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The goal of this observational study is to assess event-related potentials and habituation in patients with fibromyalgia. The main research questions are:
Participants will:
- receive randomized sensory stimuli (auditory, visual, somatosensory, audiovisual, auditory-somatosensory, visual-somatosensory, and auditory-visual-somatosensory) in blocks of 20 trials.
Fibromyalgia is a disorder characterized primarily by widespread musculoskeletal pain. It is often accompanied by symptoms such as fatigue, insomnia, cognitive difficulties, etc. In addition to chronic pain, patients frequently report hypersensitivity to sensory stimuli, both nociceptive and non-nociceptive. Studies using psychophysical and electrophysiological tests have found altered sensory processing in fibromyalgia patients.
Research focused on event-related potentials (ERPs) have found differences in amplitude in the responses to auditory, nociceptive, and non-nociceptive somatosensory stimuli in fibromyalgia patients . One key aspect evaluated through ERPs is habituation, defined as a decrease in response due to repeated stimulation. In healthy individuals, ERPs amplitude decreases with repeated sensory input due to progressive neuronal response reduction. In fibromyalgia patients, reduced habituation has been observed for laser-induced ERPs and somatosensory ERPs, though no differences were found for auditory ERPs.
ERPs not only provide information about sensory modalities but also contain non-specific components related to stimulus expectation, motor preparation, and attentional orientation. Previous studies have attempted to isolate this non-specific component, as part of habituation may stem from a decrease in its amplitude rather than from a direct sensory response reduction. Using an analytical model, researchers successfully separated this component in experiments with individually or simultaneously presented stimuli, yielding promising results.
In the present study, participants (both fibromyalgia patients and healthy controls) will attend one experimental session in which stimulation in different sensory modalities will take place along with electroencephalographic (EEG) recordings. For each stimulus type, 2 blocks of 20 trials will be performed.The order of the stimulus will be selected randomly, but they can be divided into three categories:
Unimodal stimulus
Bimodal stimulus
Trimodal Stimulus
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fibromyalgia Patients | Patients with primary fibromyalgia diagnosis. May include other chronic pain comorbidities, but the pain associated with those diseases should be less severe than the pain caused by fibromyalgia. |
| |
| Healthy Controls | Volunteers with no clinical history of chronic pain, musculoskeletal or articular disorders |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Auditory Stimulation | Other | A tone at a 1000 Hz frequency, delivered through speakers at a comfortable volume |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentual Habituation | Relative reduction in the amplitude of evoked potentials between consecutive stimuli | Immediately after the intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Fibromyalgia Impact Questionnaire-Revised version (FIQR) | Instrument for the assessment and evaluation of fibromyalgia patient's status. Scores range from 0 to 100, with a higher number indicating more impacts of fibromyalgia symptoms in daily life | 10 minutes before the intervention |
| Symptoms Impact Questionnaire (SIQ) |
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Inclusion Criteria:
Fibromyalgia patients:
Healthy controls:
Exclusion Criteria:
Fibromyalgia patients:
Healthy controls:
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The cohorts of patients and healthy controls wil be selected from the city of Paraná and surrounding areas. Through the ONG "Fibromialgia Entre RÃos Asociación Civil", the patients will be reached out and asked wether or not they are willing to participate. Additionally, flyer will be hung in major health facilities in the city and made public on social media. The cohort of healthy volunteers will be recruited after the patients for age, genre and socieconomic matching
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| Name | Affiliation | Role |
|---|---|---|
| Biurrun Manresa | National Council of Scientific and Technical Research, Argentina (CONICET) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Faculty of Engineering-National University of Entre RÃos | Oro Verde | Entre RÃos Province | 3100 | Argentina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16427613 | Background | Gondan M, Roder B. A new method for detecting interactions between the senses in event-related potentials. Brain Res. 2006 Feb 16;1073-1074:389-97. doi: 10.1016/j.brainres.2005.12.050. Epub 2006 Jan 20. | |
| 5324565 | Background | Thompson RF, Spencer WA. Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev. 1966 Jan;73(1):16-43. doi: 10.1037/h0022681. No abstract available. |
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Individual participant data (IPD) will be made available on the 'Open Science Framework' after undergoing the process of anonymization to remove any participant-identifying information. The data will consist of the raw EEG signals and raw behavioral responses to cognitive tasks. Additionally, the statistical analysis and Jupyter notebooks used to process the data will also be shared
The participant's data and the processing pipeline will be available after the data collection is finished. The supporting information (including the study protocol, the statistical analysis plan and the informed consent) will be uploaded as soon as possible.
The data will be publicly available.
