Skip to main content

Advertisement

SpringerLink
Log in

Increased Delta and Theta Power Density in Sickle Cell Disease Individuals with Chronic Pain Secondary to Hip Osteonecrosis: A Resting-State Eeg Study

  • Original Paper
  • Published:
Brain Topography Aims and scope Submit manuscript

Abstract

Purpose

Identify the presence of a dysfunctional electroencephalographic (EEG) pattern in individuals with sickle cell disease (SCD) and hip osteonecrosis, and assess its potential associations with depression, anxiety, pain severity, and serum levels of brain-derived neurotrophic factor (BDNF).

Methods

In this cross-sectional investigation, 24 SCD patients with hip osteonecrosis and chronic pain were matched by age and sex with 19 healthy controls. Resting-state EEG data were recorded using 32 electrodes for both groups. Power spectral density (PSD) and peak alpha frequency (PAF) were computed for each electrode across Delta, Theta, Alpha, and Beta frequency bands. Current Source Density (CSD) measures were performed utilizing the built-in Statistical nonparametric Mapping Method of the LORETA-KEY software.

Results

Our findings demonstrated that SCD individuals exhibited higher PSD in delta and theta frequency bands when compared to healthy controls. Moreover, SCD individuals displayed increased CSD in delta and theta frequencies, coupled with decreased CSD in the alpha frequency within brain regions linked to pain processing, motor function, emotion, and attention. In comparison to the control group, depression symptoms, and pain intensity during hip abduction were positively correlated with PSD and CSD in the delta frequency within the parietal region. Depression symptoms also exhibited a positive association with PSD and CSD in the theta frequency within the same region, while serum BDNF levels showed a negative correlation with CSD in the alpha frequency within the left insula.

Conclusion

This study indicates that individuals with SCD experiencing hip osteonecrosis and chronic pain manifest a dysfunctional EEG pattern characterized by the persistence of low-frequency PSD during a resting state. This dysfunctional EEG pattern may be linked to clinical and biochemical outcomes, including depression symptoms, pain severity during movement, and serum BDNF levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Al-Otaibi ML (2022) An overview of pathophysiology and treatment options of osteonecrosis of femoral head in sickle cell Disease. Saudi Med J 43:1192–1199

    Article  PubMed  Google Scholar 

  • Baliki MN, Mansour AR, Baria AT, Apkarian AV (2014) Functional reorganization of the default mode network across chronic pain conditions. PLoS ONE 9:e106133

    Article  PubMed  PubMed Central  Google Scholar 

  • Ballas SK, Darbari DS (2020) Review/overview of pain in sickle cell Disease. Complement Ther Med 49:102327

    Article  PubMed  Google Scholar 

  • Boord P, Siddall PJ, Tran Y et al (2008) Electroencephalographic slowing and reduced reactivity in neuropathic pain following spinal cord injury. Spinal Cord 46:118–123

    Article  CAS  PubMed  Google Scholar 

  • Buchanan DM, Ros T, Nahas R (2021) Elevated and slowed EEG oscillations in patients with post-concussive syndrome and Chronic Pain following a motor vehicle collision. Brain Sci 11. https://doi.org/10.3390/brainsci11050537

  • Campbell CM, Moscou-Jackson G, Carroll CP et al (2016) An evaluation of Central Sensitization in patients with Sickle Cell Disease. J Pain 17:617–627

    Article  PubMed  PubMed Central  Google Scholar 

  • Case M, Zhang H, Mundahl J et al (2017) Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell Disease. Neuroimage Clin 14:1–17

    Article  PubMed  Google Scholar 

  • Case M, Shirinpour S, Zhang H et al (2018) Increased theta band EEG power in sickle cell Disease patients. J Pain Res 11:67–76

    Article  PubMed  Google Scholar 

  • Caumo W, Antunes LC, Elkfury JL et al (2017) The Central Sensitization Inventory validated and adapted for a Brazilian population: psychometric properties and its relationship with brain-derived neurotrophic factor. J Pain Res 10:2109–2122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cavanna AE, Trimble MR (2006) The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129:564–583

