Search

Fibromyalgia (FM) and ankylosing spondylitis (AS) are both rheumatic diseases characterized by significant musculoskeletal pain. In this study, we investigated the differences of the resting-state network (RSN) connectivity and gray matter volume (GMV) between FM, AS and healthy controls (HCs). We recruited 38 FM patients, 82 AS patients and 61 HCs in this study. All the participants underwent resting-state functional MRI (rs-fMRI) scans in a GE 3.0T MR system. Independent component analysis (ICA) was conducted on the rs-fMRI data, and group differences of the rsFC between different resting-state networks were calculated using dual regression. We also conducted voxel-based morphometry (VBM) analysis to investigate the differences of the GMV in FM, AS and HCs. The rsFC between the dorsal default mode network (DDMN) and the body of left caudate nucleus was significantly decreased in FM patients in comparison to AS patients (87 voxels, p = 0.025). VBM analysis showed that the GMV of the left posterior lobe of cerebellum was significantly increased in FM patients compared with AS patients (88 voxels, p = 0.036). Neither ICA nor VBM analysis revealed significant differences of RSN connectivity or GMV between FM patients and HCs. The altered rsFC between DMN and the caudate nucleus suggested an aberrant cortico-striato-thalamo-cortical circuit in FM patients, indicating aberrant reward processing, with potential association with mood, motivation and cognitive functions. The increased GMV in the left posterior lobe of cerebellum indicated the participation of cerebellum in the abnormal pain processing in FM patients., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Research Ethics Board of the Third Affiliated Hospital of Sun Yat-sen University. Written informed consent was obtained from patients prior to the inclusion of this study according to the Declaration of Helsinki. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Few neuroimaging studies have investigated structural brain differences associated with variations in pain distribution., Objective: To explore structural differences of the brain in fibromyalgia (FM), temporomandibular disorder pain (TMD) and healthy pain-free controls (CON) using structural and diffusion MRI., Methods: A case-control exploratory study with three study groups with different pain distribution were recruited: FM (n = 16; mean age [standard deviation]: 44 [14] years), TMD (n = 17, 39 [14] years) and CON (n = 10, 37 [14] years). Participants were recruited at the University Dental Clinic in Malmö, Sweden. T1-weighted and diffusion MRIs were acquired, clinical and psychosocial measures were obtained. Main outcome measures were subcortical volume, cortical thickness, white matter microstructure and whole brain grey matter intensity., Results: Patients with FM had smaller volume in the right thalamus than patients with TMD (p = .020) and CON (p = .030). The right thalamus volume was negatively correlated to pain intensity (r = -0.37, p = .022) and pain-related disability (r = -0.45, p = .004). The FM group had lower cortical thickness in the right anterior prefrontal cortex than CON (p = .005). Cortical thickness in this area was negatively correlated to pain intensity (r [37] = - 0.48, p = .002)., Conclusions: This study suggests that thalamus grey matter alterations are associated with FM and TMD, and that anterior prefrontal cortex grey matter alterations are associated with FM but not TMD. Studies on chronic overlapping pain conditions are needed in relation to possible nociplastic pain mechanisms in the brain and central nervous system., (© 2024 The Author(s). Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

To provide objective diagnostic markers for fibromyalgia symptoms (FMS) diagnosis, we have created interpretable extreme gradient boosting (XGBoost) models using radiomics to aid in the diagnosis of chronic pain (CP) and to develop nomogram models for diagnosing subgroups of FMS. A group of 54 patients with CP and 71 healthy controls was randomly separated into training and validation groups, using a 7:3 ratio. Radiomics features were extracted from grey-matter and white-matter in the filtered mwp0* image. The Mann-Whitney U test, Spearman's rank correlation test, and least absolute shrinkage and selection operator (LASSO) were utilized to select features. An XGBoost model was created based on these features, and Shapley Additive exPlanations (SHAP) was used for personalization and visual interpretation. A nomogram was developed for the diagnosis of FMS subgroups, utilizing radiomics scores and clinical predictors. The efficacy of the nomogram was evaluated using the area under the receiver operating characteristic curve, while decision curve analysis was employed to evaluate its clinical efficacy. The XGBoost model displays stability in the training validation group, indicating lower overfitting of CP model. The nomogram model combined with the rad-score has a greater ability to distinguish between typical and sub-clinical than the clinical factor model alone. We developed and validated a CP diagnosis model by XGBoost and realized model visualization through SHAP. The rad-score obtained by machine learning was used to build a nomogram model that combines clinical scales to distinguish patients with typical and sub-clinical fibromyalgia., (© 2024. The Author(s).)

Fibromyalgia (FM) is a chronic condition marked by widespread pain, fatigue, sleep problems, cognitive decline, and other symptoms. Despite extensive research, the pathophysiology of FM remains poorly understood, complicating diagnosis and treatment, which often relies on self-report questionnaires. This study explored structural and functional brain changes in women with FM, identified potential biomarkers, and examined their relationship with FM severity. MRI data from 33 female FM patients and 33 matched healthy controls were utilized, focusing on T1-weighted MRI and resting-state fMRI scans. Functional connectivity (FC) analysis was performed using a machine learning framework to differentiate FM patients from healthy controls and predict FM symptom severity. No significant differences were found in brain structural features, such as gray matter volume, white matter volume, deformation-based morphometry, and cortical thickness. However, significant differences in FC were observed between FM patients and healthy controls, particularly in the default mode network (DMN), somatomotor network (SMN), visual network (VIS), and dorsal attention network (DAN). The FC metrics were significantly associated with FM severity. Our prediction model differentiated FM patients from healthy controls with an area under the curve of 0.65. FC measures accurately estimated FM symptom severities with a significant correlation (r = 0.45, p = 0.007). Functional connections in the DMN, VIS, and DAN were crucial in determining FM severity. These findings suggest that integrating brain FC measurements could serve as valuable biomarkers for identifying FM patients from healthy individuals and predicting FM symptom severity, improving diagnostic accuracy and facilitating the development of targeted therapeutic strategies., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest on their part., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Fibromyalgia syndrome (FMS) is a prevalent rheumatic disorder, and its pathogenesis includes genetic, neuroendocrine, and autonomic abnormalities, which may impact ocular structures. The aim was to conduct a comparative analysis of the ophthalmic vasculature and the retinal nerve fiber layer (RNFL) thickness between FMS and control groups using optical coherence tomography (OCT) and OCT angiography (OCTA)., Methods: This cross-sectional comparative study included 43 FMS patients and 40 healthy controls recruited from a tertiary education and research hospital between January 2024 and May 2024. All patients satisfied the 2016 American College of Rheumatology criteria for FMS and consented. OCT and OCTA were used to assess the RNFL thickness and the retinal microvasculature structure. The Fibromyalgia Impact Questionnaire (FIQ) was performed to evaluate disease severity., Results: The study found significantly higher total retinal parafoveal thickness and foveal density in FMS patients (p = 0.017 and p = 0.044, respectively). Nevertheless, there were no significant differences among the groups concerning total retinal foveal thickness, foveal avascular zone characteristics, superficial and deep capillary plexus densities, choriocapillaris flow area, and outer retinal flow area values (p > 0.05). The RNFL thickness in all quadrants did not reveal significant differences between the groups (p > 0.05). Furthermore, there was no significant correlation between FIQ scores and OCTA parameters or RNFL thickness values (p > 0.05)., Conclusion: The study revealed slight differences in retinal parafoveal thickness and foveal density in FMS patients, but no substantial vascular or neurodegenerative alterations were observed compared to healthy controls. These data indicate that FMS may not substantially affect ocular structures, contrary to earlier hypotheses., (© 2024. The Author(s).)

Fibromyalgia (FM) is a central sensitization syndrome that is strongly associated with the cerebral cortex. This study used bidirectional two-sample Mendelian randomization (MR) analysis to investigate the bidirectional causality between FM and the cortical surface area and cortical thickness of 34 brain regions. Inverse variance weighted (IVW) was used as the primary method for this study, and sensitivity analyses further supported the results. The forward MR analysis revealed that genetically determined thinner cortical thickness in the parstriangularis (OR = 0.0567 mm, PIVW = 0.0463), caudal middle frontal (OR = 0.0346 mm, PIVW = 0.0433), and rostral middle frontal (OR = 0.0285 mm, PIVW = 0.0463) was associated with FM. Additionally, a reduced genetically determined cortical surface area in the pericalcarine (OR = 0.9988 mm2, PIVW = 0.0085) was associated with an increased risk of FM. Conversely, reverse MR indicated that FM was associated with cortical thickness in the caudal middle frontal region (β = -0.0035 mm, PIVW = 0.0265), fusiform region (β = 0.0024 mm, SE = 0.0012, PIVW = 0.0440), the cortical surface area in the supramarginal (β = -9.3938 mm2, PIVW = 0.0132), and postcentral regions (β = -6.3137 mm2, PIVW = 0.0360). Reduced cortical thickness in the caudal middle frontal gyrus is shown to have a significant relationship with FM prevalence in a bidirectional causal analysis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Fibromyalgia (FM) is a chronic pain disorder that takes a severe physical and psychological toll on patients and severely reduces their quality of life. In recent years, an increasing number of studies have used functional magnetic resonance imaging (fMRI) to investigate its pathogenesis. However, a recent summary analysis of functional connectivity in patients with FM is lacking., Methods: We searched bibliographic databases, including PubMed, Web of Science (from inception until September 1st, 2022). Two separate researchers assessed the bias and quality of the studies. In order to further explain the core mechanism for FM, the abnormal brain function of FM was investigated by Activation Likelihood Estimation (ALE) analysis., Results: Twenty-six FM publications (1,056 subjects) were eligible to be included in an ALE analysis. We found that the anterior cingulate (ACC) and insula (Ins) were abnormally active in patients with FM. In particular, the peak coordinates of (8,46,4) and (-46, -4,10) correspond to brain regions that were less active than healthy individuals. Furthermore, the Z-values were 4.46 and 4.97, while the p-values were 4.06 and 3.38. Surprisingly, we found that the degree of pain was negatively correlated with the activation of Ins (SDM-Z = -2.714)., Conclusions: This study demonstrates abnormal brain activation which could lead to increased sensitivity of pain in patients with FM. The study sheds light on the central mechanisms of FM and provides the basis for further research.

