related tissues and communicate the best strategies for diagnosis, treatment, and prevention of bone problems, aims to analyze the association between nutrition and bone health, risk behaviors for low bone mass, and the economic impact that prevention of low bone mass represents for the health care system. RESULTS: Addressing therapeutic management with pharmacological and non-pharmacological approaches, we emphasize the important role the patient plays in the doctor-patient relationship, both in the consulting room and in daily life. Furthermore, the AMMOM defines its position on calcium and vitamin D supplement use as an effective, safe, and cost-effective initiative to prevent low bone mass. CONCLUSIONS: In summary, most research and clinical practice related to osteoporosis have focused on diagnosis and treatment, but general measures for primary prevention based on addressing modifiable risk factors as a public health priority to delay the onset of loss of bone mass have not been considered by Mexican authorities. Consequently, the AMMOM task force also seeks to provide information on concrete actions to prevent low bone mass.

Defective Endogenous Pain Modulation in Fibromyalgia: A Meta-Analysis of Temporal Summation and Conditioned Pain Modulation Paradigms.

To study the characteristics of temporal summation (TS) and conditioned pain modulation (CPM) in fibromyalgia (FM) patients, we systematically searched Pubmed and EMBASE for studies using TS or CPM comparing FM patients with healthy controls. We computed Hedges' g, risk of bias, sensitivity analysis, and meta-regression tests with 10,000 Monte-Carlo permutations. Twenty-three studies (625 female and 23 male FM patients and 591 female and 81 male healthy controls) were included. The meta-analyses showed an effect size of .53 for TS (P < .001; 95% confidence interval = .23-.83), which is a 68% relative difference between patients and controls, and of .57 for CPM (P < .001; 95% confidence interval = -.88 to -.26), representing a 65% relative difference between the groups. The qualitative analyses revealed large heterogeneity between study protocols. Although studies were of low risk of bias, lack of blinding was substantial. Sensitivity analysis and meta-regression identified type and site of stimulation, age, lab, sample size, and medication control as important sources of between-study variability. We showed a significant alteration of pain modulation mechanisms in FM patients. PERSPECTIVE: This novel meta-analysis provides evidence for defective endogenous pain modulation in FM patients. We explored the effect of covariates on between-study variability in these paradigms. These biomarkers may aid in diagnosis, and treatment of patients. However, validation requires further investigation under strict methodological settings, and into individual patient covariates.

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.