    Article  PubMed  Google Scholar 

  • Da Silva JT, Letzen JE, Haythornthwaite JA et al (2019) Do chronic pain and comorbidities affect brain function in sickle cell patients? A systematic review of neuroimaging and treatment approaches. Pain 160:1933–1945

    Article  PubMed  Google Scholar 

  • Dampier C, Palermo TM, Darbari DS et al (2017) AAPT Diagnostic Criteria for Chronic Sickle Cell Disease Pain. J Pain 18:490–498

    Article  PubMed  Google Scholar 

  • Darbari DS, Hampson JP, Ichesco E et al (2015) Frequency of hospitalizations for Pain and Association with altered Brain Network Connectivity in Sickle Cell Disease. J Pain 16:1077–1086

    Article  PubMed  PubMed Central  Google Scholar 

  • Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including Independent component analysis. J Neurosci Methods 134:9–21

    Article  PubMed  Google Scholar 

  • Di Pietro F, Macey PM, Rae CD et al (2018) The relationship between thalamic GABA content and resting cortical rhythm in neuropathic pain. Hum Brain Mapp 39:1945–1956

    Article  PubMed  PubMed Central  Google Scholar 

  • Fallon N, Chiu Y, Nurmikko T, Stancak A (2016) Functional connectivity with the default Mode Network is altered in Fibromyalgia patients. PLoS ONE 11:e0159198

    Article  PubMed  PubMed Central  Google Scholar 

  • Ficat P, Arlet J, Vidal R et al (1971) [Therapeutic results of drill biopsy in primary osteonecrosis of the femoral head (100 cases)]. Rev Rhum Mal Osteoartic 38:269–276

    CAS  PubMed  Google Scholar 

  • Fingelkurts AA, Fingelkurts AA (2015) Altered structure of dynamic electroencephalogram oscillatory pattern in major depression. Biol Psychiatry 77:1050–1060

    Article  PubMed  Google Scholar 

  • Gallace A, Bellan V (2018) The parietal cortex and pain perception: a body protection system. Handb Clin Neurol 151:103–117

    Article  PubMed  Google Scholar 

  • González-Roldán AM, Cifre I, Sitges C, Montoya P (2016) Altered dynamic of EEG oscillations in Fibromyalgia patients at Rest. Pain Med 17:1058–1068

    PubMed  Google Scholar 

  • Gram M, Erlenwein J, Petzke F et al (2017) The cortical responses to evoked clinical pain in patients with hip osteoarthritis. PLoS ONE 12:e0186400

    Article  PubMed  PubMed Central  Google Scholar 

  • Haukoos JS, Lewis RJ (2005) Advanced statistics: bootstrapping confidence intervals for statistics with difficult distributions. Acad Emerg Med 12:360–365

    PubMed  Google Scholar 

  • Inui K, Wang X, Qiu Y et al (2003) Pain processing within the primary somatosensory cortex in humans. Eur J Neurosci 18:2859–2866

    Article  PubMed  Google Scholar 

  • Jensen MP, Sherlin LH, Fregni F et al (2014) Baseline brain activity predicts response to neuromodulatory pain treatment. Pain Med 15:2055–2063

    Article  PubMed  Google Scholar 

  • Kanda M, Nagamine T, Ikeda A et al (2000) Primary somatosensory cortex is actively involved in pain processing in human. Brain Res 853:282–289

    Article  CAS  PubMed  Google Scholar 

  • Karafin MS, Chen G, Wandersee NJ et al (2019) Chronic pain in adults with sickle cell Disease is associated with alterations in functional connectivity of the brain. PLoS ONE 14:e0216994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kisler LB, Kim JA, Hemington KS et al (2020) Abnormal alpha band power in the dynamic pain connectome is a marker of chronic pain with a neuropathic component. Neuroimage Clin 26:102241

    Article  PubMed  PubMed Central  Google Scholar 

  • Llinás RR, Ribary U, Jeanmonod D et al (1999) Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A 96:15222–15227

    Article  PubMed  PubMed Central  Google Scholar 

  • Llinás R, Urbano FJ, Leznik E et al (2005) Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect. Trends Neurosci 28:325–333