Fibromyalgia is a heterogenous chronic pain disorder diagnosed by symptom-based criteria. The aim of this study was to clarify different pathophysiological characteristics between subgroups of patients with fibromyalgia. We identified subgroups with distinct pain thresholds: those with a low pressure pain threshold (PL; 16 patients) and those with a normal pressure pain threshold (PN; 15 patients). Both groups experienced severe pain. We performed resting-state functional MRI analysis and detected 11 functional connectivity pairs among all 164 ROIs with distinct difference between the two groups (p < 0.001). The most distinctive one was that the PN group had significantly higher functional connectivity between the secondary somatosensory area and the dorsal attention network (p < 0.0001). Then, we investigated the transmission pathway of pain stimuli. Functional connectivity of the thalamus to the insular cortex was significantly higher in the PL group (p < 0.01 - 0.05). These results suggest that endogenous pain driven by top-down signals via the dorsal attention network may contribute to pain sensation in a subgroup of fibromyalgia patients with a normal pain threshold. Besides, external pain driven by bottom-up signals via the spinothalamic tract may contribute to pain sensations in another group of patients with a low pain threshold. Trial registration: UMIN000037712., (© 2024. The Author(s).)

An altered brain-gut axis is suspected to be one of the pathomechanisms in fibromyalgia (FM). This cross-sectional study investigated the associations among altered microbiota, psychological distress, and brain functional connectivity (FC) in FM. We recruited 25 FM patients and 25 healthy people in the present study. Psychological distress was measured using standardized questionnaires. Microbiota analysis was performed on the participants' stools. Functional magnetic resonance imaging data were acquired, and seed-based resting-state FC (rs-FC) analysis was conducted with the salience network nodes as seeds. Linear regression and mediation analyses evaluated microbiota, symptoms, and rs-FCs associations. We found altered microbiota diversity in FM, of which Phascolarctobacterium and Lachnoclostridium taxa increased the most and Faecalibacterium taxon decreased the most compared to controls. The Phascolarctobacterium abundance significantly predicted Beck depression inventory (BDI-II) scores in FM (β = 6.83; P = .033). Rs-FCs from salience network nodes were reduced in FM, of which rs-FCs from the right lateral rostral prefrontal cortex (RPFC) to the lateral occipital cortex, superior division right (RPFC-sLOC) could be predicted by BDI-II scores in patients (β = -.0064; P = .0054). In addition, the BDI-II score was a mediator in the association between Phascolarctobacterium abundance and rs-FCs of RPFC-sLOC (ab = -.06; 95% CI: -.16 to -9.10 -3 ). In conclusion, microbial dysbiosis might be associated with altered neural networks mediated by psychological distress in FM, emphasizing the critical role of the brain-gut axis in FM's non-pain symptoms and supporting further analysis of mechanism-targeted therapies to reduce FM symptoms. PERSPECTIVE: Our study suggests microbial dysbiosis might be associated with psychological distress and the altered salience network, supporting the role of brain-gut axis dysfunction in fibromyalgia pathomechanisms. Further targeting therapies for microbial dysbiosis should be investigated to manage fibromyalgia patients in the future., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Reward motivation is essential in shaping human behavior and cognition. Both reward motivation and reward brain circuits are altered in chronic pain conditions, including fibromyalgia. In this study of fibromyalgia patients, we used a data-driven independent component analysis (ICA) approach to investigate how brain networks contribute to altered reward processing. From females with fibromyalgia (N = 24) and female healthy controls (N = 24), we acquired fMRI data while participants performed a monetary incentive delay (MID) reward task. After analyzing the task-based fMRI data using ICA to identify networks, we analyzed 3 networks of interest: motor network (left), value-driven attention network, and basal ganglia network. Then, we evaluated correlation coefficients between each network timecourse versus a task-based timecourse which modeled gain anticipation. Compared to controls, the fibromyalgia cohort demonstrated significantly stronger correlation between the left motor network timecourse and the gain anticipation timecourse, indicating the left motor network was more engaged with gain anticipation in fibromyalgia. In an exploratory analysis, we compared motor network engagement during early versus late phases of gain anticipation. Across cohorts, greater motor network engagement (i.e., stronger correlation between network and gain anticipation) occurred during the late timepoint, which reflected enhanced motor preparation immediately prior to response. Consistent with the main results, patients exhibited greater engagement of the motor network during both early and late phases compared with healthy controls. Visual-attention and basal ganglia networks revealed similar engagement in the task across groups. As indicated by post-hoc analyses, motor network engagement was positively related to anxiety and negatively related to reward responsiveness. In summary, we identified enhanced reward-task related engagement of the motor network in fibromyalgia using a novel data-driven ICA approach. Enhanced motor network engagement in fibromyalgia may relate to impaired reward motivation, heightened anxiety, and possibly to altered motor processing, such as restricted movement or dysregulated motor planning., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to evaluate the prevalence of idiopathic intracranial hypertension (IIH) in fibromyalgia (FMS) patients by utilizing ultrasound to measure the optic nerve sheath diameter (ONSD), a marker of elevated intracranial pressure and also to investigate the relationship with function, fatigue, quality of life (QOL), central sensitization (CS) and neuropathic pain., Methods: The study encompassed 80 female FMS patients and 75 healthy controls. Ultrasound was employed to measure the average ONSD in both groups. Conditions potentially elevating intracranial pressure were ruled out following neurological assessments. Pain (via visual analog scale, VAS), function (revised Fibromyalgia Impact Questionnaire, r-FIQ), QOL (Short Form-36, SF-36), fatigue (fatigue severity scale, FACIT), CS (Central Sensitization Scale), and neuropathic pain (Douleur Neuropathique-4) were evaluated., Results: The average ONSD was significantly higher in the patient group than the control group. Patients with ONSD >5.5 mm consistent with IIH were categorized as Group 1 (n = 54, 67.5%), while those with a diameter of 5.5 mm and below-formed Group 2. VAS pain (p = .033) and FIQ-R scores (p = .033) were significantly higher in Group 1 than Group 2. Headache was found more common in Group 1., Conclusion: This study unveils a substantial occurrence (67.5%) of IIH in FMS patients, suggesting shared pathophysiological mechanisms contributing to symptoms like fatigue, headache, and cognitive dysfunction. Additionally, these findings implicate heightened functional impairment, CS, headache, and fatigue in FMS patients with IIH., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: Juvenile-onset fibromyalgia (JFM) is a paradigmatic chronic pain condition for which the underlying neurobiological substrates are poorly understood. This study examined, for the first time, data-driven resting-state functional connectivity (rsFC) alterations in 37 female adolescents with JFM compared with 43 healthy female adolescents and identified associations with bodily pain., Methods: Whole-brain voxel-wise rsFC alterations were assessed using the intrinsic connectivity contrast, a measure of node centrality at each voxel, and seed-based analyses for interpretability. We studied the relationship between rsFC alterations in somatosensory systems and the location and extension of bodily pain., Results: Adolescents with JFM had voxel-wise rsFC reductions in the paracentral lobule (PCL)/primary somatosensory cortex (S1) (T = 4.89, family-wise error corrected p-value (pFWE) < 0.001) and left midcingulate cortex (T = 4.67, pFWE = 0.043). Post hoc analyses revealed reduced rsFC spanning major cortical sensory hubs (T > 4.4, pFWE < 0.030). Cortico-cortical rsFC reductions within PCL/S1 in JFM occurred in locations innervated by bodily areas where the pain was most frequent (F = 3.15; positive false discovery rate = 0.029) and predicted widespread pain (T > 4.4, pFWE < 0.045). Conversely, adolescents with JFM had increases in PCL/S1-thalamus (T = 4.75, pFWE = 0.046) and PCL/S1-anterior insula rsFC (T = 5.13, pFWE = 0.039)., Conclusion: Reduced cortico-cortical sensory integration involving PCL/S1 and spanning the sensory systems may underly critical pain sensory features in youth with JFM. Reduced sensory integration is paralleled by augmented cross-talk between sensory and affective/salience-processing regions, potentially indicating a shift toward more affectively colored sensory experiences to the detriment of specific sensory discrimination., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Fibromyalgia, a condition characterized by chronic pain, is frequently accompanied by emotional disturbances. Here we aimed to study brain activation and functional connectivity (FC) during processing of emotional stimuli in fibromyalgia. Thirty female patients with fibromyalgia and 31 female healthy controls (HC) were included. Psychometric tests were administered to measure alexithymia, affective state, and severity of depressive and anxiety symptoms. Next, participants performed an emotion processing and regulation task during functional magnetic resonance imaging (fMRI). We performed a 2 × 2 ANCOVA to analyze main effects and interactions of the stimuli valence (positive or negative) and group (fibromyalgia or HC) on brain activation. Generalized psychophysiological interaction analysis was used to assess task-dependent FC of brain regions previously associated with emotion processing and fibromyalgia (i.e., hippocampus, amygdala, anterior insula, and pregenual anterior cingulate cortex [pACC]). The left superior lateral occipital cortex showed more activation in fibromyalgia during emotion processing than in HC, irrespective of valence. Moreover, we found an interaction effect (valence x group) in the FC between the left pACC and the precentral and postcentral cortex, and central operculum, and premotor cortex. These results suggest abnormal brain activation and connectivity underlying emotion processing in fibromyalgia, which could help explain the high prevalence of psychopathological symptoms in this condition., (© 2023. The Author(s).)

