Poster No:
2054
Submission Type:
Abstract Submission
Authors:
Albert Leung1,2, Valerie Le3, Caleb Lopez4, Michael Ho4, Lauren Collin5, Anni Zeynalvand6, Elise kim6, Stephen Kim7, Thomas Rutledge7, Roland Lee8
Institutions:
1UC San Digo, School of Medicine, La Jolla, CA, 2VA San Diego Healthcare System. Center for Pain and Headache Research, San Diego, CA, 3California Health Sciences, College of Osteopathic Medicine, Frensno, CA, 4VA San Diego Healthcare System, Center for Pain and Headache Research, San Diego, CA, 5VA San Diego Healthcare System. Centerf for Pain and Headache Research, San Diego, CA, 6UC San Diego, La Jolla, CA, 7VA San Diego Healthcare System, San Diego, CA, 8UCSD School of Medicine, La Jolla, CA
First Author:
Albert Leung, Professor
UC San Digo, School of Medicine|VA San Diego Healthcare System. Center for Pain and Headache Research
La Jolla, CA|San Diego, CA
Co-Author(s):
Valerie Le
California Health Sciences, College of Osteopathic Medicine
Frensno, CA
Caleb Lopez
VA San Diego Healthcare System, Center for Pain and Headache Research
San Diego, CA
Michael Ho
VA San Diego Healthcare System, Center for Pain and Headache Research
San Diego, CA
Lauren Collin
VA San Diego Healthcare System. Centerf for Pain and Headache Research
San Diego, CA
Stephen Kim
VA San Diego Healthcare System
San Diego, CA
Introduction:
Transcranial magnetic stimulation (TMS) at the prefrontal cortices addresses both depressive and pain symptoms which are highly prevalent in Veterans with Gulf War illness (GWI)(Kuzma & Black, 2006; Rayhan et al., 2013). This study assessed how the severity of depressive symptoms may affect underlying supraspinal prefrontal cortices (PFC) pain modulatory functional connectivity (FC) in the Veterans with GWI-related chronic Headache, And body muscle and joint Pain conditions (GWI-HAP).
Methods:
Veterans in the age range of 18 to 65 years old who served in the Persian Gulf for at least 30 consecutive days between August 1990 and July 1991(Lei et al., 2020), meeting both Center for Disease Control and Prevention (CDC)(Fukuda et al., 1998) and Kansas(Steele et al., 2012) Criteria for GWI and International Headache Society Criteria for Migraine Headaches without aura and study body (muscle and joint) pain criteria were enrolled. Enrolled subjects were divided into two groups based on their Hamilton Rating Scale for Depression (HRSD) scores. Resting functional magnetic resonance imaging (fMRI) was conducted using the GE Discovery MR750w 3T MRI machine. The 8HRBRAIN coil was used to allow for volumetric imaging. During the scanning (approximately 10 mins), the subjects were asked to keep their heads still with eyes closed. Foam pads and earphones were used to keep the participants' heads steady and for them to be able to communicate with the researchers. fMRI data were obtained via a 3T GE scanner with T2*- weighted EPI-sequence (TE = 30 ms, TR = 2.0 s, a = 90°, TH = 4 mm, 32 slices, FOV = 220 × 220 mm2, MA = 64 × 64). In addition, T1-weighted anatomical brain scans were obtained with rapid gradient echo sampling: 168-176 slices T1, 256x256 and 1mm-1.2mm slice thickness. rs-fMRI data analyses were performed using self-grouping Independent Component Analysis (ICA) in CONN(Whitfield-Gabrieli S, 2012) (Nieto-Castanon A, 2021) and SPM (Statistical Parametric Mapping)(Penny WD, 2011).
