Tools for the Differential Diagnosis of Fibromyalgia Based on Cognitive Tasks

Development of Complementary Tools for the Differential Diagnosis of Fibromyalgia Based on Cognitive Task Performance

The goal of this observational study is to test for behavioural and neurophysiological biomarkers in fibromyalgia patients. The main questions it aims to answer are:

• Is there a measurable decline in working memory?
• Could these measures help in fibromyalgia differential diagnosis?

Participants will:

• perform Color Comparison tasks
• perform n-back tasks

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Other: Color Comparison Task; Other: N-back Task

Detailed Description

Fibromyalgia is a disease characterized by the presence of generalized musculoskeletal pain, accompanied by non-specific symptoms such as depression, sleep disturbances, anxiety, cognitive disabilities, among others. While widespread musculoskeletal pain is the predominant symptom in patients with fibromyalgia, cognitive impairments have also been widely reported, including decreased ability to concentrate, decreased short-term memory, and inability to multitask, which differentiate fibromyalgia patients from those with other chronic pain syndromes. Specifically, quantitative evidence has been found of impairment in executive functions in this group of patients, particularly in the domains of inhibitory control and working memory.

In the present study, participants (both healthy individuals and those diagnosed with fibromyalgia) will perform two cognitive tasks designed to assess the capacity and retrieval of information from working memory. The first task is the Color Comparison task, in which colored squares will appear on a computer screen for a short period of time. After a blank delay, a new set of squares will appear, and a decision has to be made about whether or not the squares are the same as the ones shown first. The task will be divided into 10 blocks of 30 trials each, with 10 trials comparing 2 colored squares, 10 trials comparing 4 colored squares, and 10 trials comparing 6 colored squares. A resting period will be given between each block. The behavioral results of this task will include reaction times and hit rates. At the same time, electroencephalographic data will be recorded to evaluate the Contralateral Delay Activity (CDA). The amplitude of this waveform is linked to the number of items allocated in working memory.

The second task that will be carried out by the participants is the n-back task. A sequence of letters will be presented, and participants will be asked to indicate whether the current stimulus matches the one presented two stimuli earlier. Sixty-two stimuli will be presented per block, and 5 blocks will be carried out. The results will be analyzed in terms of behavioral analysis and Event-Related Potentials (ERPs) analysis.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Argentina
  • Entre Ríos
    • Oro Verde, Entre Ríos, Argentina, 3100
      • Center for Nuclear and Molecular Medicine Entre Ríos (CEMENER)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The cohorts of patients and healthy controls wil be selected from the city of Paraná and surrounding areas. Through the ONG "Fibromialgia Entre Ríos 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

Description

Inclusion Criteria:

Fibromyalgia patients:

• Primary diagnosis of fibromyalgia according to the criteria used by the healthcare professional in charge of the patient.
• Other comorbidities are accepted as long as the pain caused by them is less severe than the pain caused by fibromyalgia.
• Willingness and ability to fully understand the content and scope of the experiment and to comply with the experiment instructions.
• Normal or corrected-to-normal vision.

Healthy controls:

• No history of neurological diseases, chronic pain or musculoskeletal disorders.
• Willingness and ability to fully understand the content and scope of the experiment and to comply with the experiment instructions.
• Normal or corrected-to-normal vision.

Exclusion Criteria:

Fibromyalgia patients:

• Pregnancy
• History of addictive behavior, defined as alcohol, cannabis, opioids or other drugs abuse.
• Presence of fever, tuberculosis, malignant tumors, infectious processes, acute inflammatory processes.
• Lack of cooperation

Healthy controls:

• Pregnancy
• History of chronic pain or musculoskeletal or articular disorders
• History of addictive behavior, defined as alcohol, cannabis, opioids or other drugs abuse.
• Presence of fever, tuberculosis, malignant tumors, infectious processes, acute inflammatory processes.
• Lack of cooperation

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Other: Color Comparison Task; Participants are presented with a series of colored squares and are instructed to compare the colors of two sequentially presented stimuli.; Other: N-back Task; Participants are presented with a sequence of letters and they must indicate whether the current stimulus matches the one presented 2 steps back in the sequence.
Healthy Controls; Volunteers with no clinical history of chronic pain, musculoskeletal or articular disorders.	Other: Color Comparison Task; Participants are presented with a series of colored squares and are instructed to compare the colors of two sequentially presented stimuli.; Other: N-back Task; Participants are presented with a sequence of letters and they must indicate whether the current stimulus matches the one presented 2 steps back in the sequence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of correct answers in the Color Comparison task	Percentage of correct answers over total number of trial in the Color Comparison Task	Immediately after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibromyalgia Impact Questionnaire-Revised version (FIQR)	Instrument for the assessment and evaluation of fibromyalgia patient's status	10 minutes before the intervention
Symptoms Impact Questionnaire (SIQ)	Instrument to assess healthy control's status regarding relevant clinical symptoms experienced in the last week.	10 minutes before the intervention
Hospital Anxiety and Depression Scale (HADS)	Widely used instrument to evaluate anxiety and depression	10 minutes before the intervention
Brief Pain Inventory-Short Form (BPI-SF)	It is an instrument to assess the severity of pain and its impact on functioning.	10 minutes before the intervention
Power in EEG bands	Analysis of EEG spectrum bands	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

Collaborators and Investigators

• Sponsor: National Council of Scientific and Technical Research, Argentina
• Collaborators: Center for Nuclear and Molecular Medicine Entre Ríos
• Investigators: Principal Investigator: José A Biurrun Manresa, PhD, National Council of Scientific and Technical Research, Argentina (CONICET)

Publications and helpful links

General Publications

• Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10. doi: 10.1002/acr.20140.
• Kravitz HM, Katz RS. Fibrofog and fibromyalgia: a narrative review and implications for clinical practice. Rheumatol Int. 2015 Jul;35(7):1115-25. doi: 10.1007/s00296-014-3208-7. Epub 2015 Jan 13.
• Bell T, Trost Z, Buelow MT, Clay O, Younger J, Moore D, Crowe M. Meta-analysis of cognitive performance in fibromyalgia. J Clin Exp Neuropsychol. 2018 Sep;40(7):698-714. doi: 10.1080/13803395.2017.1422699. Epub 2018 Feb 1.
• Adam KCS, Robison MK, Vogel EK. Contralateral Delay Activity Tracks Fluctuations in Working Memory Performance. J Cogn Neurosci. 2018 Sep;30(9):1229-1240. doi: 10.1162/jocn_a_01233. Epub 2018 Jan 8.
• Shalchy MA, Pergher V, Pahor A, Van Hulle MM, Seitz AR. N-Back Related ERPs Depend on Stimulus Type, Task Structure, Pre-processing, and Lab Factors. Front Hum Neurosci. 2020 Oct 28;14:549966. doi: 10.3389/fnhum.2020.549966. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2023
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: June 15, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Electroencephalography; Contralateral Delay Activity; Cognitive task
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Fibromyalgia; Myofascial Pain Syndromes
• Other Study ID Numbers: IS003981

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: The data will be publicly available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No