Objective: Fibromyalgia (FM) is characterized by pervasive pain-related symptomatology and high levels of negative affect. Mind-body treatments such as cognitive behavioral therapy (CBT) appear to foster improvement in FM via reductions in pain-related catastrophizing, a set of negative, pain-amplifying cognitive and emotional processes. However, the neural underpinnings of CBT's catastrophizing-reducing effects remain uncertain. This randomized controlled mechanistic trial was designed to assess CBT's effects on pain catastrophizing and its underlying brain circuitry., Methods: Of 114 enrolled participants, 98 underwent a baseline neuroimaging assessment and were randomized to 8 weeks of individual CBT or a matched FM education control (EDU) condition., Results: Compared with EDU, CBT produced larger decreases in pain catastrophizing post treatment (P < 0.05) and larger reductions in pain interference and symptom impact. Decreases in pain catastrophizing played a significant role in mediating those functional improvements in the CBT group. At baseline, brain functional connectivity between the ventral posterior cingulate cortex (vPCC), a key node of the default mode network (DMN), and somatomotor and salience network regions was increased during catastrophizing thoughts. Following CBT, vPCC connectivity to somatomotor and salience network areas was reduced., Conclusion: Our results suggest clinically important and CBT-specific associations between somatosensory/motor- and salience-processing brain regions and the DMN in chronic pain. These patterns of connectivity may contribute to individual differences (and treatment-related changes) in somatic self-awareness. CBT appears to provide clinical benefits at least partially by reducing pain-related catastrophizing and producing adaptive alterations in DMN functional connectivity., (© 2023 American College of Rheumatology.)

Abstract: Fibromyalgia has been characterized by augmented cross-network functional communication between the brain's sensorimotor, default mode, and attentional (salience/ventral and dorsal) networks. However, the underlying mechanisms of these aberrant communication patterns are unknown. In this study, we sought to understand large-scale topographic patterns at instantaneous timepoints, known as co-activation patterns (CAPs). We found that a sustained pressure pain challenge temporally modulated the occurrence of CAPs. Using proton magnetic resonance spectroscopy, we found that greater basal excitatory over inhibitory neurotransmitter levels within the anterior insula orchestrated higher cross-network connectivity between the anterior insula and the default mode network through lower occurrence of a CAP encompassing the attentional networks during sustained pain. Moreover, we found that hyperalgesia in fibromyalgia was mediated through increased occurrence of a CAP encompassing the sensorimotor network during sustained pain. In conclusion, this study elucidates the role of momentary large-scale topographic brain patterns in shaping noxious information in patients with fibromyalgia, while laying the groundwork for using precise spatiotemporal dynamics of the brain for the potential development of therapeutics., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Introduction: Fibromyalgia (FM) is a chronic painful condition frequently associated with rheumatoid arthritis (RA), which may falsely increase RA activity. The aim of our study was to compare clinical scoring and ultrasound (US) assessment in RA patients with concomitant FM with those without FM., Methods: A cross-sectional study including patients with RA according to the ACR/EULAR 2010 criteria was conducted. Patients were divided into two groups: RA patients meeting ACR 2016 FM criteria (cases) and RA patients not meeting FM criteria (controls). Clinico-biological and US assessments of RA activity were performed on the same day for each patient., Results: Eighty patients distributed into 40 patients in each group were recruited. Biologic DMARD prescription was more frequent in RA with FM patients than the control group (p = 0.04). DAS28 was significantly greater than DAS28 V3 in RA with FM group (p = 0.002). FM group had significantly less US synovitis (p = 0.035) and less Power Doppler (PD) activity (p = 0.035). Grey scale US score (p = 0.87) and DP US score (p = 0.162) were similar in the two groups. The correlation between the clinical and the ultrasonographic scores was strong to very strong in both groups with the strongest correlation found between DAS28 V3 and US DAS28 V3 (r = 0.95) in RA + FM group., Conclusion: Our study confirms the overestimation of disease activity by the clinical scores in RA with concomitant FM. DAS28 V3 score and US assessment would represent a better alternative., (© 2023 John Wiley & Sons Ltd.)

Purpose: The glymphatic system is a fluid exchange pathway that clears waste products that is crucial for the maintenance of brain homeostasis. However, the exact role it plays in the emergence of fibromyalgia (FM) is still not fully understood. Here, we explored the changes in non-invasive MRI proxy probably related to the glymphatic function in FM patients, and explored brain-behavior relationships., Methods: A total of 40 participants, consisting of 20 individuals with FM and 20 healthy controls (HCs), were included in the study. The participants underwent structural T1-weighted MRI, diffusion tensor imaging (DTI), and clinical assessment. The data was obtained from an open access dataset. The study compared non-invasive MRI indices, including choroid plexus (CP) volume and DTI analysis along the perivascular space (ALPS), between the FM and HC groups. Furthermore, correlation analysis was conducted to determine the correlation between clinical parameters and both CP volume and DTI-ALPS index., Results: Patients with FM had significantly higher CP volume and a lower DTI-ALPS index than HCs adjusting for age and intracranial volume. Higher CP volume was associated with lower DTI-ALPS index, and longer disease duration., Conclusion: Our findings demonstrate aberrant glymphatic function in FM, and that dysfunction in the brain glymphatic system may play a role in the neural mechanisms underlying FM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Neuroimaging studies employing analyses dependent on regional assumptions and specific neuronal circuits could miss characteristics of whole-brain structural connectivity critical to the pathophysiology of fibromyalgia (FM). This study applied the whole-brain graph-theoretical approach to identify whole-brain structural connectivity disturbances in FM., Methods: This cross-sectional study used probabilistic diffusion tractography and graph theory analysis to evaluate the topological organization of brain white matter networks in 20 patients with FM and 20 healthy controls (HCs). The relationship between brain network metrics and clinical variables was evaluated., Results: Compared with HCs, FM patients had lower clustering coefficient, local efficiency, hierarchy, synchronization, and higher normalized characteristic path length. Regionally, patients demonstrated a significant reduction in nodal efficiency and centrality; these regions were mainly located in the prefrontal, temporal cortex, and basal ganglia. The network-based statistical analysis (NBS) identified decreased structural connectivity in a subnetwork of prefrontal cortex, basal ganglia, and thalamus in FM. There was no correlation between network metrics and clinical variables (false discovery rate corrected)., Conclusions: The current research demonstrated disrupted topological architecture of white matter networks in FM. Our results suggested compromised neural integration and segregation and reduced structural connectivity in FM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as measured with positron emission tomography using [ 18 F]DPA-714, a second-generation radioligand for the translocator protein (TSPO). Fifteen women with FM and 10 HCs underwent neuroimaging. Distribution volume (V T ) was calculated for in 28 regions of interest (ROIs) using Logan graphical analysis and compared between groups using multiple linear regressions. Group (FM vs HC) was the main predictor of interest and TSPO binding status (high- vs mixed-affinity) was added as a covariate. The FM group had higher V T in the right postcentral gyrus ( b = 0.477, P = 0.033), right occipital gray matter (GM; b = 0.438, P = 0.039), and the right temporal GM ( b = 0.466, P = 0.042). The FM group also had lower V T than HCs in the left isthmus of the cingulate gyrus ( b = -0.553, P = 0.014). In the subgroup of high-affinity binders, the FM group had higher V T in the bilateral precuneus, postcentral gyrus, parietal GM, occipital GM, and supramarginal gyrus. Group differences in the right parietal GM were associated with decreased quality of life, higher pain severity and interference, and cognitive problems. In support of our hypothesis, we found increased radioligand binding (V T ) in the FM group compared with HCs in several brain regions regardless of participants' TSPO binding status. The ROIs overlapped with prior reports of increased TSPO binding in FM. Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

