Brain Topography

, Volume 30, Issue 4, pp 539–547 | Cite as

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

  • Alberto J. González-VillarEmail author
  • Marina Pidal-Miranda
  • Manuel Arias
  • Dolores Rodríguez-Salgado
  • María T. Carrillo-de-la-Peña
Original Paper


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


Fibromyalgia Working memory n-Back Attention Theta Alpha 



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

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10548_2017_561_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 KB)


  1. Attridge N, Noonan D, Eccleston C, Keogh E (2015) The disruptive effects of pain on n-back task performance in a large general population sample. Pain 156(10):1–28Google Scholar
  2. Awh E, Vogel EK, Oh SH (2006) Interactions between attention and working memory. Neuroscience 139(1):201–208CrossRefPubMedGoogle Scholar
  3. Bar-On Kalfon TB, Gal G, Shorer R, Ablin JN (2016) Cognitive functioning in fibromyalgia: the central role of effort. J Psychosom Res 87:30–36CrossRefPubMedGoogle Scholar
  4. Beck AT, Steer RA, Carbin MG (1988) Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev 8:77–100CrossRefGoogle Scholar
  5. Berryman C, Stanton TR, Jane Bowering K, Tabor A, McFarlane A, Lorimer Moseley G (2013) Evidence for working memory deficits in chronic pain: a systematic review and meta-analysis. Pain 154(8):1181–1196CrossRefPubMedGoogle Scholar
  6. Cagnie B, Coppieters I, Denecker S, Six J, Danneels L, Meeus M (2014) Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI. Semin Arthritis Rheum 44(1):68–75CrossRefPubMedGoogle Scholar
  7. Carrillo-de-la-Peña MT, Triñanes Y, González-Villar A, Romero-Yuste S, Gómez-Perretta C, Arias M et al (2015 ) Convergence between the 1990 and 2010 ACR diagnostic criteria and validation of the Spanish version of the Fibromyalgia Survey Questionnaire (FSQ). Rheumatol Int 35(1):141–151CrossRefPubMedGoogle Scholar
  8. Cavanagh JF, Frank MJ (2014) Frontal theta as a mechanism for cognitive control. Trends Cogn Sci 18(8):414–421CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cavanagh JF, Zambrano-Vazquez L, Allen JJB (2012) Theta lingua franca: a common mid-frontal substrate for action monitoring processes. Psychophysiology 49(2):220–238CrossRefPubMedGoogle Scholar
  10. Ceko M, Gracely JL, Fitzcharles MA, Seminowicz DA, Schweinhardt P, Bushnell MC (2015) Is a responsive default mode network required for Successful working memory task performance? J Neurosci 35(33):11595–11605CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cohen MX (2014) Analyzing neural time series data: theory and practice. MIT Press, CambridgeGoogle Scholar
  12. Cohen MX, Van Gaal S (2013) Dynamic interactions between large-scale brain networks predict behavioral adaptation after perceptual errors. Cereb Cortex 23(5):1061–1072CrossRefPubMedGoogle Scholar
  13. Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods 134(1):9–21CrossRefPubMedGoogle Scholar
  14. Demirci S, Savas S (2002) The auditory event related potentials in episodic and chronic pain sufferers. Eur J Pain Lond Engl 6(3):239–244CrossRefGoogle Scholar
  15. Diamond A (2014) Executive Functions. Annu Rev Clin Psychol 64:135–168CrossRefGoogle Scholar
  16. Dick B, Eccleston C, Crombez G (2002) Attentional functioning in fibromyalgia, rheumatoid arthritis, and musculoskeletal pain patients. Arthritis Rheum 47(6):639–644CrossRefPubMedGoogle Scholar
  17. Ersek M, Cherrier MM, Overman SS, Irving GA (2004) The cognitive effects of opioids. Pain Manag Nurs 5:75–93CrossRefPubMedGoogle Scholar
  18. Gazzaley A, Nobre AC (2012) Top-down modulation: bridging selective attention and working memory. Trends Cogn Sci 16(2):129–135CrossRefPubMedGoogle Scholar
  19. Gelonch O, Garolera M, Valls J, Rosselló L, Pifarré J (2016) Executive function in fibromyalgia: comparing subjective and objective measures. Compr Psychiatry 66:113–122CrossRefPubMedGoogle Scholar
  20. Gevins A, Smith M, McEvoy L, Yu D (1997) High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. Cereb Cortex 374–385Google Scholar
  21. Glass JM (2009) Review of cognitive dysfunction in fibromyalgia: a convergence on working memory and attentional control impairments. Rheum Dis Clin N Am 35(2):299–311CrossRefGoogle Scholar
