Neurochemical and Functional Connectivity Signatures of Resilience in Trauma-Exposed Refugees
Poster No:
1673
Submission Type:
Abstract Submission
Authors:
Nibal Khudeish1,2, Ravichandran Rajkumar1,2, Ezequiel Farrher1, Abdulrahman Sawalma1, Raghad Kiwan1, Shukti Ramkiran1, N. Jon Shah1,3,4,5, Irene Neuner1,2,3
Institutions:
1Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4, Jülich, Germany, 2Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, Aachen, Germany, 3Jülich Aachen Research Alliance - Brain (JARA – BRAIN) – Translational Medicine, Aachen, Germany, Aachen, Germany, 4Institute of Neuroscience and Medicine, Institute of Neuroscience and Medicine (INM-11), Forschungszentrum Jülich GmbH, Jülich, Germany, Jülich, Germany, 5Department of Neurology, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH) Aachen University, Aachen, Germany, Aachen, Germany
First Author:
Nibal Khudeish
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany
Jülich, Germany|Aachen, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany
Jülich, Germany|Aachen, Germany
Co-Author(s):
Ravichandran Rajkumar
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany
Jülich, Germany|Aachen, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany
Jülich, Germany|Aachen, Germany
Ezequiel Farrher
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
Abdulrahman Sawalma
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
Raghad Kiwan
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
Shukti Ramkiran
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4
Jülich, Germany
N. Jon Shah
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Jülich Aachen Research Alliance - Brain (JARA – BRAIN) – Translational Medicine, Aachen, Germany|Institute of Neuroscience and Medicine, Institute of Neuroscience and Medicine (INM-11), Forschungszentrum Jülich GmbH, Jülich, Germany|Department of Neurology, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH) Aachen University, Aachen, Germany
Jülich, Germany|Aachen, Germany|Jülich, Germany|Aachen, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Jülich Aachen Research Alliance - Brain (JARA – BRAIN) – Translational Medicine, Aachen, Germany|Institute of Neuroscience and Medicine, Institute of Neuroscience and Medicine (INM-11), Forschungszentrum Jülich GmbH, Jülich, Germany|Department of Neurology, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH) Aachen University, Aachen, Germany
Jülich, Germany|Aachen, Germany|Jülich, Germany|Aachen, Germany
Irene Neuner
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany|Jülich Aachen Research Alliance - Brain (JARA – BRAIN) – Translational Medicine, Aachen, Germany
Jülich, Germany|Aachen, Germany|Aachen, Germany
Institute of Neuroscience and Medicine, Forschungszentrum Jülich GmbH, Jülich, Germany INM-4|Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany|Jülich Aachen Research Alliance - Brain (JARA – BRAIN) – Translational Medicine, Aachen, Germany
Jülich, Germany|Aachen, Germany|Aachen, Germany
Introduction:
Understanding resilience mechanisms in trauma-exposed populations is vital for precision psychiatry. The thalamus integrates sensory and emotional information, relaying signals between cortical and subcortical regions∧1. Altered thalamic connectivity is linked to PTSD and anxiety disorders∧2.
The posterior cingulate cortex (PCC), part of the default mode network, supports self-referential processing, emotional regulation, and memory integration-functions disrupted in trauma-related conditions∧3. PCC neurochemicals, particularly gamma-aminobutyric acid (GABA) and N-acetylaspartate (NAA) reflect inhibitory control and neuronal integrity, essential for resilience∧4.
This study integrates 7T MR spectroscopy data from the PCC with thalamic rs-FC to examine neurochemical-connectivity relationships in symptomatic and asymptomatic trauma-exposed refugees. We hypothesize that higher GABA and NAA levels will correlate with reduced thalamic connectivity to sensory and salience networks in asymptomatic individuals.
The posterior cingulate cortex (PCC), part of the default mode network, supports self-referential processing, emotional regulation, and memory integration-functions disrupted in trauma-related conditions∧3. PCC neurochemicals, particularly gamma-aminobutyric acid (GABA) and N-acetylaspartate (NAA) reflect inhibitory control and neuronal integrity, essential for resilience∧4.
