Thalamic NAA/Cr reduction and increased connectivity in Parkinson’s disease with pain.
Poster No:
179
Submission Type:
Abstract Submission
Authors:
Jieun Kim1, Jung-Hee Jang1, CHANGJIN JUNG1, Seulgi Eun1, Hyungjun Kim1
Institutions:
1Korea Institute of Oriental Medicine, Daejeon, Korea, Republic of
First Author:
Co-Author(s):
Introduction:
Pain is a prevalent non-motor symptom of Parkinson's disease (PD), affecting a substantial proportion of patients, with reported incidence rates ranging from 40% to 86% (de Tommaso et al., 2016). Pain in PD patients is typically categorized into three subtypes based on underlying mechanisms: nociceptive, neuropathic, and nociplastic pain (Mylius et al., 2021). Emerging evidences suggest that altered thalamic connectivity plays a critical role in the manifestation of non-motor symptoms in PD (Agosta et al., 2014; Owens-Walton et al., 2019). Additionally, previous study has shown correlations between thalamic metabolite ratios, such as N-acetylaspartate to creatine (NAA/Cr), and clinical symptoms in PD (Shoeibi et al., 2022). In this study, we aim to investigate the association between thalamic connectivity, clinical pain, and thalamic metabolite concentrations in PD patients with pain. By exploring these relationships, we seek to advance the understanding of the neural circuitry underlying pain processing in PD.
Methods:
PD patients with pain were recruited for this study, and all participants underwent a MRI scan, including resting-state functional MRI (rs-fMRI) and MR spectroscopy (MRS) runs. Pain severity was assessed using self-reported questionnaires, including the King's Parkinson's Disease Pain Scale (KPPS) and the Numeric Rating Scale (NRS) for clinical pain ratings.
MRI data were acquired using a 3.0T Philips Achieva scanner. Resting-state fMRI (BOLD) parameters were as follows: TR/TE = 1500/35 ms, flip angle = 90°, 46 axial slices, voxel size = 2.75 × 2.75 × 3.2 mm³. Proton MRS (¹H-MRS) spectra were obtained using single-voxel point-resolved spectroscopy (PRESS) with TE/TR = 28/2000 ms and a voxel size of 20 × 20 × 20 mm³, positioned in the left thalamus. Data from 60 PD patients (33 females; mean age 66.9 ± 7.9 years) with pain were included in the analysis.
Rs-fMRI data preprocessing included slice timing correction, head motion correction, nuisance regression, spatial smoothing (6 mm FWHM), temporal filtering (f > 0.008 Hz), and nonlinear registration to the 2009c ICBM152 template using ANTs. MRS data were analyzed using LCModel (Provencher, 2001), and metabolite concentrations were included in statistical analyses only if the Cramer-Rao bounds were <20%.
The left thalamus from the MRS run was used as the seed for functional connectivity analysis. Seed-to-voxel correlation analysis was performed to generate whole-brain connectivity maps for the thalamus. Correlations between thalamic connectivity, clinical pain metrics, and metabolite concentrations were then examined. Statistical thresholds for whole-brain connectivity maps were set at a voxel-wise threshold (Z > 2.56) and a cluster-level significance threshold corrected at p < 0.05.
MRI data were acquired using a 3.0T Philips Achieva scanner. Resting-state fMRI (BOLD) parameters were as follows: TR/TE = 1500/35 ms, flip angle = 90°, 46 axial slices, voxel size = 2.75 × 2.75 × 3.2 mm³. Proton MRS (¹H-MRS) spectra were obtained using single-voxel point-resolved spectroscopy (PRESS) with TE/TR = 28/2000 ms and a voxel size of 20 × 20 × 20 mm³, positioned in the left thalamus. Data from 60 PD patients (33 females; mean age 66.9 ± 7.9 years) with pain were included in the analysis.