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| Visual Stimulation | Other | A checkerboard pattern displayed on a monitor, with colors alternating every 25 ms |
|
| Somatosensory Stimulation | Other | A train of three electrical stimuli, each lasting 1 ms, separated by 8 ms, at an intensity that clearly elicits a pricking sensation |
|
| Auditory-Visual Stimulation | Other | Stimulation using auditory and visual stimuli concomitantly |
|
| Visual-Somatosensory Stimulation | Other | Stimulation using visual and somatosensory stimuli concomitantly |
|
| Auditory-Somatonsensory Stimulation | Other | Stimulation using auditory and somatosensory stimuli concomitantly |
|
| Auditory-Visual-Somatosensory Stimulation | Other | Stimulation using auditory, visual and somatosensory stimuli concomitantly |
|
Instrument to assess healthy control's status regarding relevant clinical symptoms experienced in the last week. Scores range from 0 to 100, with a higher number indicating more impacts of their symptoms in daily life activities |
| 10 minutes before the intervention |
| Hospital Anxiety and Depression Scale (HADS) | Widely used instrument to evaluate anxiety and depression. It is divided into 7 questions assessing anxiety and 7 assessing depression. The scores range from 0 to 21, with higher scores indicating worse clinical symptoms. | 10 minutes before the intervention |
| Numeric Rating Scale Pain (NRSp) | Pain at the moment of the experimental session. Scores range from 0 to 10, with higher number indicating worse pain. | 10 minutes before the intervention |
| Stimulus saliency | A number reflecting the ability of a stimulus to stand out relative to the sensory background or relative to the preceding stimuli | Immediately after the intervention |
| Event-related potentials amplitude | Amplitude, in microvolts, of event-related brain potentials | Immediately after the intervention |
| Event-related potentials latency | Latency, in milliseconds, of event-related brain potentials | Immediately after the intervention |
| Non-specific components amplitude | Amplitude, in microvolts, of the non/specific component derived from the ERPs | Immediately after the intervention |
| Non-specific components latency | Latency, in milliseconds, of the non-specific component derived from the ERPs | Immediately after the intervention |
| 16732548 | Background | Montoya P, Sitges C, Garcia-Herrera M, Rodriguez-Cotes A, Izquierdo R, Truyols M, Collado D. Reduced brain habituation to somatosensory stimulation in patients with fibromyalgia. Arthritis Rheum. 2006 Jun;54(6):1995-2003. doi: 10.1002/art.21910. |
| 10025076 | Background | Lorenz J. Hyperalgesia or hypervigilance? An evoked potential approach to the study of fibromyalgia syndrome. Z Rheumatol. 1998;57 Suppl 2:19-22. doi: 10.1007/s003930050228. |
| 20685171 | Background | de Tommaso M, Federici A, Santostasi R, Calabrese R, Vecchio E, Lapadula G, Iannone F, Lamberti P, Livrea P. Laser-evoked potentials habituation in fibromyalgia. J Pain. 2011 Jan;12(1):116-24. doi: 10.1016/j.jpain.2010.06.004. Epub 2010 Aug 4. |
| 14986061 | Background | Alanoglu E, Ulas UH, Ozdag F, Odabasi Z, Cakci A, Vural O. Auditory event-related brain potentials in fibromyalgia syndrome. Rheumatol Int. 2005 Jun;25(5):345-9. doi: 10.1007/s00296-004-0443-3. Epub 2004 Feb 21. |
| 8880834 | Background | McDermid AJ, Rollman GB, McCain GA. Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. Pain. 1996 Aug;66(2-3):133-44. doi: 10.1016/0304-3959(96)03059-x. |
| 35983754 | Background | Young EL, Mista CA, Jure FA, Andersen OK, Biurrun Manresa JA. An analytical method to separate modality-specific and nonspecific sensory components of event-related potentials. Eur J Neurosci. 2022 Oct;56(7):5090-5105. doi: 10.1111/ejn.15798. Epub 2022 Aug 31. |
| 33636370 | Background | Staud R, Godfrey MM, Robinson ME. Fibromyalgia Patients Are Not Only Hypersensitive to Painful Stimuli But Also to Acoustic Stimuli. J Pain. 2021 Aug;22(8):914-925. doi: 10.1016/j.jpain.2021.02.009. Epub 2021 Feb 23. |
| 26992095 | Background | Lim M, Roosink M, Kim JS, Kim HW, Lee EB, Son KM, Kim HA, Chung CK. Augmented Pain Processing in Primary and Secondary Somatosensory Cortex in Fibromyalgia: A Magnetoencephalography Study Using Intra-Epidermal Electrical Stimulation. PLoS One. 2016 Mar 18;11(3):e0151776. doi: 10.1371/journal.pone.0151776. eCollection 2016. |
| ID | Term |
|---|---|
| D005356 | Fibromyalgia |
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000161 | Acoustic Stimulation |
| D010775 | Photic Stimulation |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D026421 | Sensory Art Therapies |
| D000529 | Complementary Therapies |
| D010812 | Physical Stimulation |
| D008919 | Investigative Techniques |
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