The ability to accurately predict pain is an adaptive feature in healthy individuals. However, in chronic pain, this mechanism may be selectively impaired and can lead to increased anxiety and excessive avoidance behavior. Recently, we reported the first data demonstrating brain activation in fibromyalgia (FM) patients during conditioned pain responses, in which FM patients revealed a tendency to form new pain-related associations rather than extinguishing irrelevant ones. The aim of the present study was to extend our previous analysis, to elucidate potential neural divergences between subjects with FM (n = 65) and healthy controls (HCs) (n = 33) during anticipatory information (ie, prior to painful stimulus onset). Using functional magnetic resonance imaging (fMRI), the current analyses include 1) a congruently cued paradigm of low and high pain predictive cues, followed by 2) an incongruently cued paradigm where low and high pain predictive cues were followed by an identical mid-intensity painful pressure. During incongruently cued high-pain associations, FM exhibited reduced left dorsolateral prefrontal cortex (dlPFC) activation compared to HCs, which was followed by an altered subsequent pain experience in FM, as patients continued to rate the following painful stimuli as high, even though the pressure had been lowered. During congruently cued low pain anticipation, FM exhibited decreased right dlPFC activation compared to HCs, as well as decreased brain connectivity between brain regions implicated in cognitive modulation of pain (dlPFC) and nociceptive processing (primary somatosensory cortex/postcentral gyrus [S1] and supplementary motor area [SMA]/midcingulate cortex [MCC]). These results may reflect an important feature of validating low pain expectations in HCs and help elucidate behavioral reports of impaired safety processing in FM patients. PERSPECTIVE: FM exhibited a stronger conditioned pain response for high-pain associations, which was associated with reduced dlPFC activation during the incongruent trial. During (congruent and incongruent) low pain associations, FM dlPFC brain activation remained indifferent. Imbalances in threat and safety pain perception may be an important target for psychotherapeutic interventions., (Published by Elsevier Inc.)

Functional somatic syndromes (FSS) include fibromyalgia, irritable bowel syndrome (IBS), and others. In FSS patients, merely viewing negative affective pictures can elicit increased physical symptoms. Our aim was to investigate the neural mechanisms underlying such negative affect-induced physical symptoms in FSS patients. Thirty patients with fibromyalgia and/or IBS and 30 healthy controls (all women) watched neutral, positive and negative affective picture blocks during functional MRI scanning and rated negative affect and physical symptoms after every block. We compared brain-wide activation during negative versus neutral picture viewing in FSS patients versus controls using robust general linear model analysis. Further, we compared neurologic pain signature (NPS), stimulus intensity-independent pain signature (SIIPS) and picture-induced negative emotion signature (PINES) responses to the negative versus neutral affect contrast and investigated whether they mediated between-group differences in affective picture-induced physical symptom reporting. More physical symptoms were reported after viewing negative compared to neutral pictures, and this effect was larger in patients than controls (p = 0.025). Accordingly, patients showed stronger activation in somatosensory regions during negative versus neutral picture viewing. NPS, but not SIIPS nor PINES, responses were higher in patients than controls during negative versus neutral pictures (p = 0.026). These differential NPS responses partially mediated between-group differences in physical symptoms. In conclusion, picture-induced negative affect elicits physical symptoms in FSS patients as a result of activation of somatosensory and nociceptive brain patterns, supporting the idea that affect-driven alterations in processing of somatic signals is a critical mechanism underlying FSS., (© 2023. Springer Nature Limited.)

Fibromyalgia syndrome (FMS) is a type of rheumatology that seriously affects the normal life of patients. Due to the complex clinical manifestations of FMS, it is challenging to detect FMS. Therefore, an automatic FMS diagnosis model is urgently needed to assist physicians. Brain functional connectivity networks (BFCNs) constructed by resting-state functional magnetic resonance imaging (rs-fMRI) to describe brain functions have been widely used to identify individuals with relevant diseases from normal control (NC). Therefore, we propose a novel model based on BFCN and graph convolutional network (GCN) for automatic FMS diagnosis. Firstly, a novel fused BFCN method is proposed by fusing Pearson's correlation (PC) and low-rank (LR) BFCN, which retains information and reduces data redundancy to construct BFCN. Then we combine the feature of BFCN with non-image information of subjects to obtain nodes and adjacency matrices, which builds a graph with edge attention. Finally, the graph is sent to the GCN layer for FMS diagnosis. Our model is evaluated on the in-house FMS dataset to achieve 82.48% accuracy. The experimental results show that our method outperforms the state-of-the-art competing methods.

Background and Purpose: Although fibromyalgia (FM) is considered a central sensitization syndrome, studies investigating peripheral nerves in this condition are not available. The primary objective of this study is to investigate the sonographic changes (ie, increased cross-sectional area [CSA]), of peripheral nerves in patients with FM compared to healthy controls. The secondary objective is to identify potential clinical correlations associated with increased CSA in patients with FM., Methods: In this cross-sectional observational study, consecutive female patients with FM underwent sonographic assessment using a standardized scanning protocol. The CSA of seven nerves was measured bilaterally at 11 anatomic sites by an experienced sonographer. Differences in CSA of nerves were compared with those of healthy subjects by one-way analysis of variance. Patients underwent clinimetric evaluation aimed at investigating disease severity, neuropathic pain features, depression, anxiety, fatigue, and autonomic symptoms to explore the possible correlation between CSA and clinical features., Results: Forty-seven patients and 20 healthy controls were enrolled. Differences in terms of increased CSA between patients and healthy controls were identified at multiple levels, mainly at the level of the sural nerve, vagus nerve, and sixth cervical nerve root (for all, p < .001). Sonographic findings, however, did not correlate with the clinical features explored., Conclusions: Patients with FM show higher CSA of nerves than healthy subjects. The increased CSA is most evident at the sural nerve, vagus nerve, and sixth cervical nerve root. Ultrasound, a relatively easy-to-use technique, could identify morphological changes, in peripheral nervous structures in patients with FM., (© 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Objectives: Although primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement., Materials and Methods: In a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively. Each session was performed with an anode placed on the left M1 and a cathode on the contralateral supraorbital region. The subjects also participated in resting-state functional magnetic resonance imaging (fMRI) at baseline and after sham and active tDCS. We compared the BOLD signal variability (SD BOLD ), defined as the standard deviation of the BOLD time-series, between the tDCS conditions. Baseline SD BOLD was compared to 15 healthy female controls., Results: At baseline, FM patients showed reduced SD BOLD in the ventromedial prefrontal cortex (vmPFC), lateral PFC, and anterior insula and increased SD BOLD in the posterior insula compared to healthy controls. After active tDCS, compared to sham, we found an increased SD BOLD in the left rostral anterior cingulate cortex (rACC), lateral PFC, and thalamus. After sham tDCS, compared to baseline, we found a decreased SD BOLD in the dorsomedial PFC and posterior cingulate cortex/precuneus. Interestingly, after active tDCS compared to sham, pain reduction was correlated with an increased SD BOLD in the rACC/vmPFC but with a decreased SD BOLD in the posterior insula., Conclusion: Our findings suggest that M1-tDCS might revert temporal variability of fMRI signals in the rACC/vmPFC and posterior insula linked to FM pain. Changes in neural variability would be part of the mechanisms underlying repetitive M1-tDCS analgesia in FM., (Copyright © 2022. Published by Elsevier Inc.)

Background: Previous studies have repeatedly found distinct brain morphometric changes in patients with fibromyalgia (FM), mainly affecting gray and white matter abnormalities in areas related to sensory and affective pain processing. However, few studies have thus far linked different types of structural changes and not much is known about behavioral and clinical determinants that might influence the emergence and progression of such changes., Methods: We used voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) to detect regional patterns of (micro)structural gray (GM) and white matter (WM) alterations in 23 patients with FM compared to 21 healthy controls (HC), while considering the influence of demographic, psychometric, and clinical variables (age, symptom severity, pain duration, heat pain threshold, depression scores)., Results: VBM and DTI revealed striking patterns of brain morphometric changes in FM patients. Bilateral middle temporal gyrus (MTG), parahippocampal gyrus, left dorsal anterior cingulate cortex (dACC), right putamen, right caudate nucleus, and left dorsolateral prefrontal cortex (DLPFC) showed significantly decreased GM volumes. In contrast, increased GM volume was observed in bilateral cerebellum and left thalamus. Beyond that, patients displayed microstructural changes of WM connectivity within the medial lemniscus, corpus callosum, and tracts surrounding and connecting the thalamus. Sensory-discriminative aspects of pain (pain severity, pain thresholds) primarily showed negative correlations with GM within bilateral putamen, pallidum, right midcingulate cortex (MCC), and multiple thalamic substructures, whereas the chronicity of pain was negatively correlated with GM volumes within right insular cortex and left rolandic operculum. Affective-motivational aspects of pain (depressive mood, general activity) were related to GM and FA values within bilateral putamen and thalamus., Conclusions: Our results suggest a variety of distinct structural brain changes in FM, particularly affecting areas involved in pain and emotion processing such as the thalamus, putamen, and insula., (© 2023. The Author(s).)

