Pain expressions and inhibitory control in patients with fibromyalgia: behavioral and neural correlates

Fibromyalgia (FM) is a generalized chronic pain condition associated with a variety of symptoms, including altered cognitive and emotional processing. It has been proposed that FM patients show a preferential allocation of attention to information related to the symptoms of the disease, particularly to pain cues. However, the existing literature does not provide conclusive evidence on the presence of this attentional bias, and its effect on cognitive functions such as inhibitory control. To clarify this issue, we recorded the electroencephalographic activity of 31 women diagnosed with FM and 28 healthy women, while performing an emotional Go/NoGo task with micro-videos of pain, happy, and neutral facial expressions. We analyzed behavioral data, performed EEG time-frequency analyses, and obtained the event-related potentials (ERPs) N2 and P3 components in NoGo trials. A series of self-reports was also administered to evaluate catastrophic thinking and the main symptoms of fibromyalgia. Pain expressions were associated with longer reaction times and more errors, as well as with higher theta and delta power, and P3 amplitude to NoGo stimuli. Thus, behavioral and psychophysiological data suggest that increased attention to pain expressions impairs the performance of an inhibitory task, although this effect was similar in FM patients and healthy controls. N2 amplitude was modulated by type of facial expression (larger to pain faces), but only for the control group. This finding suggests that the presentation of pain faces might represent a smaller conflict for the patients, more used to encounter pain stimuli. No main group effects were found significant for N2 or P3 amplitudes, nor for time-frequency data. Using stimuli with greater ecological validity than in previous studies, we could not confirm a greater effect of attentional bias toward negative stimuli over inhibitory performance in patients with FM. Studying these effects allow us to better understand the mechanisms that maintain pain and develop intervention strategies to modify them.Galician Government (Consellería de Cultura, Educación e Ordenación Universitaria; axudas para a consolidación e estruturación de unidades de investigación competitivas do Sistema Universitario de Galicia [grant number GPC2014/047] and funding from the Spanish Government (Ministerio de Economía y Competitividad) [grant number PSI2013-45818-R]. AG-V was supported by a grant from the Deputación da Coruña (Bolsas de investigación en ciencias da saúde 2017) and Xunta de Galici

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 researchThis work was supported by funding from the Galician Government (Consellería de Cultura, Educación e Ordenación Universitaria; axudas para a consolidación e Estruturación de unidades de investigación competitivas do Sistema universitario de Galicia [grant number GPC2014/047] and funding from the Spanish Government (Ministerio de Economía y Competitividad) [Grant Number PSI2013-45818-R]. Alberto González-Villar was supported by a grant from the Fundación Ramón DomínguezS

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 modulationThis study was funded by the Spanish State Research Agency (Call: Retos 2016. Project reference: PSI2016-75313-R) and Consellería de Cultura, Educación e Universidades, Xunta de Galicia (Code: ED431C 2021/04)S

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 therapiesThis study was supported by Spanish Government Funding (Ministerio de Economía y Competitividad: grant PSI2013-45818-R). The genotyping service was carried out at CEGEN-PRB3-ISCIII; it is supported by grant PT17/0019, of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. MCG and LAN are part of the Center for Neuroplasticity and Pain (CNAP) which is supported by the Danish National Research Foundation (DNRF121)S

Funcionamiento cognitivo en mujeres con fibromialgia: caracterización, variables asociadas y efecto de la neuromodulación

El objetivo principal de esta tesis es estudiar el funcionamiento cognitivo en pacientes con fibromialgia (FM). Para ello, comparamos el rendimiento cognitivo de una muestra de pacientes con FM y un grupo control en una serie de medidas objetivas de memoria de trabajo, identificando qué subcomponentes estarían afectados. A continuación, pretendemos identificar la relación entre el funcionamiento en estos procesos cognitivos y las características sociodemográficas y variables clínicas de las pacientes, y valuar la asociación del impacto funcional y las quejas cognitivas subjetivas. El objetivo último de esta tesis es probar la eficacia de un tratamiento con estimulación eléctrica transcraneal por corriente directa en el funcionamiento cognitivo de estas pacientes.2022-11-2

Active and sham transcranial direct current stimulation (tDCS) improved quality of life in female patients with fibromyalgia

Purpose: Fibromyalgia (FM) is a chronic pain syndrome with a strong impact on quality of life (QoL). Treatment of this condition remains a challenge, due to the scarce evidence for the effectiveness of the therapeutic approaches available. Current attention is focused on transcranial direct current stimulation (tDCS), which has yielded promising results for pain treatment. Rather than focusing only on pain relief, in this study, we aimed to determine how active or sham tDCS (over three cortical targets -the primary motor cortex, the dorsolateral prefrontal cortex and the operculo-insular cortex-) affect QoL in patients with FM. Methods: Using a double-blind, placebo-controlled design, we applied fifteen tDCS sessions of 20’ to initial 130 participants (randomized to any of the four treatment groups). We evaluated the QoL (assessed by SF-36) and the symptoms’ impact (assessed by FIQ-R) in baseline, after treatment and at 6 months follow-up. Results All groups were comparable as regards age, medication pattern and severity of symptoms before the treatment. We found that QoL and symptoms’ impact improved in all treatment groups (including the sham) and this improvement lasted for up to 6 months. However, we did not observe any group effect nor group*treatment interaction. Conclusions: After the intervention, we observed a non-specific effect that may be due to placebo, favoured by the expectations of tDCS efficacy and psychosocial variables inherent to the intervention (daily relationship with therapists and other patients in the clinic). Therefore, active tDCS is not superior to sham stimulation in improving QoL in FMOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The Spanish Government (Ministerio de Economia y Competitividad; number PSI2016-75313-R) supported this research. Moreover, AJG-V was supported by a grant from the Portuguese Foundation for Science and Technology within the scope of the Individual Call for Stimulus to Scientific Employment 2017. NS-V was benefited from a grant from the Spanish Government (Ministerio de Economía y Competitividad; grant number BES-2017–082684)S

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

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.This study has been funded by the Spanish Government (Ministerio de Economía y Competitividad; ref PSI2016-75313-R). In addition, A.J. González-Villar was supported by a grant from the Portuguese Foundation for Science and Technology within the scope of the Individual Call for Stimulus to Scientific Employment 2017. N. Samartin-Veiga was supported by a grant from the Spanish Government (Ministerio de Economía y Competitividad; grant number BES2017-082684)