Altered Pain Processing and Temporal Dynamics of Brain Microstates in Sickle Cell Disease Adults
Poster No:
2055
Submission Type:
Abstract Submission
Authors:
Joel Dzidzorvi Kwame Disu1, Nahom Mossazghi2, Elizabeth Meinert-Spyker1, Lara Abdelmohsen1, Sossena Wood1
Institutions:
1Carnegie Mellon University, Pittsburgh, PA, 2Carnegie Mellon University, PIttsburgh, PA
First Author:
Co-Author(s):
Introduction:
Pain is a common comorbidity in Sickle Cell Disease (SCD), caused by sickle hemoglobin, deforming red blood cells, and triggering vaso-occlusive crises (VOC) (Rees et al., 2010). VOC pain can develop into chronic pain, affecting over 50% of adults for more than 95% of their days and impacting emotional and social well-being. Quantitative Sensory Testing (QST) uses thermal stimuli to assess pain sensitivity and central/peripheral sensitization (Kenney et al., 2024). Electrophysiology (EEG) also offers further insight into SCD pain through brain microstates-transient neural patterns reflecting functional dynamics (May et al., 2021). Altered microstates C, D, and E, associated with pain intensity and reduced duration, have been observed in fibromyalgia (Osumi et al., 2024). We aim to assess how microstate dynamics during QST contribute to pain perception in SCD. We hypothesize altered mean duration and occurrence of microstates alongside changes in temperature detection and pain thresholds in SCD compared to controls, reflecting abnormal pain processing.
Methods:
We enrolled nine adults in the study, including five healthy controls (age: 28.2 ± 8.41) and four individuals with steady-state SCD (age: 30.25 ± 7.41) screened by genotype (1 HbSC, 2 HbSS, and 1 Hb beta-thalassemia) and pain levels (Brief Pain Inventory: worst and least pain scores of 6.33±1.25 and 1.00±0.82). QST was performed on the non-dominant forearm using a thermal probe to assess central and peripheral sensitization through thermal detection (cold/warm) and pain thresholds (cold/hot) (5 stimuli per condition), with safety limits of 0°C for cold pain and 50.1°C for hot pain. Neural activity was recorded simultaneously via EEG with 32 electrodes at a sampling rate of 5000Hz. EEG data preprocessing included artifact correction, downsampling to 250 Hz, and filtering (0.5–50 Hz). Independent component analysis (ICA) was applied to remove physiological artifacts. Epochs were extracted for each QST test, and k-means clustering identified 5 optimal microstates (Pascual-Marqui et al., 1995), reordered using a second-level clustering algorithm and back fitted to the EEG data. Microstate features were extracted, including mean duration (how long a microstate persists before transitioning) and occurrence (recurrences per second). Independent t-tests compared controls and patients.
Results:
Changes in mean thermal values from the baseline (32°C) differed between controls and SCD across all QST measures (Fig 1A-B). For cold detection, the mean change was (-2.76±1.25°C) in controls and in SCD (-7.67±3.45°C, p=0.16). Cold pain thresholds averaged (-23.23±4.89°C) for controls and SCD (-16.32±5.26°C, p=0.37). Warm detection thresholds were significantly higher in SCD (8.16±3.42°C) compared to controls (2.35±0.41°C, p=0.09). Pain thresholds were slightly lower in SCD (11.78±2.64°C) than in controls (13.31±1.98°C, p=0.65). Microstate mean durations were longer in SCD for A, B, D, and F but shorter for C during detection and pain thresholds respectively. Microstate occurences were higher in controls for A, B, C, and F, but higher in SCD for D across all QST measures (Fig 2A-H).
·Figure 1: Changes in the mean thermal values from baseline (32°C) between 5 Controls and 4 SCD.
·Figure 2: Temporal parameters of microstates between 5 Controls and 4 SCD.
Conclusions:
Our study is the first to our knowledge to perform simultaneous QST and EEG microstate analysis to assess pain processing in SCD. Consistent with the literature, patients with SCD exhibited reduced thermal sensitivity for detection thresholds but heightened sensitivity for pain thresholds (Molokie et al., 2020). Shorter microstate C durations align with studies on migraine and fibromyalgia, suggesting altered salience network activity, and pain processing (Qiu et al., 2023). Longer mean durations A, B, D, and F suggest reduced brain flexibility indicating less dynamic network reorganization. Microstate D, linked to the attention network, occurred more frequently in patients with SCD, possibly reflecting increased cognitive effort tied to neurocognitive deficits. Future work will validate these findings with BOLD signals.
Genetics:
Genetics Other
Modeling and Analysis Methods:
EEG/MEG Modeling and Analysis 2
Novel Imaging Acquisition Methods:
EEG
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Keywords:
ADULTS
Data analysis
Electroencephaolography (EEG)
Experimental Design
Pain
Somatosensory
Other - Sickle Cell Disease, Quantitative Sensory Testing, EEG Microstate Analysis
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
2. May, E. S., Ávila, C. G., Dinh, S. T., Heitmann, H., Hohn, V. D., Nickel, M. M., Tiemann, L., Tölle, T. R., & Ploner, M. (2021). Dynamics of brain function in patients with chronic pain assessed by microstate analysis of resting-state electroencephalography. Pain, 162(12), 2894. https://doi.org/10.1097/j.pain.0000000000002281
3. Molokie, R. E., Wang, Z. J., Yao, Y., Powell-Roach, K. L., Schlaeger, J. M., Suarez, M. L., Shuey, D. A., Angulo, V., Carrasco, J., Ezenwa, M. O., Fillingim, R. B., & Wilkie, D. J. (2020). Sensitivities to Thermal and Mechanical Stimuli: Adults With Sickle Cell Disease Compared to Healthy, Pain-Free African American Controls. The Journal of Pain, 21(9), 957–967. https://doi.org/10.1016/j.jpain.2019.11.002
4. Osumi, M., Sumitani, M., Iwatsuki, K., Hoshiyama, M., Imai, R., Morioka, S., & Hirata, H. (2024). Resting-state Electroencephalography Microstates Correlate with Pain Intensity in Patients with Complex Regional Pain Syndrome. Clinical EEG and Neuroscience, 55(1), 121–129. https://doi.org/10.1177/15500594231204174
5. Pascual-Marqui, R. D., Michel, C. M., & Lehmann, D. (1995). Segmentation of brain electrical activity into microstates: Model estimation and validation. IEEE Transactions on Biomedical Engineering, 42(7), 658–665. IEEE Transactions on Biomedical Engineering. https://doi.org/10.1109/10.391164
6. Qiu, S., Lyu, X., Zheng, Q., He, H., Jin, R., & Peng, W. (2023). Temporal dynamics of electroencephalographic microstates during sustained pain. Cerebral Cortex, 33(13), 8594–8604. https://doi.org/10.1093/cercor/bhad143
7. Rees, D. C., Williams, T. N., & Gladwin, M. T. (2010). Sickle-cell disease. The Lancet, 376(9757), 2018–2031. https://doi.org/10.1016/S0140-6736(10)61029-X