To identify central metabolites and peripheral measures associated with neuroinflammation in fibromyalgia (FM), we scanned [11C]-(R)-PK11195 positron emission tomography and magnetic resonance spectroscopy in FM patients. We measured associations between neurometabolite levels measured by magnetic resonance spectroscopy and the extent of neuroinflammation inferred by the distribution volume ratios of [11C]-(R)-PK11195 positron emission tomography in 12 FM patients and 13 healthy controls. We also examined the associations between peripheral parameters, such as creatinine and C-reactive protein, and neuroinflammation. In FM patients, we found negative correlations between neuroinflammation and the creatine (Cr)/total creatine (tCr; Cr + phosphocreatine) ratios in the right (r = -0.708, P = .015) and left thalamus (r = -0.718, P = .008). In FM patients, negative correlations were apparent between neuroinflammation and the glutamate/tCr ratio in the right insula (r = -0.746, P = .005). In FM patients, we found negative correlations between neuroinflammation in the left thalamus (r = -0.601, P = .039) and left insula (r = -0.598, P = .040) and the blood creatinine levels. Additionally, we found significant correlations of other peripheral measures with neuroinflammation in FM patients. Our results suggest that both central metabolites, such as Cr and glutamate, and peripheral creatinine and other parameters are associated with neuroinflammation in patients with FM., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Some women with breast implants report systemic and cognitive symptoms known as breast implant illness (BII), which are very similar to those of fibromyalgia. Functional MRI (fMRI) has shown altered brain activity in fibromyalgia patients., Objectives: The aim of this pilot study was to investigate whether brain alterations could be observed in BII patients by fMRI., Methods: Women aged 18 to 76 with silicone breast implants for cosmetic reasons were recruited through a Dutch online BII support organization (MKS) and through the Maastricht University Medical Center. Study participants comprised 12 women with BII and 12 women without symptoms. Participants completed questionnaires regarding demographic characteristics, medical history, psychosocial complaints (Four-Dimensional Symptom Questionnaire), cognitive failure (Mini-Mental State Examination), and pain intensity and pain-related disability (Chronic Pain Grade Scale). Subsequently, brain images of all participants were obtained by resting-state fMRI and diffusion tensor imaging in a 3-T MRI scanner (Siemens Medical System, Erlangen, Germany)., Results: Eleven BII patients and 12 healthy controls were included in the analysis. Baseline characteristics were similar in the 2 groups and the mean silicone exposure was 15 years. Patients scored significantly higher than controls on both pain intensity and disability. Patients scored worse on depression, somatization, distress, and anxiety compared with asymptomatic women. Mini-Mental State Examination scores were normal. However, the analyses of both functional connectivity and structural integrity showed no significant differences between the 2 groups., Conclusions: This pilot study showed no evidence of brain alterations in BII patients. However, patients scored significantly worse on psychosocial symptoms than controls. Psychological factors appear to play an important role in BII and should be further investigated., (© 2022 The Aesthetic Society.)

The perceived lack of control over the experience of pain is arguably-one major cause of agony and impaired life quality in patients with chronic pain disorders as fibromyalgia (FM). The way perceived control affects subjective pain as well as the underlying neural mechanisms have so far not been investigated in chronic pain. We used functional magnetic resonance imaging (fMRI) to examine the neural correlates of self-controlled compared to computer-controlled heat pain in healthy controls (HC, n = 21) and FM patients (n = 23). Contrary to HC, FM failed to activate brain areas usually involved in pain modulation as well as reappraisal processes (right ventrolateral (VLPFC), dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC)). Computer-controlled (compared to self-controlled) heat revealed significant activations of the orbitofrontal cortex (OFC) in HC, whereas FM activated structures that are typically involved in neural emotion processing (amygdala, parahippocampal gyrus). Additionally, FM displayed disrupted functional connectivity (FC) of the VLPFC, DLPFC and dACC with somatosensory and pain (inhibition)-related areas during self-controlled heat stimulation as well as significantly decreased gray matter (GM) volumes compared to HC in DLPFC and dACC. The described functional and structural changes provide evidence for far-reaching impairments concerning pain-modulatory processes in FM. Our investigation represents a first demonstration of dysfunctional neural pain modulation through experienced control in FM according to the extensive functional and structural changes in relevant sensory, limbic and associative brain areas. These areas may be targeted in clinical pain therapeutic methods involving TMS, neurofeedback or cognitive behavioral trainings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Fibromyalgia (FM) represents a condition that is still controversial in its entity, pathophysiology, diagnosis and management. The aim of this review is to focus on imaging aspects of FM, especially on novel approaches in molecular imaging, with a special focus on neuroimaging. Novel functional and molecular imaging findings may represent, eventually, future biomarkers both in research settings and in terms of clinical practice. Several imaging techniques have already been tested in clinical trials in the FM field, including functional MRI, positron emission tomography (PET) imaging with 18 F-FDG in FM, PET imaging of the dopaminergic system, PET imaging of the GABAergic system, PET imaging with neuroinflammation and neuroimmune parameters, PET imaging of the opioid system and H 2 15 O-PET activation studies. Therefore, the potential role in the FM field of fMRI and different PET tracers has been discussed in different settings, serving as a comprehensive guide of novel imaging options both in research and in the clinical field.

Background: Although neuroanatomical studies correlated to fibromyalgia (FM) are gaining increasing interest, the cortical morphology of patients are largely unknown, and data on cortical gyrification are scarce. The objective of the present study is to assess the cortical morphology in female patients with FM compared with healthy controls (HC) using surface-based morphometry (SBM) analysis of magnetic resonance imaging (MRI)., Methods: T1-MRIs and clinical data of 20 FM patients and 20 HC subjects were obtained from a public data set via OpenNeuro. For each subject, surface parameters including cortical thickness, local gyrification index (LGI), sulcal depth, and fractal dimensionality were estimated using SBM analysis. These data were compared between two groups controlled by age. The correlations between regional SBM parameters showing group differences and clinical profiles were analyzed., Results: Compared with HC subjects, FM patients showed reduced cortical thickness in right primary motor cortex, lower LGI in right rostral anterior cingulate and higher sulcal depth in right precuneus (P < 0.05 cluster level family- wise error corrected). In FM patients, correlation analysis showed that the cortical thickness in right primary motor cortex were inversely correlated with scores of pain catastrophizing scale (r = -0.498, P = 0.030) and pain self-perception scale (r = -0.527, P = 0.020), and disease duration (r = -0.488, P = 0.034), respectively., Conclusions: Our findings provide evidence of neuroanatomical aberrations in FM patients, which may provide insight into the neuropathology of FM., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The pathogenesis of fibromyalgia syndrome (FMS) is unclear. Transcranial ultrasonography revealed anechoic alteration of midbrain raphe in depression and anxiety disorders, suggesting affection of the central serotonergic system. Here, we assessed midbrain raphe echogenicity in FMS., Methods: Sixty-six patients underwent transcranial sonography, of whom 53 were patients with FMS (27 women, 26 men), 13 patients with major depression and physical pain (all women), and 14 healthy controls (11 women, 3 men). Raphe echogenicity was graded visually as normal or hypoechogenic, and quantified by digitized image analysis, each by investigators blinded to the clinical diagnosis., Results: Quantitative midbrain raphe echogenicity was lower in patients with FMS compared to healthy controls (p<0.05), but not different from that of patients with depression and accompanying physical pain. Pain and FMS symptom burden did not correlate with midbrain raphe echogenicity as well as the presence and severity of depressive symptoms., Conclusion: We found reduced echogenicity of the midbrain raphe area in patients with FMS and in patients with depression and physical pain, independent of the presence or severity of pain, FMS, and depressive symptoms. Further exploration of this sonographic finding is necessary before this objective technique may enter diagnostic algorithms in FMS and depression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Üçeyler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Neuroimaging investigations have already uncovered alterations to cerebral microstructural integrity in patients with fibromyalgia (FM). In the meantime, these patients commonly suffer from depression and anxiety., Objective: In this study, microstructure changes within white matter were examined in patients with FM with consideration of concurrent physiological factors., Study Design: A cross-sectional case-control study., Setting: A university hospital., Methods: Diffusion tensor imaging was performed on 20 patients with FM and 20 healthy controls. The 4 diffusional indices, namely, fractional anisotropy (FA), mean, radial, and axial diffusivity (MD, RD, AD) were calculated using tract-based spatial statistics. The relationships between the diffusional parameters and pain scales were also examined., Results: The patients with FM exhibited enhanced FA, reduced MD, RD, and AD in numerous white matter tracts, including the corpus callosum, corona radiata, internal capsule, corticospinal tract, posterior thalamic radiation, cerebellar peduncle, sagittal stratum, and superior fronto-occipital fasciculus. When depression and anxiety were added as covariates, most between-group diffusional difference disappeared except for AD reduction in the corona radiate, internal capsule, and cerebellar peduncle (P < 0.05, threshold-free cluster enhancement corrected). The diffusion tensor imaging measures were not correlated with clinical variables., Limitation: A relatively small sample size., Conclusion: Our results demonstrate that disrupted white matter microstructure in patients with FM is mainly restricted to tracts associated with pain sensory processing and motor control, adjusting for psychosocial factors. A considerable degree of difference in white matter characteristics may be explained by the patients with FM group's greater level of psychological distress.