Results:
rs-fMRI region of interest (ROI)-to-ROI PFC analyses indicated the Veterans with GWI-HAP and moderate to severe depressive symptoms reflected by HRSD score ≥14(GWI≥14, N=33) showed significantly enhanced FC of the left medial prefrontal cortex (PFC) with the adjacent prefrontal cortical area (Brodmann Area[BA] 44; P < 0.001; t = 4.64) and the contralateral Insula(BA 13; P < 0.001; t = 7.14), and two regions of contralateral thalamus(P < 0.01, P < 0.001; t = 5.32, t = 5.25 respectively); and decreased FC with the ipsilateral premotor cortex(BA 6; P < 0.01; t = -3.34) and contralateral anterior cingulate cortex(BA 32; P < 0.001; t = -3.64) than their counterparts with no or mild depressive symptoms with HRSD <14(GWI<14, N=33). The GWI≥14 group demonstrated significantly (P<0.01) more pain symptomology, and functional and quality of life impairments than the GWI<14 group.
Regression analysis demonstrated the McGill Pain Question (MPQ) muscle Pain scale can successfully predict the PFC-thalamus functional connectivity. In addition, MPQ-muscle Pain scale score and HRDS can successfully predict the PFC and SSC2 functional connectivity. However, both parametric (Pearson) and non-parametric (Spearman) correlation analyses indicated a significant (P=0.038, P=0.041) negative correlation between HRSD and PFC-Insula FC correlation coefficient in the GWI≥14 group only, suggesting as the severity of depressive symptom increases, the FC between PFC and insula inversely diminishes.
Conclusions:
These results suggest that both the severities of body pain and co-morbid depressive symptoms can significant impact supraspinal prefrontal pain modulatory functions. Potential neuromodulatory interventions such as transcranial magnetic stimulation applicable for addressing both highly prevalent co-morbid conditions may incorporate this mechanistic correlation in formulating corresponding therapeutic strategy.
Brain Stimulation:
TMS 2
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Keywords:
Headache
Pain
Transcranial Magnetic Stimulation (TMS)
Other - pain modulation, prefrontal cortices
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
Yes
Are you Internal Review Board (IRB) certified?
Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Yes, I have IRB or AUCC approval
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.
Yes
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.
Not applicable
Please indicate which methods were used in your research:
Functional MRI
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
SPM
FSL
Provide references using APA citation style.
Fukuda, K., Nisenbaum, R., Stewart, G., Thompson, W. W., Robin, L., Washko, R. M., Noah, D. L., Barrett, D. H., Randall, B., Herwaldt, B. L., Mawle, A. C., & Reeves, W. C. (1998). Chronic multisymptom illness affecting Air Force veterans of the Gulf War. JAMA, 280(11), 981-988. https://www.ncbi.nlm.nih.gov/pubmed/9749480
Kuzma, J. M., & Black, D. W. (2006). Chronic widespread pain and psychiatric disorders in veterans of the first Gulf War. Curr Pain Headache Rep, 10(2), 85-89. https://doi.org/10.1007/s11916-006-0017-z
Lei, K., Kunnel, A., Metzger-Smith, V., Golshan, S., Javors, J., Wei, J., Lee, R., Vaninetti, M., Rutledge, T., & Leung, A. (2020). Diminished corticomotor excitability in Gulf War Illness related chronic pain symptoms; evidence from TMS study. Sci Rep, 10(1), 18520. https://doi.org/10.1038/s41598-020-75006-8
Nieto-Castanon A, W.-G. S. (2021). CONN functionality connectivity toolbox: RRID SCR_009550. https://doi.org/10.56441/hilbertpress.2161.7292
Penny WD, F. K., Ashburner JT, Kiebel SJ, Nichols TE. (2011). Statistical parametric mapping: the analysis of functional brain images. Elsevier.
Rayhan, R. U., Ravindran, M. K., & Baraniuk, J. N. (2013). Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation. Front Physiol, 4, 181. https://doi.org/10.3389/fphys.2013.00181
Steele, L., Sastre, A., Gerkovich, M. M., & Cook, M. R. (2012). Complex factors in the etiology of Gulf War illness: wartime exposures and risk factors in veteran subgroups. Environ Health Perspect, 120(1), 112-118. https://doi.org/10.1289/ehp.1003399
Whitfield-Gabrieli S, N.-C. A. (2012). Conn: A functinal connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity, 2(3), 125-141.
No