This study integrates 7T MR spectroscopy data from the PCC with thalamic rs-FC to examine neurochemical-connectivity relationships in symptomatic and asymptomatic trauma-exposed refugees. We hypothesize that higher GABA and NAA levels will correlate with reduced thalamic connectivity to sensory and salience networks in asymptomatic individuals.
Methods:
MR data were collected from 46 right-handed refugees from the Levant region using a 7T MAGNETOM Terra scanner (Siemens Healthineers). Participants were split into symptomatic (n = 23; mean age = 30.3 ± 10.2 years; 7 females) and asymptomatic (n = 23; mean age = 25.2 ± 4.8 years; 6 females) groups based on MINI∧5 and CAPS∧6 assessments. Resilience scores (RS-25) were reported∧7.
Data Acquisition:
Resting-state fMRI data were acquired with TE/TR = 25/2000 ms, across 305 volumes (10 min), with a 168 × 168 matrix, 220 × 220 mm² FOV, and 1.3 mm isotropic resolution. Structural images were obtained using an MP2RAGE sequence (TR/TE = 4500/1.99 ms, 0.75 mm³ resolution). Single-voxel MRS data were collected from the PCC using a STEAM sequence (TE = 4.6 ms, TM = 28 ms, TR = 8200 ms, voxel size = 20 × 20 × 20 mm³, 64 averages).
MRI Data Analysis:
Data were preprocessed and analyzed in CONN (v22.a)∧8 and SPM12 (MATLAB R2024a). Seed-to-voxel analyses targeted eight bilateral thalamic subregions (Human Brainnetome Atlas)∧9. Group differences (Symptomatic > Asymptomatic) were tested at p < 0.001(voxel-level) and p < 0.05 (FDR-corrected cluster-level).
MRS Data Processing:
Spectra were preprocessed (motion, frequency, phase drift corrections) using the FID-A package and quantified in LCModel (6.3-0I).
Statistical Analysis:
Spearman correlations examined relationships between metabolite levels (GABA, NAA) and z-transformed FC values in significant clusters, with FDR correction for multiple comparisons.
Data Acquisition:
Resting-state fMRI data were acquired with TE/TR = 25/2000 ms, across 305 volumes (10 min), with a 168 × 168 matrix, 220 × 220 mm² FOV, and 1.3 mm isotropic resolution. Structural images were obtained using an MP2RAGE sequence (TR/TE = 4500/1.99 ms, 0.75 mm³ resolution). Single-voxel MRS data were collected from the PCC using a STEAM sequence (TE = 4.6 ms, TM = 28 ms, TR = 8200 ms, voxel size = 20 × 20 × 20 mm³, 64 averages).
MRI Data Analysis:
Data were preprocessed and analyzed in CONN (v22.a)∧8 and SPM12 (MATLAB R2024a). Seed-to-voxel analyses targeted eight bilateral thalamic subregions (Human Brainnetome Atlas)∧9. Group differences (Symptomatic > Asymptomatic) were tested at p < 0.001(voxel-level) and p < 0.05 (FDR-corrected cluster-level).
MRS Data Processing:
Spectra were preprocessed (motion, frequency, phase drift corrections) using the FID-A package and quantified in LCModel (6.3-0I).
Statistical Analysis:
Spearman correlations examined relationships between metabolite levels (GABA, NAA) and z-transformed FC values in significant clusters, with FDR correction for multiple comparisons.
Results:
In the asymptomatic group, resilience scores correlated negatively with PCC metabolites:
• GABA (r = −0.541, p = 0.008)
• NAA (r = −0.522, p = 0.011).
GABA and NAA showed a positive correlation (r = 0.573, p = 0.004), linking inhibitory neurotransmission and neuronal health. No significant correlations were found in the symptomatic group.