The aim of this study was to determine whether there is a decrease or an increase in the volume of different regions of the brain by comparing brain morphometry ofpatients diagnosed with Fibromyalgia Syndrome and healthy control subjects. The study included 23 female patients who were diagnosed with fibromyalgia, and 18 females, age-matched healthy subjects. Structural Mitral Regurgitation data was processed using Surface-Based Morphometry (SBM) on the Freesurfer 6.0 programme (http://surfer.nmr.mgh.harvard.edu). As a result of the surface-based analyses, a statistically significant reduction was determined in the Fibromyalgia Syndrome patient group in some brain region. A statistically signficant increase was determined in the FMS patient group with respect to the left anterior occipital sulcus volume, left inferior temporal gyrus thickness and left anterior occipital sulcus area. The results of this study showed that FMS affected brain morphometry through the brain central pain mechanisms and the normal brain morphology was changed because of atrophy in some areas and hypertrophy in some areas.

Fibromyalgia is a chronic condition characterized by widespread pain, as well as numerous symptoms related to central sensitization such as: fatigue, cognitive disturbances, constipation/diarrhea and sensory hypersensitivity. Furthermore, depression and anxiety are prevalent comorbidities, accompanied by emotion processing and regulation difficulties. Although fibromyalgia physiopathology is still not fully understood, neuroimaging research methods have shown brain structural and functional alterations as well as neuroinflammation abnormalities. We believe that open access to data may help fibromyalgia research advance more. Here, we present an open dataset of 33 fibromyalgia female patients and 33 paired healthy controls recruited from a Mexican population. Dataset includes demographic, clinical, behavioural and magnetic resonance imaging (MRI) data. The MRI data consists of: structural (T1- and T2- weighted) and functional (task-based and resting state) sequences. The task was an emotion processing and regulation task based on visual stimuli. The MRI data contained in the repository are unprocessed, presented in Brain Imaging Data Structure (BIDS) format and available on the OpenNeuro platform for future analysis., (© 2022. The Author(s).)

The intermittent cold stress-induced generalized pain response mimics the pathophysiological and pharmacotherapeutic features reported for fibromyalgia patients, including the presence of chronic generalized pain and female dominance. In addition, the intermittent cold stress-induced generalized pain is abolished in lysophosphatidic acid receptor type-1 knockout mice, as reported in many cases of neuropathic pain models. This study aimed to identify the brain loci involved in the intermittent cold stress generalized pain response and test their dependence on the lysophosphatidic acid receptor type-1. Positron emission tomography analyses using 2-deoxy-2-[ 18 F]fluoro-d-glucose in the presence of a pain stimulus showed that intermittent cold stress causes a significant increase in uptake in the ipsilateral regions, including the salience networking-related anterior cingulate cortex and insular cortex and the cognition-related hippocampus. A significant decrease was observed in the default mode network-related posterior cingulate cortex. Almost these intermittent cold stress-induced changes were abolished in lysophosphatidic acid receptor type-1 knockout mice. There results suggest that the intermittent cold stress-induced generalized pain response is mediated by the lysophosphatidic acid receptor type-1 in specific brain loci related to salience networking and cognition, which may lead to further developments in the treatment of fibromyalgia., (© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Introduction: Previous studies have associated brain abnormalities in people with fibromyalgia with accelerated brain ageing. The prefrontal cortex is located in the anterior pole of the mammalian brain. It is defined as the part of the cerebral cortex that receives projections from the mediodorsal nucleus of the thalamus., Aim: This study aimed to evaluate the volumetric differences in the prefrontal cortex subfields between healthy women and women with fibromyalgia using magnetic resonance imaging (MRI) and controlling for age, estimated intracranial volume, depression, and cognitive impairment., Material and Methods: A total of 47 women with fibromyalgia (recruited from a fibromyalgia local association) and 43 healthy women (retrieved from the Open Access Series of Imaging Studies database) participated in this cross-sectional study. Multiple linear regressions were used to predict the value of the prefrontal cortex subfields as well as to determine if there were volumetric differences between the groups., Results: Volume of all prefrontal cortex regions decreased with each year of age. Healthy women showed higher volume in all the prefrontal cortex subfields than women with fibromyalgia. Regarding partial correlations performed, no significant relation were found between the fibromyalgia impact and the brain volumes analyzed, controlling for depression., Conclusions: Women with fibromyalgia showed reduced volume in the right caudal middle frontal gyrus, rostral middle frontal gyrus, left inferior frontal gyrus pars opercularis, inferior frontal gyrus pars triangularis, inferior frontal gyrus pars orbitalis, lateral orbitofrontal cortex, right medial orbitofrontal cortex, right rostral anterior cingulate gyrus subfields of the prefrontal cortex and total gray matter compared to healthy women. Furthermore, through an analysis of multiple linear regressions, the left rostral middle frontal gyrus and left lateral orbitofrontal cortex showed significantly volumetric decreases related to depression levels. The total gray matter also shows a significant decrease related to age observed through the analysis of multiple linear regressions. No significant relation were found between the impact of the disease and the brain volumes analyzed, controlling for depression in women with fibromyalgia., (Copyright © 2022. Published by Elsevier B.V.)

Brain corticostriatal circuits are important for understanding chronic pain and highly relevant to motivation and cognitive processes. It has been demonstrated that in patients with chronic back pain, altered nucleus accumbens (NAcc)-medial prefrontal cortex (MPFC) circuit fMRI-based activity is predictive of patient outcome. We evaluated the NAcc-MPFC circuit in patients with another chronic pain condition, fibromyalgia, to extend these important findings. First, we compared fMRI-based NAcc-MPFC resting-state functional connectivity in patients with fibromyalgia (N = 32) vs. healthy controls (N = 37). Compared to controls, the NAcc-MPFC circuit's connectivity was significantly reduced in fibromyalgia. In addition, within the fibromyalgia group, NAcc-MPFC connectivity was significantly correlated with trait anxiety. Our expanded connectivity analysis of the NAcc to subcortical brain regions showed reduced connectivity of the right NAcc with mesolimbic circuit regions (putamen, thalamus, and ventral pallidum) in fibromyalgia. Lastly, in an exploratory analysis comparing our fibromyalgia and healthy control cohorts to a separate publicly available dataset from patients with chronic back pain, we identified reduced NAcc-MPFC connectivity across both the patient groups with unique alterations in NAcc-mesolimbic connectivity. Together, expanding upon prior observed alterations in brain corticostriatal circuits, our results provide novel evidence of altered corticostriatal and mesolimbic circuits in chronic pain., (© 2022. The Author(s).)

Objective: Juvenile fibromyalgia (FM) is a prevalent chronic pain condition affecting children and adolescents worldwide during a critical period of brain development. To date, no published studies have addressed the pathophysiology of juvenile FM. This study was undertaken to characterize gray matter volume (GMV) alterations in juvenile FM patients for the first time, and to investigate their functional and clinical relevance., Methods: Thirty-four female adolescents with juvenile FM and 38 healthy adolescents underwent a structural magnetic resonance imaging examination and completed questionnaires assessing core juvenile FM symptoms. Using voxel-based morphometry, we assessed between-group GMV differences and associations between GMV and functional disability, fatigue, and pain interference in juvenile FM. We also studied whether validated brain patterns predicting pain, cognitive control, or negative emotion were amplified/attenuated in juvenile FM patients and whether structural alterations reported in adult FM were replicated in adolescents with juvenile FM., Results: Compared to controls, juvenile FM patients showed GMV reductions in the anterior midcingulate cortex (aMCC) region (family-wise error corrected P [P FWE-corr ] = 0.04; estimated with threshold-free cluster enhancement [TFCE]; n = 72) associated with pain. Within the juvenile FM group, patients reporting higher functional disability had larger GMV in inferior frontal regions (P FWE-corr  = 0.006; TFCE estimated; n = 34) linked to affective, self-referential, and language-related processes. Last, GMV reductions in juvenile FM showed partial overlap with findings in adult FM, specifically for the anterior/posterior cingulate cortices (P = 0.02 and P = 0.03, respectively; n = 72)., Conclusion: Pain-related aMCC reductions may be a structural hallmark of juvenile FM, whereas alterations in regions involved in emotional, self-referential, and language-related processes may predict disease impact on patients' well-being. The partial overlap between juvenile and adult FM findings strengthens the importance of early symptom identification and intervention to prevent the transition to adult forms of the disease., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The aim of this cross-sectional study was to compare cervical extensor muscle thickness measurements in patients with fibromyalgia (FM) with chronic neck pain and an asymptomatic control group, and to examine the relationship between cervical extensor muscle thickness and pain, quality of life, and disability., Methods: The study included 41 patients with FM and 41 asymptomatic control subjects. The thickness of the cervical extensor muscles (multifidus, semispinalis capitis, semispinalis cervicis, splenius capitis and trapezius muscles) was evaluated with ultrasonography. The severity of FM was evaluated with the Fibromyalgia Impact Questionnaire (FIQ), neck disability with the Neck Disability Index (NDI) and pain severity with a Numeric Rating Scale (NRS)., Results: The mean sonographic thickness values of all the neck extensor muscles were significantly decreased in the FM group compared with the control group (p < 0.001). There were negative correlations between the FIQ and multifidus, splenius capitis and trapezius thickness values. NDI was significantly negatively correlated with multifidus and trapezius thickness. There was no significant correlation between neck extensor muscle thickness and age, duration of FM, and NRS scores., Conclusion: This study demonstrated a decrease in cervical extensor muscle thickness in patients with FM with chronic neck pain. Cervical extensor muscle morphologies should be considered by the clinician when planning treatment in patients with FM with neck pain., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Some studies have reported the presence of histological alterations, such as myofiber disorganization and abnormalities in the number and shape of mitochondria, in patients with fibromyalgia syndrome (FMS). Although Ultrasound imaging (US) is used to quantitatively characterize muscle tissues, US studies in patients with FMS are lacking. Therefore, we aimed to describe morphological and qualitative cervical multifidus (CM) muscle US features in women with FMS and to assess their correlation with clinical indicators., Design: Observational study., Setting: AFINSYFACRO Fibromyalgia Association (Madrid, Spain)., Subjects: Forty-five women with FMS participated., Methods: Sociodemographic variables (e.g., age, height, weight, body mass index) and clinical outcomes (e.g., pain as assessed on a numerical pain rating scale, evolution time, pain-related disability as assessed by the Fibromyalgia Impact Questionnaire) were collected. Images were acquired bilaterally at the cervical spine (C4-C5 level) and measured by an experienced examiner for assessment of muscle morphology (e.g., cross-sectional area, perimeter, and shape) and quality (mean echo intensity and intramuscular fatty infiltration). Side-to-side comparisons and a correlational analysis were conducted., Results: No significant side-to-side differences were found for morphology or quality features (P > 0.05). None of the clinical indicators were associated with US characteristics (all, P > 0.05)., Conclusion: Our results showed no side-to-side differences for CM morphology and quality as assessed with US. No associations between CM muscle morphology or quality and Fibromyalgia Impact Questionnaire, pressure pain threshold, numerical pain rating scale score, or evolution time were observed. Our preliminary data suggest that muscle morphology is not directly related to pain and pain-related disability in women with FMS., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case-control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials., (© 2022. The Author(s).)

