Background & Aims

Central post stroke pain (CPSP) is a frequent consequence of stroke typically developing within 3 – 6 months after a stroke affecting the somatosensory system (Leijion et al., 1989). It is often refractory to medical treatment impairing patients’ quality of life dramatically (Klit et al., 2009). In this study, we aimed to identify changes in functional connectivity between CPSP and non-pain (NPSS) patients before and after the development of pain.

Methods

77 stroke patients were recruited at Charité and followed up over a 6-month period for the occurrence of pain. Resting-state fMRI were performed before the pain (day2-10 days post-stroke) and after the pain (>60 days post-stroke). Seed-to-voxel connectivity analyses were performed using regions identified as different between CPSP and NPSS in structural MRI as seeds. We compared the two groups cross-sectionally using t-tests and also analysed groups by time interaction effects (pFDR< 0.05). Additionally, we looked at whole brain connectivity differences using connectivity gradients (Margulies et al., 2016). Gradients were constructed by decomposing the connectivity matrix using principal component analyses. Using linear regression, we analysed the difference in gradient profiles of 7 yeo networks (Yeo et al., 2011) between the two groups and over time. Results were followed up with bootstrapping (1000 iterations) and permutation tests (1000 iterations) as robustness checks. 

Results

Before pain, CPSP patients had higher functional connectivity between (i) contralesional middle temporal gyrus (MTG) and contralesional temporal fusiform cortex and ipsilesional temporal pole, (ii) bilateral subcallosal gyrus and ipsilesional middle frontal gyrus, and (iii) ipsilesional thalamus and contralesional precuneus. With pain, CPSP showed higher connectivity between contralesional MTG and ipsilesional occipital fusiform gyrus. Group-by-time interaction showed that with pain development connectivity between contralesional MTG and ipsilesional occipital fusiform gyrus decreased only in NPSS while connectivity between MTG and ipsilesional cerebellum crus1 increased in CPSP but decreased in NPSS.
In the network-level gradient analyses, we found a main effect of group in the visual network in G2, which had significantly lower scores in CPSP, and an interaction in the somatomotor network in G1, which had significantly lower scores in CPSP before but not with pain.

Conclusions

We show for the first time that functional connectivity of several brain areas differs between CPSP and NPSS. These changes are present both in regions that have shown structural differences in the two groups, and in whole-brain patterns. The network level differences present already before the onset of pain suggest that this could be an avenue pain prediction after stroke.

References

Klit H, Finnerup NB, Jensen TS. Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol. 2009 Sep;8(9):857-68. doi: 10.1016/S1474-4422(09)70176-0. PMID: 19679277.
Leijon G, Boivie J, Johansson I. Central post-stroke pain–neurological symptoms and pain characteristics. Pain. 1989 Jan;36(1):13-25. doi: 10.1016/0304-3959(89)90107-3. PMID: 2919091.
Margulies DS, Ghosh SS, Goulas A, Falkiewicz M, Huntenburg JM, Langs G, Bezgin G, Eickhoff SB, Castellanos FX, Petrides M, Jefferies E, Smallwood J. Situating the default-mode network along a principal gradient of macroscale cortical organization. Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12574-12579. doi: 10.1073/pnas.1608282113. Epub 2016 Oct 18. PMID: 27791099; PMCID: PMC5098630.
Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zöllei L, Polimeni JR, Fischl B, Liu H, Buckner RL. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011 Sep;106(3):1125-65. doi: 10.1152/jn.00338.2011. Epub 2011 Jun 8. PMID: 21653723; PMCID: PMC3174820.

Presenting Author

Xiuhui Chen

Poster Authors

Xiuhui Chen

MSc

Max Planck Institute for Human Cognitive and Brain Sciences

Lead Author

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Eleni Panagoulas

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences

Lead Author

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Jana Maidhof

Charité – Universitätsmedizin Berlin

Lead Author

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Susanna Asseyer

Charité – Universitätsmedizin Berlin

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Esra Al

Dr.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig

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Kersten Villringer

Charité – Universitätsmedizin Berlin

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Karsten Muller

Prof. Dr.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig

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Thomas Krause

Charité – Universitätsmedizin Berlin

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Gerhard Jan Jungehülsing

Charité – Universitätsmedizin Berlin

Lead Author

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Arno Villringer

Prof. Dr.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig

Lead Author

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Samyogita Hardikar

Dr.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig

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Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Central