    Article  PubMed  Google Scholar 

  • Lopes TdaS, Silva WDS, Ribeiro SB et al (2017) Does Transcranial Direct Current Stimulation Combined with Peripheral Electrical Stimulation have an Additive Effect in the Control of Hip Joint Osteonecrosis Pain Associated with Sickle Cell Disease? A protocol for a one-Session double blind, Block-Randomized Clinical Trial. Front Hum Neurosci 11:633

    Article  PubMed  PubMed Central  Google Scholar 

  • Lopes Tda, Ballas S, Santana SK JERS, et al (2022) Sickle cell Disease chronic joint pain: clinical assessment based on maladaptive central nervous system plasticity. Front Med 9:679053

    Article  Google Scholar 

  • McLain NJ, Yani MS, Kutch JJ (2022) Analytic consistency and neural correlates of peak alpha frequency in the study of pain. J Neurosci Methods 368:109460

    Article  PubMed  Google Scholar 

  • Meneses FM, Queirós FC, Montoya P et al (2016) Patients with Rheumatoid Arthritis and Chronic Pain Display enhanced Alpha Power Density at Rest. Front Hum Neurosci 10:395

    Article  PubMed  PubMed Central  Google Scholar 

  • Mussigmann T, Bardel B, Lefaucheur J-P (2022) Resting-state electroencephalography (EEG) biomarkers of chronic neuropathic pain. A systematic review. NeuroImage 258:119351

    Article  PubMed  Google Scholar 

  • Orenius TI, Raij TT, Nuortimo A et al (2017) The interaction of emotion and pain in the insula and secondary somatosensory cortex. Neuroscience 349:185–194

    Article  CAS  PubMed  Google Scholar 

  • Pinheiro ES, dos Queirós S, Montoya FC P, et al (2016) Electroencephalographic patterns in Chronic Pain: a systematic review of the literature. PLoS ONE 11:e0149085

    Article  PubMed  PubMed Central  Google Scholar 

  • Roy N, Barry RJ, Fernandez FE et al (2020) Electrophysiological correlates of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. Sci Rep 10:17915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos JG, Brito JO, de Andrade DC et al (2010) Translation to Portuguese and validation of the Douleur Neuropathique 4 questionnaire. J Pain 11:484–490

    Article  PubMed  Google Scholar 

  • Sarnthein J, Stern J, Aufenberg C et al (2006) Increased EEG power and slowed dominant frequency in patients with neurogenic pain. Brain 129:55–64

    Article  PubMed  Google Scholar 

  • Schmidt S, Naranjo JR, Brenneisen C et al (2012) Pain ratings, psychological functioning and quantitative EEG in a controlled study of chronic back pain patients. PLoS ONE 7:e31138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simão AP, Mendonça VA, de Oliveira Almeida TM et al (2014) Involvement of BDNF in knee osteoarthritis: the relationship with inflammation and clinical parameters. Rheumatol Int 34:1153–1157

    Article  PubMed  Google Scholar 

  • Simis M, Imamura M, Pacheco-Barrios K et al (2022) EEG theta and beta bands as brain oscillations for different knee osteoarthritis phenotypes according to Disease severity. Sci Rep 12:1480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sitges C, Bornas X, Llabrés J et al (2010) Linear and nonlinear analyses of EEG dynamics during non-painful somatosensory processing in chronic pain patients. Int J Psychophysiol 77:176–183

    Article  PubMed  Google Scholar 

  • Stern J, Jeanmonod D, Sarnthein J (2006) Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients. NeuroImage 31:721–731

    Article  PubMed  Google Scholar 

  • Vlcek P, Bares M, Novak T, Brunovsky M (2020) Baseline difference in quantitative electroencephalography variables between responders and non-responders to low-frequency repetitive transcranial magnetic stimulation in Depression. Front Psychiatry 11:83

    Article  PubMed  PubMed Central  Google Scholar 

  • Vuckovic A, Hasan MA, Fraser M et al (2014) Dynamic oscillatory signatures of central neuropathic pain in spinal cord injury. J Pain 15:645–655