Abstract: Despite diffuse tenderness, patients with fibromyalgia (FM) have reported a wide range of areas with musculoskeletal pain. This study investigated the neural structures and neuroanatomical networks associated with self-reported widespread pain in FM using magnetic resonance imaging. We collected clinical profiles and brain magnetic resonance imaging data of newly diagnosed patients with FM. A total of 138 patients with FM were divided into 3 subgroups based on the number of pain areas, with 3 to 8, 9 to 12, and 13 to 19 areas, respectively. Using voxel-based morphometry analysis, we first identified the neural structure that showed a trend of volumetric change across the 3 subgroups. We then used it as a candidate seed of interest with a seed-to-voxel analytical approach to explore the structural covariance (SC) networks of the whole brain. Finally, we studied the trend of changes in the distribution and strength of SC networks across subgroups of patients. We found a decreasing trend in the volumes of the right anterior insular cortex (rAIC) across the 3 subgroups that had an increased number of pain areas. An increasing trend in the number of neural substrates over the subcortical regions, especially the basal ganglion, showed SC to the rAIC, and a decreasing trend of SC strength was shown between the rAIC and the precuneus, frontal cortex, anterior and posterior cingulate, and lingual gyri, across the patient subgroups with increased pain areas. The rAIC and its altered connection with specific brain regions indicates widespread pain in patients with FM., (Copyright © 2021 International Association for the Study of Pain.)

Objective: Abnormal central pain processing is a leading cause of pain in fibromyalgia (FM) and is perceptually characterized with the psychophysical measure of temporal summation of pain (TSP). TSP is the perception of increasingly greater pain in response to repetitive or tonic noxious stimuli. Previous neuroimaging studies have used static (i.e., summary) measures to examine the functional magnetic resonance imaging (fMRI) correlates of TSP in FM. However, functional brain activity rapidly and dynamically reorganizes over time, and, similarly, TSP is a temporally evolving process. This study was undertaken to demonstrate how a complete understanding of the neural circuitry supporting TSP in FM thus requires a dynamic measure that evolves over time., Methods: We utilized novel methods for analyzing dynamic functional brain connectivity in patients with FM in order to examine how TSP-associated fluctuations are linked to the dynamic functional reconfiguration of the brain. In 84 FM patients and age- and sex-matched healthy controls, we collected high-temporal-resolution fMRI data during a resting state and during a state in which sustained cuff pressure pain was applied to the leg., Results: FM patients experienced greater TSP than healthy controls (mean ± SD TSP score 17.93 ± 19.24 in FM patients versus 9.47 ± 14.06 in healthy controls; P = 0.028), but TSP scores varied substantially between patients. In the brain, the presence versus absence of TSP in patients with FM was marked by more sustained enmeshment between sensorimotor and salience networks during the pain period. Furthermore, dynamic enmeshment was noted solely in FM patients with high TSP, as interactions with all other brain networks were dampened during the pain period., Conclusion: This study elucidates the dynamic brain processes underlying facilitated central pain processing in FM. Our findings will enable future investigation of dynamic symptoms in FM., (© 2021 American College of Rheumatology.)

Background: Fibromyalgia (FM) and generalized anxiety disorder (GAD) share common clinical features: they both affect women more than men, their diagnosis is based solely on clinical criteria, and some of the symptoms such as anxiety, aches and muscle tension, sleep disorders, and cognitive dysfunction occur in both diseases. For both conditions, an underlying dysregulation of the autonomic nervous system (ANS) has been proposed., Objective: The aims of this study were to investigate ANS dysfunction in FM and GAD and compare them with controls., Methods: Sympathetic skin response (SSR) from palm and sole and cross-sectional area (CSA) of bilateral vagus nerves (VN) were measured in 28 healthy controls, 21 FM patients, and 24 GAD patients., Results: CSA of VN was significantly smaller in FM patients (right: 1.97 ± 0.74mm 2 , left: 1.75 ± 0.65 mm2) and GAD patients (right: 2.12 ± 0.97mm 2 , left: 1.71 ± 0.86 mm 2 ) compared to controls (right: 3.21 ± 0.75 mm 2 , left: 2.65 ± 1.13 mm 2 , p < 0.001, but did not differ between the two patient groups. SSR parameters were similar between patients and controls. SSR latency correlated to clinical scales (FM Widespread Pain Index) in the FM group (r = 0.515, p = 0.02 and r = 0.447, p = 0.05) for the upper and lower limbs respectively, but no other correlation between clinical and neurophysiological parameters was identified., Conclusion: This study confirms similar ANS abnormalities in FM and GAD that fairly distinguish them from controls and support the hypothesis of a common pathophysiological substrate underlying both conditions., (© 2021. Fondazione Società Italiana di Neurologia.)

Abstract: The current study used functional magnetic resonance imaging to directly compare disease-relevant cerebral pain processing in well-characterized patient cohorts of fibromyalgia (FM, nociplastic pain) and rheumatoid arthritis (RA, nociceptive pain). Secondary aims were to identify pain-related cerebral alterations related to the severity of clinical symptoms such as pain intensity, depression, and anxiety. Twenty-six patients with FM (without RA-comorbidity) and 31 patients with RA (without FM-comorbidity) underwent functional magnetic resonance imaging while stimulated with subjectively calibrated painful pressures corresponding to a pain sensation of 50 mm on a 100-mm visual analogue scale. Stimulation sites were at the most inflamed proximal interphalangeal joint in the left hand in patients with RA and the left thumbnail in patients with FM, 2 sites that have previously been shown to yield the same brain activation in healthy controls. The current results revealed disease-distinct differences during pain modulation in RA and FM. Specifically, in response to painful stimulation, patients with FM compared to patients with RA exhibited increased brain activation in bilateral inferior parietal lobe (IPL), left inferior frontal gyrus (IFG)/ventrolateral prefrontal cortex (vlPFC) encapsulating left dorsolateral prefrontal cortex, and right IFG/vlPFC. However, patients with RA compared to patients with FM exhibited increased functional connectivity (during painful stimulation) between right and left IPL and sensorimotor network and between left IPL and frontoparietal network. Within the FM group only, anxiety scores positively correlated with pain-related brain activation in left dorsolateral prefrontal cortex and right IFG/vlPFC, which further highlights the complex interaction between affective (ie, anxiety scores) and sensory (ie, cerebral pain processing) dimensions in this patient group., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

We investigated the diagnostic value of the maximum standardized uptake value (SUV) at hand and wrist joints for differentiating rheumatic diseases via bone single-photon emission computed tomography (SPECT)/computed tomography (CT). A total of 84 patients manifesting hand and wrist pain (58 women; age, 49.8 ± 15.4 years) were finally diagnosed with rheumatoid arthritis (RA, n = 42), osteoarthritis (OA, n = 16), fibromyalgia (FM, n = 2), and other rheumatic diseases (n = 24). The SUV of each patient was measured in 32 joints including the distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal (MCP), and wrist joints bilaterally. Differences in pain and SUVs between specific rheumatic diseases were assessed using the chi-squared test or one-way analysis of variance. Using the highest SUV (hSUV) in each patient, the diagnostic performance in differentiating specific diseases was evaluated by receiver operating characteristic (ROC) curve analysis. Pain symptoms were present in 886 (33.0%) sites in a total of 2688 joints. In four joint groups (DIP, PIP, MCP, and wrist), the SUVs of joints with pain were significantly higher than those of pain-free joints (all P < 0.001). Active joint sites with higher SUVs than the median value of each joint group were the most common in RA (55.1%). RA showed the greatest hSUV in the PIP (3.0 ± 2.4), MCP (3.5 ± 3.4), and wrist (3.3 ± 1.9) joint groups. FM was characterized by the lowest hSUV of all joint groups. In ROC curve analysis, the cumulative hSUV of the PIP, MCP, and wrist joint groups showed good performance for evaluating RA (area under the curve (AUC), 0.668; P = 0.005). The summation of the hSUVs at all joint groups had an excellent predictive performance for FM (AUC, 0.878; P < 0.001). Consequently, the arthritic activity of the hand and wrist joints based on SUV differed according to specific rheumatic diseases. Quantitative SPECT/CT may provide objective information related to arthritic activity for differentiating specific rheumatic diseases., (© 2022. The Author(s).)