  22. Glass JM, Williams DA, Fernandez-Sanchez ML, Kairys A, Barjola P, Heitzeg MM, Clauw DJ, Schmidt-Wilcke T (2011) Executive function in chronic pain patients and healthy controls: different cortical activation during response inhibition in fibromyalgia. J Pain 12(12):1219–1229CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hsieh L-T, Ranganath C (2014) Frontal midline theta oscillations during working memory maintenance and episodic encoding and retrieval. Neuroimage 85:721–729CrossRefPubMedGoogle Scholar
  24. Ishii R, Shinosaki K, Ukai S, Inouye T, Ishihara T, Yoshimine T et al (1999) Medial prefrontal cortex generates frontal midline theta rhythm. Neuroreport 10(4):675–679CrossRefPubMedGoogle Scholar
  25. Ishii R, Canuet L, Ishihara T, Aoki Y, Ikeda S, Hata M, et al (2014) Frontal midline theta rhythm and gamma power changes during focused attention on mental calculation: an MEG beamformer analysis. Front Hum Neurosci 8:1–10CrossRefGoogle Scholar
  26. Jensen O, Mazaheri A. (2010) Shaping functional architecture by oscillatory alpha activity: gating by inhibition. Front Hum Neurosci 4:186CrossRefPubMedPubMedCentralGoogle Scholar
  27. Jensen O, Bonnefond M, VanRullen R (2012) An oscillatory mechanism for prioritizing salient unattended stimuli. Trends Cogn Sci 16(4):200–205CrossRefPubMedGoogle Scholar
  28. Kayser J, Tenke CE (2006) Principal components analysis of Laplacian waveforms as a generic method for identifying ERP generator patterns: II. Adequacy of low-density estimates. Clin Neurophysiol 117(2):369–380CrossRefPubMedGoogle Scholar
  29. Klimesch W, Sauseng P, Hanslmayr S (2007) EEG alpha oscillations: the inhibition-timing hypothesis. Brain Res Rev 53(1):63–88CrossRefPubMedGoogle Scholar
  30. Kondo H, Morishita M, Osaka N, Osaka M, Fukuyama H, Shibasaki H (2004) Functional roles of the cingulo-frontal network in performance on working memory. Neuroimage 21(1):2–14CrossRefPubMedGoogle Scholar
  31. Leavitt F, Katz RS (2006) Distraction as a key determinant of impaired memory in patients with fibromyalgia. J Rheumatol 33(1):127–132PubMedGoogle Scholar
  32. Luerding R, Weigand T, Bogdahn U, Schmidt-Wilcke T (2008) Working memory performance is correlated with local brain morphology in the medial frontal and anterior cingulate cortex in fibromyalgia patients: structural correlates of pain-cognition interaction. Brain 131(12):3222–3231CrossRefPubMedGoogle Scholar
  33. McCracken LM, Iverson GL (2001) Predicting complaints of impaired cognitive functioning in patients with chronic pain. J Pain Symptom Manage 21(5):392–396CrossRefPubMedGoogle Scholar
  34. McGuire BE (2013) Chronic pain and cognitive function. Pain 154:964–965CrossRefPubMedGoogle Scholar
  35. Mizuhara H, Yamaguchi Y (2007) Human cortical circuits for central executive function emerge by theta phase synchronization. NeuroImage. 36(1):232–244CrossRefPubMedGoogle Scholar
  36. Moriarty O, Finn DP (2014) Cognition and pain. Curr Opin Support Palliat Care 8(2):130–136CrossRefPubMedGoogle Scholar
  37. Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, Harris RE (2010) Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum 62:2545–2555CrossRefPubMedPubMedCentralGoogle Scholar
  38. Onton J, Delorme A, Makeig S (2005) Frontal midline EEG dynamics during working memory. Neuroimage 27(2):341–356CrossRefPubMedGoogle Scholar
  39. Owen AM, McMillan KM, Laird AR, Bullmore E (2005) N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp 25(1):46–59CrossRefPubMedGoogle Scholar
  40. Palva S, Palva JM (2011) Functional roles of alpha-band phase synchronization in local and large-scale cortical networks. Front Psychol 2:204CrossRefPubMedPubMedCentralGoogle Scholar
  41. Park DC, Glass JM, Minear M, Crofford LJ (2001) Cognitive function in fibromyalgia patients. Arthritis Rheum 44(9):2125–2133CrossRefPubMedGoogle Scholar
  42. Peirce JW (2008) Generating stimuli for neuroscience using psychopy. Front Neuroinform 2:10CrossRefPubMedGoogle Scholar
  43. Perrot S, Russell IJ (2014) More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms: non-pharmacologic versus pharmacologic treatments in FM. Eur J Pain 18(8):1067–1080CrossRefPubMedGoogle Scholar
