Background & Aims

Juvenile fibromyalgia (JFM) is a condition mainly affecting adolescent girls characterized by chronic, diffuse widespread pain, but also mood and cognitive symptoms (Kashikar-Zuck et al., 2008).
Although scarce, previous studies in adult fibromyalgia suggest self-referential processing, and self-identity might be directly affected by the disease, in association with abnormal activation and connectivity in regions of the Default Mode Network (DMN), involved in self-related processes and in affectiv e value associated with self-representations (Lee et al., 2018; Napadow et al., 2010). Despite incipient research in adult fibromyalgia, there is a gap in the literature concerning the self-referential processing and self-identity, which have not been addressed in juvenile fibromyalgia, a condition starting much earlier in the development during a critical period of brain and self-identity development.

Methods

53 JFM female patients (mean age=16.41±1.12) and 44 healthy females (mean age=16.1±1.06), comparable in age (p=0.16), ethnicity, caregiver education level and yearly household income (p’s>0.3) underwent a “self/vowel judgement” fMRI task. Participants were shown adjectives in red (self-judgement condition) or green (vowel-counting condition) in a block-design. During red blocks, participants responded with yes/no answers to whether each trait described them now; during green blocks, participants had to count the vowels of the words. Blocks were also divided into general-traits (e.g., generous, irresponsible) and words semantically related to JFM symptoms (e.g., weak, uncomplaining). We will focus on self-judgement blocks. Imaging data were preprocessed using gold-standard pipelines on the CONN Toolbox v.19 running on MATLAB-R2021a. Between-group findings are False Discovery Rate corrected at the cluster level (FDR q<0.05, individual voxel threshold p<0.01), or exploratory when T>3.50

Results

During self-judgement blocks (vs. vowel-counting), JFM patients showed hyperactivation (vs. controls) in the medial prefrontal cortex (T=3.60, qFDR-corr = 0.043) and, at an exploratory level (cluster T>3.50), in the posterior cingulate cortex (T=3.69, puncorrected = 0.012), when compared to healthy controls. During self-judgement of general traits (vs. baseline), JFM patients hyperactivated the left primary motor cortex (T=5.48, qFDR-corr < 0.001). During disease-related traits, the left premotor cortex was hyperactivated (T=4.03, qFDR-corr=0.03) and subthreshold areas in an exploratory fashion (T>3.50, KE>60) were hyperactivated in JFM: bilateral posterior insulas and medial prefrontal cortex.
Patients felt significantly more identified than controls with negative traits, especially those semantically related to JFM symptoms (T=9.64 p<0.001), and less with positive traits, predominantly disease-related (T=7.00 p<0.001). After self-judging, patients felt worse than controls (p<0.001)

Conclusions

Compared to healthy controls, JFM patients hyperactivated nodes of the DMN during self-referential blocks, regions linked with introspection and self-referential cognition (Gusnard et al., 2001; Knyazev, 2013), which may be interpreted as an over-recruitment of brain resources associated with self-representation, consistent with findings linking hyperactivation of the DMN with ruminative thinking (Zhou et al., 2020). Associations between rumination and affect-related symptoms deserve further investigation. Motor regions during self-judgement were related to linguistic production (Neurosynth) and could imply a relevant component of a magnified verbal representation of the self in patients (vs. controls).
Although so far exploratory, findings related to hyperactivation of posterior insulas, areas critically linked to pain integration and nociceptive processing (Peyron & Fauchon, 2019), and a core node of the Default Mode Network, could suggest an integration of pain in the young self

References

Gusnard, D. A., Akbudak, E., Shulman, G. L., & Raichle, M. E. (2001). Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proceedings of the National Academy of Sciences, 98(7), 4259-4264.

Kashikar-Zuck, S., Parkins, I. S., Graham, T. B., Lynch, A. M., Passo, M., Johnston, M., Schikler, K. N., Hashkes, P. J., Banez, G., & Richards, M. M. (2008). Anxiety, mood, and behavioral disorders among pediatric patients with juvenile fibromyalgia syndrome. The Clinical Journal of Pain, 24(7), 620–626. https://doi.org/10.1097/AJP.0b013e31816d7d23

Lee, J., Protsenko, E., Lazaridou, A., Franceschelli, O., Ellingsen, D. M., Mawla, I., Isenburg, K., Berry, M. P., Galenkamp, L., Loggia, M. L., Wasan, A. D., Edwards, R. R., & Napadow, V. (2018). Encoding of Self-Referential Pain Catastrophizing in the Posterior Cingulate Cortex in Fibromyalgia. Arthritis & rheumatology (Hoboken, N.J.), 70(8), 1308– 1318. https://doi.org/10.1002/art.40507

Napadow, V., LaCount, L., Park, K., As-Sanie, S., Clauw, D. J., & Harris, R. E. (2010). Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis and rheumatism, 62(8), 2545–2555. https://doi.org/10.1002/art.27497

Peyron, R., & Fauchon, C. (2019). The posterior insular-opercular cortex: An access to the brain networks of thermosensory and nociceptive processes? Neuroscience letters, 702, 34–39. https://doi.org/10.1016/j.neulet.2018.11.042

Zhou, H. X., Chen, X., Shen, Y. Q., Li, L., Chen, N. X., Zhu, Z. C., Castellanos, F. X., & Yan, C. G. (2020). Rumination and the default mode network: Meta-analysis of brain imaging studies and implications for depression. NeuroImage, 206, 116287. https://doi.org/10.1016/j.neuroimage.2019.116287

Presenting Author

Miguel Montero

Poster Authors

Miguel Montero

MSc

University of Barcelona

Lead Author

Maria Suñol

PhD

University of Barcelona

Lead Author

Jonathan Dudley

PhD

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Lead Author

Tracy V. Ting

Medical Doctor

University of Cincinnati College of Medicine; Cincinnati Children's Hospital Medical Center, Ohio

Lead Author

Robert Coghill

Cincinnati Children's Hospital Med. Ctr.

Lead Author

Susmita Kashikar-Zuck

PhD

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, US

Lead Author

Marina López-Sola

Phd

University of Barcelona

Lead Author

Topics

  • Pain Imaging