Purpose: Numerous neuroimaging and ophthalmic studies suggest optic nerve involvement in fi-bromyalgia syndrome. To further elucidate the etiopathogenesis of fibromyalgia syndrome, we compared optic nerve head blood flow area and retinal nerve fiber layer thickness between patients and controls and investigated the associations of these measures with fibromyalgia syndrome severity., Methods: Participants were divided into the following three groups according to Fibromyalgia Impact Questionnaire score: mild-moderate fibromyalgia syndrome (Group 1, n=47), severe fibromyalgia syndrome (Group 2, n=38), and healthy controls (Group 3, n=38). The optic nerve head blood flow area and retinal nerve fiber layer thickness were measured by optical coherence tomography angiography and compared among groups by ANOVA. Associations with fibromyalgia syndrome severity were evaluated by Spearman's correlation analysis., Results: Optic nerve head blood flow area did not differ between fibromyalgia syndrome Groups 1 and 2 (1.61 ± 0.08 vs.1.63 ± 0.09 mm2), but it was significantly lower in control Group 3 (1.49 ± 0.10 mm2, all p=0.001). Average retinal nerve fiber layer thickness values were significantly lower in Group 2 (101.18 ± 6.03 mm) than in Group 1 (103.21 ± 10.66 mm) and Group 3 (106.51 ± 8.88 mm) (p=0.041 and 0.020, respectively). The inferotemporal (134.36 ± 12.19 mm) and inferonasal (109.47 ± 16.03 mm) quadrant retinal nerve fiber layer thickness values were significantly lower in Group 2 than in Group 1 [inferotemporal (142.15 ± 17.79 mm), inferonasal (117.94 ± 20.53 mm)] and Group 3 [inferotemporal (144.70 ± 16.25 mm), inferonasal (118.63 ± 19.01 mm)] [inferotemporal, p=0.017 and 0.010, respectively; inferonasal, p=0.047 and 0.045, respectively]. The nasal-superior quadrant retinal nerve fiber layer thickness value was higher in Group 3 (91.08 ± 12.11 mm) than in Group 1 (84.34 ± 13.09 mm) and Group 2 (85.26 ± 13.11 mm) (p=0.031 and 0.038, respectively). A weak correlation was detected between disease severity and optic nerve head blood flow area., Conclusion: Neural and vascular structures of the eye are altered in fibromyalgia syndrome, particularly among severe cases. Therefore, optical coherence tomography angiography may provide valuable information for the diagnosis and elucidation of fibromyalgia syndrome pathophysiology.

Background: Fibromyalgia (FM) is a very prevalent and debilitating chronic pain disorder that is difficult to treat. Mindfulness-based techniques are regarded as a very promising approach for the treatment of chronic pain and in particular FM. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, a mindfulness-based group intervention, has shown beneficial effects in opioid-treated chronic pain patients, including reduced pain severity, functional interference, and opioid dosing, by restoring neurophysiological and behavioral responses to reward. The first evidence for a hypodopaminergic state and impaired reward processing in FM has been reported. However, little is known about its impact on dopamine (DA) function and in particular with regard to DA responses to monetary reward in FM. The aim of the present study protocol is to evaluate if MORE is able to restore the DA function in FM patients, in particular with regard to the DA responses to reward, and to reduce pain and mood complaints in FM., Methods: The present study is a multi-center interventional RCT with 3 time points: before the intervention, after completion of the intervention, and 3 months after completion of the intervention. Sixty-four FM patients will be randomly assigned to either the MORE intervention (N = 32) or a non-intervention control group (N = 32). Additionally, a comparison group of healthy women (N = 20) for PET measures will be enrolled and another group of healthy women (N = 15) will do the ambulatory assessments only. The MORE intervention consists of eight 2-h-long group sessions administered weekly over a period of 8 weeks. Before and after the intervention, FM participants will undergo [18F] DOPA positron emission tomography (PET) and functional MR imaging while performing a reward task. The primary outcome will be endogeneous DA changes measured with [18F] DOPA PET at baseline, after the intervention (after 8 weeks for the non-intervention control group), and at 3 months' follow-up. Secondary outcomes will be (1) clinical pain measures and FM symptoms using standardized clinical scales; (2) functional brain changes; (3) measures of negative and positive affect, stress, and reward experience in daily life using the ambulatory assessment method (AA); and (4) biological measures of stress including cortisol and alpha-amylase., Discussion: If the findings of this study confirm the effectiveness of MORE in restoring DA function, reducing pain, and improving mood symptoms, MORE can be judged to be a promising means to improve the quality of life in FM patients. The findings of this trial may inform health care providers about the potential use of the MORE intervention as a possible non-pharmacological intervention for FM., Trial Registration: ClinicalTrials.gov NCT04451564 . Registered on 3 July 2020. The trial was prospectively registered., (© 2021. The Author(s).)

Objective: There is increasing demand for prediction of chronic pain treatment outcomes using machine-learning models, in order to improve suboptimal pain management. In this exploratory study, we used baseline brain functional connectivity patterns from chronic pain patients with fibromyalgia (FM) to predict whether a patient would respond differentially to either milnacipran or pregabalin, 2 drugs approved by the US Food and Drug Administration for the treatment of FM., Methods: FM patients participated in 2 separate double-blind, placebo-controlled crossover studies, one evaluating milnacipran (n = 15) and one evaluating pregabalin (n = 13). Functional magnetic resonance imaging during rest was performed before treatment to measure intrinsic functional brain connectivity in several brain regions involved in pain processing. A support vector machine algorithm was used to classify FM patients as responders, defined as those with a ≥20% improvement in clinical pain, to either milnacipran or pregabalin., Results: Connectivity patterns involving the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) individually classified pregabalin responders versus milnacipran responders with 77% accuracy. Performance of this classification improved when both PCC and DLPFC connectivity patterns were combined, resulting in a 92% classification accuracy. These results were not related to confounding factors, including head motion, scanner sequence, or hardware status. Connectivity patterns failed to differentiate drug nonresponders across the 2 studies., Conclusion: Our findings indicate that brain functional connectivity patterns used in a machine-learning framework differentially predict clinical response to pregabalin and milnacipran in patients with chronic pain. These findings highlight the promise of machine learning in pain prognosis and treatment prediction., (© 2021 Pfizer. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Fibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood., Methods: We applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro-metabolite (e.g. combined glutamate and glutamine, Glx; myo-inositol, mIno; and combined (total) N-acetylaspartate and N-acetylaspartylglutamate, tNAA) levels and multidimensional clinical/behavioural variables (e.g. pain catastrophizing, clinical pain severity and evoked pain sensitivity) in women with fibromyalgia (N = 87)., Results: Pain catastrophizing scores were positively correlated with Glx and tNAA levels in insular cortex, and negatively correlated with mIno levels in posterior cingulate cortex (PCC). Clinical pain severity was positively correlated with Glx levels in insula and PCC, and with tNAA levels in anterior midcingulate cortex (aMCC), but negatively correlated with mIno levels in aMCC and thalamus. Evoked pain sensitivity was negatively correlated with levels of tNAA in insular cortex, MCC, PCC and thalamus., Conclusions: These findings support single voxel placement targeting nociceptive processing areas in prior 1 H-MRS studies, but also highlight other areas not as commonly targeted, such as PCC, as important for chronic pain pathophysiology. Identifying target brain regions linked to multidimensional symptoms of fibromyalgia (e.g. negative cognitive/affective response to pain, clinical pain, evoked pain sensitivity) may aid the development of neuromodulatory and individualized therapies. Furthermore, efficient multi-region sampling with 3D MRSI could reduce the burden of lengthy scan time for clinical research applications of molecular brain-based mechanisms supporting multidimensional aspects of fibromyalgia., Significance: This large N study linked brain metabolites and pain features in fibromyalgia patients, with a better spatial resolution and brain coverage, to understand a molecular mechanism underlying pain catastrophizing and other aspects of pain transmission. Metabolite levels in self-referential cognitive processing area as well as pain-processing regions were associated with pain outcomes. These results could help the understanding of its pathophysiology and treatment strategies for clinicians., (© 2021 European Pain Federation - EFIC®.)