  44. Pesonen M, Hämäläinen H, Krause CM (2007) Brain oscillatory 4–30 Hz responses during a visual n-back memory task with varying memory load. Brain Res 1138:171–177CrossRefPubMedGoogle Scholar
  45. Peyron R, Laurent B, García-Larrea L (2000) Functional imaging of brain responses to pain. A review and meta-analysis. Neurophysiol Clin 30(5):263–288CrossRefPubMedGoogle Scholar
  46. Rémy F, Frankenstein UN, Mincic A, Tomanek B, Stroman PW (2003) Pain modulates cerebral activity during cognitive performance. Neuroimage 19(3):655–664CrossRefPubMedGoogle Scholar
  47. Roth RS, Geisser ME, Theisen-Goodvich M, Dixon PJ (2005) Cognitive complaints are associated with depression, fatigue, female sex, and pain catastrophizing in patients with chronic pain. Arch Phys Med Rehabil 86(6):1147–1154CrossRefPubMedGoogle Scholar
  48. Schmidt-Wilcke T, Kairys A, Ichesco E, Fernández-Sánchez ML, Barjola P, Heitzeg M et al (2014) Changes in clinical pain in fibromyalgia patients correlate with changes in brain activation in the cingulate cortex in a response inhibition task. Pain Med 15:1346–1358CrossRefPubMedGoogle Scholar
  49. Seo J, Kim S-H, Kim Y-T, Song H, Lee J, Kim S-H et al (2012) Working memory impairment in fibromyalgia patients associated with altered frontoparietal memory network. PLoS ONE 7(6):e37808CrossRefPubMedPubMedCentralGoogle Scholar
  50. Shackman AJ, Salomons TV, Slagter HA, Fox AS, Winter JJ, Davidson RJ (2011) The integration of negative affect, pain and cognitive control in the cingulate cortex. Nat Rev Neurosci 12(3):154–167CrossRefPubMedPubMedCentralGoogle Scholar
  51. Stam CJ, Nolte G, Daffertshofer A (2007) Phase lag index: assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources. Hum Brain Mapp 28:1178–1193CrossRefPubMedGoogle Scholar
  52. Tandon OP, Kumar S (1993) P3 event related cerebral evoked potential in chronic pain patients. Indian J Physiol Pharmacol 37(1):51–55PubMedGoogle Scholar
  53. Tesio V, Torta DME, Colonna F, Leombruni P, Ghiggia A, Fusaro E et al (2014) Are fibromyalgia patients cognitively impaired? Objective and subjective neuropsychological evidence. Arthritis Care Res 67(1):143–150CrossRefGoogle Scholar
  54. Vinck M, Oostenveld R, van Wingerden M, Battaglia F, Pennartz CMA (2011) An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias. Neuroimage 55(4):1548–1565CrossRefPubMedGoogle Scholar
  55. Vogt BA (2005) Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci 6(7):533–544CrossRefPubMedPubMedCentralGoogle Scholar
  56. Voytek B, Kayser AS, Badre D, Fegen D, Chang EF, Crone NE et al (2015) Oscillatory dynamics coordinating human frontal networks in support of goal maintenance. Nat Neurosci 18:1–10CrossRefGoogle Scholar
  57. Wang C, Ulbert I, Schomer DL, Marinkovic K, Halgren E (2005) Responses of human anterior cingulate cortex microdomains to error detection, conflict monitoring, stimulus-response mapping, familiarity, and orienting. J Neurosci Off 25(3):604–613CrossRefGoogle Scholar
  58. Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Katz RS, Mease P, et al (2010) The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity. Arthritis Care Res 62(5):600–610CrossRefGoogle Scholar
  59. Womelsdorf T, Johnston K, Vinck M, Everling S (2010a) Theta-activity in anterior cingulate cortex predicts task rules and their adjustments following errors. Proc Natl Acad Sci 107(11):5248–5253CrossRefPubMedPubMedCentralGoogle Scholar
  60. Womelsdorf T, Vinck M, Leung LS, Everling S. (2010b) Selective theta-synchronization of choice-relevant information subserves goal-directed behavior. Front Hum Neurosci 4:1–13CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Alberto J. González-Villar
    • 1
    Email author
  • Marina Pidal-Miranda
    • 1
  • Manuel Arias
    • 2
  • Dolores Rodríguez-Salgado
    • 1
  • María T. Carrillo-de-la-Peña
    • 1
  1. 1.Department of Clinical Psychology and PsychobiologyUniversidade de Santiago de CompostelaSantiago de CompostelaSpain
  2. 2.Department of NeurologyComplexo Hospitalario Universitario de SantiagoSantiago de CompostelaSpain

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