Rs-fMRI data preprocessing included slice timing correction, head motion correction, nuisance regression, spatial smoothing (6 mm FWHM), temporal filtering (f > 0.008 Hz), and nonlinear registration to the 2009c ICBM152 template using ANTs. MRS data were analyzed using LCModel (Provencher, 2001), and metabolite concentrations were included in statistical analyses only if the Cramer-Rao bounds were <20%.
The left thalamus from the MRS run was used as the seed for functional connectivity analysis. Seed-to-voxel correlation analysis was performed to generate whole-brain connectivity maps for the thalamus. Correlations between thalamic connectivity, clinical pain metrics, and metabolite concentrations were then examined. Statistical thresholds for whole-brain connectivity maps were set at a voxel-wise threshold (Z > 2.56) and a cluster-level significance threshold corrected at p < 0.05.
Results:
We observed that lower NAA/Cr ratio in the thalamus were associated with increased thalamic connectivity to the substantia nigra, putamen/globus pallidus, and insular cortex. Furthermore, we identified a trend toward a negative correlation between the thalamic NAA/Cr ratio and clinical pain severity (KPPS) in PD patients with pain (r = -0.26, p = 0.051), suggesting that lower NAA/Cr ratio may be associated with greater pain.
Conclusions:
As NAA is widely recognized as a marker of neural integrity, a reduced NAA/Cr ratio in the thalamus may indicate metabolic dysfunction, consistent with previous findings of lower NAA/Cr ratios in the basal ganglia of PD patients compared to healthy individuals. Notably, our results suggest that PD patients with pain exhibit a lower thalamic NAA/Cr ratio, which is associated with greater clinical pain. This reduction in NAA/Cr is further linked to increased thalamic connectivity.
In conclusion, these findings shed light on the metabolic and connectivity-related alterations in the thalamus of PD patients with pain, emphasizing the potential role of neural integrity markers in elucidating PD-associated pain mechanisms.
In conclusion, these findings shed light on the metabolic and connectivity-related alterations in the thalamus of PD patients with pain, emphasizing the potential role of neural integrity markers in elucidating PD-associated pain mechanisms.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral
Keywords:
Degenerative Disease
FUNCTIONAL MRI
Magnetic Resonance Spectroscopy (MRS)
Pain
1|2Indicates the priority used for review
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Provide references using APA citation style.
de Tommaso, M., Arendt-Nielsen, L., Defrin, R., Kunz, M., Pickering, G., & Valeriani, M. (2016). Pain in Neurodegenerative Disease: Current Knowledge and Future Perspectives. Behav Neurol, 2016, 7576292.
Mylius, V., Perez Lloret, S., Cury, R. G., Teixeira, M. J., Barbosa, V. R., Barbosa, E. R., Moreira, L. I., Listik, C., Fernandes, A. M., de Lacerda Veiga, D., Barbour, J., Hollenstein, N., Oechsner, M., Walch, J., Brugger, F., Hagele-Link, S., Beer, S., Rizos, A., Chaudhuri, K. R., Bouhassira, D., Lefaucheur, J. P., Timmermann, L., Gonzenbach, R., Kagi, G., Moller, J. C., & Ciampi de Andrade, D. (2021, Apr 1). The Parkinson disease pain classification system: results from an international mechanism-based classification approach. Pain, 162(4), 1201-1210.
Owens-Walton, C., Jakabek, D., Power, B. D., Walterfang, M., Velakoulis, D., van Westen, D., Looi, J. C. L., Shaw, M., & Hansson, O. (2019). Increased functional connectivity of thalamic subdivisions in patients with Parkinson's disease. PLoS One, 14(9), e0222002. https://doi.org/10.1371/journal.pone.0222002
Provencher, S. W. (2001, Jun). Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed, 14(4), 260-264.
Shoeibi, A., Verdipour, M., Hoseini, A., Moshfegh, M., Olfati, N., Layegh, P., Dadgar-Moghadam, M., Farzadfard, M. T., Rezaeitalab, F., & Borji, N. (2022, Jul 6). Brain proton magnetic resonance spectroscopy in patients with Parkinson's disease. Curr J Neurol, 21(3), 156-161.