Seed-to-voxel analysis of the right medial prefrontal thalamus (mPFtha) revealed significant FC differences in sensory and salience networks. In the asymptomatic group, GABA negatively correlated with FC in:
1. Lingual Gyrus, Fusiform Cortex, Vermis (+10, -56, -06; p adj = 0.05).
2. Lateral Occipital Cortex, Occipital Pole (+22,−90,+30; p adj = 0.042).
3. Cerebellum, Lingual Gyrus −10,−58,−08; p adj = 0.05).
No significant correlations were found for NAA or in the symptomatic group.
• GABA (r = −0.541, p = 0.008)
• NAA (r = −0.522, p = 0.011).
GABA and NAA showed a positive correlation (r = 0.573, p = 0.004), linking inhibitory neurotransmission and neuronal health. No significant correlations were found in the symptomatic group.
Seed-to-voxel analysis of the right medial prefrontal thalamus (mPFtha) revealed significant FC differences in sensory and salience networks. In the asymptomatic group, GABA negatively correlated with FC in:
1. Lingual Gyrus, Fusiform Cortex, Vermis (+10, -56, -06; p adj = 0.05).
2. Lateral Occipital Cortex, Occipital Pole (+22,−90,+30; p adj = 0.042).
3. Cerebellum, Lingual Gyrus −10,−58,−08; p adj = 0.05).
No significant correlations were found for NAA or in the symptomatic group.
Conclusions:
This study reveals neurochemical-functional connectivity links with group-specific patterns reflecting resilience. In asymptomatic individuals, higher GABA levels correlated with reduced connectivity in sensory and salience networks, suggesting inhibitory mechanisms supporting resilience. The GABA-NAA relationship highlights the role of inhibitory control and neuronal health in adaptive brain function.
These findings emphasize the value of combining 7T MR spectroscopy and FC analysis to identify neurobiological signatures of resilience and psychiatric vulnerability.
These findings emphasize the value of combining 7T MR spectroscopy and FC analysis to identify neurobiological signatures of resilience and psychiatric vulnerability.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
Task-Independent and Resting-State Analysis 1
Novel Imaging Acquisition Methods:
BOLD fMRI
MR Spectroscopy
Keywords:
Anxiety
FUNCTIONAL MRI
GABA
Magnetic Resonance Spectroscopy (MRS)
MR SPECTROSCOPY
MRI
Psychiatric Disorders
Thalamus
Trauma
Other - Resilience
1|2Indicates the priority used for review
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2. Yin, Y., Jin, C., Hu, X., Duan, L., Li, Z., Song, M., et al. (2011). Altered resting-state functional connectivity of thalamus in earthquake-induced posttraumatic stress disorder: A functional magnetic resonance imaging study. Brain Research, 1411, 98–107.
3. Uddin, L. Q., Kelly, A. M. C., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2009). Functional connectivity of default mode network components: Correlation, anticorrelation, and causality. Human Brain Mapping, 30(2), 625–637.
4. Im, J. J., Namgung, E., Choi, Y., Kim, J. Y., Rhie, S. J., & Yoon, S. (2016). Molecular neuroimaging in posttraumatic stress disorder. Experimental Neurobiology, 25(6), 277.
5. Sheehan, D., Lecrubier, Y., Harnett-Sheehan, K., Janavs, J., Weiller, E., Hergueta, T., et al. (1998). The Mini International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview. Journal of Clinical Psychiatry, 59(Suppl. 20).
6. Weathers, F. W., Blake, D. D., Schnurr, P. P., Kaloupek, D., Marx, B. P., & Keane, T. M. (2015). Clinician-administered PTSD scale for DSM-5 (CAPS-5). Retrieved from National Center for PTSD: https://www.ptsd.va.gov.
7. Wagnild, G. M., & Young, H. M. (1993). Development and psychometric evaluation of the Resilience Scale. Journal of Nursing Measurement, 1(2).
8. Nieto-Castanon, A., & Whitfield-Gabrieli, S. (2022). CONN functional connectivity toolbox: RRID SCR_009550, release 22.
9. Fan, L., Li, H., Zhuo, J., Zhang, Y., Wang, J., Chen, L., et al. (2016). The Human Brainnetome Atlas: A new brain atlas based on connectional architecture. Cerebral Cortex, 26(8), 3508–3526.