    Article  PubMed  PubMed Central  Google Scholar 

  • Walton KD, Dubois M, Llinás RR (2010) Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I. Pain 150:41–51

    Article  CAS  PubMed  Google Scholar 

  • Yip DW, Lui F (2021) Physiology, motor cortical. In: StatPearls. StatPearls Publishing, Treasure Island (FL)

    Google Scholar 

  • Zebhauser PT, Hohn VD, Ploner M (2023) Resting-state electroencephalography and magnetoencephalography as biomarkers of chronic pain: a systematic review. Pain 164:1200–1221

    Article  PubMed  Google Scholar 

  • Zoon HFA, Veth CPM, Arns M et al (2013) EEG alpha power as an intermediate measure between brain-derived neurotrophic factor Val66Met and depression severity in patients with major depressive disorder. J Clin Neurophysiol 30:261–267

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors also wish to thank the Research Support Foundation of the State of Bahia (FAPESB) for funding through the Support Program for Emerging Center, 8133/2014 (PNE0020/2014). TSL received a post-doctoral fellowship from the Coordination for the Improvement of Higher Education Personnel (CAPES) (Process: 88887.801519/2023-00). AFB and FJF receive a scholarship for scientific production from the Brazilian National Council for Scientific Development (CNPq). AFB is supported by CEPID/BRAINN-The Brazilian Institute of Neuroscience and Neurotechnology (Process: 13/07559 − 369 3) and by the LIM-54 HC FMUSP. JERSS received a Ph.D. scholarship from the CAPES. PM was supported by grant PSI2017-88388-C4-1-R funded by MCIN/AEI/ https://doi.org/10.13039/501100011033).

Author information

Authors and Affiliations

  1. Center for Mathematics, Computation, and Cognition, Federal University of ABC, Santo Andre, Brazil

    Tiago S. Lopes, Jamille E. Santana, Pedro Montoya, Yossi Zana & Abrahão F. Baptista

  2. NAPEN network (Nucleus of Assistance, Research, and Teaching in Neuromodulation), São Paulo, Brazil

    Tiago S. Lopes, Jamille E. Santana, Katia N. Sá & Abrahão F. Baptista

  3. Bahia Adventist College, Cachoeira, Brazil

    Tiago S. Lopes & Wellington S. Silva

  4. Engineering, Modelling, and Applied Social Sciences Center, Federal University of ABC, Santo André, SP, Brazil

    Francisco J. Fraga

  5. Research Institute of Health Sciences, University of Balearic Islands, Palma de Mallorca, Spain

    Pedro Montoya

  6. Postgraduate and Research, Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil

    Katia N. Sá

  7. Graduate Program in Medicine and Health, Federal University of Bahia, Salvador, Brazil

    Larissa C. Lopes & Rita Lucena

  8. Laboratory of Medical Investigations 54, Clinics Hospital, São Paulo State University, São Paulo, Brazil

    Abrahão F. Baptista

Authors
  1. Tiago S. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jamille E. Santana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wellington S. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco J. Fraga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pedro Montoya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Katia N. Sá
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Larissa C. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rita Lucena
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yossi Zana
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Abrahão F. Baptista
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors T.S, A.B, W.S, J.S, P.M, R.L and K.S were involved in study conception and method development. The T.S, W.S, and J.S contributed to all data collection, while F.F and Y.Z developed the data analysis. L.S and T.S prepared all figures and the authors T.S and A.B wrote the main manuscript text. All authors critically revised the final version of the manuscript.

Corresponding author

Correspondence to Tiago S. Lopes.

Ethics declarations

Competing Interests

The authors declare no competing interests.

Additional information

Communicated by Franca Tecchio.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lopes, T.S., Santana, J.E., Silva, W.S. et al. Increased Delta and Theta Power Density in Sickle Cell Disease Individuals with Chronic Pain Secondary to Hip Osteonecrosis: A Resting-State Eeg Study. Brain Topogr (2023). https://doi.org/10.1007/s10548-023-01027-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10548-023-01027-x

Keywords

Search

Navigation